NAC + Zinc + Selen = Silver Bullett Against Mercury Poisoning

Mercury certainly is among the most dangerous and, at the same time, most ubiquitous heavy metals, we are exposed to. In a recent article (thanks to Dominique for raising my awareness of its publication) strength coach Charles Poliquin references a 2010 study from Michigan State (Wirth. 2010) :

Looking at several well-designed studies, they determined that even low exposures from cadmium, lead and mercury had an impact on semen quality and reproductive hormone levels in men.

As far as solutions to this problem are concerned, Polliquin refers somewhat dubiously to "a specific herbal combination" of "andrographis paniculata, zinc citrate, humulus lupulus, and curcuma longa" without providing scientific evidence for why he thinks this specific formula would work (guess what, Charles sells it ;-). Chances would have it, though, that Joshi et al., in a very recent study (Joshi. 2011, still ahead of print) report the beneficial effects of another, from my perspective, probably even more potent combination of nutrients/antioxidants in experimentally induced mercury poisoning:

Exposure to DMM [dimethylmercury] caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins [in rats]. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control.

Actually these results do not come as a surprise, as all three of these nutrients/antioxidants are well-known for their beneficial effects on (liver) enzyme activity and thus heavy metal clearance. Those of you, who read Tim Ferris' book The 4 Hour Body may also remember that his Brazil nut consumption (he ate them for their high selenium content, 1 ounce contains 544µg, i.e. 780% DV) along with other nutritional changes tripled his testosterone levels from low normal levels to the upper quartile of the range. In that, it is of secondary importance whether this was a mercury related effect, or not, since an increase in the detoxification abilities of the liver, as it was achieved in the study by twice a week supplementation with NAC (360mg/kg; human equivalent dose [HED] ~ 52mg/kg)  + Zn (130mg(kg; HED ~ 26mg/kg) + Se 0.5mg/kg; HED ~0.08mg/kg), will benefit the hormonal millieu via multiple pathways (increased estrogen clearance being one of them).

A word of caution: I advice against using the dosing scheme applied in the study, i.e. twice a week mega-dosing of supplements. Spread across a whole week, the human equivalent doses (for an 80kg human being) would equal roughly 600mg NAC, 300mg Zinc and 1mg* Selenium per day, which - apart from the exorbitant amount of zinc (I would not take more than 100-150mg/day even for short term interventions) - constitutes a quite reasonable nutrient stack for shorter detox protocols (4-6 weeks) for mercury, cadmium (cf. eg. Said. 2010) and other heavy metals with an increase in testosterone being one of the possible positive "side effects".

*Note on selenium toxicity: Rumors have it that selenium is toxic even at doses of >400µg. Most of these reports yet turned out to be based on anecdotal evidence from people who poisoned themselves with supplements that contained up to 200x the labeled dose (e.g. >40mg! selenium in MacFarquhar. 2010). It is thus very unfortunate that current data on the ‘Lowest Adverse Effect Level’ (LOAEL) is lacking. A 1989 study by Yang et al. give1.5mg/day as a threshold beyond which longterm supplementation may produce adverse side effects. And though this is below the 1g derived from the results of the rat study, I recommend to better err on the side of caution and to stick to max. 200-400µg supplemental selenium + a handfull of Brazil nuts from time to time as part of a safe antioxidant supplement stack.

News on USP Labs' "Pink Magic": High Dose Massularia Acuminata Increases Testosterone and Makes Bucks Horny as Hell

Faithful readers of the SuppVersity will probably remember my short write-up on USP Labs Test Booster "Pink Magic". Now that the initial fuss about how "brilliant" and "unique" the product is, is over there is finally another study on the efficiency of its main ingredient, a shrub called massularia acuminata.

Two scientists from Nigeria (Yakubo. 2011) published an article on the "Effect of Aqueous Extract of Massularia acuminata Stem on Sexual Behaviour of Male Wistar Rats" in the January issue of Evidence Based Complementary Alternative Medicine. The scientists found that supplementation with 500 and 1000mg/kg body weight (equivalent to 6.8g and 13.6g) of an aqueous extract of the stem of the botanical...

... increased the frequencies of mount and intromission. In addition, the ejaculation latency was significantly prolonged (P < .05). The latencies of mount and intromission were reduced significantly whereas ejaculation frequency increased. The extract also reduced the postejaculatory interval of the animals. Computed percentages of index of libido, mounted, intromitted, ejaculated and copulatory efficiency were higher in the extract treated animals compared to the distilled water-administered control whereas the intercopulatory interval decreased significantly.

In short: the rats were horny as hell ;-) But there was more to it:

The extract also significantly (P < .05) increased the serum testosterone content of the animals except in those administered with 250mg/kg body weight on days 1 and 3.

In view of these results it is interesting to have a look at the amount of massularia in Pink Magic. Unfortunately, USP provides no data on the amount of the individual ingredients - so, we only know that there is 1.6g of a mixture of massularia and two other botanicals in one serving. Massularia is mentioned first which tells us that it should be the main ingredient. So, let's be generous and assume that there is 1.0g of massularia per serving. USP recommends 3 servings per day. This would amount to 3.0g of massularia, which has now been clinically proven to be insufficient; and what's more even with 6.8g/day (equivalent to 500mg/kg in rats) the increase in testosterone (cf. Table 1) is still almost negligible.

Table 1: Effect of aqueous extract of Massularia acuminata stem on serum testosterone concentrations of male rats. (Yakubo. 2011)

What about all the positive feedback on various message boards, then? Well, we do not know how the dosing protocol used in rats eventually translates to human beings. The above calculation is based on a standard human equivalence dose formula, the accuracy of which is certainly questionable. Thus, the results of the study are actually good news for USP Labs, as they prove that massularia which, by the way is not a USP Labs exclusive anymore, actually works.

Date Palm (Phoenix dactylifera) as a Natural Test Booster and Ergogenic

A very recent study (Saddiq. 2010) published in the Journal of the International Society for Horticultural Science found that the seeds of Phoenix dactylifera can raise testosterone, norepenephrine (NE), dopamine (DA) and GABA levels and may counteract the negative effect of prednisolone administration in rats.

[...] the daily oral administration of pits of date palm caused the maximal increase in NE, DA and GABA content that was found in the brain stem after 2 weeks. The daily oral administration of methylprednisolone caused a decrease in NE, DA and GABA content found in the brain stem after 2 weeks. Moreover, the daily oral administration of pits of date palm and methylprednisolone caused an increase in NE content found in the brain stem after 2 weeks. The daily oral administration of pits of date palm and methylprednisolone caused a significant increase in testosterone level in serum blood of male albino rats.

While all this sounds promising, further studies would have to clarify whether it needs the cortisol-like effects of prednisone for the testosterone-boosting effect of the date seeds to take place or whether taking adequate amounts of pits of date palm would provoke similar (or even superior) increases in testosterone in rats and, most importantly, in men. Be that as it may, even the increase in neurotransmitters (NE, DA, GABA) certainly could provide real-world benefits for athletes, as well as people suffering from fatigue.

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.