Tuesday, October 21, 2008

Supplements to Naturally Increase Testosterone?

I had some questions recently if there are any compounds around that may help to increase testosterone "naturally" and if there are any data to support it.

In short, there are few but the 2 most popular appear to be 6-OXO and Novedex (product name). Both are in a class called aromatase inhibitors and they work to prevent the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

Clinically, there are drugs that do this and they are used as a potential treatment for breast cancer since breast tissue is stimulated by estrogens, thus decreasing their production is a way of suppressing recurrence of the breast tumor tissue.

So as we just learned in this short and FREE organic chemistry lesson, aromatase is responsible for the conversion of testosterone to estrogen. Blocking aromatase causes the body to decrease its levels of estrogen (primarily estradiol for those uber geeks out there), this results in increase of LH and finally testosterone. And the people rejoice!

This is all find and dandy, but are there any over the counter (currently) supplements that can do this? Here are 2 studies on two of them (below)

Another class of compounds that are supposed to have similar effects are methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation. There is a study and my notes on those at the end also.

On to the science!

Effects of eight weeks of an alleged aromatase inhibiting nutritional supplement 6-OXO (androst-4-ene-3,6,17-trione) on serum hormone profiles and clinical safety markers in resistance-trained, eugonadal males.


Rohle D, Wilborn C, Taylor L, Mulligan C, Kreider R, Willoughby D. Department of Health, Human Performance, and Recreation, Baylor University, Box 97313, Waco, TX 76798, USA. darryn_willoughby@baylor.edu.


ABSTRACT: The purpose of this study was to determine the effects of 6-OXO, a purported nutritional aromatase inhibitor, in a dose dependent manner on body composition, serum hormone levels, and clinical safety markers in resistance trained males. Sixteen males were supplemented with either 300 mg or 600 mg of 6-OXO in a double-blind manner for eight weeks. Blood and urine samples were obtained at weeks 0, 1, 3, 8, and 11 (after a 3-week washout period). Blood samples were analyzed for total testosterone (TT), free testosterone (FT), dihydrotestosterone (DHT), estradiol, estriol, estrone, SHBG, leutinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH), cortisol, FT/estradiol (T/E).


Blood and urine were also analyzed for clinical chemistry markers. Data were analyzed with two-way MANOVA. For all of the serum hormones, there were no significant differences between groups (p > 0.05). Compared to baseline, free testosterone underwent overall increases of 90% for 300 mg 6-OXO and 84% for 600 mg, respectively (p < style="font-weight: bold;">


Conclusion: Body composition did not change with supplementation (p > 0.05) and clinical safety markers were not adversely affected with ingestion of either supplement dose (p > 0.05). While neither of the 6-OXO dosages appears to have any negative effects on clinical chemistry markers, supplementation at a daily dosage of 300 mg and 600 mg for eight weeks did not completely inhibit aromatase activity, yet significantly increased free testosterone, dihydrotestosterone, and free testosterone /estradiol.



My notes:
So this small study shows that this supplement does cause some increase in testosterone and its anabolic friends although I hate it when only percentages from BASELINE are reported since it can be completely misleading.

BUT there were no body composition changes. Hmmmm. If it was increasing muscle and/or decreasing fat there would have been some body composition change. It did appear to be safe in those doses for a short length of time.



Eight weeks of aromatase inhibition using the nutritional supplement Novedex XT: effects in young, eugonadal men.

Willoughby DS, Wilborn C, Taylor L, Campbell W.

Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX 76798-7313, USA.

This study examined the effects of an aromatase-inhibiting nutritional supplement on serum steroid hormones, body composition, and clinical safety markers. Sixteen eugonadal young men ingested either Novedex XT or a placebo daily for 8 wk, followed by a 3-wk washout period. Body composition was assessed and blood and urine samples obtained at weeks 0, 4, 8, and 11.


Data were analyzed by 2-way repeated-measures ANOVA. Novedex XT resulted in average increases of 283%, 625%, 566%, and 438% for total testosterone (P=0.001), free testosterone (P=0.001), dihydrotestosterone (P=0.001), and the testosterone:estrogen ratio (P=0.001), respectively, whereas fat mass decreased 3.5% (P=0.026) during supplementation. No significant differences were observed in blood and urinary clinical safety markers or for any of the other serum hormones (P>0.05).

Conclusion: This study indicates that Novedex XT significantly increases serum androgen levels and decreases fat mass.

My Notes:
See my thoughts above about percentages. Although this one did show some body comp changes which is good. Hormones are completely non linear and while more (in general) is good of our anabolic friends, this does have a limit where the optimal amount should be is up for debate. Remember, the body has all sorts of feedback systems in place for good reason and what goes up must come down at some point.

I do like that this study was a double blind, placebo controlled flavor. Body fat was done by DEXA (gold standard), although it was statistically significant--it was still very small. I pulled the full study and it is only about 1-2 lbs total change (effect size of 0.6 for the stats geeks out there). The variation also on the changes in hormones was huge, although there did appear to be a statistical/significant change, we are still stuck that lean body mass did NOT change.

Interestingly enough, while marketed to change estrogen levels (which should therefore change testosterone levels), it was shown to NO decrease on estrogen and a non significant INCREASE in E1, E2 and E3.

So, some hormones may change but it did NOT appear to alter body composition in this study. The study was funded by Gaspari Nutrition and I do applaud them for doing a randomized, double blind study. This is WELL beyond what most supplement companies do.

Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males.

Wilborn CD, Taylor LW, Campbell BI, Kerksick C, Rasmussen CJ, Greenwood M, Kreider RB. Human Performance Lab, University of Mary Hardin Baylor, Belton, TX.

PURPOSE : Methoxyisoflavone (M), 20-hydroxyecdysone (E), and sulfo-polysaccharide (CSP3) have been marketed to athletes as dietary supplements that can increase strength and muscle mass during resistance-training. However, little is known about their potential ergogenic value. The purpose of this study was to determine whether these supplements affect training adaptations and/or markers of muscle anabolism/catabolism in resistance-trained athletes.

METHODS : Forty-five resistance-trained males (20.5 +/- 3 yrs; 179 +/- 7 cm, 84 +/- 16 kg, 17.3 +/- 9% body fat) were matched according to FFM and randomly assigned to ingest in a double blind manner supplements containing either a placebo (P); 800 mg/day of M; 200 mg of E; or, 1,000 mg/day of CSP3 for 8-weeks during training. At 0, 4, and 8-weeks, subjects donated fasting blood samples and completed comprehensive muscular strength, muscular endurance, anaerobic capacity, and body composition analysis. Data were analyzed by repeated measures ANOVA.

RESULTS : No significant differences (p > 0.05) were observed in training adaptations among groups in the variables FFM, percent body fat, bench press 1 RM, leg press 1 RM or sprint peak power. Anabolic/catabolic analysis revealed no significant differences among groups in active testosterone (AT), free testosterone (FT), cortisol, the AT to cortisol ratio, urea nitrogen, creatinine, the blood urea nitrogen to creatinine ratio. In addition, no significant differences were seen from pre to post supplementation and/or training in AT, FT, or cortisol.

CONCLUSION : Results indicate that Methoxyisoflavone, 20-hydroxyecdysone, and sulfo-polysaccharide supplementation do not affect body composition or training adaptations nor do they influence the anabolic/catabolic hormone status or general markers of catabolism in resistance-trained males.

My notes:
Don't even bother wasting ANY of your money on these. Historically this class of supplements has a horrible track record. The only thing they are good for is dropping some weight from your wallet. If anyone has any peer reviewed research that otherwise, please post it in the comments.