dehyroepiandrosterone

DHEA’s Anti-cortisol Effects

dehyroepiandrosteroneDehyroepiandrosterone (DHEA) is the most abundant hormone in the body and has a demonstrable anti-cortisol action.⁽¹⁾ It achieves this in part by inhibiting the enzyme 11β-hydroxysteroid dehydrogenase† which converts cortisone into cortisol in the cell.⁽²⁾ Because of this effect, DHEA has been shown to slow adipocye (fat cell) proliferation and decrease insulin resistance in vitro,⁽³⁾ both of which are results of high-cortisol. Cortisol and DHEA are like a yin and yang pair, and it’s the ratio that is more important than the absolute amounts.

The production of both cortisol and DHEA is stimulated by the same pituitary stress hormone, the adrenocorticotropic hormone (ACTH), which is released as a result of psycho-social stress. This has been confirmed by studies in which people were subjected to a stimulated job interview with an arithmetic test in front of an audience.⁽⁴⁾ The spike in cortisol and DHEA concentration after a stressor persists on the order of hours.

With prolonged stress, the ability of the adrenals to produce DHEA is diminished while it’s ability to produce cortisol remains nearly constant. A natural outcome of this observation is a chronically high cortisol to DHEA ratio which leads to such events as: insulin resistance, low immunity, central obesity, and weakness of the limbs. Because the production of both of these hormones is dependent on the same factor (ACTH), any decrease in their relative production is likely the result of adrenal insufficiency in the zona reticularis, where DHEA is produced in the greatest amounts.

Dehyroepiandrosterone is also produced in the brain and exerts a neuroprotective effect which offsets the stress-induced dissociation caused by high cortisol. It has even been shown in rats to prevent the damaging effects of aluminium (as AlCl₃) which causes damage by displacing iron which can produce free radicals through the well-known Fenton reaction. In this way, DHEA functions as an antioxidant and significantly reduces β-amyloid protein in the brains of aluminium-intoxicated rats.⁽⁵⁾ Beta-amyloid is characteristic of Alzheimer’s disease, and a reduction by DHEA can only be considered beneficial for those valuing their long-term memory.

The effect of DHEA on diabetes is just as exciting. Researchers have shown that within months of supplementation, sugar metabolism had increased as determined via glucose tolerance test.⁽⁶⁾ This could be interpreted as a direct action of its anti-glucocorticoid activity; it could also be interpreted in part to be due to its binding of the protein receptor PPARα, which increases the oxidation of fatty acids. In either case, the anti-diabetic effect of DHEA cannot be ignored.

Even among ostensibly healthy people, DHEA levels can still be of concern. The ability of the body to rebuild and repair after a cortisol release is primarily dependent on DHEA. Chronic high-stress and low DHEA prevents regular synthesis of collagen which leads to wrinkles, cardiovascular disease,‡ and slow would healing. In effect, the decline of DHEA while the body demonstrates symptoms of aging is not likely to be coincidental. You might be tempted to think that the lack of DHEA, in part, increases the rate of aging. In fact, this hormone has been shown to be a relatively strong predictor of longevity in a recent study.⁽⁷⁾

It should be noted that dehyroepiandrosterone is also the precursor molecule for the sex hormones testosterone and oestradiol, so the importance of this hormone shouldn’t be understated. Luckily for us, bioassays are now available for testing the concentrations of DHEA and cortisol using saliva, giving an assessment of the diurnal variation in both hormones & enabling a distinction between stage 1, 2 & 3 adrenal fatigue. For any other questions or considerations, feel free to contact Dr. Allie.

† If you are wondering how a dehydrogenase (-H) acts as a reductase (+H) in this situation, it is because this enzyme is actually known to do both functions. However, the convention is usually to simply call it 11β-hydroxysteroid dehydrogenase.

‡ See Linus Pauling’s Unified Theory of Cardiovascular Disease⁽⁸⁾

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