DHEA is a steroidal hormone produced by the adrenal glands in substantial amounts; it is a precursor from which the body makes testosterone, estradiol, and a number of other steroid hormones. DHEA is thought to have other functions, but little is known about them. As a precursor, however, DHEA has a significant impact on the body’s production of hormones and other substances, which in turn have profound physiological effects. The sulfate of DHEA, “DHEA-S”, seems to serve as a reservoir for DHEA in the blood.

DHEA was discovered in 1931. An inkling of its possible significance in aging was uncovered in the 1950s when it was found that blood DHEA levels decline dramatically as people age. The possibility that supplementing with DHEA might therefore counteract aging led to its marketing as a nutritional supplement in the early 1980s. In 1985, the U.S. FDA, acting in typical totalitarian fashion, banned products containing DHEA. Supplement companies then began selling wild yam extract, claiming that the extract is converted to DHEA in the body; however, very little such conversion actually takes place in humans. DHEA reemerged as a supplement in 1994, with passage of the federal Dietary Supplement Health and Education Act, and has been immensely popular ever since.

Typical claims made for DHEA

(1) Cancer: Reduces risk of cancers of the breast, prostate, lung, colon, liver, and skin
(2) Heart: Prevents heart disease and atherosclerosis, reduces cortisol (a promoter of heart disease)
(3) Muscle: Builds lean muscle mass, decreases breakdown of muscle tissue
(4) Fat: Reduces body fat; prevents lipodystrophy due to HIV protease inhibitors, reduces cortisol (a promoter of visceral fat)
(5) Insulin: Increases insulin-producing cells and insulin sensitivity; prevents diabetes and diabetes-induced damage
(6) Anti-aging: Increases life span by 50%
(7) Hair: Causes growth of pubic hair in people who lack it. (Not everyone would consider this a benefit, but some do.)
(8) Skin: Improves thickness, color, wrinkles, elasticity, collagen, puffiness under eyes
(9) Energy: Improves thermogenesis and energy production; treats chronic fatigue syndrome
(10) Immunity: Improves immunity and response to vaccination; treats infectious diseases
(11) Cognition: Improves memory; protects brain cells from neurotoxic neurotransmitters (e.g., NMDA)
(12) Mood: Decreases depression, anxiety, and stress; improves mood
(13) Bone: Decreases bone loss, increases in bone density
(14) Lupus: Relieves lupus erythematosus
(15) HRT: Is an effective hormone replacement therapy for men and women
(16) Sex: Increases libido, improves sexual function
(17) Fertility: Increases fertility in women; could inhibit menstruation in pre-menopausal women
(18) Other ailments: Relieves arthritis, Parkinson’s, multiple sclerosis, inflammatory bowel disease, thyroid problems, herpes infections, allergies, and hormone imbalances

Typical claims made against DHEA

(19) Cancer: Could stimulate the growth of previously dormant tumors
(20) Heart: Causes cardiac arrhythmia
(21) Hair: Causes growth of body or facial hair, scalp hair loss
(22) Skin: Causes acne and seborrhea
(23) Mood: Causes irritability and aggression; causes severe mania
(24) Prostate: Causes prostate enlargement, difficulty urinating
(25) HRT: Increases estrogen levels in men, but not testosterone levels
(26) Fertility: Increases fertility in women; could inhibit menstruation in pre-menopausal women
(27) General claims: “Hardly anything is known about DHEA”; “problems associated with hormone use might not appear until years later”; “it’s the snake oil of the ’90s”; “should be classified as an investigational drug and used only in clinical research”; “doses greater than 5 mg should require a prescription”

The known facts about DHEA

Although there have been many studies of DHEA in recent years, the great majority of them have merely looked for correlations between medical problems and DHEA levels in the body. Such studies are essentially useless for practical purposes — they do not tell us whether low DHEA levels cause the problems and they tell us nothing about DHEA supplements as treatments for them. Of the remaining studies, most are tissue-culture experiments that, again, tell us little about DHEA supplementation. A few supplementation experiments have been done in rodents, but DHEA levels in rodents are negligible compared to those in humans — suggesting that the effects of DHEA may be different in these animals. A small number of human clinical studies exist and do shed a wan light on the subject, but the results are often contradictory and there is disagreement about interpretation. From this pathetic performance by the medical research world, we will draw what conclusions we can.

But first it should be noted that DHEA’s oral bioavailability and persistence in the body are still uncertain (see “Bioavailability and half-life” below). Perhaps the muddle in which DHEA clinical research finds itself is due to inconsistent absorption and hidden complexities in the body’s hormonal regulation. Hence, when a study shows no benefit from DHEA supplementation, we cannot tell whether this is due to a failure of DHEA or merely poor bioavailability or misinterpreted measurements of hormone levels. On the other hand, it is much harder to argue with a reasonably well-performed study that does show a benefit. Therefore, when there is disagreement between different studies, it makes sense to give greater credence to the studies that show benefits than to those that don’t, and this policy will be followed in the summary below.

• Cancer (claims 1 and 19): DHEA supplementation appears to protect most tissues (except liver) from cancer initiation, but it may increase the growth rate of steroid-sensitive tumors if they already exist. Animal experiments suggest that DHEA might increase the risk of acquiring liver cancer.
• Heart disease (claims 2 and 20): DHEA supplementation improves cholesterol and other lipid patterns in women when used for 12 months, and decreases cortisol levels in healthy older men and women. (Cortisol levels are associated with risk of heart disease.) In rodents, DHEA reduces atherosclerotic plaques. Although proper clinical studies are lacking, it would be reasonable to suppose that DHEA supplementation is of use in preventing or reversing heart disease in humans. The claim that DHEA causes cardiac arrhythmia (claim 20), is based on a single case in which a man who was taking DHEA experienced arrhythmia; in view of the fact that lots of people who don’t take DHEA experience arrhythmia, it would appear that people who use DHEA are less likely to experience arrhythmia than those who don’t.
• Muscle (claim 3): Does DHEA supplementation promote muscle growth? Studies in rats suggest that it does. Several small human studies directly contradict each other on this point. In one study, however, 50 mg/day of DHEA produced a 10-20% increase of IGF-1 in both sexes. (IGF-1 is a highly anabolic growth factor that stimulates the growth of muscle and other tissues.) It seems likely that at sufficient dosages DHEA would have anabolic effects on muscle tissue.
• Fat (claim 4): The very few studies that have been done in humans (at up to 1600 mg/day) have given contradictory results. In rats, on the other hand, DHEA supplementation lowered fat consumption and prevented age-related increases in body fat. High doses of DHEA (>1000 mg) do cause an increase in metabolic rate in humans, and fat reduction would be the expected result. As for lipodystrophy, DHEA in combination with indomethacin reduces lipodystrophy caused by HIV drugs.
• Insulin (claim 5): DHEA supplementation improves insulin-sensitivity in post-menopausal women; it reduces the severity of glucocorticoid-induced diabetes. In rodents DHEA prevents diabetes-induced nerve damage, improves insulin secretion, and controls hyperglycemia. It is therefore plausible, though not proven, that DHEA supplementation can prevent or ameliorate diabetes in general.
• Anti-aging (claim 6): The claim that a 50% increase in lifespan can be achieved with DHEA supplementation appears to be a misinterpretation of experiments with tumor-prone mice. There are no clinical studies that directly show whether or not DHEA use increases longevity (these would take decades to carry out). However, if DHEA can ameliorate various ailments of aging (such as heart disease), then it must inevitably increase longevity.
• Hair (claims 7 and 21): DHEA supplementation causes growth of pubic hair in women with atrichia pubis (lack of pubic hair); it is reasonable to suppose that it would do so in men, as well. DHEA can also promote facial hair growth in some women (11% in one study). Although a correlation between DHEA-S levels and male pattern baldness has been shown in young men, no clinical study has shown that DHEA supplementation causes hair loss. In any case, if any such tendency existed, it could be counteracted by drugs such as dutasteride or finasteride.
• Skin (claims 8 and 22): Improvement in skin pigmentation has been shown in elderly women given DHEA supplements at 50 mg/day. DHEA also increases acne in some women, but not in men — presumably because women’s testosterone levels were elevated but men’s weren’t.
• Energy (claim 9): DHEA supplementation at 200-500 mg/day significantly reduced fatigue in HIV patients.
• Immunity (claim 10): In mice, a single injection of DHEA under the skin protected the animals from viral, bacterial and parasitic infections. Long-term oral ingestion also provided protection. (4-Androstenediol worked even better than DHEA.) This effect has not been studied in humans.
• Cognition (claim 11): Memory enhancement has been shown in animal studies of DHEA supplementation; the few human studies that have been done have produced contradictory results. In rats DHEA supplementation causes an increase in newly formed cells in the hippocampus (a memory center in the brain). It is reasonable to conclude that DHEA supplements have the capacity to improve memory in humans.
• Mood (claims 12 and 23): DHEA supplementation at 30-90 mg/day produces improvement of depression and anxiety in schizophrenic patients, and of depression and mood in non-schizophrenic patients. DHEA supplementation at 200-500 mg/day significantly improved mood in HIV patients. As for mania (claim 23): three cases have been reported of manic episodes in individuals who happened to be using DHEA supplements; in at least two of these cases the patients had a history of mania before they ever used DHEA. Statistically, it would seem that mania is much more likely to occur in people who don’t take DHEA than in those who do.
• Bone (claim 13): Improvement of bone turnover occurred in elderly women treated at 50 mg/day of DHEA for 6 months. Improvement in men was seen in some studies and not in others. It is reasonable to conclude that given high enough doses, DHEA supplementation would improve bone strength in both sexes, particularly where levels of estrogens and testosterone are low — as they are in people more than 40 years old.
• Lupus (claim 14): At 200 mg/day DHEA reduced the incidence of lupus flares.
• HRT (claims 15 and 25): It has been shown that in older men DHEA supplementation at 100 mg/day increases estrogen levels but not testosterone levels. In older women this dosage produces large increases in both estrogen and testosterone. Contrary to popular notions, these hormonal increases are, by and large, beneficial rather than harmful for both sexes — they improve the condition of skin, bone, and other tissues, improve cognition, and contribute to libido.
• Sex (claim 16): DHEA supplementation improves libido and other sexual measures in elderly women, women with sexual dysfunction, and younger men and women with hormone deficiencies. DHEA also decreases erectile dysfunction. Libido studies are lacking for normal young men and women; but libido enhancements are entirely possible, since DHEA supplements increase estrogen levels in males, and both estrogen and testosterone levels in females. (Both estrogens and testosterone contribute to libido.)
• Fertility (claims 17 and 26): DHEA supplementation at 80 mg/day improves lackluster responses to ovarian stimulation. General effects on fertility have not been studied. The effects of DHEA on menstruation have not been studied except in anorexic women — DHEA restores menstruation where it has been suppressed by the ailment.
• Prostate (claim 24): The idea that DHEA supplementation might cause prostate enlargement is based on theory, not observation. Higher DHEA levels in the blood correlate with higher levels of estrogens and of IGF-1 (a growth factor); higher IGF-1 levels correlate with prostate enlargement; so do estrogen levels in some studies, but in other studies they don’t. Theories as tenuous as this one are not worth the hot air they’re made of.
• Other ailments (claim 18): Rheumatoid arthritis — a small human study showed no benefit from 200 mg/day of DHEA; but a mouse study did show benefit in delaying and decreasing collagen-induced arthritis. Multiple sclerosis — DHEA treatment resulted in significantly reduced incidence and severity of a mouse disease similar to MS. Parkinson’s — Rat experiments suggest that DHEA treatment can protect the neurons whose degeneration characterizes this disease. Allergies — Mice with atopic dermatitis or dust mite allergies showed signs of benefitting from DHEA therapy. Herpes — Mice treated with DHEA were significantly protected from herpes virus type 2 encephalitis infections. Inflammatory bowel disease — no clinical studies have been done. Hormonal imbalance — this is a nonsense term with no clear medical meaning.
• General claims (claim 27): These claims are merely propaganda generated by people who want more control over other people’s lives. The medical profession in particular tends to favor eliminating public access to nutritional supplements like DHEA, because this would make people more dependent upon physicians for treatment of ailments. Every ailment that is successfully treated with DHEA represents money that bypasses the medical profession.

Usage

Doses of 20-50 mg/day will usually restore DHEA and DHEA-S levels in the blood to youthful levels in men over 40 years old. For women the range is typically 10-30 mg/day. However, there is no particular reason to think that youthful levels are optimum levels for people of any age. The levels of hormones and other substances produced by the body evolved in response to harsh conditions that no longer exist for most human beings. It would be naive to expect that these aspects of our physiology are optimum under all conditions, especially medical conditions such as disease and aging. DHEA dosages of up to 3000 mg/day have been used in various studies, sometimes with beneficial results that would not have been achieved with lower doses. It goes without saying that the long-term effects of any DHEA dosage have not been determined, but the fact that DHEA is made by the body in substantial amounts (at least in younger people) suggests that any toxicity it might have in the body must be extremely low.

Bioavailability and half-life

The oral bioavailability of DHEA is in dispute — some say it is as low as 3%, some say it is “excellent”, others say it is “variable”. The half-life of DHEA in the body is also debatable — measurements range from 15 minutes to 24 hours. The most reasonable interpretation of these figures is that both the bioavailability and half-life are highly variable, and that they depend upon the physical form of DHEA used, and upon conditions in the digestive tract and in the body. Variations in these parameters could explain the inconsistent results that have been obtained in clinical studies of DHEA. If so, then we should take the positive studies as the measure of DHEA’s potential benefits, and then attempt to achieve this potential by improving bioavailability and half-life. Bioavailability can be markedly improved by micronization. Both bioavailability and half-life can be altered by the presence of other substances that share the same enzyme systems for absorption or metabolism (see next section).

Interaction with other substances

A list of some of the substances that may alter DHEA’s metabolism, bioavailability, and half-life can be found at DHEA interactions. By the same token, the use of DHEA may alter the metabolism of these substances.