PharmacoNutrition Reviewed

Source: JBC 7 Jan 2008 (Epub)
Article Type: Original Research
Authors: Cuddihy et al.

For many people vitamin E supplementation is still the magic bullet for preventing the onset of chronic diseases and even the maladies of aging. Although vitamin E in its various forms is certainly important for cell and organ function, the present paper by Cuddihy et al. is a nice example that mother nature created the activity pattern of biomolecules not in a one-way fashion but somewhat chaotic. But read yourself…..

“Vitamin E is the major lipid soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged antioxidant properties of vitamin E, only a few studies have directly correlated levels of reactive oxygen species with vitamin E availability in animal models. We explored the relationship between vitamin E and reactive oxygen species in two mouse models of vitamin E deficiency; dietary deficiency, and a genetic model (tocopherol transfer protein, Ttp-/-, mice).

Both groups of mice developed near-complete depletion of alpha-tocopherol (the major tocopherol in vitamin E) in most organs, but not brain, which was relatively resistant to loss of alpha-tocopherol. F4-neuroprostanes, an index of lipid peroxidation, were unexpectedly lower in brain of deficient mice compared to controls. In vivo oxidation of dihydroethidium by superoxide radical was also significantly lower in brain of deficient animals. Superoxide production by brain mitochondria isolated from vitamin E deficient and Ttp-/- mice, measured by electron paramagnetic resonance spectroscopy, demonstrated a biphasic dependence on exogenously added alpha-tocopherol. At low concentrations, alpha-tocopherol enhanced superoxide flux from mitochondria, a response which was reversed at higher concentrations.

Here we propose a mechanism, supported by molecular modeling, to explain decreased superoxide production during alpha-tocopherol deficiency, and speculate that this could be a beneficial response under conditions of alpha-tocopherol deficiency.”

Image taken from: dopaminejewelery.com

Source: Nutrition Journal (2007), 6:10
Article Type: Original Research
Authors: G McNeill et al.

Image taken from: http://www.buzzle.com/img/articleImages/431619-54med.jpg

Just recently, I discussed the possibility of mutivitamin supplementation negatively affecting mortality. And there’s more bad news.
In their randomised controlled trial, Mc Neill and colleagues again confirm the inefficiency of multivitamin/-mineral supplementation (duration: 12 months) for the improvement of cognitive function in elderly (>65 years of age) subjects. As the article is freely available I will leave it to you to read the details.
I just wonder if we ever will have the chance to read the report of a prospective study assessing the impact of at least 15-20 years of multivitamin/-mineral supplementation starting well before (!) ongoing biological havoc prevents any possible health-beneficial effect of such intervention.

Source: JAMA (2007), 297: 842-857
Article Type: Review (Meta Analysis)
Authors: G Bjelakovic, D Nikolova, LL Gluud, R Simonetti, C Gluud

Image taken from: http://carbs.com/dimages/headlines/vitamins.jpg

The Meta-Analysis published by Bjelakovic et al. addresses an issue that is getting more and more controversial, recently, i.e. whether antioxidant supplements are actually health-beneficial, show no effect or are even detrimental. Based on the analysis of 69 randomized trials with more than 200.000 participants, the authors conclude that
a) vitamin C and selenium have no effect on mortality
b) beta-carotene, vitamin A and vitamin E (singly or combined) significantly increase mortality

What do these results tell us?
First of all, I am curious to read the comments this article will certainly provoke. The widely cited Miller et al. study on vitamin E and mortality, for example, caused a quite heated debate, especially regarding the statistics used.
Secondly, we (at least most of us) are not only consuming nutrients – but food; although I haven’t fully digested this meta-analysis, yet, the results are – if valid – not that surprising, because when antioxidants are taken in as part of real food they actually exert quite different effects I contrast to supplements. Also, the argument that the antioxidant supplements might reduce “beneficial ROS” is a bit sketchy.
I just wonder, how the food supplement industry is going to react to this study – I think it cannot get a lot more worse for them.

Source: European Journal of Clinical Nutrition (2007), 61: 69-76
Article Type: Original Contribution
Authors: S Valtuena, D del Rio, N Pellegrini, D Ardigo, L Franzini, S Salvatore, PM Piatti, P Riso, I Zavaroni, F Brighenti

Image taken from: http://www.healingwithnutrition.com/graphic/vitamins.gif

In my last post I pointed out the lack of disease-preventing efficiency antioxidants (e.g. polpyhenols, vtaminc C and E, carotenoids) show in many intervention studies.
In their recent paper, Valtuena et al. suggest that the total antioxidant capacity (TAC) of the diet acts as an independent predictor of plasma beta-carotene (a carotenoid) levels. They derive this conclusion from covariate analyses of their data showing a significant correlation between TAC of the diet and plasma beta-catotene levels. In contrast, the impact of oral beta-carotene intake on plasma levels was only of marginal significance, suggesting that plasma concentrations of beta-carotene are modulated by other determinants than its own intake. In summary, they conclude that a high TAC of the diet leads to enhanced plasma beta-carotene levels, possibly by preventing beta-carotene breakdown due to absorption of other antioxidants present in the diet. This in turn might also explain why high intake of fruits and vegetables not only lead to higher beta-carotene plasma concentrations but is also health beneficial, whereas supplementation with beta-carotene fails to reduce disease risk.

Aside from the TAC of the diet or food items, plasma or serum TAC is another parameter frequently reported in research papers.
The question now is whether the TAC of the diet (determined by the presence of antioxidants in the food) is linked to TAC of the plasma.
Here, I would like to draw your attention to a research article published in 2004 (Lotito et al.) showing that the consumption of apples (which are considered as antioxidant-rich food) indeed inceases plasma TAC. However, the changes in plasma TAC were due to effects of fructose (which is present in high amounts in apples, too) on plasma ureate (a major endogenous plasma antioxidant) levels (and not due to effects of ascorbate, i.e. vitamin C, present in the apples)
Taken together, those studying dietary effects on plasma TAC must rule out postprandial (and other confounding) effects on plasma TAC, prior directly linking the antioxidants present in the food under investigation to observed changes in plasma TAC.