DHEA Protects Against Heart Disease and Diabetes

DHEA Mysteries Are Yielding to Research

DHEA Protects Against
Heart Disease and Diabetes

Steroid hormone is found to improve arterial function and insulin sensitivity
By Aaron W. Jensen, Ph.D.


Our arteries are multilayered vessels that need to dilate or contract in response to changing conditions. The chemical signals for these actions are generated in the epithelial cells that line the arterial walls.
hen steroid hormones are mentioned in everyday conversation, some colorful images may come to mind: a bodybuilder (or governor?) with muscles bulging in Hulk-like fashion; or a baseball player blasting 70+ home runs in a single season; or an adolescent boy experiencing the awkward change-of-voice period; or perhaps a middle-aged woman suffering bouts of “hot flashes” that are anything but flash-like.

Steroid hormones are involved in all these processes, and we know their names well enough to toss them around casually: androstenedione (“andro” for short), testosterone, and estrogen. We can all relate to these hormones because we’ve witnessed their awesome powers—both positive and negative—first-hand. But these well-known compounds are not the only steroid hormones that play important roles in our bodies.

DHEA Levels Decline Steadily with Age

There are many other steroid hormones, such as cortisone, which functions primarily in carbohydrate metabolism and is used therapeutically as an anti-inflammatory agent; hydrocortisone (also called cortisol), which regulates carbohydrate metabolism and maintains blood pressure and is also used as an anti-inflammatory agent; and aldosterone, which helps to regulate the body’s salt and water balance.

The functions of various other steroid hormones in the body, however, are less clear. One such molecule is DHEA (dehydroepiandrosterone), which is by far the most abundant steroid hormone in both men and women.* It is well known that DHEA levels peak in our mid-twenties, then gradually decline to about 20% of their peak levels by age 70. But what does this hormone actually do?


*Actually, DHEA exists in the body primarily (about 90%) in the form of its sulfate derivative, DHEAS (dehydroepiandrosterone-3-sulfate), but that fact need not concern us here. For all practical purposes, they’re the same.


DHEA Has Multiple Roles in the Body

Like all the other steroid hormones, DHEA is synthesized in the body from pregnenolone, which is synthesized from cholesterol. DHEA is made primarily in the adrenal glands (which also produce about 150 other hormones) and released into the blood. In different organs it is converted into a variety of more commonly known steroid hormones, including androstenedione, testosterone, and estrogen.

Unlike those hormones, however, DHEA appears to play a role in cardiovascular function and helps to regulate blood glucose levels. Indeed, recent research in Japan reveals that a modest daily supplement of DHEA seems to be effective in improving cardiovascular function and reducing blood glucose levels.1 The significance of this finding is underscored by the continuing rise in the incidence of diseases such as heart disease and diabetes (see the sidebar).

The Metabolic Syndrome Is Avoidable

Never heard of the metabolic syndrome? You’re not alone—but that doesn’t mean that it isn’t widespread and rapidly becoming one of the leading health problems of the day. The metabolic syndrome (which is often called “syndrome X” in the popular press) is a cluster of symptoms—notably obesity, high blood pressure, unhealthy levels of cholesterol and triglycerides (fats), and high levels of blood sugar (glucose)—that together greatly increase the risk for heart disease and diabetes.

It is estimated that between 10 and 25% of the adult population, or up to 40 million Americans, have the metabolic syndrome. That’s startling, but equally disturbing is the fact that most of these people haven’t been diagnosed with the condition and are walking around (or more likely sitting around) completely unaware of the major health problems brewing within them.

The American Heart Association lists six risk factors whose simultaneous presence in the same person spells metabolic syndrome:1

  • Central obesity—excess fat primarily around the abdomen
  • High levels of triglycerides (fats) and low levels of HDL-cholesterol (“good cholesterol”)
  • High blood pressure—greater than 130 over 85
  • Insulin resistance—the body’s inability to utilize insulin efficiently in controlling blood sugar levels
  • Prothrombotic state—high levels of proteins such as fibrinogen or PAI-1 in the blood
  • Proinflammatory state—elevated levels of C-reactive protein (CRP) in the blood

The primary underlying causes of the metabolic syndrome are obesity (it’s both a cause and a symptom), physical inactivity, and genetic factors. So what can you do to decrease your risk? Well, it’s the same old prescription you’ve heard over and over again: lose weight, exercise, and improve your eating habits. That doesn’t mean, however, that you have to drop 50 pounds, run a marathon, and subsist on tofu and broccoli.

Small improvements can yield big rewards. For example, reducing your weight by 10–15% can significantly decrease your blood pressure, improve your blood lipid profile, and increase your cells’ sensitivity to insulin. And walking 20–30 minutes per day (aim for up to 150 minutes per week) has similar benefits. Exercise, even in the absence of weight loss, can pay big dividends, since it helps to increase HDL-cholesterol levels in the blood. Nutritional supplements can be helpful as well in this regard (see, e.g., “Cholesterol Showdown: Policosanol vs. Atorvastatin” in Life Enhancement, May 2003).

Finally, eating more nutritious foods provides a wide range of phytochemicals (plant-based compounds) that can improve blood lipid and glucose levels, among other things, and judiciously chosen nutritional supplements can greatly augment the benefits obtainable from food alone. And don’t forget that strategic changes in your diet—such as cutting back on cookies, chips, and other items loaded with refined carbohydrates, and replacing them with fresh fruits and vegetables—just might give you a new lease on life.

For help with weight control, see “Lose Weight with 5-HTP and EGCG” in Life Enhancement (April 2003) and “Skipping Meals Regularly May Be Good for Your Health” (July 2003). And for help in enhancing your willpower for losing weight, see “Catecholamines Kick Out the Demons of Depression” (September 2003).

  1. American Heart Association. http://www.americanheart.org

DHEA Improves Arterial Dilation

A number of past studies have suggested that as DHEA levels decrease, the risk of coronary artery disease increases. But how are these two conditions related? The lack of answers prompted the Japanese researchers to recruit 24 men (average age 54) who appeared healthy but who had relatively high cholesterol levels—more than 220 mg/dL (milligrams per deciliter)—for a 12-week clinical trial to observe the effects of DHEA supplementation on their cardiovascular function. None of the men showed any signs of heart disease or diabetes, and they had normal blood pressure and did not smoke. They were randomly divided into two groups that received a daily dose of either DHEA or placebo. The DHEA dose was 25 mg/day, an amount shown by previous work to restore plasma DHEA levels in this age group to those observed in young adult males.

In several aspects of cardiovascular function, including total cholesterol levels, heart rate, and arterial blood pressure, the researchers observed no change in either the DHEA group or the control group. In the DHEA group, however, two different clinical measurements showed significant improvement in the function of epithelial cells, the cells that line the inner surface of blood vessels and that play a major role in the vessels’ ability to dilate and contract as needed.

The first measurement was that of flow-mediated vasodilation, which indicates the ability of arteries to dilate when needed in response to epithelial signals. This is important because arteries that do not dilate properly can restrict blood flow throughout the body, a condition that is a good predictor of future cardiovascular problems. In the Japanese study, the measure of arterial dilation that was used more than doubled after 12 weeks of DHEA supplementation, and significant improvements were noted in as little as 4 weeks.

DHEA Inhibits Blood Clots

The other factor that improved with DHEA supplementation is directly related to the health of epithelial cells. When these cells become dysfunctional, they stimulate the release of a protein called plasminogen activator inhibitor type 1 (PAI-1), which inhibits the body’s ability to dissolve tiny blood clots that constantly and spontaneously form in the bloodstream. These clots can lead to serious problems down the line if they become large enough to block blood flow to critical organs—a condition called thrombosis. Such clots can have devastating, even fatal, results if they strike the heart (a heart attack) or the brain (a stroke).

In the study, DHEA supplementation appeared to restore normal epithelial cell function and decrease the blood levels of PAI-1, thus ensuring that tiny blood clots could more easily and quickly be dissolved before they could become harmful. Here again, the placebo had no effect.

DHEA Reduces Blood Glucose Levels

Another objective of the Japanese study was to measure the response of blood glucose levels to DHEA supplementation. In the same group of men, the researchers observed that after 12 weeks, DHEA had reduced steady-state blood glucose levels by 26%, whereas the placebo had had no effect. It is interesting to note that the blood levels of insulin in both groups of men remained unchanged during the course of the study. This means that some factor other than insulin production was altered by the DHEA. It has been suggested that our cells become more responsive to insulin in the presence of DHEA. Thus, although insulin levels may not change, the cells’ greater sensitivity makes the insulin more effective, resulting in lower blood glucose levels.


The measure of arterial dilation that
was used more than doubled after
12 weeks of DHEA supplementation,
and significant improvements were
noted in as little as 4 weeks.


Because none of the men in this study had diabetes, their blood glucose levels were within the normal range to begin with. Whether DHEA supplementation would have had the same effect on diabetic patients with high blood glucose levels is not known, but it will surely be the subject of future research. Stay tuned.

The Insulin Sensitivity Question

There are conflicting reports in the medical literature on the subject of DHEA and insulin sensitivity. A DHEA dose of 50 mg/day was effective in some previous studies but not in others. Even the huge dose of 1600 mg/day (64 times higher than in the study reported above) used in some earlier studies showed no effect on insulin sensitivity. There are many possible reasons for these discrepancies, among which are differences in the average age and health status of the test subjects involved. Some studies used much younger subjects, whose DHEA levels may not have been low enough to begin with to have responded positively to DHEA supplementation.

Furthermore, the subjects in the current study were all mildly hypercholesterolemic, and it may turn out that blood glucose levels respond particularly favorably to DHEA in this population. The authors acknowledge that research is needed on other groups of subjects, such as men with normal cholesterol levels, to shed more light on the matter. Regardless, the fact that 25 mg/day of DHEA seems to improve insulin sensitivity in middle-aged men with elevated cholesterol levels is exciting and gratifying.

May You Live Long and Healthy

Heart disease and diabetes are on the rise around the world. This is appalling, because we all know how to reduce our risk for both of these debilitating diseases (see “Our Cholesterol Levels Are Still Too High” on page 21 of this issue). Common sense, in the form of a good diet, regular exercise, weight control, and the judicious use of nutritional supplements, is our best ally in warding off these twin evils. So gather your wits about you and do what you need to do to live a long and healthy life.

Reference

  1. Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab 2003;88:3190-5.


Dr. Jensen is a cell biologist who has conducted research in England, Germany, and the United States. He has taught college courses in biology and nutrition and has written extensively on medical and scientific topics.

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