November 2015 Issue

Vitamins and Supplements: DHEA Supplements — A Review of the Science to Find the Truth Behind the Hype
By Carrie Dennett, MPH, RDN, CD
Today's Dietitian
Vol. 17 No. 11 P. 18

In the 500 years since Juan Ponce de León went searching for the fountain of youth, an antidote for the aging process has continued to be a holy grail. With 17% of the North American population aged 60 or older, antiaging medicine remains a fast-growing industry,1 and dehydroepiandrosterone (DHEA) supplements have been touted as an antiaging "magic bullet" and cure for myriad health problems. Does the hope match the hype, or are consumers getting more—or less—than they expect when buying DHEA over the counter?

From Stock Hormone to Dietary Supplement
DHEA is a steroid prohormone that the human body transforms into androgens (including testosterone) or estrogens as needed. Our adrenal glands produce most of our DHEA, but small amounts come from the testes, ovaries, and brain. DHEA production changes dramatically with age, peaking between the ages of 20 and 30, then steadily declining. By ages 70 to 80, DHEA levels are about 10% to 20% of young adult levels.2,3

In the United States, DHEA was available as an over-the-counter nonprescription drug for a few years in the early 1980s until the FDA banned its sale in 1985, citing a lack of data on health benefits or long-term safety. However, the 1994 Dietary Supplement Health and Education Act allowed DHEA to be sold again in the United States as a dietary supplement. Production went through the roof while quality control plummeted. Depending on the brand, the quantity of DHEA found in a supplement could be between 0% and 150% of the amount stated on the label.4

A recent Consumer Lab review of the efficacy and safety of several popular brands of DHEA found that while the brands tested did contain the amount of DHEA stated on the label, recommended dosages varied by as much as 2,000%, and the cost to get an equivalent amount of DHEA varied by as much as 500% among brands. This is bad news from both a financial and health perspective, because while 50 mg/day is enough to restore DHEA levels to the young-adult range of 1.33 to 7.78 ng/mL,1,5 doses as low as 200 mg/day have caused androgenic side effects such as acne, hair loss, and insulin resistance.4

Antiaging Hope in a Bottle?
Because DHEA levels decrease with age, DHEA supplements often are marketed as a "superhormone" with antiaging, immune-boosting, and cognitive benefits.1,6 But is artificially restoring youthful DHEA levels the answer to boosting immunity and cognition?

In animal studies, low DHEA levels have been associated with reduced lifespan and other involuntary age-related changes, including sarcopenia, osteopenia, obesity, diabetes, atherosclerosis, immune deficiency, and cognitive mood impairment.5 In nonhuman primates, DHEA levels are associated with longevity, and epidemiologic studies in humans appear to bear this out. However, association is not causation, and the evidence remains limited or weak for many of the claims.

For example, most studies looking at the effects of DHEA supplementation on cognition showed no effect or only a small effect on specific cognitive domains such as verbal fluency or working memory, even when circulating DHEA was restored to "youthful levels."3,7,8 A 2006 Cochrane review of DHEA supplementation for cognitive function in healthy elderly people concluded that the little evidence there is from controlled trials doesn't support its use to improve memory or other aspects of cognitive function in nondemented middle-aged or elderly people.9

Wendy Kohrt, PhD, a professor in the division of geriatric medicine at the University of Colorado Denver, has conducted National Institutes of Health (NIH)-funded research on the biological effects of DHEA in the elderly. She says the strongest evidence to date suggests that DHEA supplementation may have beneficial effects on bone mineral density and lean body mass in women but not men.10 "The likely explanation for the sex-specific benefit is that the effects of DHEA are mediated through its conversion to androgens and estrogens, and these naturally occurring hormones decline at a younger age in women than in men," she says.11

Because DHEA is a prohormone, could it be a safer alternative to hormone replacement therapy? Kohrt says maybe yes, maybe no. "Because DHEA is converted to androgens and estrogens, the risks may be the same as those for estrogen or testosterone therapy. However, there's the potential that the risks are lower," she says.

Kohrt says the theory—yet unproven—is it may be safer to give DHEA systemically than it is to give androgens and estrogens, because DHEA is a less active biological agent that can be converted into the more active androgens and estrogens in the specific tissues where it's needed, such as muscle and bone.

Other Health Claims
The claims attached to DHEA supplements go well beyond antiaging. DHEA is used to reduce side effects of adrenal insufficiency, including decreased sexual desire in women and muscle fatigue. It's also used to treat systemic lupus erythematosus, inflammatory bowel disease, chronic fatigue, fibromyalgia, asthma, menopausal symptoms, and infertility. The data so far are more promising with regard to mood disorders—primarily depression.3 However, for most conditions there's little solid evidence at this time of DHEA's efficacy. It may be that people with adrenal insufficiency see more symptom relief from these conditions than do people with normal adrenal function.6

"There's limited data to support any benefits of DHEA,"12 says John Morley, MD, director of the division of geriatric medicine and acting director of the division of endocrinology at Saint Louis University School of Medicine. "While more research may elucidate some benefits, a solid body of research has failed to find any in humans."

For example, DHEA carries claims to decrease cardiovascular disease risk, although the relationship between DHEA levels and cardiovascular risk factors like blood cholesterol and glucose tolerance is inconsistent.3 A 2011 study, of which Kohrt was a coauthor, found that restoring serum DHEA levels in older adults to young adult levels for one year decreased serum triglycerides but also lowered the good HDL cholesterol.13

Interest has increased in using DHEA to enhance ovarian function in women with premature ovarian insufficiency and improve outcomes in women who aren't responding well to in vitro fertilization (IVF).6,14,15

Judy Simon, MS, RDN, CD, CHES, who specializes in reproductive nutrition at Mind Body Nutrition in Bellevue, Washington, says that the scientific evidence in favor of DHEA for infertility is inconsistent. "DHEA may be recommended when a woman is a poor responder to IVF or has low ovarian reserve," Simon says. "It's not recommended for women with PCOS [polycystic ovary syndrome], and women are advised to discontinue its use when pregnant." Because DHEA is a precursor to testosterone and estrogen, Simon also advises her patients to discuss its safety and efficacy with a physician before taking it.

Balancing the Risks and Benefits
Research results on DHEA health effects have been inconsistent for a variety of reasons, including overreliance on animal research for a hormone that's inherently human, and often using variable doses in such research that in some cases are high enough to be unachievable in humans.16 Based on current data, DHEA is possibly safe when used in the short term in appropriate doses, but may be unsafe when used in high doses. Most studies have been too short to evaluate long-term safety and efficacy of DHEA supplementation.3,4

"There have been a handful of NIH-sponsored randomized, controlled trials of DHEA supplementation in older adults that have been of relatively high quality," Kohrt says, noting that both the sample sizes (100 to 200 per study) and the period of intervention (one to two years) has been limited, largely because of the nature of the NIH grants. "These studies have yielded some benefits and no serious risks of DHEA. However, a true understanding of the potential benefits and risks of DHEA use will require a larger, multisite trial with a longer period of intervention."

Bottom Line
Although DHEA clearly is important in the body, some experts question which comes first: health or healthful DHEA levels? While life expectancy may be longest in populations with higher DHEA levels, it could be that people who are healthier simply tend to have higher DHEA levels.5

It's also possible that DHEA replacement therapies may have limited effectiveness because of an age-related decline in the enzymes necessary to convert DHEA to estrogen or androgens.17 The bottom line is that although a growing body of evidence supports the idea that DHEA has benefits for some human diseases, large-scale randomized, controlled trials are needed to clarify where the benefits lie, and at what doses. Clinicians should inform patients of the lack of long-term data regarding both effectiveness and safety.

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times and speaks frequently on nutrition-related topics. She also provides nutrition counseling and therapy via the Menu for Change program in Seattle.

1. Samaras N, Papadopoulou MA, Samaras D, Ongaro F. Off-label use of hormones as an anti-aging strategy: a review. Clin Interv Aging. 2014;9:1175-1186.

2. Labrie F, Bélanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab. 1997;82(8):2396-2402.

3. Samaras N, Samaras D, Frangos E, Forster A, Philippe J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res. 2013;16(4):285-294.

4. DHEA. Natural Medicines Comprehensive Database website.
. Updated October 1, 2015. Accessed August 18, 2015.

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8. Kritz-Silverstein D, von Muhlen D, Laughlin GA, Bettencourt R. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) trial. J Am Geriatr Soc. 2008;56(7):1292-1298.

9. Grimley Evans J, Malouf R, Huppert F, Van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev. 2006;(4):CD006221.

10. Jankowski CM, Gozansky WS, Schwartz RS, et al. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J Clin Endocrinol Metab. 2006;91(8):2986-2993.

11. Jankowski CM, Gozansky WS, Kittelson JM, Van Pelt RE, Schwartz RS, Kohrt WM. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin Endocrinol Metab. 2008;93(12):4767-4773.

12. Morley JE. Scientific overview of hormone treatment used for rejuvenation. Fertil Steril. 2013;99(7):1807-1813.

13. Jankowski CM, Gozansky WS, Van Pelt RE, Wolfe P, Schwartz RS, Kohrt WM. Oral dehydroepiandrosterone (DHEA) replacement in older adults: effects on central adiposity, glucose metabolism, and blood lipids. Clin Endocrinol (Oxf). 2011;75(4):456-463.

14. Tartagni M, Cicinelli MV, Baldini D, et al. Dehydroepiandrosterone decreases the age-related decline of the in vitro fertilization outcome in women younger than 40 years old. Reprod Biol Endocrinol. 2015;13:18.

15. Narkwichean A, Maalouf W, Campbell BK, Jayaprakasan K. Efficacy of dehydroepiandrosterone to improve ovarian response in women with diminished ovarian reserve: a meta-analysis. Reprod Biol Endocrinol. 2013;11:44.

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17. Sorwell KG, Urbanski HF. Dehydroepiandrosterone and age-related cognitive decline. Age (Dordr). 2010;32(1):61-67.