DHEA (dehydroepiandrosterone)

Many new supplement crazes occur simply because a novel supplement has been introduced into the market. In the case of DHEA, its popularity has soared because an old drug has recently become available as an off-the-shelf supplement in the U.S.

This occurred because the 1994 U.S. Dietary Supplement Health and Education Act was passed, allowing many substances to be sold without prescription. Products like melatonin, DHEA, pregnenolone, progesterone, and androstenedione are all now readily and legally available in many U.S. health food stores, and also in some pharmacies and supermarkets. The wide U.S. availability of these substances has allowed a kind of black market to flourish in Canada and other countries where supplement laws are more strict but not necessarily enforced. Many health food stores in Canada sell these supplements from under the counter. Customers can enter a health food store and ask for a particular product and the shop keeper will pull them out from a hiding place (perhaps from the back store room or literally from under the counter).

I’ve received quite a few inquiries from endurance athletes about DHEA, and will address this hormone by presenting its relevance and potential application for the endurance athlete. It’s really beyond the scope of this article to examine all of the claimed benefits and effects of DHEA, so we will just look at how it relates to the endurance athlete.

DHEA is the acronym for dehydroepiandrosterone, an androgen occurring naturally in humans and synthesized from cholesterol.
It is the most abundant steroid in the human body and is secreted primarily from the adrenal cortex, but is also synthesized by the skin, testes and brain. The adrenal cortex is the outer shell of of the adrenal gland, a small triangular-shaped endocrine (hormone secreting) gland situated at the top of each kidney (there are 2 adrenal glands). The adrenal cortex synthesizes and secretes more than 30 different steroids which are classified into three groups: the glucocorticoids (ie. cortisol), the mineralocorticoids (ie. aldosterone), and the androgens (ie. DHEA, androstenedione and testosterone).

In the manufacturing of DHEA, cholesterol must first enter the adrenal cortex where it is transformed into pregnenolone.
The pregnenolone is then converted into DHEA. In humans, DHEA in its original form is quickly metabolized in the adrenal cortex to its sulphated derivative, DHEA-S, before it is exported out into the blood. Dehydroepiandrosterone sulphate (DHEA-S) is the predominant and active form of DHEA circulating in the body, and when we talk of DHEA in the body, we are usually talking of the sulphated form. However, when we talk of DHEA supplements, we are usually talking of DHEA in its original form. Both forms of DHEA come as a supplement, but the DHEA-S form is much more expensive and has no apparent advantage.

DHEA levels remain very low for the first 7-10 years of life, after which they start to rise with peak levels reached at 20-24 years of age (9). After age 30, DHEA levels decline by about 20% for every ten years. At ages 85-90, DHEA levels are about 95% lower than they were at their peak. The role of DHEA supplementation may be most relevant with older athletes above 40 years of age.
One group of researchers found an anti-fatigue effect of DHEA in the elderly (6).

It is interesting to note that during times of high stress or illness there is a shift in the pregnenolone metabolism that creates a reduced production of DHEA and an increased output of the glucocorticoids, like cortisol (4,11). There is evidence that this shift causes a decline in immune function (10), perhaps due to impaired testosterone production and increased cortisol levels. Potentially, DHEA supplementation during times of heavy training (high stress) may be useful to raise DHEA levels back to their natural levels, hopefully eliciting greater testosterone production.

Also, because cortisol is a catabolic hormone, it would be logical to believe that DHEA supplementation may block its effects and promote anabolism and recovery. In fact, one study has demonstrated glucocorticoid blocking effects with the use of DHEA (4).
This suggests that perhaps endurance athletes of any age may benefit from small amounts of DHEA supplementation during times of heavy training to offset the decline in DHEA production. This, of course, is speculation, but has potential.

Getting back to some biochemistry, DHEA is the precursor to androstenedione, androstenediol, estradiol, estrone, estriol, testosterone, dihydrotestosterone, and etiocholanolone. Incidentally, you may have heard or read that men have a little estrogen circulating in their bodies, while women have some testosterone circulating around. But you could never understand how, since men don’t have ovaries to produce the estrogen and women don’t have testes to produce the testosterone.

Well, it’s because we all produce DHEA, which is then converted to estrogen or testosterone, or into several other possible hormones, through the activity of special enzymes within the adrenal cortex (See Figure I). Women are completely dependent on these special enzymes to convert other existing hormones into testosterone, the most important anabolic/androgenic hormone in the body. This may explain why women are said to respond and benefit from DHEA supplementation more than men do. Women may be better equipped (have more enzymes) to convert greater quantities of DHEA into androgens.

This brings me to a quick point. A reader asked me if there are any other supplements that are necessary to take in order to protect themselves from any unwanted side effects of DHEA use. The reader brought up zinc as one possible supplement. From my reading I haven’t found any information on protective effects of zinc while taking DHEA, but I have found some other

supplements that may be protective. I’ll get to those in a moment. Firstly, Zinc has possibilities, but not as a protective nutrient.
As I was just describing, special enzymes are needed to convert DHEA into other androgens. If micronutrients like zinc, copper and magnesium are not present in sufficient amounts, then enzyme activity will decline and the conversion of DHEA will be impaired. In fact, not just zinc, copper and magnesium are important, all micronutrients (all vitamins and minerals) are necessary for the production of every enzyme in the body. As I’ve said time and time again, its undoubtedly essential to use a good multivitamin and mineral supplement.

Back to protective nutrients while using DHEA. Two studies using male rats were used to determine the effects of vitamin E, DHEA and exercise on antioxidant status in plasma, skeletal muscle and heart muscle (3a, 3b). Both investigations found that the steroidal hormone DHEA exacerbates or worsens oxidative stress, especially when coupled with strenuous exercise, as indicated by markers of lipid peroxidation and its effects on scavenger enzymes.

Basically, for both studies two groups of rats were given DHEA for 5 weeks; one group was also given vitamin E. After the 5 week period the rats from both groups ran for 1 hour on a motorized rodent treadmill. It was found, as mentioned above, that DHEA worsens oxidative levels, especially during exercise.

The researchers found indicators of oxidative stress in all muscle fiber types, including cardiac muscle. This is important because some researchers speculate that oxidative stress to the cardiac muscle, in the long term, may be one of the causes of cardiac disease. As well, oxidative stress to skeletal muscle has been thought to be one of the causes of delayed onset muscle soreness, and this added oxidative damage may increase the amount of time for muscle repair and recovery.

Importantly, these two studies show that supplementation with vitamin E can help reduce the amount of oxidative stress induced by DHEA. So, remember to take your vitamin E daily, and perhaps the other antioxidants may be helpful as well. I believe, whether you use DHEA or not, antioxidant supplements should be an important component of your diet.

This research is interesting. It provides another story that manufacturers of DHEA are not telling us. DHEA has been touted as a powerful antioxidant, yet these studies show quite the opposite. In fact, DHEA is such a powerful pro-oxidant that researchers actually use it as a tool to induce elevations in oxidative stress in lab animals and humans as a means to study, for example, the efficacy of antioxidant supplements-in this case vitamin E.

This makes me conclude that high doses of DHEA for extended periods of time may not be a good idea, especially concerning cardiac health. Although it has been around for some time as a drug, DHEA is still a very new off-the-shelf supplement and much still needs to be learned before we can conclude its usefulness.

For men, DHEA use has one added risk and that is benign prostatic hypertrophy (BPH). Enlarged prostate is believed to be caused by excessive levels of dihydrotestosterone (DHT), an androgen that has a high affinity for the prostate. The herb saw palmetto and the drug Proscar (finesteride) are important for controlling excessive DHT levels. You should discuss this topic with your doctor.

Knowing that DHEA is the precursor to testosterone compels some people to believe that it could be useful as an ergogenic aid. And, in fact, it appears that this may be true; supplementing with high doses of DHEA has been shown to raise testosterone levels. The earliest study (1962) found that when a group of women were given a 100 mg of DHEA per day, their testosterone levels climbed significantly (5). In women, a normal serum testosterone level is around 80 ng/dl; the normal range for men is between 300 and 1,000 ng/dl. In this study, the women’s testosterone levels climbed from base level (80 ng/dl) to 160 ng/dl in the first 30 minutes after intake. After 60 minutes the women’s testosterone levels peaked at 280 ng/dl. Then after 90 minutes, testosterone levels declined to 130 ng/dl.

A more recent 1995 study examined the effects of a 50-mg daily oral dose of DHEA in men and women over the age of 50 (12).
The researchers discovered that this daily dose raised the subjects’ DHEA levels to those of young adults within two weeks.
The subjects in this study had their immune systems assessed through the measurement of lymphocytes, T-cells, and natural killer cells. The DHEA supplementation increased the levels of these cells by 67% in men and 84% in women. The researchers performed a follow-up study in which 100 mg of DHEA was used. They found the expected rise in DHEA levels and in the immune system response, but were surprised to find that the subjects also experienced gains in lean body mass and a substantial increase in muscular strength. The male subjects also experienced a significant decrease in body fat. It is speculated that the increase in lean body tissue and decrease in body fat is due to increased testosterone levels.

One anecdotal story revealed that a 55-year old man recovering from minor surgery consumed 100 mg of DHEA per day. His presupplementation blood test showed DHEA levels were 261 mcg/dl and testosterone at 479 ng/dl. Both of these levels were within normal ranges. After a couple months of DHEA use, the man reported that his DHEA levels had increased to 630 mcg/dl, and his testosterone increased to 1,066 ng/dl. He also reported that he felt like a young teenager again.

Another study examined very high dosages of DHEA (1,600 mg/day) in postmenopausal women and found a 31% decrease in body fat in 28 days and a concurrent increase in lean body mass (7). Warning, this dose is huge and should never be attempted by anyone. Researchers think that the decline in body fat in many of the studies is far greater than what can be accounted for by increased energy use by new and increased lean body mass. In other words, they don’t think the new muscle is burning all that fat. The investigators think that the DHEA supplementation has a thermogenic (heat generating) effect. It seems to make the body run harder and produce more heat at the expense of body fat. This, however, could be of some concern for endurance athletes.

If an athlete is lean and has no need to burn excess calories to lose body fat, then possibly the use of DHEA may be more of a hindrance than of help. Although a thermogenic agent increases the use of fat to generate heat, it also increases the combustion of carbohydrate. This could lead to vulnerability to hypoglycemia during training. Also, because additional heat is generated, you may be at more risk of heat injury. These concerns are speculation. These cited studies and results seem promising if you are an endurance athlete over the age of 50 and even more promising if you are a female athlete over the age of 50, but is there any evidence that DHEA is of benefit to people under 30 years of age?

A 1988 study reported that the oral administration of DHEA at a dose of 1600 mg/day to 22- to 25-year-old men for 28 days resulted in lowering of cholesterol and LDL cholesterol without changes in other lipid parameters and glucose disposal (8). Body fat significantly decreased, especially in the more obese individuals. And importantly, the DHEA supplementation caused an increase in muscle mass. This study, like the other high-dose study, demonstrates the apparent safety of DHEA use up to 1,600 mg per dayÐat least for a one-month period of supplementation.

A television news magazine (48 Hours or something like that) aired a program looking at the recent trend of DHEA supplementation. On the program a middle-aged woman reported that after supplementing with DHEA for several months she had her HDL-LDL cholesterol levels measured. She was astonished to find that her LDL (bad cholesterol) had skyrocketed and her HDL (good cholesterol) had plummeted. The interview was several months after the woman had ceased taking DHEA and she claimed that her blood cholesterol was still impaired. It is not known how much DHEA she was using, or if perhaps she had some underlying problem that predisposed her to this effect, or if the DHEA had anything to do with it.

Elevated LDL and lowered HDL are two side effects that often occur in steroid users. Maybe in some people, DHEA supplementation causes severe elevations in androgens, like testosterone, which may impair blood lipid parameters. This, however, contradicts the previously cited research and other research that has shown that DHEA supplementation reduces physiological factors that influence coronary mortality (1,2,3,8,7).

It’s very important to remember that DHEA is a serious hormone that is now being marketed like a vitamin. Indiscriminate use of DHEA could potentially be very dangerous. For those over 40 years of age, I believe, for long term use, the intake of about 25 mg per day is not risky, and perhaps daily dosages up to 100 mg may be safe. However, young athletes who consume 400-800 mg a day, and I’ve heard reports of this, may be jeopardizing their health. DHEA supplementation raises the androgens, testosterone, dihydrotestosterone and androstenedione. In women this may cause masculinizing effects, and in men, this may cause problems like enlarged prostate and feminizing effects from increased estrogen.

I’ve found DHEA sold as 25, 50 and 100 mg capsules. It seems like just about every supplement company out there now has a DHEA supplement. Companies like Weider (Schiff) in the U.S. and Ultimate Nutrition in Canada are good choices. Even GNC has its own brand of DHEA that is probably of good quality. Prices vary, but are around $30.00 for fifty 25 mg capsules.

It appears that DHEA use may work best for female athletes over the age of 40. Men of this age may benefit somewhat as well.
The potential for DHEA use to work for younger male and female athletes is there, but is still unknown. If anyone does try DHEA to augment their training, drop me a quick note to tell me how it goes.

If I were to use DHEA, and the thought has crossed my mind, I would use about 200 mg a day, in divided doses, for 2-4 weeks during a heavy training phase or overreaching period as a means to augment my training just before my most important competition. It’s important to use DHEA in divided doses because testosterone levels climb, peak and decline back to normal levels in a very short period of time (120 minutes). If you take DHEA 2-4 times per day you will be able to sustain higher average levels. It may be important as well to avoid DHEA use in the evening. There is some anecdotal evidence that DHEA has a bit of stimulative, mood elevating effect which could interfere with sleep.

For safety reasons I would probably only use DHEA once or twice a year for a short period. These are hormones that we are messing around with. Until more science shows conclusively that DHEA supplementation is safe, I wouldn’t use this stuff for any extended period of time. For men, there is risk of shutting down, or at least diminishing, your own natural testicular production of testosterone when using DHEA. This also goes for your own natural production of DHEA. The natural feedback mechanisms in the body will sense an overabundance of testosterone and/or DHEA, and will signal the testes to reduce testosterone production, and signal the adrenals to slow DHEA output. It is unknown whether DHEA use will raise testosterone levels significantly enough to cause this to happen, however. Oh, and remember, don’t forget to take your antioxidants while using the stuff.

Also, if I were to use DHEA, I would get some blood work done before I started DHEA supplementation, and then get second tests done after I finished my short supplementation period. It’s a bit of a hassle, but we are messing with stuff that, frankly, shouldn’t be sold to us without prescription. I have to say that I am absolutely marvelled that DHEA, and the other hormones like melatonin and progesterone, can be purchased off the shelf of a health food store. If someone discovers testosterone growing in some green stuff on a tree, it will surely become legal to purchase without prescription as well.

I’ve heard rumors that DHEA has recently become an IOC banned substance-this is not confirmed. DHEA, however, is definitely banned by the NCAA in the U.S. Also, there is potential for testing positive for elevated testosterone levels when using DHEA.
I will not go into morals and ethics of using such a drug. Frankly, whining about how wrong it is to use ergogenic aids and drugs bores me. Don’t get me wrong, though. I also don’t endorse the use of drugs. I just have this keen interest and like to write about them.

As for research with athletes and DHEA supplementation, there is absolutely none available as far as I can tell. The use of DHEA as a sport supplement is in its infancy, in fact, you could say it hasn’t even been born yet. Needless to say, much work is still needed before we know for sure whether DHEA supplementation is of any benefit to athletes. It’s best to discuss with your doctor the possible role DHEA may have in your sport supplement program before use. You may think DHEA is an exciting supplement in terms of potential ergogenicity, however, wait til next month when I review another, now available, hormone called androstenedione. It may knock your socks off!

References:

1. Belanger, et al., Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J. Clin. Endocrinol. Metab. 79:1086-1090, 1994.
2. Barratt-Conner, et al., A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease. N. Eng. Med. 315:1519-1524, 1986.
3. Barratt-Conner and Khaw, The epidemiology of DHEAS with particular reference to cardiovascular disease: The Rancho Bernado study. In: The Biologic Role of Dehydroepiandrosterone (DHEA). New York, Walter de Gruyter, pp.281-298, 1990.
3a. Goldfarb, et al., Vitamin E effects on indexes of lipid peroxidation in muscle from DHEA-treated and exercised rats. J. Appl. Physiol. 76:1630-1635, 1994.
3b. Goldfarb, et al., Vitamin E attenuates myocardial oxidative stress induced by DHEA in rested and exercised rats. J. Appl. Physiol. 80:486-490, 1996.
4. Kalimi, et al., Anti-glucocorticoid effects of Dehydroepiandrosterone (DHEA). Mol. Cell Biochem. 131:99-104, 1994.
5. Mahesh and Greenblatt, The In Vivo Conversion of Dehydroepiandrosterone and Androstenedione to Testosterone in the Human. Acta. Endocrinologica. 41:211-218, 1962.
6. Morales, et al., Effect of replacement dose of dehydroepiandrosterone in men and woman of advancing age. J. Clin. Endocrinol. Metab. 78:1360-1367, 1994.
7. Mortola and Yen, The Effects of Oral Dehydroepiandrosterone on Endocrine-Metabolic Parameters in Postmenopausal woman. J. Clin. Endocrinol. Metab. 71:696-704, 1990.
8. Nestler, et al., Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J. Clin. Endocrinol. Metab. 66:57-61, 1988.
9. Orentreich, et al., Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J. Clin. Endocrinol. Metab. 59:551-555, 1984.
10. Padgett and Loria, In vitro potentiation of lymphocyte activation by DHEA, andostenediol and andostenetriol. J. Immunol. 153:1544-1552, 1994.
11. Prough, et al., Effect of DHEA on rodent liver microsomal mitochondrial and peroximal proteins. In: The Biologic Role of Dehydroepiandrosterone (DHEA). New York, Walter de Gruyter, pp.253-279, 1990.
12. Yen, et al., Replacement of DHEA in Aging Men and Woman: Potential Remedial Effects. Annals of the New York Academy of Sciences. 774:128-142, 1995.

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