Posted by Larry Hoover on November 11, 2004, at 15:43:19
In reply to Re: Vit E and increased death risk?, posted by Larry Hoover on November 11, 2004, at 8:35:02
I suppose I oughta copy some of my own post to sci.med.nutrition here, as well.
There's a totally uncontrolled aspect of supplementation with vitamin E, here, in that most supplements reported in these studies are d-alpha, or d-,l-alpha tocopherol. As alpha tocopherol has substantially higher binding affinity to transport proteins than do delta- or gamma-, there is a marked substitution of the former for the latter two in tissues, even if diet is otherwise adequate. In the discussion in this paper, it seems this suppression of especially gamma-tocopherol concentrations persists for two years, and delta-tocopherol concentrations became undetectable. As gamma-tocopherol in particular is thought to be selective for NOx pro-oxidants, this may permit an increase in the formation of peroxynitrite from NO and superoxide anion. That's bad news for health.Full-text (link), abstract below:
http://www.nutrition.org/cgi/content/full/133/10/3137
J Nutr. 2003 Oct;133(10):3137-40.
Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans.
Huang HY, Appel LJ.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. hyhuang@jhsph.edu
Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients. We studied the effects of supplementing diets with RRR-alpha-tocopheryl acetate (400 IU/d) on serum concentrations of gamma- and delta-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of gamma- and delta-tocopherol from baseline to the end of the 2-mo experimental period. Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001). Consistent with trial
results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum gamma-tocopherol than nonusers. In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted.************************
> And it is little wonder that people who take high dose Vitamin E or
> beta carotene fare poorly. Indeed, it's rather suprising to me that
> the increased mortality risk is so low!George, I think you are right on the money. There is quite an array of tocopheryl radical quenchers, including vitamin C, alphalipoic acid, glutathione, carotenoids, Co Q10, xanthines, lutein, on and on. What is the key criterion is the localized half-life of the tocopheryl radical. It is pro-oxidant, but only if the formation of this radical exceeds the net quenching capacity of the other inter-related anti-oxidants.
It's a trade-off, the destruction of more reactive (and thus more destructive) radicals for less reactive ones of longer half-life. The chain must be unbroken, up to the point where two less reactive, longer half-life radicals, react to form a stable molecule. Stalling the chain at e.g. tocopheryl radical (or ascorbyl radical, or whatever) will sustain oxidative capacity. The damage done by those "antioxidants turned oxidants" will differ based on the chemistry of the particular radical itself. The tocopheryl radical will damage lipids preferentially, for example, due to its hydrophobic physical characteristics.
Reductionist science will never discover this relationship. It is not part of the mindset. Methodologies with one independent variable do not provide you with generalizable information, the way some scientists think they do. The statistics hold there value in other populations if and only if all other variables are similarly constrained. The reasonable conclusion from this study might be that taking vitamin E as sole antioxidant supplement may be injurious if you exceed the antioxidant capacity for tocopheryl quenching.
Lar
P.S. I'm getting rid of my cheapo synthetic vitamin E supps, and buying some proper mixed tocopherols.
poster:Larry Hoover
thread:412398
URL: http://www.dr-bob.org/babble/alter/20041108/msgs/414650.html