Androst-4-ene,3,6,17-trione (6-OXO)
syn. 4-Etioallocholen-3,6, 17-Trione syn. 6-oxo-androstenedione
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Description:
Androst-4-ene,3,6,17-trione (6-OXO) is a naturally occurring metabolite/intermediary in androgen biosynthesis. Although no primary dietary source of this compound has been identified, it is found in trace amounts in some animal products. It has not been shown to have a necessary biological function, and is not considered an essential dietary nutrient. In humans, 6-OXO has been shown to inhibit the aromatase enzyme, which is responsible for converting testosterone and certain other steroid hormones to estrogens (such as estradiol and estrone). 6-OXO is widely sold in sports nutrition, where it is promoted to increase testosterone levels and augment the anabolic effects of resistance training in men.
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6-OXO is classified as a Type-I inhibitor of aromatase.92 It irreversibly binds the aromatase enzyme, preventing it from interacting with steroid hormones and producing estrogen. This can significantly increase serum testosterone levels by two mechanisms. First, feedback inhibition of testosterone biosynthesis from estrogen is reduced (the brain reads high estrogen as a sign of high testosterone).93 Second, less free testosterone will be metabolized to estrogens, and thus left intact. Since testosterone is a strongly anabolic (muscle-tissue building) hormone in humans,94 an increase in its levels might support an increase in muscle mass and strength.95 The ergogenic benefits of testosterone increases within or near normal levels, however, remain speculative.
At the doses studied and recommended (300-600 mg per day), 6-OXO exhibits an incomplete level of aromatase inhibition. Estrogen levels tend to remain relatively stable (or even increase slightly) during treatment. This may be due to a new homeostatic balance being reached, with lower levels of aromatase being countered by increased availability of aromatizable substrates. Since estrogen has been shown to play a beneficial role with regard to the management of serum lipids and cardiovascular disease risk,96 and aromatase inhibition with other drugs has been shown to negatively alter cholesterol levels in men,97 significant estrogen suppression may actually not be as desirable.
Studies also suggest that 6-OXO can increase steroid metabolism by the 5-alpha reductase enzyme. This enzyme is responsible for converting testosterone to a more androgenic metabolite (dihydrotestosterone) in various androgen responsive target tissues such as the skin, scalp, and prostate. While DHT is speculated to impart beneficial effects with regard to exercise performance, it also is linked to the unwanted androgenic effects of steroid therapy (such as acne and male pattern hair loss). There have been, however, no reports in the cited clinical studies of significant androgenic side effects. The net metabolic effect of the DHT increase with 6-OXO remains unclear.
Clinical studies support the use of 6-OXO to increase free testosterone levels in recreationally-active men. Given the known importance of testosterone in the muscle anabolic process, it is speculated that 6-OXO can increase the rate of muscle accumulation in response to regular resistance exercise. While clinical studies have not evaluated the effects of this supplement on exercise performance, empirical evidence seems to strongly support such use. Further research is needed to confirm, and better understand, the potential ergogenic properties of 6-OXO.
Promoted Benefits:
6-OXO is promoted to increase testosterone levels in men, and support muscle and strength gains in response to resistance training.
Clinical Studies:
This ingredient has been shown in human placebo-controlled studies to improve a metabolic marker (free testosterone levels) often linked to positive changes in body composition or performance. It has a Clinical Support Rating of 3 (3/5).
There has been only one published placebo-controlled clinical study on the use of 6-OXO in exercising adults.98 In this study, subjects consumed 300 mg or 600 mg of the supplement daily for a period of eight weeks. Body composition, hormone levels, and various markers of clinical safety were evaluated at baseline, and various points during and after supplementation. Subjects taking 300 mg and 600 mg noticed a 90% and 84% increase in free testosterone levels (respectively) compared to placebo. There was also a 192% and 265% increase in dihydrotestosterone with the 300 and 600 mg groups, respectively. Body composition (muscle, fat mass) did not change significantly. Given the methodological difficulties with proving body composition changes in small group clinical studies like this, it is difficult to draw conclusions based on this result. Unfortunately, exercise performance (which tends to be easier to quantify) was not evaluated.
These results support the use of 6-OXO to increase testosterone levels in healthy exercising men. However, further research is needed to confirm this is accompanied by consistent tangible ergogenic value.
Empirical Evidence:
6-OXO is widely available as a stand-alone nutritional supplement. The feedback on its use as a sport supplement has been strongly positive. Most users sensitive to changes in their hormone levels are able to attribute a tangible increase in relative androgenicity to the use of this supplement. For many, this is accompanied by a noticeable increase in the gains (strength, muscle mass) of regular resistance exercise. Testosterone boosters have become a strong class of dietary supplements in the sports nutrition market, and 6-OXO has solidified its position as one of the most reliable such products available. A small minority of users do feel they cannot attribute any positive changes in exercise performance to use of this supplement. Whether this is due to individual insensitivity to 6-OXO, or an inability of a moderate increase in free testosterone to effect substantial gains in some users, remains unclear. 6-OXO has an Empirical Evidence Rating of 5 (5/5).
Effective Dosage:
Based on clinical studies, a dosage of 300-600 mg per day is recommended.
Side Effects / Safety:
6-OXO was well tolerated during clinical studies, with no side effects reported. Furthermore, there were no negative changes in various markers of clinical safety including cholesterol levels, blood pressure, liver and kidney enzymes, and blood cell counts.
