Dehydroepiandrosterone (DHEA) is a precursor to testosterone. In the biochemical pathway to testosterone, it lies two steps away . DHEA was one of the first prohormones to enter the dietary supplement market after the 1994 DHEA . It is found in wild yams and in the pollen or seeds of the Austrian pine.Because DHEA is a precursor to testosterone it was thought that it would increase testosterone production if supplemented in the diet. However, research has shown that DHEA-may have biological activity itself. DHEA exists in two forms within the body –
- Free-DHEA and
- The sulfated form, DHEAS
The exact physiological role of DHEAS and its parent compound DHEA are not entirely known, however, research is beginning to provide us with Dehydroepiandrosterone (DHEA) can be converted to testosterone via two pathways, one is through the conversion of androstenedione, the other through androstenediol. more information about its function. It is known that DHEA decreases with age. Because aging is associated with an increase in obesity, insulin resistance, and atherosclerosis, some researchers are investigating the interaction of DHEA supplementation with obesity and related physiological problems.
Animal Studies
Numerous animal studies have reported that DHEA supplementation is able to lower body fat stores even during periods of high fat intake in rats In young rodents DHEA inhibits fat accumulation whereas in adult rats, supplementation of DHEA decreases body fat. Furthermore, DHEA supplementation has been reported to lower cholesterol and triacylglycerol levels, as well as improve insulin sensitivity in old and obese rats.
After knowing where DHEA falls in the metabolic pathway of testosterone biosynthesis, one would assume that the antiobesity effect of DHEA could have been brought about by an increase in downstream androgen levels. However, if one reviews the literature, it is not clear whether DHEA influences androgen production. This could mean that DHEA is producing the effect itself or through other mechanisms. It appears that DHEA prevents the accumulation or storage of body fat by increasing resting metabolic rate and heat production through futile cycling and/or by increasing the flux of fatty acids through ß-oxidation in peroxisomes. The increase in fatty acid oxidation may be caused by an increase in mitochondrial protein, which may include an increase in carnitine palmitoyltransferase, an enzyme that shuttles activated fatty acids from the cytosol into the mitochondrial matrix.
Another mechanism through which DHEA may alter fat stores is by decreasing food intake and creating a negative caloric balance. If you remember, one possible mechanism by which fat loss may be promoted is through a decrease in food intake. Neurotransmitters within the brain control satiety and hunger. A few researchers have reported that exogenous DHEA can alter levels of serotonin and dopamine causing a feeling of fullness or satiety. Furthermore, the decrease in food intake may be primarily fat intake, based on research in Zucker rats.
One question that has not been answered is whether the physiological effects described are originating from DHEA or a metabolite of DHEA. Two metabolites of DHEA are 3a-hydroxyetiocholanolone and 3ß-hydroxyetiocholanolone. In one research study, researchers have reported that an effective dose of these etiocholanolones is 25% of the effective dose for DHEA. What were once thought to be inert end products of steroid metabolism could possess beneficial physiological effects. More research should investigate the actions of these etiocholanolones.
Human Studies
An important physiological difference between rats and humans is that the adrenal gland in rats does not produce DHEA. However, rat tissues are able to respond to DHEA when it is supplemented in the animals’ diets. Because of this important physiological difference between rats and humans, humans may respond differently to DHEA supplementation.
The positive outcomes of DHEA supplementation in rats has led to a number of studies investigating the relationship of DHEA to obesity in humans. Research indicates that a positive relationship exists in women for endogenous DHEA and the amount of fat located on the trunk, suggesting that higher levels of endogenous DHEA are associated with abdominal obesity and insulin resistance in women. In men, there does not appear to be a relationship between endogenous DHEA and abdominal obesity.
Studies that have investigated the effects of exogenous DHEA on body composition in humans have produced mixed results and the positive results cannot necessarily be linked to dosage, sex, weight, or age. Based on the relationship between endogenous DHEA and body fat, it would appear that DHEA would not be advisable for women, because higher levels of DHEA are associated with abdominal obesity. Before we actually decide whether DHEA supplementation is beneficial or not, we should review the literature.
One study in young men (mean age, 24 years) reported that 1600 mg/day for 28 days resulted in a significant reduction in percent body fat (31%) with no change in total body weight. However, another study, also using young men (mean age, 26 years) and supplementing DHEA at 1600 mg/day reported no changes in body weight, fatfree mass (total body water and total body potassium), resting metabolic rate, or protein metabolism. The second study reported that DHEA does not affect resting metabolic rate, therefore, it is difficult to speculate why the subjects in the first study experienced a decline of almost 4 pounds of body fat over the 4-week period.
In older individuals, there appears to be possible dosing and sex effects. In 1994, Morales and colleagues. reported that a 50-mg dose of DHEA for 6 months did not result in changes in percent body fat or BMI in either men or women. However, a follow-up study by the same group reported that older men experienced a significant reduction in body fat mass following 6 months of DHEA supplementation at 100 mg/day. Older women experienced a significant increase in body weight, but no change in composition.
And finally, in obese individuals there does not seem to be an effect of DHEA supplementation. Adult males who had a mean BMI of 31.5 ± 2.9 kg/m had no change reported in body weight or fat mass following 28 days of supplementation at 1600 mg/day. Furthermore, neither did obese teenagers who received 80 mg/day for 8 weeks experience any change in body weight, fat mass, and lean body mass.
While research in animals supports the use of DHEA as an antiobesity agent, research in humans does not support the same conclusions. The differences are more than likely caused by the constant level of DHEA that is always circulating in humans, but not in rodents.
Safety and Toxicity
Supplementation of DHEA in men does not seem to pose a health risk. In fact, there is some research that reports that DHEA reduced serum total and LDL cholesterol in men. However, in women, DHEA supplementation has been associated with increases in androgen levels, decreases in HDL, and a decline in insulin sensitivity. Two of these studies investigated the effects of DHEA in postmenopausal women. Recent research has indicated that postmenopausal women have an increased risk for heart disease. If this population of women were consuming DHEA, it would appear that their risk for heart disease would increase further because of the decline in HDL and insulin sensitivity, both part of the deadly quartet.