DHEA Improves Mental Function and Combats Depression
In cases of serious illness, restoring DHEA levels can provide improvement

ormones - those tiny molecular messengers that are produced in one part of your body but perform their functions in other parts - are what allow your organs to communicate with one another and thus to function as an efficient whole. Imagine what your life would be like without insulin, growth hormone, testosterone, estrogen, or adrenaline, for example. It would be a lot different, that's for sure - as indeed it is for anyone with a hormone deficiency. Normally, hormones beautifully orchestrate the body's responses to a variety of environmental factors, both internal and external.

You may be surprised to learn that steroid hormones play important roles in determining your mood, not to mention influencing every metabolic process in your body. And you may think that all steroid hormones, such as testosterone, estrogen, and progesterone, are produced by the reproductive organs, but this is not true. The most abundant steroid hormone in the bloodstream - about 20 times more abundant than any other - is produced primarily by your adrenal glands, those small endocrine glands that sit atop your kidneys. They are perhaps best known for producing adrenaline and cortisol at times of stress, but here we are talking about their production of the hormone dehydroepiandrosterone, or DHEA.*

*Most of the DHEA that your body produces is quickly converted to DHEA sulfate, or DHEAS, which appears to be the biologically active form of the hormone. For our purposes, however, we'll just refer to both forms collectively as DHEA, since your body can easily convert the molecule to either form as needed.

Not all DHEA is produced by the adrenal glands, however. Both the reproductive organs and the brain make small amounts of this important hormone. In the nervous system, DHEA is made by individual neurons (nerve cells) and is classified as a neurosteroid, or neural hormone. In severely depressed individuals, it plays an important role in improving mood. Thus it could be surmised that in some circumstances, supplementation with DHEA might also lead to improvements in mental function. Indeed, a recent article suggests that DHEA is especially beneficial in improving mental function in patients with advanced HIV disease.1

DHEA levels peak in both males and females at the age of about 20 to 25. Thereafter, there is a steady decline until late in life, when levels of the hormone are only about 20% or less of the youthful peak value. Researchers have also discovered that, regardless of age, DHEA levels are lower in patients with chronic diseases, such as cancer and AIDS, than in age-matched controls who do not have these diseases.

Based on this information, researchers in Paris set out to investigate the specific relationships between DHEA levels and various aspects of mental function in patients with advanced cases of HIV disease. Thirty-two patients enrolled in the trial, 17 of whom were clinically diagnosed with AIDS. The patients were divided into two groups: 14 were treated with DHEA (50mg/day for four months), while 18 received a matching placebo for the same period of time. Each patient was monitored on a monthly basis until the trial ended. Not surprisingly, serum DHEA levels increased dramatically (by around 300%) in the DHEA-treated group, while they remained unchanged in the control group.

In order to determine whether the treatment group's increased DHEA levels correlated with improved health, the patients were required to fill out a Medical Outcomes Study HIV Health Survey (MOS-HIV). This is a 30-item questionnaire that health professionals routinely use to assess the health-related quality of life of HIV patients. The survey encompasses ten different dimensions, as they are called, of the patient's life:

  • Health transition
  • Bodily pain
  • Physical functioning
  • Social functioning
  • Cognitive functioning
  • Role limitation
  • Mental health
  • Vitality
  • Health distress
  • General health

In two of these dimensions - mental health and health distress - the patient staking DHEA showed statistically significant improvement compared with the controls. On the mental health portion, they improved from a score of 57.4 at the start of the trial to 70.0 (a 0-100-point scale was used) after 16 weeks. On the health distress portion, they improved from a score of 66.1 to 84.0. The control group showed no improvement in either of these dimensions. The data from this study indicate that HIV patients, when they assess their own mental health, observe improvements in their quality of life as a result of DHEA supplementation.

Given that DHEA is so abundant in our bodies, it is surprising that it isn't better understood. Like its chemical relatives testosterone and estrogen, DHEA is synthesized in the body from cholesterol (and you thought cholesterol just stuck to the insides of blood vessels to cause atherosclerosis). But unlike these other steroid hormones, whose functions in the body are well understood, DHEA remains aloof and mysterious - at least at the molecular level.

Your Marvelous Immune System,
and What Can Go Wrong
Your immune system is a true marvel of biological engineering. It is designed to recognize and inactivate germs of all sorts that cause disease and infection. It does this by employing an army of different immune cells with specific functions and some catchy names. Cytotoxic T cells, natural killer cells, antigen-presenting cells, helper T cells, and macrophages are just a few of the different types of white blood cells (also called leukocytes) that constantly patrol your body, seeking out foreign invaders with the intent to immobilize and destroy them.

Considering that your body encounters many millions of potentially dangerous germs each day, a strong and efficient immune system is a must for remaining healthy. But not all of us are so lucky. Consider individuals with AIDS, for instance: they have a compromised immune system because the human immunodeficiency virus (HIV) has infected a select group of immune cells (CD4 T cells) and prevents their normal function.

CD4 T cells (so named because they have a certain protein, called CD4, on their surface) play two crucial roles in the immune system. First, they encourage macrophages to engulf and destroy bacteria that they encounter in the body. Second, they stimulate the activity of antibody-producing cells (also called B cells). Antibodies are proteins that specifically recognize foreign particles, such as bacteria and viruses, and either inactivate them or target them for destruction by other immune cells. In this instance, the T cell is called a helper T cell because it helps other immune cells perform their function.

When an individual is infected with HIV, the virus binds to the CD4 protein on the CD4 T cell and enters the cell. HIV proliferates inside the infected cell, and, through a mechanism that is still not well understood, it kills the cell or at least suppresses its function. Because the CD4 T cell is so important for stimulating other cells in the immune system to function effectively, a decline in its numbers is very detrimental to immune function overall. The result is that bacterial and viral infections occur at an increased rate, and they become much more severe in individuals with AIDS.

The difference between being HIV-positive and having full-blown AIDS (acquired immune deficiency syndrome) is the degree of infection. One can be HIV-positive and still have a fully functional immune system. As time goes by, however, the decline in T cells is likely to progress if the condition is left untreated. The normal CD4 T cell count is 1000 cells per microliter of blood (one microliter is one-thousandth of a milliliter); AIDS occurs when the CD4 T cell count falls below 200 cells per microliter. At this low level, the immune system becomes overwhelmed and can no longer effectively counteract all the insults that it encounters. The results are devastating.

At the functional level, however, we have a better understanding of DHEA. Several research studies suggest a direct role between elevated DHEA and improved mood in patients with clinical depression. For example, depression is more common in women with nondetectable DHEAS levels than in women with detectable levels.2 Another study has shown that in institutionalized patients, DHEAS levels are lowest in those patients (both men and women) being treated for depression.3

Importantly, the reverse of this situation is also true. That is, higher levels of DHEA are associated with participating in and enjoying pleasurable activities. In fact, one research paper consolidates information from a number of trials by reporting that ". . . higher serum levels of DHEA and DHEAS have been associated with greater amount, frequency, and enjoyment of leisure activities; higher 'dominance' and 'expansive personality' ratings; and greater 'sensation-seeking' attributes."4 Translation: the people are happier.

To investigate the effect of DHEA on depression, researchers at the University of California, San Francisco, performed a six-week study involving 22 severely depressed patients.4 Eleven patients received DHEA (30 mg/day for two weeks, followed by 60 mg/day for two weeks, followed by 90 mg/day for the last two weeks), and 11 patients received matching placebos for the entire six weeks. Based on a standardized clinical analysis, the patients receiving DHEA were less depressed than those who were not. Specifically, five of the 11 DHEA patients showed a 50% or greater decrease in depressive symptoms, whereas no patients in the control group posted this degree of improvement.

DHEA levels peak at the age of
about 20 to 25. Thereafter, they
decline steadily until late in life,
to about 20% or less of the
youthful peak value.

While DHEA yields positive mood-enhancing results in depressed individuals, its impact on normal (i.e., nondepressed) individuals is less clear. Although the scientific literature has appeared to support the benefit of DHEA on normal elderly individuals,5 a recent study puts this in question. Specifically, researchers in England found that supplementation with DHEA for three months in normal elderly men produced no improvement in mood, memory, or sense of well-being.6 The role of DHEA in normal elderly women was not investigated in this study, however, so it is possible that they may benefit even if men do not - particularly since DHEA is known to have significantly different effects in men and women in some other aspects of its function.

If you suffer from clinical depression, or if your mental function is impaired due to HIV, it could be in part because these conditions depress your DHEA levels. You can restore your DHEA to its youthful levels through supplementation, an approach that may help you to reconnect with a positive mental attitude. And even if you don't fall within either of these categories, it's quite possible that boosting your DHEA levels - especially if you're getting on in years - will make you feel more like you used to in the halcyon days of your youth.

Higher levels of DHEA are
associated with participating in
and enjoying pleasurable


  1. Piketty C, Jayle D, Leplege A, et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin Endocrinol 2001;55:325-30.
  2. Yaffe K, Ettinger B, Presseman A, et al. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry 1998;43:694-700.
  3. Legrain S, Berr C, Frenoy N, et al. Dehydroepiandrosterone sulfate in a long-term-care aged population. Gerontology 1995;41:343-51.
  4. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 1999;156:646-9.
  5. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endrocrinol Metab 1994;78:1360-7. Erratum: J Clin Endocrinol Metab 1995;80:2799.
  6. Van Niekerk JK, Juppert FA, Herbert J. Salivary cortisol and DHEA:association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinology 2001;26:591-612.

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