Epidemiological Study Shows Correlation Between Anti-Oxidant Intake and C-Reactive Protein & Homocystein

After a sudden onset of discussions around the beneficial or even detrimental effects of vitamin supplements in general and antioxidants in particular in the mid to late 2000s, vitamins and, even more, other anti-oxidants have been put back on the map, lately.

A recent epidemiological study from the University of Connecticut (Floegel. 2011) provides further evidence for the hypothesis that, after all, consumption of adequate amounts of vitamins C and E, beta carotene, flavonoids and selenium would be beneficial to your overall health

Intakes of vitamins C and E and carotene were inversely associated with the probability of having serum CRP concentrations >3 mg/l in multivariate logistic regression models. Flavonoid and Se intakes were not associated with the odds of elevated serum CRP concentrations. The mean plasma Hcy concentration was 8·61 (95 % CI 8·48, 8·74) μmol/l. Intakes of vitamins C, E, carotenes and Se were inversely associated with the odds of plasma Hcy [Homocysteine] concentrations >13 μmol/l after adjusting for covariates

While all these results appear to be quite unambiguous, you still have to keep in mind that they support the interpretation "antioxidants are healthy" only, if we assume that the relation between high C-Reactive Protein [CRP], inflammation and the metabolic syndrome, as well as the relation between homocysteine and heart disease is more than just a correlative one; and, to my best knowledge, no study has yet been able to show that injection of homocysteine caused heart disease or an increase in CRP increases inflammation or causes tissue damage. In this context, for example, the hitherto hardly understood involvement of "positive inflammation", such as an exercise induced rise in IL-6 levels, come to mind. In this context, studies such as Ristow et al. (2009) that found the positive effects of exercise being blocked by antioxidant supplementation would warrant further research into what - irrespective of reductions in purported markers of inflammation and cardiac disease - the actual health outcome of higher antioxidant intakes are.


Note: Don't get me wrong. I do not want to argue against a diet rich in natural antioxidants. I just want YOU to be aware that the proven health benefits from eating healthy, antioxidant-rich foods cannot be extrapolated to high (or even mega-dose) vitamin & flavonoid supplements and that taking megadoses of isolated antioxidants such as alpha-tocopherol (especially in its synthetic form and without the complementary tocopherols and -trienols), which is the most commonly sold form of vitamin E, may in fact do more harm than good.

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.

Loss of Trace Elements not a Concern in Well-Hydrated Athletes

If you are a hard-training athlete you need more than "trace amounts" of trace elements, don't you? No, actually not. You may be somewhat disappointed now, but the expensive trace element supplement you just ordered might turn out to be a complete waste of money - at least, this is what the results of a recently published study by Carlos González-Haro et al. (González-Haro. 2010) suggest.

Figure 1: Changes in plasma trace element levels (Zn, Mn, Se and Co) for the different relative exercise intensities studied and the 7 min recovery period.

As figure 1 (above) shows, lactate concentrations constantly increased in the course of the 7 minutes after a cycloergometer test, where, after a warm-up of 10 min at 2.0 W kg⁻¹, workload had been increased by 0.5 W kg⁻¹ every 10 min until exhaustion. The trace mineral concentration, on the other hand, remained stable over the whole study period (exercise + recovery). This observation led the scientists to conclude ...

[...] in euhydrated well-trained endurance athletes no effects on plasma levels of Zn, Se, Mn and Co were observed either during medium duration exercise, at a full range of intensities (41–92%VO_2peak), or during a seven-minute recovery period. These subjects showed no deficiency in Zn or Se and probably were not deficient in Mn or Co either (though cutoff levels are not known).

So, if you have not opened your "high quality trace element" supplement yet, make use of your 14-days conversion right ;-)