FitSugar

Healthy Cooking Tip: Slow Cooker and Steaming

FitSugar — Fri, 14 Nov 2008 08:00:00 -0800

To me, falling temperatures at sunset mean cooked veggies for dinner. Raw carrots just don't cut it when it is sweater weather inside my house. But don't just boil your vegetables, because how you prepare your produce affects its nutritional quality. Two simple methods help preserve vital nutrients: steaming and slow cooking.

Steaming helps veggies retain nutrients better than other methods, especially when compared to boiling. The vitamins and minerals are leached out into the hot water when you throw your veggies into boiling water, but steaming preserves more of the nutrients. The slow cooker is not only convenient, but cooking foods at lower temperatures may help preserve nutrients that can be lost when food is cooked rapidly at high heat, like grilling. Plus it is great to load the slow cooker with a bunch of veggies and lean protein.

This reminds me, I need to find some new recipes for my slow cooker. Got any you want to share?

Source

Avoid Crash Diets: Healthy Weight-Loss Tips

FitSugar — Thu, 10 Sep 2009 03:00:55 -0700

I read a very sad and unfortunate tale of an English bride-to-be's death after crash dieting. After eating only 530 calories a day for 11 weeks, the 34-year-old collapsed. Having weighed 244 pounds at the start of the controversial LighterLife diet, Samantha Clowe had lost 42 pounds when she collapsed and died of heart failure. Her family and fiancé are in my thoughts, and in light of this tragedy, I would like to review five rules for healthy and sustainable weight loss.

To lose weight you need to be in a caloric deficit, meaning you consume fewer calories than you are expending. Think of it like this: calories coming in need to be fewer than calories going out. It really is pretty simple.
To lose one pound a week you need to be in a caloric deficit of 3,500 calories. The best way to do this is to combine eating fewer calories and burning more calories - that means exercise! Cardio is great for burning calories. See these posts for ideas to freshen up your cardio routine.

Learn the other three tips when you continue reading.

Diabetes diet

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lifestyle Changes Essential for People at Risk for Diabetes

Lifestyle interventions that include weight loss, dietary changes, and increased physical activity can definitely help prevent or delay the progression to diabetes among at-risk people, suggest several recent studies. Weight loss through diet and exercise is especially important for overweight people with pre-diabetes.

Grain Fiber Important for Diabetes Prevention

Eating whole-grain, fiber-rich, cereal foods may help reduce the risk of developing type 2 diabetes, indicates a 2007 study in the Archives of Internal Medicine. In the study, people who consumed the most fiber from grains and cereals had a 33% lower risk of developing diabetes than people with the lowest fiber intakes. The study also found an association between high magnesium intake and reduced diabetes risk. Although fruits and vegetables also contain fiber, they did not appear to affect diabetes risk.

Low-Fat Dairy Products

Incorporating low-fat dairy products (such as yogurt and milk) into a healthy diet may help reduce diabetes risk for women, suggests a study in Diabetes Care.

Beware of Internet Dietary Supplement Scams

In 2006, the FDA alerted consumers not to be misled by dietary supplements advertised on the Internet as treatments or cures for diabetes. These products have not been scientifically studied or approved.

Low-Glycemic Index Diets

Food low on the glycemic index -- such as whole grains, fruits, lentils, and soybeans -- can help promote weight loss and heart health. Illustrating the complexity of this area, a 2006 study in the New England Journal of Medicine indicated that a low-carb, low-glycemic index diet was beneficial while another study in the Archives of Internal Medicine suggested advantages for a high-carb, low-glycemic index diet.

Low-Fat Vegan Diets

A low-fat diet that excludes meat and dairy products may help improve glycemic control and increase insulin sensitivity, suggests a Diabetes Care study. Researchers think that the high fiber content of these diets, in addition to their reduced fat, may be a factor.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes. [See In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It normally works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal insulin rises to its peak level.
Insulin then enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

Click the icon to see an image of the liver.

In type 1 diabetes, the disease process is more severe than with type 2, and onset usually begins in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."

Click the icon to see an image of the pancreas.

Patients with type 1 diabetes need to take insulin. Dietary control in type 1 diabetes is very important and focuses on balancing food intake with insulin intake and energy expenditure from physical exertion. [See In-Depth Report #9: Diabetes - type 1.]

Type 2 diabetes is the most common form of diabetes, accounting for up to 95% of all diabetes cases. About 20 million Americans have type 2 diabetes, and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that the disease may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance. Patients whose blood glucose levels are higher than normal, but not yet high enough to be classified as diabetes, are considered to have “pre-diabetes.” It is very important that people with pre-diabetes control their weight to stop or delay the progression to diabetes.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Obesity is common in patients with type 2 diabetes and this condition appears to be related to insulin resistance. The primary dietary goal for overweight type 2 patients is weight loss and maintenance. Studies indicate that when people with type 2 diabetes maintain intensive exercise and diet modification programs, many can minimize or even avoid medications. Weight loss medications or bariatric surgery may be appropriate for some patients. [See In-Depth Report #60: Diabetes - type 2 and In-Depth Report #53: Weight control and diet.]

General Dietary Guidelines

For people who have pre-diabetes, or who are at high risk of developing type 2 diabetes, lifestyle changes of diet and exercise are extremely important. Several studies have shown that lifestyle interventions are very effective in preventing or postponing the progression to diabetes. These interventions are especially important for overweight people -- even moderate weight loss can help reduce diabetes risk.

The American Diabetes Association recommends that people at high risk for type 2 diabetes eat high-fiber (14g fiber for every 1,000 calories) and whole-grain foods. A 2007 study in the Archives of Internal Medicine also suggested that high intake of fiber and magnesium, especially from whole grain cereals and breads, can help reduce type 2 diabetes risk.

For people who have diabetes, the treatment goals for a diabetes diet are:

Achieve near normal blood glucose levels. People with type 1 diabetes and people with type 2 diabetes who are taking insulin or oral medication must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin are now allowing more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. Overweight patients with type 2 diabetes who are not taking medication should aim for a diet that controls both weight and glucose. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

For example, a patient with type 2 diabetes who is overweight and insulin-resistant may need to have a different carbohydrate-protein balance than a thin patient with type 1 diabetes in danger of kidney disease. Because regulating diabetes is an individual situation, everyone with this condition should get help from a dietary professional in selecting the best method.

Healthy eating habits along with good control of blood glucose are the basic goals in managing this complex disease, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.
Lose weight if body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

Several different dietary methods are available for controlling blood sugar in type 1 and insulin-dependent type 2 diabetes:

Diabetic Exchange Lists (for maintaining a proper balance of carbohydrates, fats, and proteins throughout the day)
Carbohydrate Counting (for tracking the number of grams of carbohydrates consumed each day)
Glycemic index (for tracking which carbohydrate foods increase blood sugar)

Tests for Glucose Levels. Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to monitor blood glucose levels carefully. Patients should aim for the following measurements:

Pre-meal glucose levels of 90 - 130 mg/dL
Bedtime levels of 110 - 150 mg/dL

In general, patients who are tightly controlling glucose levels need to take readings four or more times a day. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend that these patients measure blood levels only once or twice a day. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Tests for Glycosylated Hemoglobin. Another test examines blood levels glycosylated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycosylated hemoglobin is useful for determining the severity of diabetes. The test is not affected by food intake so it can be taken at any time. A home test has been developed that may make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Other Tests. Other tests are needed periodically to determine potential complications of diabetes, such as high blood pressure, unhealthy cholesterol levels, and kidney problems. Such tests may also indicate whether current diet plans are helping the patient and whether changes should be made. Annual urine tests showing even microscopic traces of a protein known as albumin can indicate a future risk for serious kidney disease.

For prevention of long-term complications of diabetes, experts now recommend that all patients with diabetes aim at keeping blood levels as close to normal as possible. Such intensive insulin treatment can increase the risk of hypoglycemia, which occurs when blood sugar is extremely low (below 60 mg/dL). The following tips may help avoid hypoglycemia or prepare for attacks.

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients on therapies that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Food Labels. Every year thousands of new foods are introduced, many of them advertised as nutritionally beneficial. It is important for everyone, most especially people with diabetes, to be able to differentiate advertised claims from truth. The current food labels show the number of calories from fat, the amount of nutrients that are potentially dangerous (fat, cholesterol, sodium, sugars) as well as useful nutrients (fiber, carbohydrates, protein, vitamins).

Labels also show "daily values," the percentage of a daily diet that each of the important nutrients offers in a single serving. Unfortunately, the daily value is based on 2,000 calories, generally much higher than most patients with diabetes should have, and the serving sizes may not be equivalent to those on the Exchange Lists. Most people will need to recalculate the grams and calories listed on food labels to fit their own serving sizes and calorie needs.

Weighing and Measuring. Weighing and measuring food is extremely important in order to get the correct number of daily calories.

Along with measuring cups and spoons, choose a food scale that measures grams. (A gram is very small, about 1/28th of an ounce.)
Food should be weighed and measured after cooking.
After measuring all foods for a week or so, most people can make fairly accurate estimates by eye or by holding food without having to measure everything every time they eat.

Timing. Meals should not be skipped, particularly for those who are on insulin. Skipping meals can upset the balance between food intake and insulin and also can lead to weight gain if the patient eats extra food too often to offset low blood sugar levels.

The timing of meals is particularly important for people taking insulin:

Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
They should try to take an insulin injection 30 minutes before they eat, although this timing could vary, depending on the form. Some experts recommend a fast acting insulin (insulin lispro) at each meal and a longer (basal) insulin at night.

Diabetes can lead to kidney disease and failure. People with early-stage kidney failure need to follow a special diet that slows the build-up of wastes in the bloodstream. The diet restricts protein, potassium, phosphorus, and salt intake. Fat and carbohydrate intake may need to be increased to help maintain weight and muscle tissue.

People who have late-stage kidney disease usually need dialysis. Once patients are on dialysis, they must have more protein in their diet. Patients must still be very careful about restricting salt, potassium, phosphorus, and fluids. Patients on peritoneal dialysis may have fewer restrictions on salt, potassium, and phosphorus than those on hemodialysis.

Major Food Components

Compared to fats and protein, carbohydrates have the greatest impact on blood sugar. Both the amount and type of carbohydrate affect blood glucose. Carbohydrate types are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 40 - 65% of the daily caloric intake. Carbohydrate intake should not fall below 130 grams/day. Most experts do not recommend low-carb diets for diabetes management or weight control.

Vegetables, fruits, whole grains, and beans are good sources of carbohydrates. Whole grain foods provide more nutritional value than pasta, white bread, and white potatoes. Brown rice is a better choice than white rice. Patients should try to consume a minimum of 20 - 35 grams of fiber daily (ideally 50 grams/day), from vegetables, fruits, whole grain cereals, breads, nuts and seeds.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over carbohydrates found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most of these are high in fiber, which is important for health. Whole-grains specifically are extremely important for people with diabetes or at risk for it. [For specific benefits, see Box Whole Grains, Nuts, and Fiber-Rich Foods and Table Some Examples of Healthy Foods.]

Simple Carbohydrates (Sugar). Sugars are generally one of two types:

Sucrose (table sugar). Sucrose has been associated with higher triglycerides and harmful cholesterol levels. A 2002 study suggested that a high level of sugar consumption may also reduce levels of HDL cholesterol, the so-called good cholesterol.
Fructose (sugar found in fruits). Fructose may produce a slower increase in blood sugar than sucrose, which may have some advantages for people with diabetes. Dark-colored fruits are rich in important vitamins and other nutrients, and studies continue to report their benefits for the heart and health in general. Other fruits, such as apples and grapes also have important beneficial food chemicals.

Sugar itself, either as sucrose or fructose, adds calories, increases blood glucose levels quickly, and provides no other nutrients. High levels of sugar consumption -- both fructose and sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factor in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice in fact may be singled out as major contributors to childhood obesity.

People with diabetes should avoid products listing more than 5 grams of sugar per serving, and some doctors recommend limiting fruit intake. If specific amounts are not listed, patients should avoid products with either sucrose or fructose listed as one of the first four ingredients on the label. [See Box Fat Substitutes and Artificial Sweeteners.]

Of increasing interest to researchers is possible harm from sugar from advanced glycation end-products (called AGEs). These are end-products of the chemical reaction between sugar and protein. This reaction occurs most intensively when cooking at high temperatures -- particularly animal fats. (Steaming or cooking food in water does not produce these chemicals. Low, slow cooking also produces fewer AGEs.) AGEs can also be formed by chemical reactions in the body itself. They may promote factors in the inflammatory response that cause a number of diseases or their complications, including diabetes and other serious conditions (Alzheimer's, atherosclerosis, cataracts, and osteoporosis).

The Carbohydrate Counting System. Some people plan their carbohydrate intake using a system called carbohydrate counting. It is based on two premises:

All carbohydrates (either from sugar or starch) will raise blood sugar to a similar degree. In general, 1 gram of carbohydrates raises blood sugar by 3 points in people who weigh 200 pounds, 4 points for people who weigh 150 pounds, and 5 points for 100 pounds.
Carbohydrates have the greatest impact on blood sugar; fats and protein play only minor roles.

In other words, the amount of carbohydrates eaten (rather than fats or proteins) will determine how high blood sugar levels will rise. There are two options for counting carbohydrates: advanced and simple. Both rely on collaboration with a doctor, dietitian, or both. Once the patient learns how to count carbohydrates and adjust insulin doses to their meals, many find it more flexible, more accurate in predicting blood sugar increases, and easier to plan meals than other systems.

The basic goal is to balance insulin with the amount of carbohydrates eaten in order to control blood glucose levels after a meal. The steps to the plan are as follows:

The patient must first carefully record a number of factors that are used to determine the specific requirements for a meal plan based on carbohydrate grams:

Multiple blood glucose readings (taken several times a day)
The time of meals
Amount in grams of all the carbohydrates eaten
Time, type, and duration of exercise
The time, type, and dose of insulin or oral medications
Other relevant factors, such as menstruation, illness, and stress

The patient works with the dietitian for two or three 45 - 90 minute sessions to plan how many grams of carbohydrates are needed. There are three carbohydrate groups:

Bread/starch
Fruit
Milk

One serving from each group should contain 12 - 15 carbohydrate grams. (Patients can find the amount of carbohydrates in foods from labels on commercial foods and from a number of books and web sites.)

The dietitian creates a meal plan that accommodates the patient's weight and needs, as determined by the patient's record, and makes a special calculation called the carbohydrate to insulin ratio. This ratio determines the number of carbohydrate grams that a patient needs to cover the daily pre-meal insulin needs.

Eventually, patients can learn to precisely adjust their insulin doses to their meals.

Patients who choose this approach must still be aware of protein and fat content in foods. These food groups may add excessive calories and saturated fats. Patients must still follow basic healthy dietary principles.

The Glycemic Index. The glycemic index helps determine which carbohydrate-containing foods raise blood glucose levels more or less quickly after a meal. The index uses a scale of numbers for specific foods that reflect greatest to least delay in producing an increase in blood sugar after a meal. The lower the index number, the better the impact on glucose levels. Some evidence suggests that the benefit of foods with a low glycemic index is due to their ability to increase insulin levels quickly and so remove blood sugar rather than their ability to slow the release of blood sugar itself.

There are currently two indices in use. One uses a scale of 1 - 100 with 100 representing a glucose tablet, which has the most rapid effect on blood sugar [See Table The Glycemic Index of Some Foods]. The other common index uses a scale with 100 representing white bread (so some foods will be above 100).

A major 2003 analysis suggested that choosing foods with a low glycemic index scores may have a small but significant effect on controlling the surge in blood sugar after meals. Many of these foods are also high in fiber and so have heart benefits as well. Substituting low- for high-glycemic index foods may also help prevent weight gain.

One easy way to improve glycemic index is to simply replace starches and sugars with whole grains and legumes (dried peas, beans, and lentils). However, there are many factors that affect the glycemic index of foods, and maintaining a diet with low glycemic load is not straightforward. The following are some considerations:

The numbers attributed to each carbohydrate-rich food cannot be added to equal a certain number. In other words, adding All Bran cereal (index of 49) to a banana (index of 61) does not equal 110.
Adding certain fats to a food (for example butter to potato) can slow down the food's impact on blood sugar. One study reported that when patients ate fatty foods first, their blood glucose levels were significantly lower an hour after the meal than when carbohydrates were eaten first.
Adding foods with organic acids (pickles, yogurt) to meals may reduce the impact of foods with high glycemic scores on blood sugar. (It should be noted that yogurt alone, however, has the same high glycemic index as regular milk.)

No one should use the glycemic index as a complete dietary guide, since it does not provide nutritional guidelines for all foods. It is simply an indication of how the metabolism will respond to certain carbohydrates. Some experts believe it is too complicated to be practical and that simply tracking carbohydrates, eating healthily, and maintaining a healthy weight is sufficient. Nevertheless, a study on children with type 1 diabetes suggested that the glycemic index offered as many choices as the exchange diet, and they did not report feeling any greater limitations. [For additional information on low-glycemic index diets, see "Heart-Healthy Diets" section of this report.]

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants, (particularly vegetables), fruits, whole grains, nuts, and legumes (dried beans, peanuts, and peas). (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis appears to provide many important benefits, especially for people with type 2 diabetes. Whole grains may even lower the risk for type 2 diabetes in the first place. Of special note, nuts, such as almonds, macadamia, and walnuts may be highly heart protective, independent of their fiber content. However, nuts are high in calories.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly reducing blood pressure as well. Evidence on the heart benefits of beans continues to grow. For example, a 2001 study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may be beneficial. Psyllium is taken from the husk of a seed grown in India. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds), and other products. In a 2002 study, patients with type 2 diabetes who consumed psyllium (Plantaben) for breakfast for 11 weeks experienced lower total and LDL cholesterol levels. There was no difference in glucose or HbA1c levels. Psyllium can increase sodium so people who increase their levels of soluble fiber should also increase water and fluid intake.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat replacer (derived from oats) as part of a low-calorie diet. At the end of 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from your diet can be harmful to general health. Some fat substitutes include:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that their use can allow lower doses of statins (cholesterol -lowering drugs). These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They can be hydrogenated, however, and can contain some trans-fatty acids.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Simply adding snacks containing olestra do not appear to have any effect on cholesterol or weight loss.) However, it can cause cramping and diarrhea. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The adverse health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date do not show any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners in beverages and foods and reduced their sugar intake weighed less over time than those who ate similar types and amounts of drinks and food containing sugar. However, using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain as long as the total caloric intake is under control. There is some public concern about chemicals used to produce many of these sweeteners and adverse effects in studies using rats. Natural low-calorie sweeteners that may be more acceptable to many people are also available. Low-calorie sweeteners include:

Saccharin (Sugar Twin, Sweet n’Low, Sucaryl, and Featherweight). Saccharin has been used for years but is not used as commonly now. Some studies found that large amounts of saccharin caused bladder cancer in rats. Although the rats were fed huge amounts that do not apply to human diets, some evidence suggests that people who have six or more servings of saccharin per day may have an increased risk.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of neurologic disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a rare genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing hydroxyl atoms with chlorine atoms. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the US since 1988 with no reported adverse effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced calorie sweetener is a novel low-calorie sweetener derived from lactose, which is found in dairy products and other foods. It may be specifically beneficial for people with type 2 diabetes and have additional benefits that aid the intestinal tract.
Alitame (Aclame) is formed from amino acids. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been rigorously tested.

Other artificial sweeteners being investigated include, glycyrrhizin (derived from licorice), and dihycrochalcones (derived from citrus fruits).


Based on 100 = a Glucose Tablet
BREADS
pumpernickel	49
sour dough	54
rye	64
white	69
whole wheat	72
GRAINS
barley	22
sweet corn	58
brown rice	66
white rice	72
BEANS
soy	14
red lentils	27
kidney (dried and boiled, not canned)	29
chickpeas	36
baked	43
DAIRY PRODUCTS
milk	30
ice cream	60
CEREALS
oatmeal	53
All Bran	54
Swiss Muesli	60
Shredded Wheat	70
Corn Flakes	83
Puffed Rice	90
PASTA
spaghetti-protein enriched	28
spaghetti (boiled 5 minutes)	33
spaghetti (boiled 15 minutes)	44
FRUIT
strawberries	32
apple	38
orange	43
orange juice	49
banana	61
POTATOES
sweet	50
yams	54
new	58
mashed	72
instant mashed	86
white	87
SNACKS
potato chips	56
oatmeal cookies	57
corn chips	72
SUGARS
fructose	22
refined sugar	64
honey	91
Note. These numbers are general values, but may vary widely depending on other factors, including if and how they are cooked and foods they are combined with.

Protein intake in diabetes is complicated. Protein recommendations vary among experts and depend on various factors. These factors include whether a patient has type 1, type 2, or pre-diabetes. There are additional guidelines for patients who show signs of kidney damage (nephropathy).

In general, diabetes dietary guidelines recommend that proteins should provide 12 - 20% of total daily calories. This daily amount poses no risk to the kidney in people who do not have kidney disease. Protein is important for strong muscles and bone. Some experts recommend a higher proportion of protein (20 - 30%) for patients with pre- or type 2 diabetes. They think that eating more protein helps people feel more full and thus reduces overall calories. In addition, protein consumption helps the body maintain lean body mass during weight loss.

Because protein causes the kidneys to work harder, patients with diabetic nephropathy need to limit their intake of protein. A typical protein-restricted diet limits protein intake to no more than 10% of total daily calories. Patients with kidney damage also need to limit their intake of phosphorus, a mineral found in dairy products, beans, and nuts. (However, patients on dialysis need to have more protein in their diets.) Potassium and phosphorus restriction is often necessary as well.

One gram of protein contains 4 calories. Protein is commonly recommended as part of a bedtime snack to maintain normal blood sugar levels during the night, although studies are mixed over whether it adds any protective benefits against nighttime hypoglycemia. If it does, only small amounts (14 grams) may be needed to stabilize blood glucose levels.

Good sources of protein include fish, skinless chicken or turkey, nonfat or low-fat dairy products, soy (tofu), and legumes (kidney beans, black beans, chick peas, lentils).

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglycerides and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

The most healthy fish are oily fish such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. Three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Some studies have reported a higher incidence of heart attack in men who ate fish daily. Such findings may be due to mercury toxicity, which has harmful effects on the heart. High mercury content has been observed in swordfish and shark and, to some extent, in tuna, trout, pike, tilapia, and bass.

Fish oil supplements may also have some adverse effects on LDL levels and glucose control in type 2 diabetes. More research is needed to further define the risk and benefits of fish, but at this time most guidelines recommend eating fish two or three times a week.

Soy. Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans). Soy sauce is not a good source. It contains only a trace amount of soy and is very high in sodium.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet, but does not recommend using isoflavone supplements.

Meat and Poultry. Lean cuts of meat are the best choice for heart health and diabetes control. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. For patients with diabetes, experts recommend choosing skinless chicken or turkey over red meat. (Fish is an even better choice.) A large, long-term 2006 study found that high heme iron intake from red meat increases the risk of developing type 2 diabetes in women. Another 2006 study suggested that replacing red meat with chicken improves kidney function and lipid levels in patients with diabetic nephropathy.

Dairy Products. A 2002 study reported that a high intake of dairy products can lower risk factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol). Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, because many dairy products are high in saturated fats and calories, doctors recommend that patients choose low-fat and nonfat dairy items. Other studies have indicated that increasing the amount of low-fat diary products in a daily diet may help reduce type 2 diabetes risk, particularly for women.

Some fat is essential for normal body function. Fats can have good or bad effects on health, depending on their chemistry. New research suggests that the type of fat is more important than the total amount of fat when it comes to reducing heart disease.

Current dietary guidelines for diabetes and heart health recommend that total fat be 25 - 35% of total daily calories. Monounsaturated fats (olive oil, canola oil, peanut oil, nuts, avocados) and omega-3 polyunsaturated fats (fish, flaxseed, walnuts) should be the first choice for fats. Omega-6 polyunsaturated fats (corn oil, safflower, oil, sunflower oil, soybean oil) are the second choice. Limit saturated fat to less than 7% of total daily calories. Limit trans-fats (margarine, commercial baked goods, snack and fried foods) to less than 1% of total calories.

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (1 fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what the source, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

Try to replace saturated fats and trans fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids, which are found in fish and plant sources, are a good source of unsaturated fats. Generally, two servings of fish per week provide a healthful amount of omega-3 fatty acids.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. To complicate matters, there are also trans-fatty acids, which are not natural but are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (called hydrogenation).

Harmful Fats. Reducing consumption of saturated fats and trans-fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.)
Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL and raises LDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006.

Beneficial Fats and Oils. Some fat is essential for health, and fat is essential for healthy development in children. Public attention has mainly focused on the possible benefits or hazards of monounsaturated (MUFA) and polyunsaturated (PUFA) fats.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements.

Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing these oils may also be heart-protective. Supplements or foods containing these oils may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Omega-6 polyunsaturated fatty acids are found in corn, safflower, soybean, and sunflower oil. PUFA oils containing omega-6 fatty acids constitute most of the oils consumed in the US. Some omega-6 fatty acids are important for health. However, high intake of these fats may be associated with weight gain in the abdomen (the so-called apple shape), a risk factor for heart disease. High consumption is also associated with a higher risk for certain cancer and some chronic diseases.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Research suggests that a healthy balance of all these fats may be important and that our current Western diet contains an unhealthy ratio of omega-6 to omega-3 fatty acids (10 to 1). Omega-9 fatty acids may also contain chemicals that block harmful factors found in omega-6 fatty acids. Researchers suggest that the most benefits may be found in mixture of all three fatty acids found in both poly- and monounsaturated oils, but in modest amounts that do not add too many calories.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. [See Box Fat Substitutes and Artificial Sweeteners.]

The story on cholesterol found in the diet is not entirely straightforward. The body produces cholesterol naturally or obtains it through meals. Animal-based food products contain cholesterol. High amounts occur in meat, dairy products, egg yolks, and shellfish. (Plant foods, such as fruits, nuts, grains, do not contain cholesterol.) The American Heart Association recommends no more than 300 mg of dietary cholesterol per day for the general population and no more than 200 mg daily for those with high cholesterol.

Antioxidant Vitamins. Vitamins C and E are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. In addition, vitamin E had no effect on preventing cancer or heart disease.

Because of the lack of scientific evidence for benefit, the American Diabetes Association does not recommend regular use of vitamin supplements, except for people who have vitamin deficiencies. Researchers, however, are still studying the treatment possibilities of antioxidants. A 2006 study suggested that alpha-lipoic acid, another type of antioxidant, may have promise as a treatment for diabetic peripheral neuropathy, the nerve damage condition that is a common complication of diabetes.

B Vitamins and Folic Acid. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure.

Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks. Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid, B6, and B12 vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A doctor should prescribe niacin in order to ensure its safety and effectiveness.

Patients with type 2 diabetes who take metformin (Glucophage) should be aware that this drug can interfere with vitamin B12 absorption. Calcium supplements may help counteract metformin-associated vitamin B12 deficiency.

Most experts recommend salt restriction in people who have high blood pressure. Some people, however, are much more sensitive to harmful effects from salt than others:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Simply eliminating table and cooking salt can be beneficial. Salt substitutes, such as Cardia, (containing mixtures of potassium, sodium, and magnesium) are available, but they are expensive. About 75% of the salt in the typical American diet comes from processed or commercial foods, not from food cooked at home, so the benefits of table-salt substitutes are likely to be very modest. Some sodium is essential to protect the heart, but most experts agree that the amount is significantly less than that found in the average American diet. If people cannot significantly reduce the amount of salt in their diets, adding potassium-rich foods might help to restore a healthy balance.

Calcium. Calcium supplements may be important in older patients with diabetes to help reduce the risk for osteoporosis, particularly if their diets are low in dairy products.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. In fact, there is some evidence that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Current guidelines support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people with normal or high blood pressure (who have no risk factors for excess potassium levels). This goal is particularly important in people who have high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

However, patients with diabetic nephropathy (kidney disease) and kidney failure need to restrict dietary potassium, as well as phosphorus. Kidney problems can cause potassium overload and medications commonly used in diabetes, (such as ACE inhibitors or potassium-sparing diuretics), also limit the kidney's ability to excrete potassium. No one should take potassium supplements without consulting a doctor. The best source of potassium is from the fruits and vegetables that contain them.

Magnesium. Magnesium deficiency may have some role in insulin resistance and high blood pressure. Research indicates that magnesium-rich diets may help lower type 2 diabetes risk. Whole grain breads and cereals, nuts (almonds, cashews, soybeans), and certain fruits and vegetables (spinach, avocados, beans) are excellent dietary sources of magnesium. Dietary supplements do not provide any benefit. Persons who live in soft water areas, who use diuretics, or who have other risk factors for magnesium deficiency may require more dietary magnesium than others.

Chromium. Some studies have reported an association between deficiencies in the mineral chromium and a higher risk for type 2 diabetes. Studies on fat rats that were given chromium reported improvement in insulin sensitivity and glucose metabolism. Most studies on type 2 patients, however, reported little or no effect on glucose metabolism and some even reported adverse side effects.

Selenium. Selenium, a trace mineral, does not reduce diabetes risk. In fact, it may increase it. In a 2007 study, researchers found that people who took selenium supplements had more than 1.5 times the risk of developing type 2 diabetes as those who did not take the supplements. The higher the blood level of selenium, the greater the risk. An average healthy diet supplies adequate amounts of selenium and there is no need to take dietary supplements.

Zinc. Many patients with type 2 diabetes are also deficient in zinc; more studies are needed to establish the benefits or risks of taking supplements. Zinc has some toxic side effects, and some studies have associated high zinc intake with prostate cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Traditional herbal remedies for diabetes include bitter melon, fenugreek, and Gymnema sylvestre. These herbs may have properties that help lower blood sugar. However, there have been few well-designed studies and there is not enough evidence to recommend them for prevention or treatment of diabetes.

Several recent preliminary studies suggest that cinnamon may help improve blood sugar and lipid levels. One small study found beneficial effects for people with type 2 diabetes who took between 1 - 6 grams (equivalent to 0.25 - 1.25 teaspoons) of cinnamon each day.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Water. Many heart risk factors, especially those associated with blood clotting, are elevated with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found that light to moderate intake of alcohol may provide protection from heart disease and type 2 diabetes. Some research suggests that alcohol has anti-inflammatory properties that protect arteries from injury. Red wine in particular may have specific benefits for people with type 2 diabetes. It has strong antioxidant effects that benefit the heart. Some evidence also suggests that red wine may improve insulin sensitivity and reduce blood glucose levels and may even protect against type 2 diabetes. The American Diabetes Association recommends limiting alcoholic beverages to 1 drink per day for non-pregnant adult women and 2 drinks per day for adult men.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea is especially is rich in chemicals that offer protection against damaging forms of LDL. In one study, for example, higher intake, particularly by women, was associated with a lower risk for severe coronary artery disease. Black tea has also been associated with heart health. In one study oolong tea, a partially fermented tea, was specifically associated with lower blood sugar levels in patients with type 2 diabetes.

Coffee. Many studies have noted an association between coffee consumption and reduced risk for developing type 2 diabetes. A 2006 study of 29,000 postmenopausal women confirmed this reduced risk. Compared to non-coffee drinkers, women who drank at least 6 cups a day of coffee (either regular or decaf) were 22% less likely to develop type 2 diabetes. Decaffeinated coffee was even more beneficial -- women who drank at least 6 cups a day of decaf were 33% less likely to develop diabetes than women who did not drink coffee. Researchers are still not certain how coffee protects against diabetes. Neither the caffeine in coffee nor the mineral magnesium have a preventive effect. It may be that coffee contains antioxidant properties that protect the pancreas’ insulin-producing cells.

Weight Control for Type 2 Diabetes

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Even modest weight loss can reduce the risk factors for heart disease and diabetes. There are many approaches to dieting and many claims for great success with various fad diets. They include calorie restriction, low-fat/high-fiber, or high protein and fat/low carbohydrates. Some evidence suggests that people may respond differently to specific diets depending on whether their weight is overly distributed around the abdomen.

Lifelong changes in eating habits, physical activity, and attitudes about food and weight are essential to weight management. Unfortunately, although many people can lose weight initially, it is very difficult to maintain weight loss. People with type 2 diabetes may have a particularly difficult time. Here are some general suggestions that may be helpful:

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 7% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29: Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including orlistat (Xenical) and sibutramine (Meridia). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. A non-prescription form of orlistat, Alli, is now available. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Calorie restriction has been the cornerstone of obesity treatment. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, 1 pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds and is mildly active might need only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might need 25 calories per pound (2,025 calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Avoid saturated fats (found in animal products).

Heart-Healthy Diets

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 - 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish -- such as salmon, mackerel, and sardines -- are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Limit beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Dietary guidelines from the National Cholesterol Education Program recommend:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains and legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides or low HDL or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (such as Benecol or Take Control). Avoid trans fatty acids found in commercial products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet's main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Low-carb diets, such as South Beach, The Zone, and Sugar Busters, rely on a concept called the "glycemic index (GI)," which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include white bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans.

A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women. However, another 2006 study suggested that low-glycemic index diets that are high in carbohydrates can also promote weight loss and reduce body fat.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels. A 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides, but had no effect on LDL levels nor insulin or glucose measurements. Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in slightly better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even a moderate weight loss can help improve heart health.

Although low-carbohydrate diets may produce good short-term weight loss, they do not appear to help patients maintain weight loss in the long term. The American Diabetes Association does not recommend low-carb diets (less than 130 g of carbohydrates per day) for treatment of overweight and obesity.

Dietary guidelines recommend keeping total fat intake to 25 - 35% of total daily calories, with saturated fat less than 7% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated and omega-3 polyunsaturated) and bad fats (saturated and trans fats).

Another 2006 study indicated that low-fat, vegan diets may help improve glycemic control and increase insulin sensitivity. The higher fiber content of these diets, plus lower intake of total and saturated fat, may account for some of these benefits. A vegan diet eliminates all meat and dairy products.

The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both, which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein or monounsaturated fats may help reduce heart disease risk factors. [See In-Depth Report #14: High blood pressure.]

Diabetic Exchange Lists

The objective of using diabetic exchange lists is to maintain the proper balance of carbohydrates, proteins, and fats throughout the day. Patients should meet with a dietician or diabetes nutrition expert for help in learning this approach.

In developing a menu, patients must first establish their individual dietary requirements, particularly the optimal number of daily calories and the proportion of carbohydrates, fats, and protein. The exchange lists should then be used to set up menus for each day that fulfill these requirements.

The following are some general rules:

The diabetic exchanges are six different lists of foods grouped according to similar calorie, carbohydrate, protein, and fat content; these are starch/bread, meat, vegetables, fruit, milk, and fat. A person is allowed a certain number of exchange choices from each food list per day.
The amount and type of these exchanges are based on a number of factors, including the daily exercise program, timing of insulin injections, and whether or not an individual needs to lose weight or reduce cholesterol or blood pressure levels.
Foods can be substituted for each other within an exchange list but not between lists even if they have the same calorie count.
In all lists (except in the fruit list) choices can be doubled or tripled to supply a serving of certain foods. (For example 3 starch choices equal 1.5 cups of hot cereal or 3 meat choices equal a 3-ounce hamburger.)
On the exchange lists, some foods are "free." These contain less than 20 calories per serving and can be eaten in any amount spread throughout the day unless a serving size is specified.

The following are the categories on exchange lists:

Starches and Bread. Each exchange under starches and bread contains about 15 grams of carbohydrates, 3 grams of protein, and a trace of fat for a total of 80 calories. A general rule is that a half-cup of cooked cereal, grain, or pasta equals one exchange. One ounce of a bread product is 1 serving.

Meat and Cheese. The exchange groups for meat and cheese are categorized by lean meat and low-fat substitutes, medium-fat meat and substitutes, and high-fat meat and substitutes. Use high-fat exchanges a maximum of 3 times a week. Fat should be removed before cooking. Exchange sizes on the meat list are generally 1 ounce and based on cooked meats (3 ounces of cooked meat equals 4 ounces of raw meat).

Vegetables. Exchanges for vegetables are 1/2 cup cooked, 1 cup raw, and 1/2 cup juice. Each group contains 5 grams of carbohydrates, 2 grams of protein, and 2 - 3 grams of fiber. Vegetables can be fresh or frozen; canned vegetables are less desirable because they are often high in sodium. They should be steamed or cooked in a microwave without added fat.

Fruits and Sugar. Sugars are included within the total carbohydrate count in the exchange lists. Sugars should not be more than 10% of daily carbohydrates. Each exchange contains about 15 grams of carbohydrates for a total of 60 calories.

Milk and Substitutes. The milk and substitutes list is categorized by fat content similar to the meat list. A milk exchange is usually 1 cup or 8 ounces. Those who are on weight-loss or low-cholesterol diets shoudl follow the skim and very low-fat milk lists -- while avoiding the whole milk group. Others should use the whole milk list very sparingly. All people with diabetes should avoid artificially sweetened milks.

Fats. A fat exchange is usually 1 teaspoon, but it may vary. People, of course, should avoid saturated and trans fatty acids and choose polyunsaturated or monounsaturated fats instead.


Calories	1,200	1,500	1,800	2,000	2,200
Starch/Bread	5	8	10	11	13
Meat	4	5	7	8	8
Vegetable	2	3	3	4	4
Fruit	3	3	3	3	3
Milk	2	2	2	2	2
Fat	3	3	3	4	5

Exercise

Sedentary habits, especially watching TV, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercises. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself. (In general, patients with diabetes should aim for a heart rate target of 55 - 85% of their maximum heart rate when exercising.)

Strength Training. Strength training, which increases muscle and reduces fat, may also be helpful for people with diabetes.

Some Precautions for People with Diabetes Who Exercise. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dl or under 100 mg/dl.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.

Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure. [See In-Depth Report #29: Exercise.]

Chronic stress has been associated with the development of insulin resistance, a primary factor in diabetes. Stress can also worsen existing diabetes by impairing the patient's ability to manage the disease effectively. Stress-relieving techniques include meditation, biofeedback, relaxation response, and yoga. One study reported that yoga helped patients with type 2 diabetes reduce their need for oral medications. Studies have also indicated that yoga and Tai Chi (an ancient Chinese exercise involving slow relaxing movements) may lower blood pressure almost as well as moderate-intensity aerobic exercises. [See In-Depth Report #31: Stress.]

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.kidney.org -- National Kidney Foundation
www.joslin.org -- Joslin Diabetes Center
www.eatright.org -- American Dietetic Association
www.nal.usda.gov/fnic -- Food and Nutrition Information Center
www.gourmetconnection.com/diabetic -- Diabetic Gourmet Magazine

References

American Diabetes Association. Nutrition recommendations and interventions for diabetes: A position statement of the American Diabetes Association. Diabetes Care. 2007 Jan;30 Suppl 1:S48-65.

American Heart Association Nutrition Committee; Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006 Jul 4;114(1):82-96. Epub 2006 Jun 19.

Barnard ND, Cohen J, Jenkins DJ, Turner-McGrievy G, Gloede L, Jaster B, et al. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care. 2006 Aug;29(:1777-83.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006 Nov 11;368(9548):1673-9.

Liu S, Choi HK, Ford E, Song Y, Klevak A, Buring JE, et al. A prospective study of dairy intake and the risk of type 2 diabetes in women. Diabetes Care. 2006 Jul;29(7):1579-84.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007 Jul 9; [Epub ahead of print]

Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006 Oct 9;166(18):1975-9.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70.

Review Date:
7/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Vitamins

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

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Review Date:
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Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Heart-healthy diet

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Dietary Changes
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

General Dietary Guidelines

In 2006, the American Heart Association (AHA) revised its dietary and lifestyle recommendations. The new guidelines specifically recommend limiting daily saturated fat intake to less than 7% and trans fats to less than 1% of total daily calories.
The AHA recommends consuming plenty of deep-colored vegetables and fruits, eating oily fish at least twice a week, and including whole grains in your daily diet.

Fish

Women with existing heart disease may consider taking fish oil supplements, suggests 2007 AHA guidelines. Women should include a variety of low-mercury fish in their diet. Women who are of childbearing age or nursing should avoid high-mercury fish (such as swordfish) and limit tuna consumption to no more than 6 ounces a week.
The benefits of fish outweigh its risks, according to a 2006 Journal of the American Medical Association (JAMA) study. The researchers found that eating fish 1 – 2 times a week may help reduce the risk of heart-related death by 36%.

Diet Plans

Low-carbohydrate diets do not increase heart disease risks for women, indicates a 2006 New England Journal of Medicine study. A 2007 JAMA study found that people lost somewhat more weight on the Atkins diet compared with three other popular diet plans. The Atkins diet also helped raise HDL (“good”) cholesterol levels, reduce triglycerides, and improve blood pressure. Some experts think that the weight loss may have been the main factor for the heart benefits.
However, according to a 2006 study in the Archives of Internal Medicine, diets that are high in carbohydrates but low on the glycemic index may also help promote weight loss, reduce body fat, and improve heart disease risk factors.
The Mediterranean diet is better than a low-fat diet in quickly lowering blood pressure, cholesterol levels, and blood sugar levels, according to a 2006 Annals of Internal Medicine study.

Introduction

Heart-Healthy Goals. The goals of a heart-healthy diet are to eat foods that help obtain or maintain healthy levels of cholesterol and fatty molecules called lipids. You can achieve this by:

Reducing overall cholesterol levels and low-density lipoproteins (LDL), which are harmful to the heart
Increasing high-density lipoproteins (HDL), which are beneficial for the heart
Reducing other harmful lipids (fatty molecules), such as triglycerides and lipoprotein(a)

Any diet should also help keep blood pressure and weight under control.

General Recommendations

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

Women

The AHA guidelines for women are similar to the general dietary recommendations. However, the AHA suggests that women with existing heart disease consider taking omega-3 fatty acid supplements (850 - 1,000 mg/day of EPA and DHA). For women with high triglyceride levels, higher doses (2 - 4 g/day) may be appropriate. The AHA recommends against women taking antioxidant vitamin supplements (C, E, beta-carotene) or folic acid supplements for prevention of heart disease.

In addition, women who are pregnant or breast-feeding should avoid eating fish that is high in mercury content (shark, swordfish, mackerel, and tile fish). Choose fish and shellfish that are lower in mercury content and eat about 12 ounces/week. (The AHA recommends a higher weekly fish amount for women than for men. However, women of childbearing age should limit tuna to 6 ounces a week to reduce the risks for mercury contamination.)

Children

Atherosclerosis, the build-up of plaque in the arteries, begins in childhood. Experts stress the importance of heart-healthy dietary guidelines for children and adolescents to help prevent the development of heart disease later in life. Children should eat foods that are low in saturated fat, trans fat, and cholesterol. These foods include:

Fruits and vegetables
Whole grains
Low-fat and nonfat dairy products
Beans, fish, and lean meats

Cholesterol is a soft, waxy substance that is present in parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions, including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

[See In-Depth Report #23: Cholesterol; Report #3: Coronary artery disease and angina; Report #14: High blood pressure; Report #53: Weight control and diet.]

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (one fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what source they are from, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. Trans fatty acids are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (a process called hydrogenation). This process helps keep foods fresh, or may be performed to produce a solid fat product, such as margarine.

Harmful Fats. Reducing consumption of saturated fats and trans fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.) The American Heart Association recommends limiting saturated fat consumption to less than 7% of total calories per day.

Click the icon to see an image of saturated fats.

Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006. The American Heart Association recommends limiting daily consumption of trans fats to less than 1% of total daily calories.

Click the icon to see an image of trans fatty acids.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Click the icon to see an image of omega-3 fatty acids.

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may make heart rhythm problems worse in some patients.
Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia, and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing alpha-linolenic acid may also be heart-protective. Supplements or foods containing alpha-linolenic acid may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Click the icon to see an image of different types of weight gain.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories.

Plants substances known as sterols, and their derivatives called stanols, reduce cholesterol by blocking its absorption in the intestinal tract. Margarines containing sterols (Benecol, Take Control) are available. Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol. In one study, consuming a sterol-based margarine doubled the LDL-lowering effects of a statin (a common cholesterol-lowering drug) compared to a standard margarine. These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They may be hydrogenated and include some trans fatty acids, however.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it helps improve cholesterol levels and may help overweight people lose weight. Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date have not shown any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar. One study suggested that people who consume foods that contain fat substitutes do not learn to dislike fatty foods, while people who learn to cook using foods naturally lacking or low in fat eventually lose their taste for high-fat diets.

Click the icon to see an image of foods that contain cholesterol.

Carbohydrates are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 50 - 60% of the daily caloric intake. Many studies report that people can protect their heart and circulation by eating plenty of fruits and vegetables.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most complex carbohydrates are high in fiber, which is important for health. Whole grains specifically are extremely important for people with diabetes or at risk for it.

Click the icon to see an image of complex carbohydrates.

Simple Carbohydrates (Sugar). Experts recommend that no more than 10% of daily calories should come from sugar. (Currently, Americans eat nearly half a pound of sugar a day on average, and sugar intake constitutes 25% of a day's calories.) Sugars are usually one of two types:

Click the icon to see an image of simple carbohydrates.

Sucrose. Source of most dietary sugar, found in sugar cane, honey, and corn syrup.
Fructose. Found in fruits and vegetables. Although fructose does not appear to be have any different effects in the body than sucrose, most of the fruits and vegetables that contain it are vital for good health.

High levels of sugar consumption -- whether fructose or sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factors in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice are major contributors to childhood obesity.

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants. (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. High-fiber diets (up to 55 grams a day) can be very helpful. Different fiber types may have specific benefits:

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis may lower the risk for heart disease and heart failure, improve factors involved with diabetes, and lower the risk for type 2 diabetes. (Wheat bran taken as a supplement has not been associated with any benefits. The whole grain may be needed for good health.) High consumption of nuts (such as almonds, macadamia, and walnuts) may be highly heart protective, independent of their fiber content.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) may help achieve healthy cholesterol levels and possibly reduce blood pressure as well. For example, one study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%. Oat bran has also been highly studied for its benefits on the heart.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may also be beneficial. Psyllium is taken from the husk of a seed grown in India and is very effective for lowering total and LDL cholesterol. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds, Plantaben), and other products. However, some studies suggest that psyllium increases triglyceride levels in postmenopausal women. Sodium levels may also rise. People who increase intake of soluble fiber should also drink more water.

Click the icon to see an image of soluble and insoluble fiber.

In general, experts recommend that proteins should provide 12 - 20% of daily calories. One gram of protein contains four calories. Protein is important for strong muscles and bones and may have specific benefits on blood pressure. The best sources of protein are fish, poultry, and soy. Restrict intake of red meat or any meat that is not lean.

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglyceride and HDL levels and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

Click the icon to see an image of stroke.

The most healthy fish are oily fish, such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. A 2006 Journal of the American Medical Association (JAMA) study suggested that modest consumption of oily fish can reduce the risk of heart-related death by 36% and death from all causes by 17%. On average, three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Most guidelines recommend eating fish at least twice a week. Doctors may recommend that people with existing heart disease or high triglyceride levels consume extra quantities or take DHA-EPA supplements.

Women of childbearing age or nursing mothers should avoid fish that contains high amounts of mercury (shark, swordfish, golden bass, king mackerel) and limit intake of tuna to 6 ounces/week. They should, however, try to eat at least 12 ounces/week of a variety of lower mercury-containing fish and shellfish (catfish, salmon, haddock, perch, tilapia, trout, crab, shrimp, scallops). According to the JAMA study, the benefits of fish intake (especially from low-mercury fish) outweigh the potential risks.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet but does not recommend using isoflavone supplements.

Meat and Poultry. For heart protection, choose lean meat. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. It is best to eat skinless chicken or turkey. However, the leanest cuts of pork (loin and tenderloin), veal, and beef are nearly comparable to chicken in calories and fat as well as their effect on LDL and HDL levels. However, even chicken and lean meat do not improve cholesterol levels and, in terms of heart health, fish is a more desirable choice.

Dairy Products. The best dairy choices are low-fat or fat-free products. A 2006 study indicated that consuming low-fat dairy products can help lower blood pressure. In the study, patients who ate the most low-fat dairy products had lower systolic blood pressure. A 2002 study also reported a lower incidence of factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol) with a high intake of dairy products. Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, at least with high blood pressure, many studies indicate that the helpful effects of dairy products are not directly related to calcium.


Foods	Important Phytochemicals (Plant chemicals) Contained in the Foods	Vitamins and other valuable food components	Possible Benefits
Apples	Flavonoids	Fiber	May protect against certain cancers (lung), heart disease, asthma, and type 2 diabetes.
Avocados		Vitamin E, vitamin B6, folate	May be heart protective.
Beans	Flavonoids	Folate, iron, potassium and zinc, fiber	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored (especially blueberries)	Ellagic Acid	Vitamin C, minerals	May protect the aging brain. (Many studies recommend blueberries.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, Isothiocyanates	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protects against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, Beta carotene	Vitamin A (converted from carotenoids), vitamin C, fiber	Protect heart, eyes, lungs. (Cooking carrots may increase their benefits.)
Fish (particularly oily fish, such as mackerel, salmon, sardines)		Vitamins B3 and B12, essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Although garlic does not appear to help lower cholesterol levels, it still may protect against heart disease. Possible infection fighter.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes and red wine	Flavonoids, resveratrol		Fight heart disease and cancer. May have activity against asthma, and type 2 diabetes.
Nuts (such as almonds, macadamia, and walnuts)		Vitamin E, Vitamin B1, Essential fatty acids, folate, fiber	May lower cholesterol levels, reduce sudden death rates from heart disease, and help prevent stroke and type 2 diabetes.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung), heart disease, asthma, and type 2 diabetes.
Oranges and orange juice	Monoterpenes	Vitamin C, folate, potassium, fiber	Many health benefits. Increase HDL levels and helps maintain normal blood pressure.
Potatoes (Sweet)		Vitamins A, C, and E	Many health benefits.
Soy: Four ounces of tofu equals about 8 - 13 grams of soy. A soy burger contains about 18 grams of soy.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins		May have effects similar to estrogen, including maintaining bone and benefiting the heart. May protect against prostate cancer and possibly other cancers. Possible protection against mental decline.
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects heart, lungs and brain.
Tomatoes	Lycopene, flavonoids	Vitamin C, biotin, minerals	Protects heart. Studies suggest reductions in prostate and other cancers. Infection fighters.

Antioxidant Vitamins E, C, and A. Vitamins E, C, and A are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants ). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and preventing build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. Results from the long-term Women’s Health Study, also released in 2005, showed that vitamin E supplements do not protect women from attacks or stroke.

Click the icon to see an image of the benefits of vitamin C.

Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful:

Oxygen-free radicals can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including diabetes, cancer, heart disease, cataracts, and even the aging process itself.

They can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of coronary artery disease.

Antioxidant vitamins (A, C, and E), beta carotene, and many phytochemicals can neutralize free radicals and have been studies for possible benefits. It is clear that such vitamins are required to prevent deficiency diseases. In addition, foods rich in antioxidants are important disease fighters. To date, however, there is no strong evidence that antioxidant supplements offer any real protection.

Special Warning on High-Dose Antioxidant Supplements. Some studies suggest that excessive use of antioxidant supplements may interfere with other nutrients or convert into pro-oxidants and become harmful. Some of the findings are as follows:

A 2002 randomized study of postmenopausal women found a higher risk for heart disease in people who took vitamin E and C supplements. A 2005 study found that vitamin E supplements can increase the risk of heart failure, especially for patients with diabetes or vascular diseases.
Of particular concern are studies that have found an increase in lung cancer and overall mortality rate among smokers who took beta carotene supplements. A 2000 study further reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. Even more worrisome, in people with existing cancer, high doses of antioxidant vitamins, such as vitamin C or beta carotene, may actually protect cancer cells (just as they do healthy cells).

Click the icon to see an image of a cataract.

Click the icon to see an image of coronary artery disease.

Click the icon to see an image of phytochemicals.

B Vitamins (Folic Acid). Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid and B6 and B12 vitamins and those who received placebo. And, the vitamins seemed to increase risks for patients who had undergone stenting. A 2006 Journal of the American Medical Association study also found that folic acid supplements did not help reduce the risk of heart disease or stroke in patients with a history of vascular disease. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see an image of sources of folate.

Click the icon to see an image of sources of B12.

Potassium, Magnesium, and Calcium. Some experts believe that sufficient intake of minerals, particularly potassium, magnesium, and calcium, may be even more beneficial than salt restriction for reducing blood pressure.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. Some evidence suggests that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Expert guidelines now support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people who have no risk factors for excess potassium levels. (People who take potassium-sparing diuretics should not take potassium supplements.) This goal is particularly important for people who have a high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.
Magnesium. Some studies report that magnesium supplements may cause small but significant reductions in blood pressure. The recommended daily allowance is 320 mg. People who live in soft water areas, who use diuretics, or who have other risk factors for magnesium loss may require more dietary magnesium than others. No major studies have been done on long-term benefits or risks of magnesium supplements.
Calcium. Calcium regulates the tone of the smooth muscles lining blood vessels. Studies have found that people who consume enough dietary calcium on a daily basis have lower blood pressure than those who do not. Hypertension increases calcium loss from the body. The effects of extra calcium on blood pressure, however, are mixed, with some showing higher pressure.

Click the icon to see an image of sources of calcium.

In the past, everyone was advised to consume less than 2,400 mg (about one teaspoon) of sodium (salt) each day. However, in February 2004, a long-awaited report by the Institute of Medicine (IOM) recommended that individuals slash their salt intake in half. The IOM report stressed that no one should consume more than 1,500 mg/day. Because blood pressure tends to rise with age, the Institute also suggested that people over 50 reduce their sodium intake to less than 1,300 mg daily; those over 70 should not eat more than 1,200 mg a day. Reducing sodium may also help protect against heart failure. Unfortunately many people find it very difficult to achieve these goals. Experts disagree on the overall benefits of salt restriction for everyone. Still, the following people should take particular measures to restrict salt:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African-Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Water. Many heart risk factors, especially those associated with blood clotting, are increased with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found heart protection from moderate alcohol intake (one or two glasses a day). The benefits reported include higher HDL levels, blood clot prevention, and anti-inflammatory properties plus lower rates of heart failure and heart attack. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

On the negative side, an estimated 10% of hypertension cases are caused by alcohol abuse. Men with high blood pressure should limit their intake to an average of no more than one or two drinks a day, and women (especially those at risk for breast cancer) and lighter people should only have one drink a day. (A “drink” is equivalent to a 12-ounce bottle of beer, a 4-ounce glass of wine, or a 1.5-ounce shot of hard liquor.) Alcohol may raise a man’s risk for atrial fibrillation according to a study in the Archives of Internal Medicine. Pregnant women, people who can't drink moderately, and people with liver disease should not drink at all. People who are watching their weight should be aware that alcoholic beverages are very high in calories.

Caffeinated Beverages.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea especially is rich in chemicals that may offer protection against damaging forms of LDL. A 2006 study of Japanese adults who drank high amounts of green tea (3 or more cups a day) found that green tea consumption was associated with reduced risk of death from heart disease. Green tea did not, however, appear to offer any protection against cancer.
Coffee. Coffee, like red wine, contains phenol, which helps prevent oxidation of LDL cholesterol. However, unfiltered coffee (Turkish coffee, Scandinavian boiled or French pressed coffee, and espresso) contains an alcohol called cafestol, which may raise cholesterol and triglyceride levels. Filtered coffee does not contain this residue. Coffee drinking is associated with small increases in blood pressure, but the risk it poses is very small in people with normal blood pressure. Moderate coffee consumption (1 - 2 cups a day) poses no heart risks and a 2006 Circulation study found that long-term coffee consumption did not increase the risk for heart disease in most people, even if they consumed large daily amounts.

Dietary Changes

The Atkins diet restricts healthful complex carbohydrates in vegetables and particularly in fruits that are known to protect against heart disease. The Atkins diet also causes excessive calcium excretion in urine, which increases the risk for kidney stones and osteoporosis, and the release of ketones. An overload of ketones leads to ketosis, which can cause nausea, lightheadedness, and bad breath.

Low-carb diets such as South Beach, The Zone, and Sugar Busters rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

There has been debate about whether Atkins and other low-carbohydrate diets can increase the risk for heart disease, especially as people who follow these diets tend to eat more animal-saturated fat and protein and less fruits and vegetables. A 2006 New England Journal of Medicine study of over 80,000 women found that diets lower in carbohydrates and higher in protein do not increase heart disease risk. In fact, if people select vegetable sources of fat and protein (such as soy and nuts), these diets may even moderately reduce the risk of heart disease.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall cholesterol and LDL (“bad”) cholesterol levels. In contrast, a 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides (although it had no effect on LDL levels). Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even moderate weight loss can help improve heart health.

The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Experts think that the main health benefit of olive oil is oleic acid, which is a type of monounsaturated fatty acid. Olive oil also contains polyphenol, which are phytochemicals that contain antioxidant properties. A 2006 study found that virgin olive oil, which comes from the first pressing of olives, contains a higher polyphenol content than refined olive oil, which comes from later pressings.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Positive Arguments. Even though fats make up about 40% of the calories found in the traditional Mediterranean diet, they are largely unsaturated. Growing evidence continues to support the heart-protective properties of the Mediterranean diet. Research has shown that such a diet reduces the risk for a second heart attack and helps cholesterol-lowering statin drugs work better.

Seniors who combine a Mediterranean diet with healthy lifestyle habits live longer lives, according to a 2004 study in The Journal of the American Medical Associationstudy. Researchers observed the effect of a Mediterranean diet on more than 2,000 elderly people for a period of 10 years, and measured the diet's effects on death rates alone and in combination with three risk factors: smoking, physical activity, and alcohol use. Overall, seniors who followed the Mediterranean diet decreased their risk of death from all causes by 23%. The elimination of each additional risk factor boosted their life expectancy rate even more. For example, non-smoking seniors on the diet who exercised regularly and drank only a moderate amount of alcohol reduced their death rates by 65%.

Negative Arguments. Weight gain due to a high intake of fats and risk for alcohol abuse can be problems with the Mediterranean diet. However, a 2006 study that compared several types of Mediterranean diets to a low-fat diet found that the Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

Other concerns include reduced iron levels and possible calcium loss resulting from a reduced consumption of dairy products. People on the diet should eat foods rich in iron or vitamin C, which aids in iron absorption. They should also ask their doctor if a calcium supplement may be needed because of a lack of dairy products. People should avoid wine if they have risk factors for complications from alcohol. Such people include women who are pregnant or at risk for breast cancer and anyone prone to alcohol abuse.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

DASH diet recommendations:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal.)
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include calcium-rich dairy products that are non- or low-fat.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.)
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with protein-rich foods from plant sources (nuts, seeds, soy) or monounsaturated fats (canola or olive oil) may help reduce heart disease risk factors.

Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

The Ornish program is a very demanding regimen:

It excludes all oils and animal products except nonfat yogurt, nonfat milk, and egg whites.
Foods stressed are whole grains, legumes, and fresh fruits and vegetables.
People in the program exercise for 90 minutes at least three times a week.
Stress reduction techniques are used.
People do not smoke or drink more than two ounces of alcohol per day.

Positive Arguments.

Low-fat programs may help keep weight off.
Low-fat diets that are high in fiber, whole grains, legumes, and fresh produce offer health advantages in addition to their effects on cholesterol. These foods are also lower on the glycemic index than high-glycemic foods such as bread, potatoes, and pasta. Lowering the glycemic index (by, for example, cutting down on starchy vegetables and replacing pasta with whole grains) may help increase weight loss and heart benefits for high-carbohydrate diets.
The Ornish program directors have reported a 91% reduction in angina after 1 year and a 72% reduction after 4 years in spite of significant HDL cholesterol reduction. One study reported that the diet reduced LDL levels to recommended levels without the addition of a cholesterol-lowering drug.

Negative Arguments.

In 2006, the largest study-to-date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 – 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).
The American Heart Association notes that the Ornish program is so difficult to maintain that it will not benefit many people. In a 2007 study comparing various weight loss plans, patients on the Ornish diet lost slightly less weight than those on Atkins. The difficulty of the Ornish diet may have been one factor.
Very low-fat diets may reduce calcium absorption, which may be particularly harmful for women at risk for osteoporosis.
Many people who reduce their fat intake do not consume enough of the basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low fat diets should consume a wide variety of foods and take a multivitamin if appropriate.

Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced, diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calories requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 15% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29:Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including sibutramine (Meridia) and orlistat (Xenical). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Lifestyle Changes

Inactivity is a major risk factor for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol lower their risk for heart disease only when they also follow a regular aerobic exercise program.

Research strongly supports the benefits of exercise on coronary artery disease:

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than do sedentary people. Even moderate exercise reduces the risk of heart attack.
People who lose weight and exercise regularly have a significantly better chance of maintaining weight loss compared to those who do not exercise.
Some studies suggest that for the greatest heart protection, it is not the duration of the exercise that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to confer the greatest protection against coronary artery disease, particularly by raising HDL (the so-called good cholesterol) levels. (It may take up to a year of sustained exercise for HDL levels to show significant improvement, but in terms of raising HDL levels, more is better.)
Aerobic exercise also appears to open up the blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit by reducing LDL (the so-called bad cholesterol) levels.
Exercises that train and strengthen the chest muscles may be very important for patients with angina.

[See In-Depth Report #29: Exercise.]

Stress is always highly associated with negative effects on the heart and other parts of the body. A number of techniques are available to help people relax and reduce tension. [See In-Depth Report #31: Stress.]

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.eatright.org -- American Dietetic Association
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
http://fnic.nal.usda.gov -- Food and Nutrition Information Center

References

Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006 Dec 13;296(22):2720-6.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41.

Djousse L, Pankow JS, Hunt SC, Heiss G, Province MA, Kabagambe EK, et al. Influence of saturated fat and linolenic acid on the association between intake of dairy products and blood pressure. Hypertension. 2006 Aug;48(2):335-41.

Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006 Jul 4;145(1):1-11.

Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 2006 Sep 13;296(10):1255-65.

Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, Stampfer MJ, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006 May 2;113(17):2045-53.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K,et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Mozaffarian D, Prineas RJ, Stein PK, Siscovick DS. Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. J Am Coll Cardiol. 2006 Aug 1;48(3):478-84.

Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99.

Mukamal KJ, Chiuve SE, Rimm EB. Alcohol consumption and risk for coronary heart disease in men with healthy lifestyles. Arch Intern Med. 2006 Oct 23;166(19):2145-50.

Review Date:
4/9/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

adam.com

Calcium

FitSugar — Wed, 08 Oct 2008 17:35:15 -0700

Overview

Overview
Dietary Sources
Available Forms
How to Take It
Precautions
Possible Interactions
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Calcium is the most abundant mineral in the body. It is essential for the development and maintenance of strong bones and teeth, the location of about 99% of the body's calcium. Calcium also helps the heart, nerves, muscles, and other body systems work properly. It is probably best known for its effects in preventing osteoporosis. Your body needs several other nutrients in order for calcium to be absorbed and used properly, including magnesium, phosphorous, and especially vitamins D and K.

The best way to get calcium is through food (see Dietary Sources). But although many foods are fortified with calcium, some people may still need to take calcium supplements. In fact, according to the National Institutes of Health, many Americans consume less than half the amount of calcium recommended to build and maintain healthy bones. It is especially important to get enough calcium as you age. Postmenopausal women, people who consume large amounts of caffeine, alcohol, or soda, and those who take corticosteroid medications may need calcium supplements. Calcium deficiency can be found in people with malabsorption problems, such as Crohn's disease, celiac disease, and surgical intestinal resection.

Getting enough calcium can help prevent or treat the following conditions:

Osteoporosis

Calcium is necessary to help build and maintain healthy bones and strong teeth. Studies have shown that calcium, particularly in combination with vitamin D, can help prevent bone loss associated with menopause, as well as the bone loss experienced by older men. If you do not get enough calcium in your diet, taking a supplement may be necessary.

Hypoparathyroidism

People with this condition have underactive parathyroid glands, which are four small glands that sit on the four corners of the thyroid in the neck and produce a hormone that regulates calcium, phosphorous, and vitamin D levels in the body. People with this condition should follow a high-calcium, low-phosphorous diet as prescribed by their doctor. Most often, they will also need to take calcium supplements.

Premenstrual Syndrome (PMS)

One large, well-designed study showed that women who took 1,200 mg of calcium per day reduced their symptoms of PMS by 50%, including headache, moodiness, food cravings, and bloating. A smaller study suggested that calcium may help reduce menstrual pain.

High Blood Pressure

People who do not get enough calcium may be at higher risk for hypertension, and there is some mixed evidence that suggests increasing calcium levels may lower blood pressure slightly. However, not all studies have found that benefit; and researchers aren’t sure whether calcium supplements would have any benefit, or whether it’s the effects of a diet that includes low-fat dairy products (which contain calcium) that is responsible. If you want to try calcium supplements, do not stop taking your blood pressure medication; talk to your doctor and let the doctor determine the proper dose of calcium for you. You may need to take calcium for 6 - 8 weeks before you see any improvement in blood pressure.

Some studies suggest that calcium supplementation may play a role in the prevention of pregnancy-induced high blood pressure and preeclampsia (a combination of high blood pressure, fluid retention, and high levels of protein in the urine that some women develop in the last trimester of pregnancy). However, not all studies show the same benefit. A prenatal vitamin, which provides magnesium, folic acid, and many other nutrients, together with adequate calcium intake through the diet, may lower the risk of developing high blood pressure during pregnancy.

Obesity

Some animal and human studies have found that consuming low-fat dairy products may help you lose or maintain a proper weight. However, researchers aren’t sure whether the calcium in the dairy products affects weight, some other nutrient -- or even a combination of nutrients. In addition, not all studies have found any benefit; and there’s no sound evidence that calcium supplements (as opposed to dairy products) would help in losing weight. More research is needed.

High Cholesterol

Preliminary studies in animals and people suggest that calcium supplements, in the range of 1,500 to 2,000 mg per day, may help to lower cholesterol slightly. From these studies, it appears that calcium supplements (along with exercise and proper diet) may be better at keeping cholesterol at normal levels than at lowering them once cholesterol is already high. More research in this area is needed.

Rickets

Rickets causes softening and weakening of the bone in children. Although virtually eliminated in North America and Western Europe, where milk consumption is common, it still occurs in many parts of the world. Researchers have thought that rickets is caused by a lack of vitamin D; however, a study in 2000 showed that calcium supplementation is an effective treatment.

Other Uses

Stroke -- In a population-based study (one in which large groups of people are followed over time), women who take in more calcium, both through their diet and with supplements, were less likely to have a stroke over a 14-year period. More research is needed.

Colon Cancer -- Although not all studies agree, some show that people who consume higher amounts of calcium, vitamin D, and milk in their diets are less likely to develop colorectal cancer than those who consume low amounts of the same nutrients. But researchers are not sure whether calcium supplements would have the same effect as calcium in the diet, or even whether calcium itself is responsible for the benefit.

Dietary Sources

The richest dietary sources of calcium include cheeses (such as parmesan, Romano, gruyere, cheddar, American, mozzarella, and feta), low-fat dairy products (milk, yogurt), tofu, and blackstrap molasses. Some other good sources of calcium include almonds, brewer's yeast, bok choy, Brazil nuts, broccoli, cabbage, dried figs, kelp, dark leafy greens (dandelion, turnip, collard, mustard, kale, Swiss chard), hazelnuts, oysters, sardines, and canned salmon,.

Foods that are fortified with calcium, such as juices, soy milk, rice milk, tofu and cereals, are also good sources of this mineral.

Available Forms

There are a number of forms of calcium available as dietary supplements. They differ in the amount of calcium they contain, how well they are absorbed by the body, and how much they cost. The two most popular forms are calcium citrate and calcium carbonate.

Calcium citrate: Easily absorbed and digested by the body, particularly in the elderly. It does not contain as much elemental calcium (the amount your body actually absorbs) as calcium carbonate. It is more costly than calcium carbonate, however. Also, calcium citrate should not be used with aluminum-containing antacids (see Possible Interactions).
Calcium carbonate: Less expensive than calcium citrate and contains more elemental calcium. Requires a certain amount of stomach acid to be absorbed, so it is usually taken with a glass of orange juice. Many antacids contain calcium carbonate.

Calcium supplements that are derived from oyster shells, dolomite, and bone meal are best avoided as they may contain lead, a toxic metal (particularly worrisome in children and those with kidney disease) that can harm the brain and kidneys, cause anemia, and raise blood pressure.

How to Take It

Calcium supplements should be taken in small doses (no more than 500 mg at a time -- that’s all your body can absorb in one dose) throughout the day with 6 - 8 cups of water to avoid constipation.

The following are daily dietary recommendations for general health and prevention of disease.

Pediatric

Talk to your pediatrician before giving a child any nutritional supplement.

Infants birth to 6 months: 210 mg
Infants 7 months to 1 year: 270 mg
Children 1 - 3 years: 500 mg
Children 4 - 8 years: 800 mg
Adolescents 9 - 18 years: 1,300 mg

Adult

19 - 50 years: 1,000 mg
51 years and older: 1,200 mg
Pregnant and breastfeeding females under 19 years: 1,300 mg
Pregnant and breastfeeding females 19 years and older: 1,000 mg

For prevention of colon cancer, 1,800 mg per day may be required.

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable health care provider. Total calcium intake, from combined dietary and supplemental sources, should not exceed 2,500 mg per day.

Side effects can include constipation and stomach upset. Very high doses can cause nausea, vomiting, loss of appetite, increased urination, kidney toxicity, confusion, and irregular heart rhythm.

More generally, such high levels of calcium in the body occur when the body produces too much calcium. People with hyperparathyroidism, kidney failure, sarcoidosis, or cancer could be at risk for elevated levels of calcium and should not take calcium supplements.

People with a history of kidney stones should not take calcium supplements. However, some research suggests that calcium in the diet may not increase the risk of kidney stones. If you have or have had kidney stones, talk to your doctor about whether you should restrict calcium in your diet.

Men at risk for prostate cancer should avoid calcium supplements and also talk to their doctor about restricting low-fat dairy in their diets. Several studies have shown that higher intakes of calcium, whether from supplements or dairy products, are associated with greater risk of prostate cancer.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use calcium supplements without first talking to your doctor.

Alendronate -- Calcium may interfere with the absorption of alendronate, a medication used to treat osteoporosis. Calcium-containing products should be taken at least 2 hours before or after alendronate.

Antacids that contain aluminum -- When calcium citrate is taken with aluminum-containing antacids, the amount of aluminum absorbed into the blood may be increased significantly. This is a particular problem for people with kidney disease, for whom the aluminum levels may become toxic.

Blood pressure medications -- Taking calcium with a beta-blocker (such as atenolol) may interfere with blood levels of both the calcium and the beta-blocker. Study results are conflicting, however. Similarly, it has been reported that calcium interferes with calcium channel blockers (such as verapamil), but these study results are also controversial. If you take a beta-blocker or calcium-channel blocker, do not take calcium supplements without your doctor’s supervision.

Cholesterol-lowering medications -- A class of medications known as bile acid sequestrants (including cholestyramine, colestipol, and colesevelam), used to treat high cholesterol, may interfere with normal calcium absorption and increase the loss of calcium in the urine. Supplementation, therefore, with calcium and vitamin D may be recommended by your health care provider.

Corticosteroids -- If you take corticosteroids on a long-term basis, you may need to take calcium supplements.

Digoxin -- High levels of calcium may increase the risk of a toxic reaction to digoxin, a medication used to treat irregular heart rhythms. On the other hand, low levels of calcium cause digoxin to be ineffective. If you take digoxin, your doctor should monitor your calcium levels closely.

Diuretics -- Different types of diuretics interact with calcium in opposite ways.

Thiazide diuretics (such as hydrochlorothiazide) can raise calcium levels in the blood.
Loop diuretics (such as furosemide and bumetanide) can decrease calcium levels.
Amiloride (a potassium-sparing diuretic) may decrease the amount of calcium excreted in the urine (thus increasing calcium levels in the blood), especially in people with kidney stones.

Estrogens -- Estrogens may contribute to an overall increase in calcium blood levels. Taking calcium supplements with estrogens improves bone density significantly.

Gentamicin -- Taking calcium during treatment with the antibiotic gentamicin may increase the potential for toxic effects on the kidneys.

Antibiotics -- Different types of antibiotics interact with calcium.

Quinolones: Calcium can interfere with the body's ability to absorb quinolone antibiotics (such as ciprofloxacin or Cipro; levofloxacin, norfloxacin or Noroxin; and ofloxacin). Take calcium supplements 2 - 4 hours before or after taking quinolone antibiotics
Tetracyclines: Calcium can interfere with the body's ability to absorb tetracycline antibiotics (including doxycycline, minocycline, and tetracycline). Take calcium supplements 2 -4 hours before or after taking quinolone antibiotics.

Anti-seizure medications -- Some seizure medications, such as phenytoin (Dilantin), carbamazepine, phenobarbitol, and primidone, may lower levels of calcium in the body. Some doctors recommend vitamin D along with anti-seizure drugs to try to keep calcium levels up. In addition, you should take doses of calcium and anti-seizure medications at least 2 hours apart, because each interferes with the absorption of the other.

Supporting Research

Allender PS, Cutler JA, Follmann D, Cappuccio FP, Pryer J, Elliott P. Dietary calcium and blood pressure: a meta-analysis of randomized clinical trials. Ann Intern Med. 1996;124(9):825-831.

Appel L, Moore T, Obarzonek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336:1117-1124.

Baeksgaard L, Andersen KP, and Hyldstrup L. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. Osteoporos Int. 1998;8:255-260.

Balfour JA, Wiseman LR. Moxifloxacin. Drugs. 1999;57(3):363-374.

Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. N Eng J Med. 1999;340:101-107.

Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23(9):1227-1231.

Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms [review]. J Am Coll Nutr. 2000;19(1);3-12.

Blanch J, Pros A. Calcium as a treatment of osteoporosis. Drugs Today. 1999;35:631-639.

Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet. 2000;356:1300-1306.

Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007 Apr;92(4):1415-23.

Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77-84.

Bostick RM, Fosdick L, Grandits GA, Grambsch P, Gross M, Louis TA. Effect of calcium supplementation on serum cholesterol and blood pressure. Arch Fam Med. 2000;9:31-39.

Brouwers JR. Drug interactions with quinolone antibacterials. Drug Safety. 1992;7(4):268-281.

Bryant RJ, Cadogan J, Weaver CM. The new dietary reference intakes for calcium: implications for osteoporosis. J Am Coll Nutr. 1999;18:406S-412S.

Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, LeBoff MS, et al. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Intern Med. 2007 May 14;167(9):893-902.

Chan JM, Stampfer MJ, Ma J, Gann PH, Gaziano JM, Giovannucci EL. Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. Am J Clin Nutr. 2001;74(4):549-554.

Coburn JW, Mischel MG, Goodman WG, Salusky IB. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-711.

Consensus Opinion. The role of calcium in peri- and postmenopausal women: consensus opinion of the North American Menopause Society. Menopause. 2001;8:84-95.

Davies KM, Heaney RP, Recker RR, et al. Calcium intake and body weight. J Clin Endocrinol Metab. 2000;85(12):4635-4638.

Garland CF, Garland FC, Gorham ED. Calcium and vitamin D: their potential roles in colon and breast cancer prevention. Ann NY Acad Sci. 1999;889:107-119.

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Review Date:
6/25/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Cholesterol

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Cholesterol's Effect on the...
Cholesterol's Effect on the...
Risk Factors
Symptoms
Diagnosis
Lifestyle Changes
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Children and Adolescents

In 2007, the American Heart Association (AHA) established new guidelines for assessing and treating high cholesterol in children and adolescents. According to the AHA’s scientific statement:

LDL (“bad") cholesterol goals for children should be 190 mg/dL or less for children without heart disease risk factors and 160 mg/dL or less for children with heart disease risk factors.
Children who are overweight or obese, as well as those with a family history of high cholesterol and heart disease, should get their cholesterol levels checked.
For overweight and obese children with cholesterol imbalances, diet changes and exercise should be tried before drug treatment. For children with cholesterol imbalances who have a family history of cholesterol and heart problems, statins are the best first-line drug therapy.

Herbs and Supplements

Garlic, whether raw or in supplement form, does not help lower LDL in patients with moderately high LDL levels, according to a 2007 Archives of Internal Medicine Study.
Policosanol, a dietary supplement derived from sugar cane, has no effect on cholesterol, indicates a 2006 Journal of the American Medical Association (JAMA) study.

Diet Plans

In a 2007 JAMA comparison study of four diet plans (Atkins, Ornish, Zone, and LEARN), the low-carbohydrate Atkins diet was best at raising HDL (“good cholesterol”) levels and lowering triglyceride levels, but did not affect LDL levels. The low-fat Ornish diet was best at lowering LDL levels.
The Mediterranean diet works better than a low-fat diet in quickly lowering cholesterol as well as blood pressure and blood sugar, suggests a 2006 Annals of Internal Medicine study.

Drug Research

In contrast to research findings released last year, rosuvastatin (Crestor) does not appear to reverse heart disease, according to a 2007 JAMA study. However, the statin drug did help slow the progression of arterial thickening.

Introduction

Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.

Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:

Repairing cell membranes
Manufacturing vitamin D on the skin's surface
Producing hormones, such as estrogen and testosterone
Possibly helping cell connections in the brain that are important for learning and memory

Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products, meat, and dairy products.

Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, coconut, and coconut butter -- are also high in saturated fats.

Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants.

Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the information about the effects of cholesterol and triglyceride actually concerns lipoproteins.

Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.

Cholesterol-Carrying Lipoproteins. These are the lipoproteins commonly referred to as cholesterol.

Low density lipoproteins (LDL). (Often called the "bad" cholesterol.)
High-density lipoproteins (HDL), the smallest and most dense. (Referred to as the "good" cholesterol.)

Triglyceride-Carrying Lipoproteins.

Intermediate density lipoproteins (IDL). They tend to carry triglycerides.
Very low density lipoproteins (VLDL). These tend to carry triglycerides.
Chylomicrons (largest in size and lowest in density).

Lipoprotein(a). Lipoprotein(a), or lp(a) has a size and density somewhere between LDL and HDL. The molecules carry a protein that may interfere with the body's ability to dissolve blood clots. Lipoprotein(a) is being investigated as a possible marker or cause of heart disease.

Remnant Lipoproteins. Remnant lipoproteins are byproducts of chylomicrons, very low-density lipoproteins (VLDL), or both. Some research indicates that high levels may be an important risk factor for coronary artery disease, particularly in patients who have otherwise normal cholesterol levels.

Reducing LDL and total cholesterol levels, while at the same time boosting HDL levels, can prevent heart attacks and death in all people (with or without heart disease). Reducing LDL is the primary goal of most cholesterol therapy.

Blood tests can easily measure both HDL and overall cholesterol levels. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by subtracting HDL and triglyceride levels from total cholesterol. The exact formula is:

LDL = TOTAL CHOLESTEROL - HDL - TRIGLYCERIDES/5.

In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

The risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Two or more of these risk factors increases by 20% the chance of having a heart attack within 10 years.

The LDL cholesterol level is one of the most important factors in determining whether a patient needs cholesterol therapy and whether the treatment is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Risk Level	Goal (d/L)	OptimalGoal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

The following chart summarizes all goals.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dL is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dL or below for people with two or more risk factors; 100 mg/dL is an optimal goal. 160 mg/dL or below for people at less risk (one or zero risk factors); 130 mg/dL is an optimal goal. Anything above 160 is high, with levels above 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/dL are optimal.	Below 150 mg/dL is normal. 150 - 199 is borderline high. 200 - 499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men (before age 65 for women), smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dL. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Although current guidelines as described in the table are extremely useful, they do have pitfalls. For example, the following cholesterol levels pose some dilemmas:

Low LDL levels (protective) accompanied by low HDL, high triglycerides, or both (harmful)
High total cholesterol (harmful) accompanied by high HDL (protective)

Would individuals with these cholesterol balances be at high risk or low risk for developing heart disease? To resolve this dilemma, experts have devised a calculation for a risk ratio by dividing the total cholesterol by either total HDL or LDL. It is not clear at this point which ratio is a better predictor of heart disease, although the HDL ratio may be superior. Using this ratio, the following results indicate better to worse outlook:

The ideal ratio is 3.5 or below.
A ratio of 4.5 carries an average risk.
Ratios of 5 or higher are potentially dangerous.

For example, if a person has a high total cholesterol of 280 mg/dL but a high HDL level of 70 mg/dL, the risk ratio is 4, which actually carries a lower than average risk. The use of this ratio may predict coronary artery disease more accurately than using total cholesterol levels alone. Still, the primary goal of lipid-lowering therapy is reducing LDL levels. Evidence strongly suggests that the lower the LDL levels, the lower the risk for heart disease.

Cholesterol's Effect on the Heart

Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

As many as half of these deaths were probably due to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

Click the icon to see an image of the developmental process of atherosclerosis.

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, the risk is compounded.

The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.

On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.

The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.

Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.

When LDL collects on arterial walls these oxidants are released from the wall membranes.
Oxidants are missing an electron and tend to bind with other molecules in the body, a process called oxidation.
When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.

Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:

White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.

Click the icon to see an image of the cut section of an artery.

Immune factors that increase the risk for blood clots are also mobilized.
Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels and allow blood to flow freely.

High density lipoprotein (HDL) appears to benefit the body in two ways:

It removes cholesterol from the walls of the arteries and returns it to the liver.

Click the icon to see an image of the liver.

It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.

HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.

Triglycerides are major troublemakers for the heart. They appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.

The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.

Some evidence also suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), also known as or lp(a). This lipoprotein falls somewhere between HDL and LDL in density and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, few experts recommend drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences.

Cholesterol's Effect on the Brain

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. A 2002 study suggested that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.

Evidence points to high cholesterol levels, along with high blood pressure and a family history of the disease, as independent risk factors for AD. A major research target for common factors between cholesterol levels and AD has been apolipoprotein E (ApoE). ApoE plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD.

High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. Some studies report that cholesterol is important within the brain for cell communication and memory.

Risk Factors

About half of all American adults have total cholesterol levels over 200 mg/dL. Over 25% have been told by doctors that they have unhealthy levels. Total cholesterol levels have been declining over the last several decades, at least among middle-aged and older adults. This decline may be partly due to the increased use of statins and other lipid-lowering medications. However, total cholesterol levels are getting higher among younger adults (ages 25 – 34 years). The major risk factor for these high rates may be the Western lifestyle. The typical high-fat/low-fiber American diet coupled with sedentary habits is largely responsible for this unfortunate trend.

Men. Heart disease is the major cause of death in men. On average, men develop coronary artery disease 10 - 15 years earlier than women do and have a greater risk for dying of heart disease at a younger age. A 2006 study suggested that high total cholesterol may also contribute to the development of high blood pressure in men.

Women. Coronary artery disease is also the number one killer of women. Women between the ages of 20 and 34, and after menopause (around age 55), have higher cholesterol levels than men. Some evidence suggests that HDL levels may be more significant in women than in men. In one study, at total cholesterol levels above 200, women with HDL levels below 50 had a higher death rate than those with levels above 50, regardless of their LDL cholesterol levels. Women also appear to be more susceptible to the high-triglyceride low-HDL syndrome, which may be a particular risk factor for heart disease.

Children and Adolescents. Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish “normal” cholesterol levels in children. Changes in cholesterol levels occur between the ages of 8 - 18, and vary between genders and population groups. Cholesterol levels tend to naturally rise sharply until puberty, then decrease sharply, and then rise again.

In 2007, the American Heart Association established general LDL goals for children that take into account these fluctuations. The association’s LDL goals are 190 mg/dL or less for children with no additional heart disease risk factors and 160 mg/dL or less for children with additional risk factors (such as family history of high cholesterol, heart disease, and diabetes).

It is also clear that children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Studies have confirmed that childhood LDL levels and body-mass index (BMI) are strongly associated with cardiovascular risk during adulthood. The American Heart Association recommends that children who are overweight and obese, as well as those with a family history of high cholesterol, undergo cholesterol screening. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.

As in adults, the primary source of unhealthy cholesterol levels in children comes from diets high in unhealthy fats: Saturated fats (found mainly in animal and dairy products) and trans fatty acids (found in commercial food products). Over-consumption of unhealthy fats increases the risk for both obesity and heart disease.

Less common causes of unhealthy cholesterol levels in children include:

Low-birth weight (associated with low HDL levels)
Low thyroid levels (hypothyroidism)
Kidney or liver diseases
Homozygous familial hypercholesterolemia. This is an uncommon inherited condition that causes severe cholesterol imbalances and can result in very early heart disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane)

Young and Middle-Aged Adults. The strongest evidence of unhealthy cholesterol levels and heart disease is in adults over age 45. However, a 2006 analysis found that while total cholesterol levels are decreasing among older adults, they are increasing in those age 25 - 34 years. Research strongly suggests that the younger a person is when unhealthy cholesterol levels develop, the greater the chance for serious heart and blood vessel problems in the future. A 2006 study in the New England Journal of Medicine indicated that keeping LDL levels low from an early age can help prevent heart disease later in life. In one important study, young men (ages 16 - 34) who had cholesterol levels at or above 240 mg/dL had two to four times the risk of dying from heart attack or other cardiac problems than did men whose cholesterol was lower than 200 mg/dL. Young men without cholesterol problems had a higher life expectancy, by up to 8 years. Other studies have suggested similar risks from unhealthy cholesterol in young women as well.

Elderly Adults. About 85% of people who die from coronary artery disease are over the age of 65. Because high cholesterol is an important risk factor for heart disease, experts strongly recommend statin or other lipid-lowering therapy for elderly people with high cholesterol levels. Surveys indicate that total cholesterol levels have been declining in older people over the last few decades. Many experts believe this is due in part to increased use of statin drugs.

In the U.S., obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, obese individuals tend to have high triglyceride levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects (high blood pressure, increase in inflammation) that pose major risks to the heart.

Obesity is a particularly hazard when it is one of the components of the metabolic syndrome, formerly known as syndrome X. This syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Many experts recommend that patients with metabolic syndrome should be aggressively treated with high-dose statin therapy to lower LDL levels.

Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.

Low thyroid levels (hypothyroidism) are associated with unhealthy lipid levels. (Lipids are fat molecules). Specifically, people with hypothyroidism are at higher risk for high total and LDL cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition can significantly reduce cholesterol levels. Some experts suggest that patients with high cholesterol should be evaluated for thyroid function before they are given cholesterol-lowering drugs. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels. [See In-Depth Report #38: Hypothyroidism.]

Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.

Genetics play a major role in determining a person's blood cholesterol levels. Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old. Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a).

Some inherited disorders and genetic abnormalities have been identified:

Familial hypercholesterolemia causes dangerous increases in cholesterol. It may be more common than previously thought. One European study reported familial hypercholesterolemia in 1 out of every 400 people.
Familial lipoprotein lipase deficiency is a very rare disorder that causes depletion of lipoprotein lipase. This is an enzyme that appears to be important in the removal of lipoproteins that are rich in triglycerides. People who are deficient in it have high levels of cholesterol and fat in their blood. A very low-fat diet is essential and is an effective treatment for these individuals.
Several studies have found a genetic mutation affecting neuropeptide Y in people with high total cholesterol and LDL levels. Neuropeptide Y is a compound in the brain that regulates appetite.
Researchers have identified a gene called APOAV, which may help detect patients at risk for elevated levels of triglycerides.

Other medical conditions strongly associated with unhealthy cholesterol levels include:

Polycystic ovarian syndrome. Women with this disorder, particularly those who are obese, appear to be at increased risk for high triglyceride and low HDL levels. This risk may be due to higher levels of the male hormone testosterone in these women.

Click the icon to see an image of a polycystic ovary.

Kidney disease

Symptoms

There are no warning signs for high LDL cholesterol levels. When symptoms finally occur, they usually take the form of angina or heart attack in response to the buildup of atherosclerotic plaque in the patient's arteries. This is definitely a condition where it pays to invest in preventive medicine before dangerous complications occur.

Diagnosis

A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated using total cholesterol and HDL levels.

To obtain a reliable cholesterol reading, experts advise:

Avoid strenuous exercise for 24 hours before the test.
Do not eat or drink anything but water for 12 hours beforehand.
If the test results are abnormal, a second test should be performed between 1 week and 2 months after the first test.

Home Tests. Tests are available for home use and in public locations, such as shopping malls and pharmacies. For example, the CholesTrak Test can be taken at home with results in 10 minutes, but it measures only total cholesterol. The BioSafe Cholesterol Panel Test is also a home test, but it needs to be sent to a laboratory. This test, however, is very accurate and provides a full lipid profile.

Certain blood tests for factors associated with inflammation in the arteries indicate a higher risk for heart disease, even in people without unhealthy lipids:

C-reactive protein (CRP). CRP is regulated by a very potent immune factor called interleukin-6. Elevated levels have been strongly associated with the inflammatory response and a higher risk for heart attack, even in people with normal cholesterol levels. CRP is also associated with high blood pressure, insulin resistance (the primary problem in type 2 diabetes), and obesity.
A high white blood cell count.
Elevated fibrinogen (a factor responsible for blood clotting).
Lipoprotein-associated phospholipase A2 may prove to be another marker for inflammation and heart disease. Studies suggest that it may play some causal role in coronary artery disease.

A new type of test measures cholesterol levels in the skin. High skin levels may indicate an increased risk for atherosclerosis and serious heart disease.

General Screening Recommendations. Experts groups differ slightly on when screening should start, but the following are generally accepted recommendations:

Periodic cholesterol testing in all adults starting at age 20. Adults with normal cholesterol levels do not need to have the test repeated for 5 years unless changes occur in lifestyle (including weight gain and diet). Adults with risk factors for heart disease or stroke should be rechecked every 2 years.
Selective screening of children who are at risk for high cholesterol and heart disease or familial hypercholesterolemia, which is genetically elevated cholesterol. Risk factors include having parents with total cholesterol levels greater than 240, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger.
Patients already being treated for high cholesterol should be checked every 2 - 6 months.

Lifestyle Changes

Although most studies that prove that lowering cholesterol saves lives are done using drug therapy, the absolute mandate for improving cholesterol levels is to first make changes in lifestyle (both diet and exercise). Even when drugs are used, healthy diet and physical activity are critical companions.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:·

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. Walnuts in particular have cholesterol-lowering properties and are a good source of antioxidants and alpha-linolenic acid.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart healthy food choice.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After embarking on any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce heart risk factors.

Therapeutic Lifestyle Changes (TLC) from the National Cholesterol Education Program. Guidelines from the National Cholesterol Education Program include these recommendations for preventing and managing high cholesterol levels in adults:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains, legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides, low HDL, or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (Benecol, Take Control). Avoid trans fatty acids found in commercial baked products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit dietary cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

Mediterranean Diet. The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Olive oil also contains polyphenol, which are phytochemicals that may help boost HDL levels.

A 2006 study that compared several types of Mediterranean diets to a low-fat diet found that Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season with garlic, onions, and herbs. Unfortunately, garlic does not appear to help lower cholesterol, but it may have other heart benefits. [See Herbs and Supplements in this section.]

Low-Carbohydrate Diets. The Atkins, South Beach, The Zone, and other diet restrict carbohydrate intake include. A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels.

In contrast, a 2007 Journal of the American Medical Association study that compared four different low-carbohydrate and low-fat diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet was best at raising HDL levels and reducing triglyciderides. In terms of LDL reduction, the low-fat Ornish diet produced the best improvements while the Atkins diet had no effect on LDL. The Atkins diet did result in better moderate weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors.

Glycemic Index. Low-carb diets -- such as South Beach, The Zone, and Sugar Busters -- rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. (These low-glycemic foods are also important components of low-fat diet plans.) A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

Low Fat Diets. Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories. In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).

The DASH Diet. The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure).
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein (from mostly plant sources) or monounsaturated fats may help reduce heart disease risk factors.

Calorie Restriction. Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).

Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Inactivity is one of the four major risk factors for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program.

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than sedentary people. Even moderate exercise reduces the risk of heart attack. One study of women found that just 1 hour of walking a week was associated with a lower risk for heart disease. The effects were similar even in women at high risk for developing heart disease.
Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to offer the greatest protection against coronary artery disease, most likely because it raises HDL ("good cholesterol") levels. Moderate exercise has little effect on HDL.
Aerobic exercise helps to open up blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit to aerobics by reducing LDL ("bad cholesterol") levels.
Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Cigarette smoking lowers HDL and is directly responsible for approximately 20% of all deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels in people exposed to cigarette smoke.

A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all.

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following natural remedies are of interest for cholesterol control:

Garlic. Contrary to popular belief, garlic does not significantly reduce cholesterol, according to a 2007 Archives of Internal Medicine study. Researchers tested raw garlic and two types of garlic supplements in 192 patients with moderately high LDL levels. None of the forms of garlic had any effect on LDL levels. However, the researchers note that garlic may still help people with very high LDL levels and it may contain other heart-protective properties.

Policosonol. Policosanol is a nutritional supplement derived from sugar cane that has been promoted as having lipid-lowering benefits. In a randomized, placebo-controlled trial published in 2007 in the Archives of Internal Medicine, policosanol was no better than placebo in reducing LDL levels.

Treatment

In 2004, the National Cholesterol Education Program issued its latest recommendations for cholesterol control and management. These guidelines increase the number of Americans who should be taking LDL-lowering medication.

Starting Medications. Even modest lowering of high cholesterol levels, whether through drug therapy or lifestyle changes, reduces the risk of disability and death from heart disease. Most experts now focus on lowering LDL ("bad") cholesterol. Reducing LDL levels is particularly critical for patients with diabetes.

The doctor will start or consider medication when:

LDL cholesterol is 190 mg/dL or higher.
LDL cholesterol is 160 mg/dL or higher AND patient has one risk factor for heart disease.
LDL cholesterol is 130 mg/dL or higher AND patient has either diabetes or two other risk factors for heart disease.
LDL cholesterol is 100 mg/dL or higher AND patient has heart disease. (If patient has diabetes, even without heart disease, medication may be considered for an LDL cholesterol of 100 mg/dL.)
LDL cholesterol is greater than 70 mg/dL AND patient has had a recent heart attack or has known heart disease along with diabetes, current cigarette smoking, poorly controlled high blood pressure, or the metabolic syndrome (high triglycerides, low HDL, and obesity).

Risk factors for heart disease include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Recent studies have found that aggressive lipid lowering with high-dose statin therapy is more beneficial than standard statin therapy in patients with existing heart disease. The Pravastatin or Atorvastatin Evaluation and Infection Trial (PROVE-IT) and the Reversal of Atherosclerosis with Aggressive Lipid-Lowering trial (REVERSAL) compared the benefits of standard statin therapy (pravastatin, 40 mg) with intensive statin therapy (atorvastatin, 80 mg) in treating patients with heart disease.

Results from PROVE-IT demonstrated that for high-risk patients, intensive statin therapy is more effective than standard therapy in lowering LDL cholesterol and C-reactive protein (CRP) levels, and that CRP levels predict risk even when LDL cholesterol has been lowered substantially. The REVERSAL data suggest that intensive statin therapy produces greater reductions in LDL and CRP levels, and that the more that statins can lower LDL, the more effective they are in reducing the progression of atherosclerosis.

An important 2006 study found that aggressive treatment with rosuvastatin (Crestor):

Helped lower LDL to below guideline levels
Moderately increased HDL levels
Reduced fatty plaque in the arteries

Experts hoped that these results suggested that statin therapy might have the potential to reverse coronary atherosclerosis. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue and to explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than other statins, but it also carries greater risks for more serious side effects (see Adverse Effects section). Many experts believe that the more that LDL is reduced through statin therapy, the greater the reduction in risk for heart disease, heart attack, and stroke.

It is important to emphasize that cholesterol-lowering medications are used along with healthy lifestyle habits, not in place of them.

Choosing the Correct Lipid-Lowering Medication. Experts now recommend that drug treatments be tailored for raising or lowering specific lipids, depending on the patient's blood lipid picture:

Statins are now the standard drugs for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. If LDL goals are not achieved, combinations of a statin with a bile-acid resin or niacin should be considered.
Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

Considerations for Children and Adolescents. In 2007, the American Heart Association (AHA) issued a scientific statement addressing the use of cholesterol drugs in children and adolescents. The AHA recommends that for children who are overweight or obese, lifestyle modifications (diet, exercise) are preferred over drug therapy and should be the first step in lowering cholesterol.

For children and adolescents who have high-risk cholesterol imbalances -- and have a family history of high cholesterol, heart attack, stroke, and diabetes -- the AHA now recommends statins as the first-line drug therapy.

Considerations for People with Diabetes. At this time, statins are recommended as the best drugs for improving cholesterol and lipid levels in people with diabetes. Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Furthermore, in one study, a statin was shown to reduce the risk of developing diabetes by 30% in people with high cholesterol. Fibrates may also be useful for people with type 2 diabetes. Niacin (nicotinic acid) has the best effect on the cholesterol profile of people with diabetes but it also increases blood sugar levels. One well-controlled study, however, found that people with diabetes who used niacin had little trouble with glucose control, and some experts believe it now may be used as an alternative to or in combination with statins.


	Effect on High LDL	Effect on Low HDL	Effect on High Triglycerides	Effect on Lp(a)
Statins	Decrease (18 - 55%)	Modest increase (5 - 15%)	Decrease (7 - 30%)	No change
Nicotinic acid (Niacin)	Modest decrease (5 - 25%) In combination with statins, may convert more dangerous LDL type to less dangerous.	Increase (15 - 35%) Drugs of choice for improving HDL levels	Decrease (20 - 50%) Drug of choice for lowering triglycerides	Decrease
Fibrates	Effect varies, but in general has little effect or modest decrease (5 - 20%)	Modest increase (6 - 20%)	Decrease (20 - 50%)	No change
Bile acid-binding resins	Decrease (15 - 30%)	Very modest increase (3 - 5%)	No change	No change

Statins are the most effective drugs for the treatment of high cholesterol, and may even prove important drugs for many people at risk for heart disease who have normal cholesterol levels. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks, in both adult women and men of any age with unhealthy cholesterol levels. Experts estimate a 25 - 30% reduction in mortality rates when patients take statins after a heart attack. (Some believe the decrease may even be greater.) These drugs may also help improve the outcome in patients with heart disease who have had angioplasty.

Important studies have reported lower rates of heart attack, stroke, and mortality rates from all causes in statin users who were at high risk for heart disease, even if they had normal or low cholesterol levels. Benefits were similar in these people regardless of gender, age, or the presence of specific heart risk factors, such as diabetes or peripheral artery disease.

Brands. Statins are currently categorized into four groups:

So-called natural statins, including lovastatin (Mevacor, generics), pravastatin (Pravachol), and simvastatin (Zocor, generics). These are the most studied statins and have proven effectiveness and good safety record.
Synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor). Studies using atorvastatin suggest they may reduce LDL more effectively than natural statins. In 2007, Lipitor was approved for additional indications to reduce the risk of heart attacks, strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is also approved for children.
The newer statins include rosuvastatin (Crestor), which was approved in 2003. Trial results have suggested that rosuvastatin is more effective in improving lipid profiles than atorvastatin, simvastatin, or pravastatin. However, like all statin drugs, rosuvastatin can cause serious side effects (see the Adverse Effects section in this report). The risks may be higher for Asian patients; this population should be started on the lowest rosuvastatin dose (5 mg).
Fixed-dose combination statins, which combine two drugs in one pill, first appeared on the market in 2004. Ezetimibe/simvastatin (Vytorin) combines two cholesterol medications that work in different ways. Simvastatin blocks cholesterol production in the liver, while ezetimibe (a non-statin cholesterol medication) blocks cholesterol absorption in the digestive tract. A 2005 study found that Vytorin was more effective than atorvastatin in lowering LDL and increasing HDL levels. Amlodipine/atorvastatin (Caduet) is a dual-therapy medication that combines the antihypertensive calcium channel blocker amlodipine with atorvastatin. It is used to treat simultaneously high blood pressure and high cholesterol.

Statins are generally administered once a day, typically in the evening because most cholesterol synthesis occurs between midnight and 3 a.m. (Atorvastatin and rosuvastatin, however, can be taken in the morning.) Statins are often prescribed along with other cholesterol-lowering drugs such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.

Beneficial Effects on the Heart and Circulation.

Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs. (The newer statins appear to produce more significant increases in HDL.) Evidence now strongly suggests that statins may offer other health benefits beyond lowering cholesterol:

Statins may improve the function of the endothelium (the lining of blood vessels), thereby improving blood flow. (This benefit apparently does not extend to people with diabetes.)
Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
Some evidence suggests that statins may help prevent blood clotting, a major factor in heart attacks.

Beneficial Effects Outside the Heart. Studies also suggest that the benefits of statins go beyond the heart. At this time, nearly all studies on the following conditions have used natural statins:

Stroke. Statins may reduce the risk for ischemic stroke in high-risk patients with a wide range of cholesterol and lipid levels. (Ischemic strokes occur from blockage in the blood vessels that lead to the brain.) In 2003, statin therapy was shown to reduce both fatal and non-fatal stroke in patients with hypertension and at least three additional cardiovascular risk factors. A 2004 study of stroke patients found that those who were receiving statin therapy at the time of their stroke had more favorable long-term outcomes than patients who were not on statin therapy, suggesting that statin therapy may provide additional benefits to patients who develop stroke.
Diabetes. Statins may have a number of effects that are helpful for patients with diabetes, and may even prevent diabetes in some people with high cholesterol. Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients. A major 2003 study found that statin therapy helped prevent cardiovascular events including coronary death, heart attack, stroke, and the need for revascularization therapy in patients with diabetes, even in those who did not have high cholesterol levels or established coronary disease.
High Blood Pressure. In an important 2002 study, patients with high blood pressure but normal hMG-CoA reductase or slightly high cholesterol levels had fewer heart attacks and strokes when they took the statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study showed similar benefits with the statin simvastatin.
Alzheimer's Disease. A number of studies have reported a significantly lower risk for Alzheimer's disease in people who take specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Statins showing the greatest promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor.) These statins appear to reduce levels of beta-amyloid. Other statins have not been associated with a lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.
Kidney Disease. Statins may prove to protect against heart disease development in patients with mild kidney disorders. According to a 2004 study, statins may also help slow the progression of existing kidney disease.
Eye Disease. Studies are investigating whether statins can help prevent macular degeneration, an age-related eye disease that can lead to blindness. Research is still preliminary, and results have been mixed.

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more common and is characterized by the thinning of the retina and drusen, small white deposits that form within the retina. The dry form of macular degeneration is usually mild. Wet macular degeneration can happen more quickly and be more serious. It occurs when vessels under the retinal layer hemorrhage and cause the retinal cells to die, creating blind spots or distorted vision in the central vision. The disease becomes increasingly common among people in each succeeding decade over 50.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. A specific myopathy, called rhabdomyolysis, can lead to kidney failure. Reports of rhabdomyolysis prompted the recall of cerivastatin (Baycol) in 2001. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.

In 2005, the FDA issued a public health advisory for rosuvastatin (Crestor), noting that this drug, like other statins, increased the risk for myopathy and rhabdomyolysis. The risks were greatest at the highest dose level (40 mg). The FDA advises that patients should not start therapy at this dose. In addition, the FDA reported the results of a post-marketing study that found that people of Asian heritage had twice the blood levels of the drug as Caucasians who had taken the same dose. Because of this difference in drug metabolism, the FDA advises that Asian Americans should start treatment at the lowest rosuvastatin dose (5 mg). In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.

Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. Similarly, high statin doses increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).

Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.

Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is the first choice for patients with low HDL levels. Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin drugs. Although niacin is available over the counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.

Benefits. When used in high doses, it has the following benefits:

Raises HDL levels higher than other anti-cholesterol drugs
Reducing triglyceride levels very effectively
Lowers LDL-cholesterol and lipoprotein(a)
Costs less than other anti-cholesterol drugs

Combinations with other drugs, particularly statins, may add significant benefits.

Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of nicotinic acid. About a quarter of patients who use rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They usually occur between 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does eventually become tolerant to these effects, and they generally subside.

The following may reduce flushing and itching:

Starting with low doses taken at mealtime and gradually working up to the prescribed dose.
Taking low-dose aspirin about 30 minutes before taking nicotinic acid. This may help prevent flushing.
Avoiding hot drinks.
Choosing an extended release form. (Even with this form, it is wise to gradually increase the bedtime dose over time and take a low-dose aspirin a half-hour beforehand.)

Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 30% of patients who take niacin experience elevated levels in blood glucose, which can be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies report that people with diabetes who use niacin have little trouble with blood sugar control.

Potentially Serious Complications. About 3 - 5% of people taking nicotinic acid develop liver problems, which disappear after the medication is discontinued. The extended form (Niaspan) appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should also avoid nicotinic acid because it elevates uric acid.

Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:

Bile is made in the liver and is used as one of the body's primary manufacturing components.

Click the icon to see an image of the gallbladder.

Once the resins bind to bile in the digestive tract, the bile is excreted in feces.
As the resins eliminate bile from the body, the liver takes more cholesterol from the bloodstream in order to produce more bile.
As cholesterol is taken out of the bloodstream, LDL levels drop.

When used in combination with dietary control, LDL levels are reduced by 15 - 20%. Combinations with nicotinic acid are even more effective, with reductions of 40 - 60% observed.

Brands. The bile-acid binding resins and similar drugs include cholestyramine (Questran, Questran Light). They are commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form.

Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. One study found that only half the standard dose of colestipol was needed when psyllium, (a soluble fiber supplement found in Metamucil, Fiberall, and Perdiem), was added to the drink. In addition, bloating and constipation were reduced. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.

Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.

Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.

Drug Interactions. Bile-acid binding resins may also interfere with other medications, including digoxin (Lanoxin), warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.

Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Newer fibrates, including fenofibrate (Lofibra, Tricor, Triglide), may be more effective in lowering cholesterol than gemfibrozil.

Benefits. Most fibrates have been shown to lower the risk of heart attack. In a 2001 study, men with both low HDL and LDL levels had a slightly lower risk of stroke after taking gemfibrozil. Fibric acid derivatives, or fibrates, have the following effects on cholesterol, lipids, and other factors:

They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take drugs ordinarily used for these purposes, such as nicotinic acid. In one study gemfibrozil, the standard fibrate, reduced the risk for adverse heart events by 22%.
Fibrates can produce modest reductions in LDL levels, although not as effectively as statins or other drugs. LDL may actually increase in patients with very high triglycerides who take these drugs. (The newer fibrates are much more effective in lowering LDL than gemfibrozil.)
A study on bezafibrate suggested it might have anti-inflammatory effects in patients with high triglyceride levels. Inflammation in the blood vessels is now recognized as a major contributor to the process leading to heart disease. However, according to a 2004 study, patients with diabetes or impaired fasting glucose levels were less likely to benefit from bezafibrate.
A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout). Another study, published in 2004, demonstrated that like bezafibrate, fenofibrate has significant anti-inflammatory properties in patients with high triglyceride levels.

Concerns. Fibrates do not appear to reduce mortality rates. In one study, people who took gemfibrozil had higher rates of death from other causes, including cancer. Some evidence suggests that fibrates may affect receptors involved in cancer development. However, a number of studies have found no higher incidence of cancer.

Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs.

Click the icon to see an image of gallstones in the gallbladder.

The drugs may cause abnormal heart rhythms and can affect the liver and kidney.

Drug Interactions. Fibrates interact with a number of drugs and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. In 2004, the FDA approved Vytorin, which combines ezetimbe and the statin simvastatin into a single pill.

In 2006, the FDA approved the use of ezetimbe in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone. Fenofibrate is a cholesterol drug that is used along with diet to reduce LDL and triglycerides.

CETP Inhibitors. Cholesteryl ester transfer protein (CETP) inhibitors, such as the experimental drug torcetrapib, are a new drug class that is being investigated for its effect on raising HDL ("good" cholesterol) levels while lowering LDL ("bad") cholesterol levels. Torcetrapib was the most widely studied of these drugs. However, in December 2006, the drug’s manufacturer abruptly stopped late-stage clinical trials after discovering that torcetrapib significantly increased blood pressure and risk of death.

Several studies published in 2007 in the New England Journal of Medicine revealed that while torcetrapib does greatly boost HDL levels (by 61% in one study) and lower LDL, it has no effect on arterial plaque. Scientists are trying to understand why this drug did not work. One theory is that torcetrapib may have increased the quantity of HDL, but not the quality. It is still not clear whether the failure of trocetrapib is specific to this drug or the entire CETP drug class. Given the current findings, it is also unclear whether research will continue on other CETP drugs.

Selective Estrogen-Receptor Modulators(SERMs). Selective estrogen-receptor modulators (SERMs) have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They include tamoxifen (Nolvadex), raloxifene (Evista), and droloxifene. Any beneficial effects of the SERMs on cholesterol and the heart are still unclear. SERMs pose a risk for deep vein blood clots, which may have implications for people with heart problems. Longer studies are needed on possible risks and benefits.

Recombinant ApoA-I Milano. ApoA-I Milano is a type of HDL protein that is found in people with very low levels of HDL. A 2003 study showed that treating patients with a synthetic form of HDL, derived from ApoA-I Milano, caused a significant regression of atherosclerosis. Ongoing trials will evaluate whether this drug can prevent cardiovascular events such as heart attack or death.

Plasmapheresis and Familial Hypercholesterolemia. Plasmapheresis is a blood-filtering procedure that is used to dramatically reduce triglycerides and may also be used to remove LDL. The procedure may be beneficial for patients with severe hereditary forms of high cholesterol who do not respond to other therapies. Studies suggest, for example, that plasmapheresis is particularly useful for patients with familial hypercholesterolemia. The process takes about 3 hours. If not performed regularly, its benefits last only about 2 weeks. People using this procedure are still advised to maintain a healthy diet and continue to take any prescribed medications to control cholesterol.

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

References

Berthold HK, Unverdorben S, Degenhardt R, Bulitta M, Gouni-Berthold I. Effect of policosanol on lipid levels among patients with hypercholesterolemiaor combined hyperlipidemia: a randomized controlled trial. JAMA. 2006 May 17;295(19):2262-9.

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006 Sep 9;368(9539):919-28.

Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006 Sep 5;114(10):1056-62. Epub 2006 Aug 28.

Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Review Date:
7/23/2007
Reviewed By:
Alan Greene, MD, FAAP, Chief Medical Officer, A.D.A.M., Inc.; and Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Osteoporosis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Fractures
Risk Factors
Diagnosis
Lifestyle Changes
Medications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration (FDA) approved zoledronic acid (Reclast) for postmenopausal osteoporosis treatment. Zoledronic acid is given as an injection once a year. A 2007 study in the New England Journal of Medicine indicated that zoledronic acid can significantly reduce the risk of spine, hip, and other fractures.
In 2007, the FDA approved raloxifene (Evista) for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis.

Calcium and Vitamin D for Osteoporosis Prevention

In 2007, the Food and Drug Administration proposed allowing manufacturers of food and supplements to put a health claim on their products stating that the combination of calcium and vitamin D can reduce the risk of osteoporosis.
In 2007, the National Osteoporosis Foundation updated its daily intake guidelines to recommend 1,200 mg of calcium, and 800 - 1,000 IU of vitamin D3, for adults age 50 and older.
Calcium plus vitamin D is effective in preventing osteoporosis in people age 50 years and older, according to a 2007 review in the Lancet. The researchers found that a minimum of 1,200 mg of calcium and at least 800 IU of vitamin D per day gave the most protection.

Fosamax: Taking a Break (Without Breaking a Bone)

Women at low risk for fracture may be able to temporarily stop taking alendronate (Fosamax) after 5 years, suggests a 2006 study in the Journal of the American Medical Association.

Antidepressants and Osteoporosis Risk

Selective serotonin reuptake inhibitors (SSRIs), the most commonly used class of antidepressants, may increase the risk for bone loss in both older men and women, according to several studies published in 2007 in the Archives of Internal Medicine. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). The researchers did not find that other types of antidepressants are associated with reduced bone mineral density.

Introduction

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur with mild stress.

The skeleton consists of groups of bones which protect and move the body.

Until a healthy person is around age 40, the process of breaking down and building up bone by cells called osteoclasts and osteoblasts is a nearly perfectly coupled system, with one phase stimulating the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. The reasons why this occurs during aging are not clear. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.

The Function of Bones. The skeleton has a dual function:

It provides structural support for muscles and organs.
It also serves as a depot for the body’s calcium and other essential minerals, such as phosphorus and magnesium.

The skeleton holds 99% of the body’s calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.

Bone Turnover: the Breakdown and Growth of Bones. Like other organs in the body, bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:

Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.

Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The bone build up (formation)-break down (resorption) balance is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.

In women, estrogen loss after menopause is associated with rapid resorption and loss of bone density. This group, then, is at highest risk for osteoporosis and therefore for fracture.

There are two primary kinds of osteoporosis: type I and type II:

Type I. Type I, or high turnover, osteoporosis occurs in 5 - 20% of women, most often between the ages of 50 and 75. This is because of the sudden postmenopausal decrease in estrogen levels, which results in a rapid depletion of calcium from the skeleton. This is associated with fractures that occur when the vertebrae compress together, causing a collapse of the spine. It is also associated with fractures of the hip, wrist, or forearm caused by falls or minor accidents. Women have a higher risk for type 1 osteoporosis than men.
Type II. Type II, or low turnover, osteoporosis (also known as age-related or senile osteoporosis) results when the process of resorption and formation of bone are no longer coordinated, and bone breakdown overcomes bone building. (This occurs with age in everyone to some degree.) Type II osteoporosis affects both men and women and is primarily associated with leg and spinal fractures. Older women can have both type I and type II osteoporosis.

Click the icon to see an image of a compression fracture.

What determines the existence of osteoporosis, whether type I or type II, is the amount of calcium left in the skeleton and whether it places a person at risk for fracture. Someone who has exceptionally dense bones to begin with will probably never lose enough calcium to reach the point where osteoporosis occurs, whereas a person who has low bone density could easily develop osteoporosis despite losing only a relatively small amount of calcium.

Secondary osteoporosis is caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).

Click the icon to see an image of osteoporosis.

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe several different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a woman’s ovaries stop producing estrogen. Estrogen comes in several forms:

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
The other important but less powerful estrogens are estrone and estriol.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. Even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

Estrogen’s most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
One study reported that part of estrogen’s beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.

Click the icon to see an image of the adrenal glands.

Studies have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with hip fracture in women after menopause:

Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.
Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the parathyroid glands.

Several studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

Of particular interest are genetic factors that affect vitamin D, a critical nutrient for calcium absorption in the body.
Many studies are looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroid drugs (also called glucocorticoids or steroids). Oral corticosteroids can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) -- a class of antidepressants that includes fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- may be associated with bone loss in both older men and women, according to two 2007 studies in the Archives of Internal Medicine. The researchers did not find an increased risk for bone loss with other types of antidepressants.

Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.

Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years. Some, but not all, studies suggest that combination estrogen-progestin oral contraceptives increase the risk for osteoporosis later in life. Women who take birth control pills should be sure to get adequate calcium and vitamin D from diet or supplements.

Other Medications. Anti-epileptic (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists). A 2006 study in the Journal of the American Medical Association suggested that long-term (greater than 1 year) use of proton-pump inhibitors (PPIs) may increase the risk for hip fractures. PPIs are used to treat gastroesophageal reflux disease (heartburn) and include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).

Predisposing Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.

Symptoms

Many people confuse osteoporosis with arthritis and believe they can wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, the mechanisms that cause arthritis are entirely different from those in osteoporosis. Osteoporosis usually becomes quite advanced before symptoms appear.

All too often, osteoporosis becomes apparent in dramatic fashion: a fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.

Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.

Click the icon to see an image of osteoporosis.

Fractures

Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and that for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly nonviolent fractures.

Click the icon to see an animation about osteoporosis.

Each year, there are an estimated 500,000 spinal fractures, 300,000 hip fractures, 200,000 broken wrists and 300,000 fractures of other bones. About 80% of these fractures occur after relatively minor falls or accidents.

Between 25 - 60% of women older than age 60 develop spinal compression fractures. Studies on men with osteoporosis report that they have a 6% risk for hip fracture and between 16 - 25% risk for any fractures related to osteoporosis.

Click the icon to see an image of a compression fracture.

Click the icon to see an image of a hip fracture.

Unfortunately, studies continue to report inadequate treatment after a fracture. In a major 2003 study, for example, only 8.4% of women who had sustained fractures were tested for osteoporosis. Worse, less than half of these women received any treatment for osteoporosis. Overall, in the study fewer than 4% of men and half of women who had sustained fractures were evaluated and treated according to recommended guidelines. The older a woman was, the less likely she was to have adequate treatment.

Risk Factors for Fracture and Falling. The risk for fracture itself in people with low bone density is compounded by certain features. Having multiple risk factors for osteoporosis itself poses a higher risk for fractures. However, not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture.

Falling, of course, is the primary risk factor for fracture. So, additional risk factors for fracture are those that increase the risk for falling. They include:

Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), with the risk increasing with multiple health problems. Such problems may account for 30% of falls in older women.
Taking multiple medications (especially tranquilizers and antidepressants).
Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
Poor concentration or mental impairment.
Impaired vision.
Hazardous environment (such as the presence of throw rugs in the house).

Between 25 - 36% of women who experience a hip fracture die within a year afterward, and about a quarter of the patients require nursing home treatment. The mortality rates after major fractures may be even higher in older men than in older women. Mortality rates after hip fractures declined from the 1960s through the early 1980s, but they have since leveled off. Whether or not medical advances can improve mortality rates in the future, prevention of osteoporosis is extremely important.

Risk Factors

Gender. An estimated 10 million adults in the United States have osteoporosis and another 34 million have low bone mass that places them at risk for developing osteoporosis. A 2004 report from the Surgeon General's office estimates that by 2020, half of all Americans over age 50 could be at risk for this condition. Eighty percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is far lower. Nevertheless, after age 50, bone loss increases and, according to recent studies, more rapidly than previously thought.

Ethnicity. Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk. About 20% of non-Hispanic white and Asian women older than age 50 have osteoporosis, and over 50% are at risk due to low bone mass. Osteoporosis affects 10% of Hispanic women (49% at risk) and 5% of non-Hispanic black women (35% at risk). Body type can also be a factor. Osteoporosis is more common in women who have a small, thin body frame and bone structure.

Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women.

Natural and Surgical Causes of Estrogen Deficiency.

Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
Surgical removal of ovaries.
Missing periods for 3 months or longer.
Never giving birth.
Pregnancy and nursing do not increase the risk for osteoporosis even though during those times calcium is diverted from the mother to the baby. A factor believed to be associated with reduced bone density is elevated at a constant level during nursing, but as the baby is weaned, levels of the factor decline and bone formation is restored.

Female Athlete Triad. In athletes, excessive exercise plays a major role in many cases of anorexia (and, to a lesser degree, bulimia), which in turn increases the risk for low estrogen levels and bone loss. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Osteoporosis
Amenorrhea (absence or irregular menstruation)
Eating disorders

Some specific risk factors in men include:

Hormonal deficiencies, including both testosterone and estrogen, which occur in older men (although much more slowly than in women). Estrogen deficiencies may also play a major role in osteoporosis in older men. It is unknown yet what normal estrogen levels are in men.
Medical conditions that can reduce testosterone levels, such as prostate cancer treatments, testicular surgery, and mumps.
Hypogonadism, which is a severe deficiency in the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones.

Of concern, are studies suggesting that men who have osteoporosis and suffer hip fractures are far less likely to be tested and treated for low bone density than are women. In one study, only 27% of men were treated for osteoporosis compared to 71% of women.

Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies, of course, are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.

Calcium requires adequate vitamin D in order to be absorbed by the body. In the United States, many food sources of calcium such as milk are fortified with vitamin D.

Click the icon to see an image of the sources of calcium.

Lack of Exercise. Lack of exercise can put thinner people at risk for osteoporosis.

Being Underweight. Being underweight is a risk factor for osteoporosis in men as well as women. (Shortness, thinness, and narrow hips all increase the risk for fracture in people with low bone density.)

Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly it they are elderly.

Click the icon to see an image of the sources of vitamin D.

Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don’t smoke. Men who smoke also have lower bone density.

Diabetes. Diabetes changes bone quality and density and increases the risk for osteoporosis, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture.
Type 2 diabetes, on the other hand, is associated with an increased bone density. In such cases, the bone quality itself may be impaired, since people with type 2 diabetes are still at higher risk for fractures.

Older patients with any diabetes type are at high risk for falling, which compounds the risk for fracture.

The maximum density that bones achieved during the growing years is a major factor in whether a person goes on to develop osteoporosis. Persons, usually women, who never develop peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include children who are:

Born prematurely
Have anorexia nervosa (more common in girls)
Young, highly competitive athletes
Take oral corticosteroid drugs (inhaled steroids, which are common in asthma treatments, appear to pose a very low risk or none at all)
Have certain medical conditions (cystic fibrosis, epilepsy, inflammatory bowel disease, and celiac disease)
Have delayed puberty

Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).

Diagnosis

About 20 - 30% of Caucasian women in the U.S. can expect to be affected by osteoporosis, including having a spinal fracture, after age 60. Hispanic, Asian, and Native American women have an even higher risk. Nearly all of them are unaware of the condition and so fail to seek a diagnosis. Even worse, studies continue to report inadequate evaluation for osteoporosis even after a fracture.

Evidence suggests that screening for osteoporosis can help prevent fractures. Expert groups now recommend bone density screening for the following people:

All women over age 65.
Any postmenopausal women under 65 years with risk factors for osteoporosis (being thin, being a smoker, having a family history of osteoporosis, corticosteroids use, or any serious high-risk condition, such as hyperthyroidism or early menopause).
Any older men or women who suffer a fracture. (Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis. Men are especially less likely to be tested.)

Whether perimenopausal women should be screened is unclear. (Perimenopause is the period that extends a few years before and after menopause, usually ages 50 - 59.) Some experts believe that women as young as 21 who have strong risk factors for osteoporosis (such as anorexia or absence of menstruation due to over-exercising) should consider being tested. It is also important that older women continue to get bone density tests. A 2006 study found that only 10% of women over age 75 receive bone density screenings, even though they are the age group most likely to have hip fractures.

Bone Densitometry. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DEXA). DEXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Bone mineral density is usually measured at the hip rather than the spine or wrist, which appears to be the most predictive of hip fracture. (Hip fractures are the most dangerous fractures, particularly in women older than sixty.) The bone density in the spine may also be measured. (Spinal bone density in older people however may be misleading. Bone density in this group may increase because of compression on the spinal bones from arthritic changes in the spine. Therefore, bone density measurements may be normal or even high, but the patient may actually be at risk for fracture.)

Click the icon to see an image of a hip fracture.

Ultrasound. Ultrasound techniques measure bone density in the heels, fingers, and leg bones. In early studies, advanced ultrasound techniques, such as quantitative ultrasound (QUS), are promising for improving accuracy in predicting fractures when used with DEXA. Ultrasound itself is less expensive than DEXA and uses no radiation. Ultrasound bone tests are sometimes given at health fairs or other non-medical settings. It should be noted that these results typically vary widely from measurements of the hipbone and are not reliable when used alone.

Quantitative Computed Tomography. Quantitative computed tomography (QCT) scans, a form of CT scans, can provide highly detailed information about spinal density. Radiation doses from this technique are higher than the others. Whether QCT predicts fracture risk accurately is, however, unknown.

Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm. However, low scores on bone density are not very accurate in determining fracture risk without consideration of other risk factors for fracture.

In general, doctors take the following steps to determine osteoporosis:

Bone mineral density ) is measured, typically in the hipbone, using bone densitometry.
Measurements of bone mineral density are given as mg/cm.² This is the average concentration of bone mineral in the areas that are being scanned. In general, bone is normal if results are greater than 833 mg/cm.² Low bone density (osteopenia) is between 833 and 648 mg/cm.² Osteoporosis is diagnosed with results below 648 mg/cm.²

These measurements still do not always indicate the true risk for fracture. The doctor also assesses risk factors and other considerations. The next step is to compare the patient's bone mineral density to normal bone density, which is defined as the average bone mineral density in the hipbones of premenopausal Caucasian women. (This group is used as the basis for the norm because of their high risk and greater proportion in the American population.)

The health professional then uses this comparison to determine her standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:

A T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
A Z score gives the standard deviation of the patient in relationship to the norm in her own age group. Z scores may be used to monitor the effects of treatments in women who have been diagnosed with osteoporosis.

For example, the lifetime risks for a younger woman with a specific T-score would be higher than the same scores in an older woman because the younger woman would have a longer time to lose bone density. In general, the T scores in a 55-year-old woman suggest the following degrees of risk for hip fracture.

One standard deviation or less below the norm indicates normal bone mineral density. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
Between 1 and 2.5 standard deviation s below normal defines osteopenia, which is low bone density. This carries between a 20 - 50% lifetime risk for fracture.
More than 2.5 standard deviation s predicts osteoporosis and over a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, risks for falling, and especially a history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in 1 year and 28.6% over 5 years. In similar women with a previous fracture, the probability of fracture at 1 year is 11% and at 5 years is 71.8%.

Not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture. Techniques to measure bone strength may better identify women at higher or lower risk.

Note: Because the standards are based on Caucasian women, they do not necessarily apply to men, children, or to non-Caucasian women. For example, men have a lower risk for fracture at the same standard deviations as women. Researchers are attempting to establish risk guidelines for these groups as well.

Laboratory blood or urine tests for identifying certain markers of bone loss may prove to be useful in certain cases:

High levels of the chemicals deoxypyridinoline and C-telopeptide in the blood may indicate increased risk for hip fracture. These substances are produced when bone is broken down.
A urine test detecting a substance called N-telopeptide may indicate bone loss (although it is not associated with any risk for fracture).

Lifestyle Changes

Because osteoporosis affects such a considerable portion of the female population, total prevention may not be possible, particularly for high-risk groups. Once a woman goes through menopause and more rapid bone depletion occurs, the line between prevention and treatment blurs. Despite their lower risk for osteoporosis, men should also protect their bones with the same healthy lifestyle habits.

Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Everyone who is in good health should aim for more. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients, those at risk or those who have serious medical conditions, should talk to their doctors.

Specific exercises may be better than others, depending on the age group:

Children should begin exercising before adolescence, since bone mass increases during puberty and reaches its peak between ages 20 and 30. Some evidence suggests that exercise may help develop bone mass in teenagers more effectively than high calcium intake. High-intensity exercises may be particularly bone-strengthening in young people. (Such regimes should not be confused with the athlete-triad -- intense competitive exercise, eating disorders, and menstrual irregularities -- that causes osteoporosis in young athletes.)
Weight-bearing exercise applies tension to muscle and bone and, in young people, encourages the body to compensate for the added stress, increasing bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. (Young men need high-intensity exercises to increase bone mass.) Careful weight training is also very beneficial for elderly people, especially women.
Regular brisk long walks improve bone density and mobility and may relieve osteoarthritic pain. High-impact exercises can be very bone-protective in young and middle-aged adults who have no precluding medical or physical conditions. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. (Older people, particularly women who engage in jumping exercises should do so under supervision.) Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
Exercises specifically targeted to strengthen the back help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, have been found to decrease the risk of falling. In one study, tai chi reduced the risk of falling by almost half.

Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.

Click the icon to see an image of osteoporosis.

In 2007, the Food and Drug Administration (FDA) proposed a new health claim for foods and dietary supplements that contain calcium and vitamin D. The FDA’s recommendation will allow manufacturers of these products to state that the combination of calcium and vitamin D can reduce the risk of osteoporosis. Also in 2007, the National Osteoporosis Foundation (NOF) updated its recommendations for getting enough calcium and vitamin D3. The NOF now recommends 1,200 mg of calcium/day and 800 - 1,200 I.U. of vitamin D3/day for adults age 50 and older. (For strong bones, people need enough of both calcium and vitamin D.)

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. Many studies, including a 2007 review in the Lancet, show that a combination of calcium and vitamin D can help prevent osteoporosis. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve slightly (by 1%) hip bone density
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether or not you should take calcium supplements.

Appropriate Daily Doses. Recommended daily amounts of calcium depend on age and risk factors:

In young people, children ages 3 - 8 should take 800 mg of calcium per day, while children and adolescents ages 9 - 17 need 1,300 mg per day. Teenage girls who do not have enough calcium in their diets should consider taking supplements, which can help build bone density during these critical years.
The standard recommended dose for people over age 50 is about 1,200 mg per day, but actual dosage may be higher or lower depending on risk factors. Even doses of 1,000 mg may help preserve bone in many postmenopausal women without osteoporosis, including during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1,000 mg daily may not add any protective benefits without bone-building medication.
Some experts suggest that all pregnant women, adolescents, and those on corticosteroids take 1,000 - 1,300 mg of calcium every day.
Breast-feeding women should have 2,000 mg per day.

Forms of Calcium Supplements. There are several different kinds of calcium supplements, such as calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions. Their value in preserving bones depends on many different factors:

Calcium Concentrations. Forty percent of calcium carbonate is actually calcium, whereas calcium citrate is 24% calcium, and calcium gluconate is only 9% calcium.
Calcium Absorption Capabilities. The calcium must also be absorbed from the stomach into the bloodstream. Calcium citrate is better absorbed than many other calcium compounds. It was reported to be the first calcium supplement to preserve bone density after menopause. (Calcium citrate also increases iron absorption. Milk and other calcium compounds tend to reduce iron absorption.) One simple method for testing the absorbency of a particular brand of calcium tablet is to place it in a glass of white vinegar at full strength and check to be sure that it breaks up within 30 minutes. Taking large amounts of antacids can impair calcium absorption. People should take calcium supplements after meals.

Side Effects. Calcium supplements, even at normal doses of about 1,000 mg a day, can increase the risk for kidney stones. People should be careful not to exceed the upper limit of 2,500 mg per day. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Calcium may boost the effects of drugs used to treat osteoporosis.

Click the icon to see an image of kidney stones.

Although not a specific side effect of calcium, there has been much public concern about reports of a small amount of lead in calcium supplements. Although exposure to high levels of lead can cause health problems, the amount in such supplements is very small and may pose little or no hazard.

Vitamin D. Vitamin D helps the stomach and the gastrointestinal tract absorb calcium. It also is the essential companion to calcium in maintaining strong bones. Moreover, vitamin D protects against osteoporosis only in combination with calcium.

Click the icon to see an image of the benefits of vitamin D.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. People also can get it from dietary supplements.

As a person ages, vitamin D levels decline. They also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of the sources of vitamin D.

Most current adult guidelines recommend:

400 IU (10 mcg) for people aged 50 - 60.
600 IU (15 mcg) for those over age 70 who do not have sufficient exposure to sunlight. (Evidence suggests that higher doses of vitamin D -- up to 1,000 IU per day -- may help prevent fractures in people with osteoporosis.)

There are various recommendations for daily vitamin D intake. In 2007, the National Osteoporosis Foundation updated its guidelines to recommend 400 - 800 IU of vitamin D3 for adults younger than age 50, and 800 - 1,000 IU of vitamin D3 for adults age 50 and older. Vitamin D3, also called cholecalciferol, is the form of vitamin D that is best for bone health. In addition to supplements, food sources for vitamin D3 include fortified milk, egg yolks, saltwater fish, and liver.

In 2007, the U.S. National Institute of Health’s Office of Dietary Supplements released a report regarding vitamin D and bone health. Researchers were not able to definitely separate the effect of vitamin D from that of calcium, as most clinical trials evaluate the combination of these supplements. The report did indicate that a combination of daily vitamin D3 (700 - 800 IU) and calcium (500 - 1,200 mg) decreases the risks of falls, fractures, and bone loss in elderly people (ages 62 - 85 years).

Sufficient sunlight exposure and drinking milk fortified with vitamin D supply most people’s normal needs for vitamin D. One cup of whole milk provides about 100 IU of vitamin D.

Vitamin D is toxic in doses above 2,000 IU a day. No one should exceed the recommended daily intake of vitamin D except under the direction of a doctor.

Many people could become deficient in vitamin D as they avoid sunlight to prevent skin cancers and instead increase their intake of milk products, such as yogurt and skim milk, which may have little vitamin D. Such individuals may need to take supplements. People with darker skin have a higher risk for vitamin D deficiency than those with lighter skin.

Vitamin D derivatives are being investigated for treating osteoporosis. Calcitriol (Calcijex, Rocaltrol), for example, is a prescription-form of vitamin D that can increase bone mass and decrease the rate of spinal fractures. However, calcitriol increases the risk for high blood calcium levels (hypercalcemia) and requires frequent monitoring.

Vitamin K. Vitamin K has properties that protect bone and prevent fracture. Because intestinal bacteria produce vitamin K, and the vitamin is found in leafy vegetables, deficiencies are rare. Some evidence suggests, however, that people may not be consuming enough of this nutrient. Vitamin K affects blood clotting, and taking supplements is not recommended without first talking to a doctor. Vitamin K2 (menatetrenone), a form of vitamin K, may help prevent fractures in people with osteoporosis.

Click the icon to see an image of the benefits of vitamin K.

Click the icon to see an image of the sources of vitamin K.

Vitamin B12. Studies suggest that people need the right amounts of vitamin B12 and folic acid to maintain their bone mineral density.

Vitamin A. High amounts of dietary vitamin A reduce bone density and may even increase the risk for fracture in postmenopausal women. (A form of vitamin A, retinoic acid, has been found to stimulate bone breakdown.)

The DASH Diet and Low Sodium. Perhaps a good general approach for people at risk for osteoporosis (or almost any adult) is the DASH diet plus sodium (salt) restriction. The DASH (Dietary Approaches to Stop Hypertension) diet is used to help people with hypertension maintain healthy blood pressures. A 2003 study also reported that it might help protect bones and improve cholesterol levels. This diet not only is rich in important nutrients and fiber but also includes foods that contain far more potassium, calcium, and magnesium, than are found in the average American diet. All of these minerals are important for bone protection. The dietary recommendations are as follows:

Avoid saturated fat (although include calcium-rich dairy products that are no- or low-fat). When choosing fats, select monounsaturated oils, such as olive or canola oils. These fats are also found in some fish. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In one study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet.
Choose whole grains over white flour or pasta products. Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, magnesium, and other minerals that are important for bone (as well as heart) protection.
Choose protein preferably from fish, poultry, or soy products. Soy in combination with fiber-rich foods or supplements may have specific benefits. Oily fish may also be particularly beneficial. They contain omega-3 fatty acids, which have been associated with heart and nerve protection.

Salt Restriction. Reducing salt may protect both the heart and the bones. High sodium intake interferes with calcium retention. Note: Fast foods and commercial snacks are usually high in sodium and have been linked with weak bones.

Dairy Products and Calcium-Rich Foods. Although some studies have reported that dairy products benefit the bones, it is not entirely clear if high-calcium diets reduce the risk for fractures compared to adequate intake of vitamin D. Until more is known, people should be sure their diets have sufficient calcium. Dietary calcium is available from many good sources.

Milk and Dairy Products. The best source of calcium in the diet is from milk fortified with vitamin D. Four glasses of milk provide about 1,200 mg of calcium. (Skim milk and yogurt products, unfortunately, are often low in vitamin D, which is important for calcium absorption.) According to a 2003 study, girls who have low milk intake increase their risk for fracture in adulthood. One report even suggests that milk proteins actually slow bone break down. It is not clear, however, if drinking milk after menopause offers any significant bone protection.
Other Calcium-Rich Foods. Other calcium-rich foods include shrimp, canned salmon or sardines, black strap molasses, calcium-fortified tofu, and almonds. A number of commercial foods, including orange juice and some cereals, are now calcium fortified. Dark green vegetables (broccoli, kale, turnip greens) are rich in calcium but little of it is absorbed (kale is best).

Click the icon to see an image of milk and the facial bones.

Mineral-Rich Fruits and Vegetables.

Potassium. Potassium may be very important for strong bones and may help counteract negative effects of high-protein diets. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli.
Magnesium. Some studies have observed that low levels of magnesium may contribute to thinning bones. Some studies suggest that magnesium supplements help suppress the cycle that leads to bone loss. Experts recommend 350 mg a day for supplements. However, excessive magnesium may be harmful in people with diabetes or kidney disease. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut.
Other Minerals. Phosphorous, boron, and zinc have also been associated with bone protection.

Protein. Protein may be important for frail older people for improving muscle strength. Researchers, meanwhile, have associated both low and high protein intake with bone loss. Protein deficiencies appear to trigger hormonal changes that increase bone breakdown. On the other hand, high protein intake increases urinary calcium loss, which can impair bone density in people with low-calcium diets. High-protein diets, however, do not appear to cause bone loss if calcium intake is also high. The bottom line is to eat enough protein but to balance it with plenty of calcium-rich, and other mineral-rich, foods.

The protein source (meat, soy, or fish) may have some effect on bone density, although the effects are not clear. Studies are mixed on whether protein from meat has a positive or negative effect on bone loss. In any case, the best sources of protein for bone protection may be from oily fish or soy.

Choosing protein from fish (especially oily fish such as sardines, salmon, mackerel, fresh tuna, and herring) is a good option. Oily fish are high in vitamin D, which is bone protective. Such fish are also heart protective. Wild salmon has a much higher vitamin D content than farmed salmon. American brands of canned tuna, meanwhile, generally do not contain significant amounts of vitamin D.
Soy may have some modest protection against bone loss. Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. In particular, the isoflavone genistein is being studied for its effects on bone health. A small 2007 study indicated that genistein supplements, when taken with vitamin D and calcium, may help improve bone density in postmenopausal women with thinning bones. (However, other studies indicate that soy has no effect on bone density in healthy premenopausal women.) Soy food products that also contain calcium, such as tofu, may be particularly beneficial. In such cases, 3 ounces of tofu supply 60% of daily calcium requirements.

Alcohol. Alcohol has different effects on bones depending on how much is consumed. One study found that women older than age 65 who drank one to two drinks (1 - 2 oz) of alcohol weekly had higher bone density than non-drinkers. Alcohol in moderate amounts may reduce parathyroid hormone and increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Cola, Coffee, Tea and Caffeine. One study suggested that drinking tea regularly may help protect bones. Nevertheless, there has been some concern that caffeine consumption, particularly from coffee, may increase calcium levels in urine and reduce levels in the body. In one trial, consumption of lots of coffee (9 or more cups per day) was associated with an increased risk of hip fractures in women, but not in men. However, not all studies support a risk. Some evidence suggests that caffeine may pose a danger for bone loss only in elderly thin women -- but not in those who have normal or high weight. Drinking carbonated beverages, particularly cola, may increase the risk for bone fractures in people with low bone density.

Everyone who smokes should quit. The risk for osteoporosis from smoking appears to diminish after quitting.

An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:

Slow walking
Inability to walk in a straight line
Certain medications (such as tranquilizers and sleeping pills)
Low blood pressure when rising in the morning
Poor vision

Recommendations for preventing falls or fractures from falls in elderly people include:

Exercise to maintain strength and balance if there are no conflicting medical conditions. In one study of older people, this was the single best intervention for preventing falls.
Do not use loose rugs on the floors.
Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
Rooms should be well lit.
Have regular eye checkups.
Try wearing hip pads. Hip pads are specially designed to protect hipbones against falls and are worn under clothing. Evidence on their protection against fractures is weak, however, particularly since compliance is poor. Nevertheless, newer hip pads that are thinner and made with newer materials may be helpful and more appealing.
Wear thinner, hard-soled shoes. Studies indicate these shoes are just as comfortable as the popular resilient-soled footwear, but they may be difficult to find. Soft-soled high-resilient so-called athletic footwear may contribute to impaired balance and dangerous falls, in part, because these cushioned shoes offer less stability.

Medications

Many drugs are available to treat osteoporosis. Unfortunately, studies continue to report that doctors fail to evaluate and adequately treat both men and women for this condition, even after a fracture. According to one study of women over age 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their doctors. Among those who were diagnosed, only 36% received appropriate medication. Among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines, indicated two other studies. In one of the studies, only 24% of women received treatment for osteoporosis after a fracture. In both studies, the older a woman was, the less likely she was to have adequate evaluation or treatment.

Drugs Used to Treat Osteoporosis. Two types of drugs are used to treat osteoporosis:

Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
Anabolic, or Bone-Forming, Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This medicine is proving to be very effective in restoring bone and preventing fractions. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

Bisphosphonates are antiresorptive drugs. They are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, just blocking resorption will interrupt this process and impair the second half of the process -- bone formation. Some researchers think that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PTH), then following this treatment with bisphosphonates to prevent the breakdown of bone. (Administering the two drugs simultaneously is not effective because bisphosphonates interfere with the way PTH works.)

A 2006 study of the bisphosphonate alendronate (Fosamax), the most widely used osteoporosis drug, indicated that women at low risk for fracture may be able to stop using the drug after 5 years without increasing their fracture risk for another 5 years. However, the Journal of the American Medical Association study also suggested that it is safer for women at high risk for spine fractures to keep taking alendronate on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

Oral bisphosphonates. These pills include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium. Risedronate and alendronate are approved for both men and women.
Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for osteoporosis. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may experience muscle and joint pain. To avoid stomach problems, doctors recommend:

Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. In clinical studies, teriparatide (Forteo), a drug made from selected amino acids found in parathyroid hormone, reduced the risk for spinal and non-spinal fractures by 50 - 65%. It may prove to be a very useful drug for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, researchers are investigating a nasal spray version of PTH. In addition to easing patient discomfort, there is some preliminary evidence that nasal-administered PTH may be better absorbed than injections. Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone replacement therapy (HRT) is sometimes used to prevent osteoporosis. A Women’s Health Initiative (WHI) study found that women who received estrogen, or estrogen plus progestin, therapy had fewer fractures than women who received placebo.

However, WHI studies have also shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The Food and Drug Administration recommends that women first try other medications for prevention of osteoporosis.

HRT is available in many different forms, including pills and skin patches. [See In-Depth Report #40: Menopause.]

New SERMs. Bazedoxifene (Viviant) is a new selective estrogen receptor modulator (SERM) that is in phase III clinical trials. In research presented at the 2007 annual meeting of the American Society for Bone and Mineral Research (ASBMR), bazedoxifene reduced new cases of non-spine fracture by 52% compared to placebo.
Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Results presented at the 2007 ASBMR meeting indicated that denosumab may help increase bone mineral density by as much as 10.6%. Odanacatib is another biologic drug showing promise in phase IIB trials. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.
Strontium. Strontium, a chemical element found in bone, may help increase bone formation and decrease bone resorption. NB S101 is a strontium drug currently in phase II trials.

Treatment

Nonsurgical treatments for fractures include braces, plaster cases, and manipulation of the fracture. Such approaches have not been well studied to determine an optimal method, and patients should discuss all options with their doctors.

Reconstructive surgery is usually used for hip fractures and should be performed within 48 hours, assuming the patient has no other complicating medical conditions. After surgery, the patient should be mobilized within the first day. In one study, protein supplements helped people with hip fractures recover more quickly and reduced bone loss.

Percutaneous vertebroplasty and kyphoplasty are surgical procedures used to lessen pain. Research to date suggests that they are safe and provide pain relief for many patients. In some cases they may increase height. There have been few controlled trials, however, and more research is needed to determine long-term effects.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into damaged vertebrae. It is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. Success rates of over 90% have been reported. Serious complications occur in fewer than 1% of cases.

Kyphoplasty. Kyphoplasty is a variant of percutaneous vertebroplasty that may help prevent kyphosis (hunchback) in patients whose spines have collapsed. The procedure inserts a balloon into the fractured vertebrae. As the balloon inflates, the spine is moved upward, to its original location. The balloon is then removed, and the bone and the core of the newly-erect vertebrae are filled with cement. In one 2003 study, short-term symptom relief improved by 70% and was immediate. Long-term effectiveness is not yet known.

Resources

www.nof.org -- National Osteoporosis Foundation
www.niams.nih.gov/Health_Info/Bone -- National Institutes of Health, Osteoporosis and Related Bone Diseases
www.menopause.org -- North American Menopause Society
www.asbmr.org -- American Society for Bone and Mineral Research
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases

References

Agency for Healthcare Research and Quality. Effectiveness and Safety of Vitamin D in Relation to Bone Health, Structured Abstract. August 2007. Rockville, MD.

Bilezikian JP. Osteonecrosis of the jaw -- do bisphosphonates pose a risk? N Engl J Med. 2006 Nov 30;355(22):2278-81.

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007 Jun 25;167(12):1246-51.

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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