Chrysine: 5,7-dihydroxyflavone for Bigger Balls and Higher Serum Testosterone

Polyphenols in general and flavonoids in particular are every supplement producer's favorite. Its so easy to pick up some exotic plant from somewhere deep down in the jungle, extract an exotic flavonoid, give it a fancy chemical looking name and provide some in-vitro data on his anti-oxidant omnipotence or whatever. In most cases the compounds disappear from the market within weeks, yet chrysine which is extracted from the Common Passion Flower, has been around for years. A recent study (Ciftcy. 2011) by Ciftci et al. provides further evidence that its market persistence may not be without a reason.

Over the time course of the scientists fed a group of lab rats 50 mg/kg chrysin (human equivalent ~8mg/kg) or placebo for 60 days and found:

that chrysin significantly increased GSH, CAT, GSH-Px and CuZn-SOD levels, but did not change the formation of TBARS significantly. In addition, sperm motility, sperm concentration and serum testosterone levels significantly increased, whereas abnormal sperm rate significantly decreased with chrysin treatment.

In essence the improvement in antioxidant markers (vs. placebo) went hand in hand with a measurable increase in sperm health and serum testosterone.

Figure 1: Testosterone levels of rats after 60 day intervention with 50mg/kg chrysin. (Ciftcy. 2011)

 "Great", well, maybe not so... although this is an almost 50% increase in testosterone, we do not know how other important hormonal parameters such as SHBG (binds testosterone and thus renders it basically useless), estrogen or cortisol looked like. An estimation of the "muscle building effects", the producers of respective supplements are advertising, is thus futile. And, if you asked my opinion, even if SHBG did not budge and we have an appropriate increase in free testosterone, the latter is probably too little to induce noticeable changes in strength and/or body composition.

Even Low "Normal" Plasma Testosterone Levels Associated with 2.5x Higher Risk of Insulin Resistance

"Your levels are in range!" Did you ever have your doctor say that to you? It appears as if next time you hear that sentence, you better ask him "Where 'in range' are my levels, exactly?" At least, the results of a recently published study by Menendez et al. (Menendez. 2011) suggests that it might be worth digging somewhat deeper into this issue. Studying a cohort of 282 men (aged 36 to 85 years) who had "normal concentrations of total testosterone", the scientists found:

Serum concentrations of testosterone and bioavailable testosterone were negatively correlated with age, body mass index, waist circumference, blood glucose, glycated hemoglobin levels and insulin. Serum concentrations of total testosterone, bioavailable testosterone and SHBG were lower in men with glucose intolerance or diabetes than in those with normal glucose tolerance. After multivariate analysis, age and total testosterone levels were independent predictors of the presence of diabetes or glucose intolerance. The risk of glucose intolerance or diabetes mellitus was over 2.5 times higher in men with total testosterone levels in the lowest quartile than in those with total testosterone in the top quartile.

While the results of this study are certainly interesting and significant, it is unfortunately impossible to tell, whether glucose intolerance and diabetes reduce the natural production of testosterone, OR low testosterone levels reduce glucose intolerance and lead to diabetes. In other words: What comes first, low testosterone or glucose intolerance? Further research will be needed to answer this question, but if you want my opinion, I suspect that they just go hand in hand, i.e. a bad diet lowers glucose tolerance, high sugar reduces testosterone production, low androgen levels impair glucose tolerance etc. - a viscous circle.

Vitamin D Supplementation(!) Increases Testosterone in Men

Thanks to Dashforce from the MindAndMuscle-Forum we finally have evidence for the direct effect of vitamin D3 supplementation on testosterone in men. Dashforce reports on a study by scientists from Austria and Germany (Pilz. 2010) who provided 54 men, whose serum levels were previously at the lower range ~30ng/ml (the referential  minimum varies depending on which source you cite from 30-50ng/ml),with either 83 μg (3 332 IU) vitamin D daily or placebo for 1 year.

Table 1: Characteristics of the study groups at baseline and at the end of the study

As you can see in table 1,vitamin D supplementation lead to a significant increase in total testosterone from 10.7 nmol/l to 13.4 nmol/l. What's even more important, this increase (+25%) was not compensated by and an increase of SHGB, so that the amount of free testosterone rose from 0.222 n/mol to 0.267 nmol/l, i.e. by +20% (vs. +5% in the placebo group).

What is particularly interesting about this study is the fact that supplementation actually raised the level of testosterone. This is different from most previous studies, which observed a correlation between higher vitamin D levels and higher testosterone levels. If for example some probands would simply have been more healthy and thus exhibit higher levels of both, we would have had the same correlation. In the case of the Pilz study there is a clear causative effect between restauration of adequate vitamin D levels and increases in total and free testosterone.

I hope we see more trials with a similar design - also to investigate if there is a dose response relationship and whether even higher vitamin D levels would further increase testosterone. Until then, keep an eye on your vitamin D level and take a supplement to get to the upper ranges of the "normal" range ~80ng/ml.

New Study Says: Boron Does Indeed Raise Free Testosterone

There have been rumors on the Internet for quite some time - "Did you hear? Boron increases testosterone!" Hitherto, however, these claims have not been substantiated by reliable scientific research. A recent study done by a group of scientists from Iran (Naghii. 2010) yet seems to prove that this is more than the steroid-loaden phantasy of an average gymrat.

In a placebo controlled study, the scientists found that supplementation with 10mg Boron/day did not only lower SHGB and thus raise testosterone, it did also lower three inflammatory biomarkers (Interleukin-6 (IL-6), high sensitive CRP (hsCRP) and tumor necrosis factor-alpha (TNF-α)):

Table1: Hormones and inflammatory biomarkers concentration (mean ± SD) plus hormone ratios following consumption of placebo (day 0) and weekly boron supplementation (day 7)

As you can see in table 1, the testosterone to estrogen ratio more than doubled (0.31 to 0.67). This alone makes me believe that it won't take too long for supp companies to notice this little trace mineral and to include it in more and more of their products. Hitherto it is already found in some formulations, like multi-vitamins, meal replacements and other stuff that is enriched with minerals the dosages, however, are minuscule and far from the 10mg used in the present study.

The scientists also investigated the time-course of the effect of boron supplementation on day 1 of the study and interestingly it took only 6 hours for free testosterone to rise from 8.55pg/ml to 11.25pg/ml. To me, this suggests that there is more to boron supplementation than just repleting exhausted blood and/or tissue levels.

Update: I have been digging a little into the possible mechanism of action behind the increase in testosterone and my personal take it that boron is a (weak) anti-estrogen. By cutting estrogen by 50% (cf. table 1) your body will automatically reduce SHGB, which is up-regulated by estrogen. This frees testosterone and may in fact provide (minor) benefits in muscle gain, libido & fat loss. I suspect that in the end this could be related to a reduction in manganese and an increase in magnesium & calcium retention (cf. Acu-Cell information about boron) that follows the administration of large amounts of boron. These is highly speculative and may only be part of the picture, though.
Also, in view of conflicting evidence from previous studies (e.g. Nagghi. 2006), which found that supplemental boron increased (not decreased) estrogen in men, further investigations are warranted.