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DHEA: Fad and Folly or Fountain of Youth?
By Dr. John H. Maher
DHEA: FOUNTAIN OF YOUTH OR FAD & FOLLY? (Part 1)
Caveats to Consider with Oral DHEA Enhancements
In spite of the recent surge of interest in HGH oral secretagogues, sale of the original "anti-aging wonders", DHEA and melatonin, still far outstrip those of their newest rival.
Opinions as to the value of DHEA enhancement range from, "everyone past 25 should supplement their diet with DHEA" (1), to "until further work proves its benefits and determines its safety people should not take DHEA." (2)
The purpose of this paper is to review some of the data that suggests a more rational alternative to either of the above two polar extremes.
What is DHEA?
Dehydroepiandrosterone is the most abundant adrenal steroid. The average daily output for men is 31 mg. and 19 mg. for women. Levels peak at puberty and are already declining by maturity. By age 80, levels may be as little as 5 or 10% of peak puberty levels. (3)
DHEA, like all the steroid hormones, is derived from pregnenolone, which is itself derived from the steroid cholesterol.
Compared to other hormones like melatonin and cortisol, there is little circadian variation. DHEA is only about 12% higher in the AM, though this variation becomes even smaller with age. Interestingly, levels tend to be higher in autumn and winter by 13%. (4).
What Are the Functions of DHEA?
DHEA’s primary role is as a precursor for the sex hormones, i.e., testosterone and estrogen.
It also appears to buffer the brain (the hippocampus and hypothalamus) from damage related to high levels of the stress hormone, cortisol. (5) This may be part of the explanation of DHEA’s reported ability to improve memory function in both animals and the elderly. (6) A ratio of 10 to 1 DHEA over cortisol is generally considered desirable to protect the brain against the aging effects of stress.
DHEA may increase serotonin which in turn may be an explanation for its mood altering and anti-depressant effects experienced by some. (7) This may also explain why DHEA has been reported to increase REM sleep. DHEA is low in postpartum depression, anorexia nervosa, and schizophrenia.
DHEA appears to increase insulin sensitivity and lower lipids, which may be related to its reported relation to lower cardiac mortality in men. (8,9) DHEA stimulates the immune system in part by increasing IL-2 and natural killer cell activity and overcoming the immuno-suppressive effects of cortisol (stress) on T-lymphocyte function. DHEA increases lean-body-mass and bone density probably through increasing testosterone and increasing thermogenesis in the liver. ( 7) DHEA increases IGF-1, probably through enhanced HGH receptor activity. Thus it has been called, "the poor man’s hgh".
Thirty days oral administration of 1600mg of DHEA daily in healthy males caused a 31% fat loss w/ no weight loss, suggesting increased muscle mass.
So it is easy to see why Ward Dean, M.D., states, "DHEA may have impressive immuno-regulatory, anti-diabetic, anti-cancer, anti-obesity and anti-stress benefits and be useful in the prevention of atherosclerosis, hypertension, hyper-cholesterolemia, and multiple sclerosis.(8)
The Catch
So given all the benefits, why isn’t everyone in favor of DHEA supplementation?
First of all, although there have been thousands of studies done on DHEA, most have been done on animals. Human studies are much fewer and somewhat conflicting.
As DHEA is converted into the sex hormones, estrogen and testosterone, it is feared that these may cause an increase in the incidence of and the rate of growth of estrogen/testosterone sensitive tumors. Of most concern are breast, cervical, uterine, ovarian and prostate malignancies, and BHP, all believed to be estrogen sensitive and the latter two testosterone related.
There have been expressed concerns of liver damage or liver cancer with very high doses. (9)
Although animal studies have turned up no certain ill effects, there are no long-term studies in humans.Studies in cancer patients have turned up high levels of DHEA in breast and endometrial cancer.
Retrospective studies have found elevated DHEA levels in postmenopausal women not taking estrogen and who had no evidence of breast cancer, were related to significantly higher incidences of breast cancer in the next 10 years. (10 )
There is concern that DHEA supplementation may cause masculinizaton of the female fetus.
The most accepted theory of BHP and prostate cancer is that testosterone, and its metabolite, DHT, worsens or causes these conditions and therefore indirect enhancements of same via DHEA supplementation should be avoided.
Benefit/Risk Analysis
Keep in mind however, most anti-aging programs endeavor to "restore the hormones of youth" and that includes testosterone in men and testosterone and estrogen in women. The question is in each particular case, do the benefits outweigh the risks?
Briefly, testosterone enhancements are thought to restore libido, build lean body mass, combat
insulin resistance, Syndrome X, and central obesity, forestall atherosclerosis and heart disease, and increase confidence and the joy of life.
Estrogen is thought to protect the heart, bones, skin, and mind of women and prevent vaginal dryness and thinning, hot flashes and night sweats.
Interestingly, DHEA at the usual anti-aging male dosage of 25-100 mg per day, will raise DHEA levels to that of a youthful man but does not appear to raise testosterone levels in men. Yet half as much readily increases testosterone in women. (11) Pharmaceutical doses of 400 mg daily in elderly men rapidly and significantly raise testosterone and DHT (Dehydroxy-testosterone) (12)
In human and animal prostate cancer cell studies, DHEA inhibits growth. (13,14)
Physicians at the Dept. of Urology, Institute of Experimental Endocrinology at Humboldt University in Berlin, found that DHEA levels in patients with prostate cancer were significantly lower than healthy controls.
A retrospective study at John Hopkins University involved the analysis of frozen DHEA samples from 1974 and the subsequent development of prostate cancer. They found that the 81 men with prostate cancer had had 11-12% lower DHEA.'
Clear Contraindications and Caveats
The fact is there are and will continue to be mostly animal studies. Although more and more human studies are being conducted, the results of long-term studies are by definition, decades away. Still there are perhaps a few clear contraindications and caveats at present.
Those with frank liver disease, liver cancer, jaundice, hepatitis, cirrhosis, and/or elevated liver enzymes should not take DHEA without a physician’s guidance. At the same time, anti-aging doses of DHEA are not associated with hepato-toxicity and should not be a concern for those with healthy livers.
Pregnant women should not take DHEA. There is little reason for women not yet menopausal to take DHEA. DHEA for postpartum depression should be based on salivary/ blood testing demonstrating sub-optimal levels or less that optimal 10 to 1 DHEA/cortisol ratio. Long term therapeutic doses, 100- 200 mg/day DHEA, for women with diabetes or autoimmune disorders should be under a doctor’s supervision.
Women convert DHEA into estrogen and testosterone much more readily than men. Indeed, the transformation is so efficient that DHEA supplementation has been proposed as an estrogen replacement therapy for menopausal and post-menopausal women! Conversely, this same ready conversion to estrogen is also cause for concern. Therefore, women concerned with
estrogen levels and breast cancer need to weigh the risks and benefits much more carefully than men.
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