Showing posts with label NAC. Show all posts
Showing posts with label NAC. Show all posts

Wednesday, March 23, 2011

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.

Tuesday, January 18, 2011

Reactive Oxygen Specimen (ROS) Trigger Muscle Hypertrophy via IGF-1 Signaling

I have touched on the "usefulness" of oxidation, only yesterday. Now, a very recent study appears to confirm the notion that a controlled amount of inflammation is necessary in order to achieve metabolic and muscular adaptations.
Figure 1: Eesult of the quantitative analysis of myotube diameter after IGF-I and NAC treatment (Handayaningsih. 2011)
Scientists from Division of Diabetes and Endocrinology and Division of Cellular and Molecular Medicine at the Kobe University Graduate School of Medicine published a paper (Handayaningsih. 2011) describing an investigation into the role of Reactive Oxygen Specimen (ROS) in the IGF1-signaling pathway. In this study N-Acetyl-Cystein (NAC), commonly used by recreational athletes as an "ergogenic" aid, blunted myocyte response to IGF1 and thus inhibited muscle hypertophy (cf. Figure 1):
While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, thephosphorylationof FoxO1by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy.
Before you now go and flush all your vitamins and antioxidants down the toilette, you should consider that this is an in-vitro study with a narrow and limited ROS stimulation and not a large scale exercise supplementation study showing that the 500-1.000 mg of NAC you take on a daily basis will completely forestall muscle growth. If anything, it should remind you that excessive "inflammation" could be the "root of all evil" (cf. Super Human Radio), but excessive antioxidant supplementation certainly ain't a solution.