DHEA: What role in your program?
TYP site
The arguments for and against DHEA replacement have zig-zagged from fountain of youth
to dangerous. Here, we cut through the hype and hone in on the issues
important to your plaque-control program.
"I consider DHEA the superstar of the superhormones. It not only works its wonders inside the body by rejuvenating virtually every organ system, but it actually makes you look, feel, and think better…It restores energy, improves mood, increases sex drive, enhances memory, relieves stress, reduces body fat, and even makes your skin softer and your hair shinier. I think that just about every adult age forty-five or older can benefit from taking DHEA."
William Regelson, MD
The Super-Hormone Promise
"DHEA is the snake oil of the '90s. It makes me very nervous that people are using a drug we don't know anything about. I won't recommend it."
Elizabeth Barrett-Connor, MD
University of California, San Diego.
Debate on DHEA has polarized proponents and critics. Comments like those above reveal just how far apart views on this controversial hormone can be.
Let's cut through the hype, hyperbole, and hoopla. Don't believe the extravagant claims of supplement manufacturers. We also don't want to fall victim to the over-conservative medical community's reluctance to accept anything that doesn't require prescription and come with a fancy dinner provided by a drug representative.
Concerns over the safety of DHEA were raised—and rightly so—in the 1980s and 1990s when multiple clinical trials of "mega-dose" DHEA (1600–3000 mg per day) led to undesirable hormonal effects: women experienced masculinizing effects like facial hair and deepened voices, men became emotional. In other words, at high doses, women convert DHEA to testosterone, men convert it to estrogen. We definitely do not want these effects.
More recent experience suggests that, when used at doses that are "physiologic", or simply replace diminishing levels due to aging and restore youthful blood levels to those you had at age 30 or 40, the hormonal distortions don't occur. Based on the current state of knowledge about DHEA, we can expect several potential benefits through "physiologic replacement":
* A modest reduction in abdominal and visceral fat results with extended use (6 months or longer).
* A modest improvement in insulin resistance over an extended period (months).
* People feel better taking DHEA, particularly if starting levels are low.
* Men gain greater benefit than women. (Sorry, ladies.)
Along with exaggerated side-effects, outsized benefits also occurred with mega-dose DHEA, such as dramatic relief of depression, substantial increases in muscle mass and strength (in men), and intensified libido in women. These are less prominent at lower replacement doses.
Does this fascinating hormone possess any benefits for coronary plaque control? We believe it does. Used intelligently and with realistic expectations, DHEA can add advantage.
What exactly is DHEA?
Dihydroepiandrosterone, or DHEA, is a hormone produced by the two adrenal glands in the abdomen, sitting atop the kidneys. Men also produce up to 25% of total DHEA in their testes. DHEA is distributed throughout the body and is especially abundant in brain tissue, blood, kidneys, and liver. For years, DHEA's precise role has been debated.
Along with declining muscle mass, bone density, sex hormones, growth hormone, and increasing body fat, DHEA levels decline starting at age 30 in men, age 40 in women, with accelerated decline after age 50. By age 70, both men and women have plummeted to 25% of youthful peak levels (Kroboth PD et al 1999). However, age accounts for only 30% of variation in DHEA blood levels; other factors influence DHEA levels, as well (Haden ST et al 2000).
It is well established that people with features of the metabolic syndrome (low HDL, high triglycerides, small LDL, high blood pressure and blood sugar, excessive abdominal fat) have lower blood levels of DHEA, probably caused by accelerated clearance (into the urine) of DHEA induced by high insulin levels (Lavallee B et al 1997), though the association is more prominent in men than in women (Haffner SM et al 1994). Interestingly, administration of metformin (Glucophage®) to reduce blood sugar also increases DHEA blood levels 50% or more (Nestler JE et al 1994). . Weight loss also results in a substantial rise in DHEA blood levels in men (Jakubowicz DJ et al 1995).
Aging, therefore, with its declining DHEA levels, is associated with increasing levels of insulin resistance, pushing us closer and closer to metabolic syndrome and pre-diabetes.
By far the most convincing demonstration of DHEA's potential is in people (men and women) whose adrenal glands are dysfunctional and fail to produce its usual panel of hormones ("adrenal insufficiency"); these people do substantially better with replacement of hormones if DHEA is included. People feel better, are less depressed, lose weight, gain muscle, reduce cholesterol, and reduce blood pressure when DHEA is added (Arlt W et al 1999).
A drug manufacturer has seen sufficient promise in DHEA to pursue development as a drug. A pharmaceutical-grade preparation trademarked Prestara™ is in clinical trials for potential use on a prescription basis for treatment of lupus, and an intravenous form is under development to treatment acute asthma attacks and burn injuries.
(We've seen this sort of "transformation" before, going from nutritional supplement status to drug status, accompanied by the better-funded clinical trials of the drug companies. The most prominent recent example was fish oil—for many years a nutritional supplement, then a form "developed" by a drug company that passed the FDA drug approval process. The drug company then bashes the nutritional forms on the basis of purity, potency, or other factors that may or may not be important. We'll likely see the same predictable process with DHEA.)
Established benefits of DHEA
Over the past 40 years, DHEA has been studied in a number of applications, some successful, some not. Among the successes DHEA has yielded:
* In lupus, DHEA permits reduction of corticosteroid medication dose (e.g. prednisone) and partially offsets some ill-effects of therapy, such as osteoporosis (Merrill JT 2003).
* In people with adrenal failure, whose adrenal glands therefore produce little or no DHEA, DHEA replacement (50 mg per day) improves mood, physical energy and performance, and bone density when used along with standard hormone replacement therapy (e.g., cortisol) and with extended use (Arlt W et al 1999).
* DHEA may slow progression of osteoporosis in postmenopausal women (Baulieu EE et al 2000), and may increase bone density (Labrie F et al 1997).
* DHEA improves sexual dysfunction and libido in women over age 60 (Baulieu EE et al 2000).
* DHEA may improve erectile dysfunction in men who have low DHEA levels (Reiter WJ et al 2001).
* DHEA alleviates depressive symptoms such as inability to cope, worrying, lack of motivation, and sadness (Bloch M et al 1999).
* DHEA may improve symptoms of chronic fatigue syndrome (Cleare AJ 2003).
Interestingly, most studies of DHEA in athletic performance have not shown benefit, but DHEA use remains banned in Olympic athletes.
Much of the interest surrounding DHEA is for its purported youth-preserving effects. But DHEA is clearly not a fountain of youth. Nonetheless, several interesting pieces of evidence suggest that it does, indeed, modestly restore some aspects of youthfulness. For instance, both men and women taking 100 mg DHEA have been shown to have a 16–31% increase in IGF–1a, indicating an increase in effective growth hormone (Morales AJ et al 1998). (Growth hormone may be responsible for genuine age-slowing or reversing effects.) A rise in effective growth hormone might be responsible for at least some of DHEA's weight-reducing, energy-enhancing, and perhaps youth-preserving effects.
Enthusiasm for DHEA, however, has been tempered by some reports of higher DHEA and other androgens (male hormones) blood levels predicting greater risk for breast cancer in women (Dorgan JF et al 1997). No treatment trials, in which DHEA was administered to women, have been performed to further examine this question. With physiologic replacement doses, the increment in testosterone levels in women is very small and nearly always remains within the normal range for females (Morales AJ et al 1998).
Are there cardiovascular benefits to DHEA replacement?
An early large study, the Rancho Bernardo Study, suggested that men with lower DHEA levels were at three-fold greater risk for heart attack and cardiovascular events than their peers with higher levels (Barrett-Connor E et al 1986). This relationship did not hold for women, however, with higher DHEA levels associated with greater risk for heart disease (Barrett-Connor E, Khaw KT 1987). The Massachusetts Male Aging Study of 1,709 men tracked over nine years showed that men with low DHEA suffered more heart attacks than men with higher DHEA (Feldman HA et al 2001).
Other studies have demonstrated effects that are potentially beneficial from a cardiovascular standpoint: blocking the blood-clotting factor plasminogen activator inhibitor; blocking platelet aggregation (blood clot formation); and reduction of LDL cholesterol (Svec F, Porter JR 1998). However, these are effects observed at much higher DHEA doses, not at physiologic replacement doses.
How beneficial is DHEA administration in directly reducing heart disease risk? Unfortunately, that has yet to be determined. Despite all the clinical studies probing DHEA questions, no large-scale study has yet been performed to show whether or not heart attack and other cardiovascular events are affected by taking DHEA. The best we can do for now is to draw from the studies that have been performed examining whether or not DHEA replacement impacts on some aspect of heart disease risk.
DHEA and your plaque control program
You can, indeed, live without DHEA in your body, but you'd probably feel lousy. DHEA clearly plays a role in human health, though perhaps not a life-saving one. This fact has been most persuasively borne out by the observations in adrenal failure. But in people with normal adrenal function and declining DHEA levels consequent to age and metabolic syndrome, is there a role for DHEA replacement?
Provided your use is individualized, based on blood levels at the start and during replacement, and ideally with the supervision (or, at least, knowledge) of your physician, then DHEA may indeed provide benefits for your plaque control program.
Metabolic syndrome and pre-diabetes
This is probably where DHEA supplementation shines most. When taken at bedtime, DHEA enhances mobilization of abdominal fat. One of the early but carefully performed analyses performed by a University of California–San Diego group demonstrated 6% reduction in fat mass in men, though no change in women, and 2% increased muscle mass in both sexes with 100 mg per day (Yen SS et al 1995). A Washington University study enrolled 56 men and women, all of whom took either 50 mg DHEA or placebo at bedtime. Magnetic resonance imaging (MRI) of the abdomen was performed at the start and after six months (a precise measure of tissue types such as fat). Participants taking DHEA, without change in diet or exercise, experienced an 8% decrease in abdominal fat. These and similar observations suggest that DHEA may selectively mobilize visceral fat that accumulates around the intestines and generates resistance to insulin and metabolic syndrome.
Other research has shown that DHEA is a "PPAR-agonist", i.e., an agent that activates a specific pathway that clears fatty acids from the blood and thereby modulates triglyceride, lipoprotein, and insulin metabolism (Peters J 1996). Free fatty acid blood levels are increased in obesity and insulin resistance.
Lipoprotein(a)
Lipoprotein(a) treatment is a problem area, but especially for women. Since the only treatment choices are niacin and testosterone in men; niacin and estrogen in women, many women are reluctant to consider estrogen because of studies suggesting heightened risk for endometrial (uterine) and breast cancer. DHEA may be a helpful alternative that reduces Lp(a) by 18% at a dose of 50 mg/day, though it may be accompanied by a several point drop of HDL (Barnhart KT et al 1999). (If used in combination with niacin, the HDL drop is usually not an issue, since niacin generally raises HDL substantially.)
People who feel better, do better
Though difficult to quantify, DHEA replacement simply helps many people feel better: more physical stamina, a brighter outlook, more "get up and go". Problems seem just slightly less overwhelming and "lows" tend not to be quite as low. Though there are clinical data to support these "soft" effects, they are inconsistent. In our experience, people who start out with sluggishness, low energy, and a negative outlook, accompanied by a low DHEA level (measured as DHEA-s) of <250 µg/ml, are the most likely to experience positive results with DHEA replacement.
And, unfortunately for the women, it's the men who enjoy most of the benefits of DHEA replacement. After all, DHEA is principally an androgen, with characteristics shared with testosterone. Men are most likely to enjoy the reduction in abdominal fat, weight loss acceleration, partial correction of metabolic syndrome, along with feeling better.
DHEA is not without its uses in women, however. Women who also have blood levels of <250 µg/ml, suffer from physical sluggishness and the tendency to be easily overwhelmed, and/or have the characteristics of metabolic syndrome, may also experience some of the benefits of DHEA replacement, though less dramatically than in males. Doses in females tend to be lower than in males and are dependent on age (see below).
In both sexes, beware of aggressive behavior. Occasionally, DHEA supplementation will bring out aggressive behavior, such as short-temperedness, intolerance, and impatience. A reduction in dose usually resolves this issue (e.g., reduce from 50 mg to 25 mg per day).
How to take DHEA
If DHEA supplementation interests you, we've had success with the following:
Men
DHEA, 25 mg at bedtime for men ages 45–50; may increase to 50 mg over age 50. Do not increase beyond 50 mg unless directed by your doctor and safety verified by DHEA-S blood levels. We aim to achieve blood levels of 350–500 µg/dl. If you're among the occasional people who experience insomnia with DHEA at bedtime, consider switching to morning.
Women
For women ages 40–50, 10–25 mg per day at bedtime generally suffices. Over age 50, an increase in dose to 25–50 mg might be considered, ideally based on blood levels. Do not increase beyond 50 mg unless directed by your doctor and safety verified by DHEA-S blood levels. We aim to achieve blood levels of 350–500 µg/dl. If you're among the occasional people who experience insomnia with DHEA at bedtime, consider switching to morning.
Keep in mind that the benefits of DHEA tend to develop with long-term (6 months or more) use. You won't take it on Tuesday and feel rejuvenated or thinner on Thursday. Perceptible effects, like mood elevation or increased physical stamina, develop very gradually, almost imperceptibly, that may be evident only after you've stopped your DHEA months after starting.
DHEA–An unregulated supplement
"Health food shops are cashing in on the public's interest in DHEA by offering products labeled DHEA but which do not contain DHEA. Instead they contain plant sterols said to be the 'botanical building blocks of DHEA.'"
Dr. Marc E. Weksler
Cornell University Medical College
DHEA remains a problem area when it comes to supplement quality, though it has improved over the last decade. Ten years ago, a small study examining the content of 16 DHEA preparations right off the store shelves found that 7 of the 16 had substantially less than the amount listed on the label, with a few having almost none; one preparation had 149% of the labeled amount (Parasrampuria J et al 1998). More recently, the nutritional supplement testing organization, Consumer Lab (www.consumerlab.com), found that 3 of 17 products contained significantly less DHEA than claimed. They also found that the claim of "Pharmaceutical Quality" on the label did not assure potency, as three products labeled this way contained only 19–79% of the amount of DHEA claimed on the label. All products tested, however, passed Consumer Lab's testing for lack of contamination (lead, pesticides, and other undesirable contaminants) and dissolved promptly. Among brands that passed ConsumerLab's rigorous testing: Solaray, GNC, Puritan's Pride, Nature's Bounty, and KAL. (Consumer Lab is a wonderful service for those of you interested in confident supplement use. Go to www.consumerlab.com.) |
