The metabolic syndrome: Therapy

Content provided by the Faculty of the Harvard Medical School

The metabolic syndrome: Therapy

The metabolic syndrome is a cluster of five closely related cardiovascular risk factors. Each is dangerous in its own right, but when they occur together, the overall risk is greater than the sum of its parts.

Table 1 shows the metabolic syndrome’s components. The presence of any three abnormalities is sufficient to establish the diagnosis, but the hazards are even greater when four or five abnormalities are present.

It’s a common sequence in medical research: Doctors define a problem before they find its solution. But in the case of the metabolic syndrome, the outlines of therapy have already emerged.

What to do

The only proven remedies for the metabolic syndrome are exercise and weight loss. But certain specific dietary adjustments may be especially helpful, even if they don’t promote weight loss, and other lifestyle changes may also be useful. Finally, medication that can treat the syndrome’s separate abnormalities may help people who have the whole syndrome.

Here’s a summary of things that can help.

The dynamic duo

Exercise. It’s the best way to prevent the metabolic syndrome, and it’s also the mainstay of therapy once the problem has developed.

A study of 612 healthy men demonstrates the power of prevention. The subjects were between the ages of 42 and 60 when the study began, and none had the metabolic syndrome. Over the next four years, though, 107 men developed the problem. But the men who exercised regularly were only about half as likely to develop the syndrome as the inactive men. And it didn’t take heroic amounts of exercise to produce protection; just three hours a week of moderate to vigorous activity did the trick.

Exercise can also treat the metabolic syndrome. In fact, it can help correct each of the five abnormalities.

1. Obesity. By burning calories, exercise promotes weight loss. Nearly all people who win at the losing game attribute their success to exercise as much as diet. In addition, exercise seems to have a specific ability to reduce abdominal obesity. A 2003 study tracked 30 obese young men in Singapore. The men followed a four-month program of intensive exercise, but had no dietary restrictions. Although the subjects consumed more than 3,000 calories a day on average, they shed about 26 pounds each. Best of all, they lost abdominal fat preferentially. The average waist circumference declined by 14%; the average hip circumference fell by 8%.

2. Triglycerides. Exercise reduces triglyceride levels, and the reduction is greater than one would expect from weight loss alone.

3. HDL cholesterol. Regular exercise boosts HDL (“good”) cholesterol. It takes a while for the effect to kick in, but it will be substantial as long as the exercise continues. As few as eight miles of walking per week or the equivalent exercise will help, but the more you do, the higher the HDL will be.

4. Blood pressure. Exercise is one of the most important lifestyle treatments for hypertension, and it is just as helpful for the prehypertensive levels recorded by many men with the metabolic syndrome. Endurance exercise is best. Brisk walking is an example; only 30 minutes a day can be expected to reduce systolic blood pressure by 4–9 mm Hg.

5. Blood sugar. Exercise makes muscles and other body tissues more sensitive to insulin, which means that less insulin is needed to keep the blood sugar down. Exercise is an important way to prevent and treat diabetes, and its dual benefits — lower blood sugar levels and lower insulin levels — are very helpful in the metabolic syndrome.

In addition to improving all five aspects of the metabolic syndrome, exercise has other benefits for cardiovascular health. It lowers LDL (“bad”) cholesterol levels, it reduces C-reactive protein levels, it helps keep the endothelial lining of arteries flexible and healthy, and it reduces stress. A program as simple as walking for 30–45 minutes nearly every day can go a long way toward preventing the metabolic syndrome. Moderate exercise will also help treat the syndrome, but men with the diagnosis can choose to build up to double that amount to gain the extra protection they need.

Weight loss. The metabolic syndrome is rare in men with normal body weights (a body mass index [BMI] of 25 or less), but it occurs in a majority of obese men (BMI 30 or higher). Weight loss is difficult to achieve, but it is possible. Calories are the key. To reduce, burn up more calories with exercise and consume fewer calories in your diet. For sustained weight loss, all diets that reduce calories to the same degree are equally effective. But although the proof is not in, certain nutritional adjustments may have added benefits for the metabolic syndrome.

Other lifestyle adjustments

Exercise and weight loss are the only proven treatments for the metabolic syndrome, but other modifications are likely to help.

Eat the right carbs. Carbohydrates raise the blood sugar, triggering the release of insulin. Both play into the metabolic syndrome — but that doesn’t mean you should give up carbohydrates. In fact, high-carb diets have been linked to high HDL (“good”) cholesterol levels and to a low risk of diabetes and heart disease — as long as they’re the right carbohydrates. Choose carbohydrates that are digested and absorbed slowly; they will produce a slow rise in blood sugar and a modest insulin release. Foods that fill the bill have a low glycemic index. In general, they are the complex carbohydrates found in unrefined high-fiber foods such as bran cereal, whole grain products, and beans. Low-fat dairy products and various fruits, including apples, oranges, and strawberries, are also on the “good” list. But there are exceptions to the rule; Table 2 lists the glycemic index of a number of foods.

Eat the right fats. Although LDL (“bad”) cholesterol is not part of the metabolic syndrome, high levels increase the risk of heart disease and stroke. To reduce your LDL, decrease your consumption of saturated fats, found principally in meat and whole dairy products. And it’s even more important to minimize your consumption of trans fatty acids, which raise the LDL and lower the HDL. Trans fats are the partially hydrogenated vegetable oils found in stick margarine, fried foods, and many commercial snack foods and baked goods. In their place, choose the omega-3 and monounsaturated fats found in fish, certain nuts, olive oil, and other vegetable oils.

Eat for the best blood pressure. That means limiting your consumption of sodium to less than 2,300 mg a day and increasing your consumption of fruits, vegetables, and whole grains. The low-sodium version of the Dietary Approaches to Stop Hypertension (DASH) diet does it all — and it will also steer you toward the most healthful carbohydrates.

Drink with extra care. This may come as a surprise if you know that people who drink have a lower risk of heart attack, stroke, and diabetes than teetotalers as long as they limit themselves to one or two drinks a day. But even in small amounts, alcohol has two important drawbacks for the metabolic syndrome: It raises triglycerides and adds calories. On the other hand, alcohol raises HDL cholesterol levels, a big benefit. So if high triglycerides and a stubborn inability to lose weight are features of your syndrome, avoid alcohol; but if low HDL is a major issue, consider one or two drinks a day as long as you can drink safely and responsibly. Alcohol is hardly a treatment for the metabolic syndrome, but a 2004 study of 8,125 people found that those consuming low to moderate amounts of wine or beer were less likely to develop the metabolic syndrome than teetotalers.

Shun tobacco. Smoking lowers HDL cholesterol levels. That’s its only specific impact on the metabolic syndrome, but it has many other health effects, all harmful.

Lifestyle treatment works. A three-year study of 3,234 at-risk individuals found that it reduces the risk of developing the syndrome by 41%. And a 2004 study reported that the combination of a Mediterranean diet and moderate exercise corrected the metabolic syndrome and reduced levels of C-reactive protein in 55% of participants. Still, many patients with the syndrome need more.

Medication

If there’s an illness, there should be a medication; if it’s a common and serious illness, there should be a powerful medication. The logic is unassailable, but in the case of the metabolic syndrome the need has not yet been met. There is no medication for the syndrome, but many medications can help correct each of its components except obesity.

Since the metabolic syndrome is a relative newcomer, and a complex one at that, doctors don’t yet know when to start medications or what drug combinations are best. Still, medication can help. Here is a brief discussion of the categories that people with the syndrome should consider with their doctors.

Drugs for blood pressure. For otherwise healthy men, the threshold for treatment is 140/90, but for diabetics it’s 130/80. Since the metabolic syndrome has so many similarities to type 2 diabetes, the lower blood pressure target may be wise. And if that’s the case, patients might benefit most from an angiotensin converting enzyme inhibitor or, if cough prohibits its use, an angiotensin receptor blocker. Thiazide diuretics, which are generally the first drug for hypertension, and calcium channel blockers are close behind. If more help is needed, other antihypertensive medications are available.

Drugs for blood lipids. Most treatment guidelines focus on the LDL cholesterol level, which is not among the five criteria for the metabolic syndrome. But because of its very high cardiovascular risk and similarities to diabetes and hypertension, it may be reasonable to set the same stringent LDL target of 70 that is used for other high-risk patients. Nearly all people need medication to bring their LDLs all the way down to 70. Usually, that means starting with a statin drug. Atorvastatin (Lipitor) and rosuvastatin (Crestor) are the only members of the class that lower triglycerides as well as LDL cholesterol. But none of the statins is very effective at boosting the HDL cholesterol. When that’s a priority, doctors might consider using niacin (alone or with a statin) or a fibrate such as gemfibrozil (Lopid) or fenofibrate (Tricor), alone or with niacin. Combination therapy requires extra care to detect and prevent muscle inflammation.

Drugs for blood sugar. If a patient with the metabolic syndrome has diabetes, he should be treated according to current guidelines. But it’s not clear if medication would help the mild sugar elevations often seen in the metabolic syndrome. Doctors are evaluating medications that increase insulin sensitivity, such as pioglitazone (Actos) and rosiglitazone (Avandia) as well as metformin (Glucophage), a drug that reduces sugar production and release from the liver.

Aspirin. It won’t correct any of the five abnormalities of the metabolic syndrome, but low-dose aspirin can reduce the likelihood of heart attack and stroke in people at risk. Doctors often recommend 81 mg a day when aspirin is appropriate.

Surgery

Even the best surgeon can’t operate on your metabolism — but in special cases, surgery can help correct the metabolic syndrome by promoting weight loss. Although abdominal fat is the chief culprit, liposuction will not do the trick. But gastric surgery that promotes dramatic weight loss can help. In a study of 645 morbidly obese individuals who underwent the operation, the features of the metabolic syndrome resolved in 95% of patients who had the problem before surgery. Even so, gastric surgery should be a last resort for selected individuals with extreme obesity.

Combining forces

The metabolic syndrome won’t show up on many death certificates, but it is an important cause of heart disease and stroke, the first and third leading killers in America. About 47 million Americans have the syndrome, though many don’t know it. And if present trends continue, the number is sure to grow along with America’s waistline.

The metabolic syndrome is a complex abnormality with five components. Medications are available for four of the five, but doctors are just now learning how to best use them for this disorder. But for prevention as well as therapy, a combined approach is crucial. Medications will be important for many patients, but all will benefit from the combination of regular exercise and a healthful diet. They are, after all, the hand and glove of prevention and good health.

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Last updated:	August 21, 2006