DHEA

DHEA is an abbreviation for dehydroepiandrosterone and is a steroid hormone of the adrenal gland. Hormones are substances that are produced in glands or tissues and have a metabolic effect in other cells (target cells). Hormones are a heterogeneous group of substances. There are proteohormones such as Insulin, which is produced by certain cells in the pancreas and lowers blood sugar levels. They consist of chains of amino acids (peptides) or amino acid derivatives. Another group are the steroid hormones, which are derived from cholesterol. In addition to DHEA, these include the sex hormones (androgens, oestrogens) and hormones such as aldosterone (regulates kidney function) and cortisone. Due to their lipophilic nature (fat solubility), steroid hormones can easily pass through cell membranes and bind to a receptor protein inside the cells. This also explains why steroid hormones can have such a wide range of effects. The hormone-receptor complex enters the cell nucleus and stimulates transcription (reading of genes) so that specific proteins (enzymes) can be formed. DHEA is the most common hormone in the blood (15-20mg/day) and is found in even higher concentrations in the brain. DHEA was discovered in human urine in 1931 by A. Butenandt (German chemist, Nobel Prize winner). It is produced in the adrenal cortex (zona reticularis), converted by the liver into the sulphate DHEAS (discovered in 1944), circulates relatively stably in the blood, mainly during the day, and is transformed in the body into the sex hormones testosterone and oestrogen. The sexual effect is about 10% of that of testosterone. (Data f. Biochem Res. Oxford. Science Publ. 1984, p. 193)Production is highest at the age of 25, and then falls steadily to 5% of the maximum at 85. This is not the case with other steroids. The first precise determination of DHEA production as a function of age was made in 1958 by Max-Fernand Jayle, a biochemist at the University of Paris. Women produce more DHEA than men. The exact biological role is currently more or less not understood. Because of its precursor role for the sex hormones, among others, DHEA has been ascribed the role of a buffer hormone that influences the availability of other steroids. However, the addition of DHEA in animal and human experiments showed effects against ageing, cancer and viral infections, among other things. Between 1972 and 1997, more than 4000 publications on DHEA were published worldwide; until 1991, many studies proved the positive effect against various types of cancer, arteriosclerosis, weight reduction and extended lifespan in animals. From 1994 onwards, the effect on humans was mainly researched and has so far produced comparable results. In the USA and other countries, DHEA is already being marketed on a large scale and is sometimes described as a miracle cure. It is inferred from the predominantly very positive publications that DHEA supplements improve mood, increase activity and sex drive, counteract stress hormones, maintain muscle condition, strengthen the immune system and reduce the risk of cancer and heart disease. DHEA is even said to be effective against AIDS, osteoporosis and Alzheimer's disease.

DHEA and cancer

Early studies from England [Bulbrook, 1962,1971] found that DHEA was present at abnormally low levels in women who had breast cancer, even up to nine years before the disease was diagnosed. Of 5000 women in the study, 27 developed breast cancer. Most of the 27 had extremely low levels of DHEA. If low levels of DHEA promote breast cancer, is the reverse also true?

Dr. A. Schwartz of Temple University USA found that adding DHEA to cell cultures protected against the toxicity of carcinogens (cancer-causing factors). Normally, cell cultures react clearly with DNA mutations, changes in cell appearance and a high mortality rate. When DHEA was administered, all these effects were significantly reduced. In mice that were treated with carcinogenic agents, those that received additional DHEA did not develop breast cancer. In other studies, a reduction in the tumor rate of up to 80% was observed. [Schwartz 1981, 1984] The well-known DHEA researcher W. Regelsen stated: "Whenever DHEA was tested in a model environment for carcinogenesis and tumor induction, DHEA had preventive effects." Although DHEA is currently being tested in human tumors, it is not yet known whether the effects are similar in humans. It should be noted that mice and rats have been used as test subjects for a very long time prior to human testing. The results have mostly been similar or identical.

DHEA and the metabolism

DHEA and DHEAS obviously have a variety of effects on the metabolism.

Here are some of them:

Figure: DHEA concentration in the blood as a function of age

As precursor steroid hormones of the adrenal gland, they are converted into androgens (male sex hormones) and oestrogens (female sex hormones) in the target organs and tissues depending on the corresponding enzymes. Approx. 50% of the total androgens in men are formed from these two precursors, in women approx. 75%. The liver converts DHEA into DHEAS when taken orally.

Due to their fat solubility, steroid hormones can easily penetrate cell membranes, are bound to a receptor in the cell and act as a hormone-receptor complex on the DNA (genetic information) in the cell nucleus, where genes are read and realized. Various researchers have found that DHEA inhibits the enzyme glucose-6-phosphate dehydrogenase (G6PDH), an enzyme that breaks down glucose. In the process, glucose is converted via the so-called pentose phosphate pathway into ribulose-5-phosphate (for nucleotide synthesis) and 3-P-glyceraldehyde, among other things, which is reintroduced into glycolysis. This leads to the formation of BTS, which is then converted into acetylCoA, the precursor of fatty acids and thus of fats. The pentose phosphate cycle plays a role particularly in the liver, adipose tissue, adrenal gland, thyroid gland and erythrocytes (red blood cells), but not in the muscles. In most tissues, this metabolic pathway is linked to fatty acid synthesis, for example.

DHEA therefore inhibits fat synthesis.

DHEA also stimulates the activity of the antioxidant enzyme catalase in the liver, an enzyme that breaks down the H2O2 (hydrogen peroxide; cell toxin) produced during the breakdown of substances. The overall maturation (stimulation of the formation of mRNA of enzyme genes) of the peroxisomes (cell organelles, e.g. of liver cells), which contain catalase, is also promoted. [Mol. Pharmacol. 50: 67-74 (1996)] This promotes antioxidative processes. [Biochem. J. 301: 753-8 (1994)] DHEA thus protects against viral infections. [J. Endocrinol. 150: S209-S220 (1996)] DHEA promotes the formation of insulin-producing cells and increases insulin sensitivity. [Am. J. Med. Sci. 306: 320-324 (1993)] DHEA can significantly reduce the risk of myocardial infarction. [Am. J. Med. Sci. 311: 205-210 (1996)] Activation of brain metabolism in the forebrain and other parts of the brain by DHEA. It can increase the differentiation of nerve cells. [J. Neurosci. 16: 1193-202 (1996)], [Proc. Natl. Acad. Sci. U.S.A. 92: 3774-8 (1995)]

DHEA and aging

The production of DHEA in the body drops from about 30 mg at the age of 20 to less than 6 mg per day at the age of 80. According to Dr. W. Regelson, Medical College Virginia, DHEA is one of the best biochemical MARKERS of chronological age. In some people, DHEA decreases by 95% during life, the largest decrease in any major biochemical known to date. In animal studies, DHEA extended the life of rodents by 50%. The animals not only lived longer, they looked younger. The gray-haired control animals could easily be distinguished from the smooth black-haired DHEA-treated animals. DHEAS levels correlate directly with mortality (probability of dying) in humans.

In a 12-year study of 240 men aged 50 to 79, scientists found that DHEAS levels were inversely related to mortality, regardless of whether heart attack or other causes led to death. A 1mg/liter increase in DHEAS concentration corresponded to a 48% reduction in mortality from heart attack. Those with higher blood levels of DHEAS lived longer and had a lower risk of heart disease. These results suggest that DHEAS should be used as a diagnostic standard to predict disease, likelihood of death and longevity. Another study recently tested the effects of minimal doses of DHEA (50mg/day) in men and women between 40 and 70 years of age. After 2 weeks, people's blood levels had almost doubled. They slept better, felt more relaxed, had more energy and responded better to stress. No weight loss was observed in the 3 months.

If the studies in animals and humans are correct, DHEA supplementation can prevent disease, reduce the likelihood of death and prolong human life.

Improvement in brain performance

DHEA is also thought to be closely linked to protecting brain neurons from age-related degenerative processes such as Alzheimer's disease. Not only do such degenerative processes occur most frequently when DHEA levels are at their lowest, but the concentration of DHEA in the brain is far higher than in the blood. Dr. E. Roberts is a specialist in this area of research. He found that small amounts of DHEA are sufficient to increase the number of nerve cells, increase the number of their contacts with others and stimulate their differentiation in cell cultures. According to his results, DHEA also improved long-term memory in trained mice. DHEA may play a similar role in the human brain.

DHEA, the buffering steroid?

Attempts to explain its physiological function

DHEA is unique among hormones in that it has no specificity for certain hormone receptors. Vitamin E has also not been found to have any specific metabolic involvement. Only its role as an antioxidant has been demonstrated. DHEA could act in the same general way. Dr. W. Regelsen stated that DHEA could be the first example of a buffering hormone. It is a broad-acting hormone that only unfolds its effect under a certain constellation of factors. It is a buffer hormone against sudden changes in blood pH. This is why people are more susceptible to stress as they get older. If the DHEA concentration decreases with age, we lose the buffer against stress-relevant hormones. The buffering effect protects us from ageing. The decrease in DHEA with age could lead to a steady decline in the system responsible for creating the building blocks of new cells, such as lipids, nucleic acids and sex hormones. Ebeling and VA. Koivisto from the Second Department of Medicine at Helsinki University Hospital in Finland believe that DHEA has either an estrogenic or androgenic effect, depending on the hormonal environment. There are many indications of this. In some breast cancer cell lines, DHEA acts like estrogen at low estrogen concentrations and stimulates tumor growth, whereas in the absence of estradiol, DHEA counteracts it. In men with an androgenic environment, it acts like an oestrogen and protects against cardiovascular diseases.

Dosage

Recommendation: DHEA for medical purposes should be taken under medical supervision. However, local doctors are hardly aware of DHEA. There are practically no publications about DHEA in German on the Internet.

Exact doses for humans have not been precisely determined. Daily doses can vary from 5 to 10mg up to 2000mg. Up to 6-8 g have been administered to humans in trials without any major side effects. It is recommended to bring your own DHEA and DHEAS concentration up to the level at a young age. So you should take a test to determine your blood level. Otherwise, 5 to 10 mg is a good starting dose. This of course depends on the body's own concentrations, and further on the body's own absorption and metabolism. If no effect is felt after a week or so, the dose can be increased by a further 5-10 mg. This can be done until the correct blood values are reached. As a rule, 50 mg for women and 100 mg for men should be sufficient. Pure DHEA, taken orally, is mainly converted into testosterone and dihydrotestosterone; which as male sex hormones can have undesirable male side effects in women (hair fuzz and mild acne). These androgenic effects cease immediately when the dose is reduced. Micronized DHEA enters the bloodstream primarily as DHEA (Am. J. Ob. Gyn. 1992; 166: 1163 and Am. J. Ob. Gyn. 1993; 169: 1536). Specialists at Baylor Medical School USA believe that DHEA absorbed through the skin is hardly converted to testosterone; one could also try DHEA intranasally. DHEA supplements, except in very high doses, practically do not stop the body's own production. However, long-term studies have yet to confirm this. The adrenal gland produces a large amount of DHEA in the morning, but its concentration decreases during the day. Scientists therefore recommend taking DHEA in the morning in order to be in harmony with the natural daily routine. Taking it in the evening can cause insomnia. DHEA should be taken with fatty foods (butter, milk, meat).

Need in sport

Athletes report more vitality, a slight increase in physical strength and easier fat loss when DHEA is taken in a dosage of 50-100mg.

DHEA has been on the doping list since 1996. Even if there does not appear to be a change in the testosterone/epitestosterone ratio in men taking DHEA, it remains questionable how the individual reacts to the substance and whether higher doses do not lead to a positive test result. Athletes who have to undergo doping tests should avoid DHEA.

Safety and side effects

DHEA is potentially safe and harmless for most people when used for a few months. However, it can cause some side effects including acne, hair loss, stomach upset and high blood pressure. Some women may experience changes in their menstrual cycle, facial hair growth and deepening of the voice after taking DHEA.

DHEA may not be safe and harmless when used in large quantities and over a long period of time. DHEA should not be taken in doses over 50 to 100 mg per day or over a prolonged period of time. Use of higher doses or for prolonged periods may increase the risk of side effects.

Precautions and warnings

Pregnancy and lactation: DHEA may not be safe to take orally during pregnancy and lactation. It can cause increased levels of male hormones called androgens. This could be harmful to the baby. For this reason, pregnant and breastfeeding women should not use DHEA.

Hormone-sensitive diseases such as breast cancer, uterine cancer, ovarian cancer and endometriosis: DHEA is a hormone that can affect the function of oestrogen in the body. You should not use DHEA if you suffer from a disease that could be aggravated by oestrogen.

Liver problems: DHEA may aggravate liver problems. For this reason, DHEA should not be used if you suffer from liver problems.

Diabetes: DHEA can affect the action of insulin in the body. For this reason, diabetics should carefully monitor their blood sugar levels when using DHEA.

Depression and mood disorders: There are concerns that patients with a history of depression and bipolar disorder may suffer from mental side effects when using DHEA. DHEA can cause mania (excitability and impulsivity), irritability and sexual inappropriateness in people suffering from mood disorders. If you suffer from mood disorders, you should discuss the intake of DHEA with your doctor and pay attention to changes in your mood.

Polycystic ovary syndrome: Taking DHEA could aggravate this condition. Therefore, people suffering from polycystic ovary syndrome should not use DHEA.

Cholesterol problems: DHEA might lower the levels of good cholesterol. If you have low HDL cholesterol, you should discuss the use of DHEA with your doctor.

Interactions

Care should be taken when combining DHEA with the following medications:

Insulin

Insulin is used to lower blood sugar levels. Insulin can reduce the amount of DHEA in the body. By reducing the amount of DHEA in the body, insulin may reduce the effectiveness of DHEA supplements.

Letrozole

Some types of cancer are affected by hormones in the body. Estrogen-sensitive cancers are cancers that are affected by the hormone estrogen. Letrozole is used for these types of estrogen-sensitive cancers. DHEA may increase estrogen levels in the body and reduce the effectiveness of letrozole in treating cancer. For this reason, DHEA should not be used when taking letrozole.

Drugs that are broken down by the liver (cytochrome P450 3A4 (CYP3A4) substrates)

Some drugs are broken down by the liver. DHEA can reduce the rate at which the liver breaks down certain drugs. Taking DHEA in conjunction with medications that are broken down by the liver can increase the effects and side effects of some medications. For this reason, you should consult your doctor before taking DHEA if you are taking medication that is broken down by the liver.

Care should be taken when combining DHEA with the following medications:

Anti-inflammatory drugs (corticosteroids)

The body produces DHEA naturally. Some anti-inflammatory drugs may reduce the amount of DHEA the body produces. Taking some anti-inflammatory medications may reduce the effects of DHEA supplements.

Further references

1. Bosy TZ, Moore KA, Posklis A (1998) The effect of oral dehydroepiandrosterone (DHEA) on the testosterone/epitestosterone (T/E) ratio in human male volunteers urine. J Anal Toxicol 22: 455-9
2. Morales AJ, Nolan JJ, Nelson JC, Yen SS (1994) Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 78: 1360-7
3. Nestler JE, Barlascini CO, Clore JN, Blackard WG (1988) Dehydroeprandrosterone reduces serum low density lipoprotein levels and body fat but does mot alter insulin sensitivity in normal men. J Clin Endocrinol Metab 66: 57-61