The 7-Keto Story @ Once創新

The DHEA Dilemma

DHEA, also known as dehydroepiandrosterone, is synthesized in the adrenal cortex from cholesterol via pregnenolone by the action of an enzyme called cytochrome P450. It is the most abundant adrenal steroid in humans and is the precursor for many important steroid hormones which includes estrogen and testosterone. In contrast to cortisol and other adrenal steroids, DHEA levels decline with age. Levels of DHEA increase through the second decade of life and then begin to decline to negligible amounts at ages greater than 70 years. We experience a 50% reduction in DHEA levels between ages 20 and 40. Since DHEA is the major androgen precursor in humans, men have 30% higher DHEA levels than women throughout their lives.

The physiological significance of the variation in DHEA levels with advancing age is interesting and many researchers have noted some important correlations. As DHEA levels decline with age:

The incidence of diabetes, cancer, heart disease and obesity increases.
Reproductive function decreases.
Basal metabolic rate decreases.
Immune function decreases.
Age related skin changes increase.

To avoid many of these age-related maladies, many have advocated supplementing the diet with DHEA to maintain plasma levels at a more youthful level. Since DHEA is a hormone precursor and not a “true” hormone itself, the actions of DHEA must be attributed to its many metabolites. It is for this very reason that supplementation with DHEA is more difficult than it may initially appear. For example, while supplementing with DHEA for a particular indication, an individual may suffer side effects in another organ system due the accumulation of unwanted active hormone metabolites.

The Search for a Better DHEA: Dr. Henry Lardy

Recognizing that the bioactivity of DHEA must rest with one or more of its many metabolites, Dr. Henry Lardy led the search for more specific and active metabolites of DHEA. Dr. Lardy is Vilas Professor Emeritus of the Institute for Enzyme Research at the University of Wisconsin in Madison. Dr. Lardy is renown for his research on DHEA derivatives and has published over 400 studies in peer-reviewed scientific journals.

To search for possible metabolites of DHEA that might have greater biological activity, greater specificity, and fewer propensities to form sex hormones, Dr. Lardy initiated a program assaying the steroids derivable from DHEA. The activity of 150 of these metabolites was monitored by measuring the induction of two thermogenic enzymes, mitochondrial glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme. The results of this landmark study were published in the journal

Steroids in 1998 and revealed that many of these steroids did not induce the activity of these thermogenic enzymes whereas the 7-oxo DHEA (“7-Keto™”) metabolite did. In fact, 7-oxo DHEA was 2.5 times more active than DHEA at inducing the activity of these thermogenic enzymes. More importantly Dr. Lardy discovered that, in contrast to DHEA, the 7-oxo DHEA metabolite was not convertible to compounds with estrogenic or androgenic activity.

7-oxo DHEA is a naturally occurring DHEA metabolite in humans and was first discovered in the urine of human volunteers in 1958 by Gallagher. In later work by Marenich, it was discovered that the urinary excretion of 7-oxo DHEA declines with age in a similar manner to its parent steroid DHEA.