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Newsletter 12/08Antioxidant supplements under attack again
Early registration for ENA Conference still possible
Antioxidant supplements under attack again
Recent large-scale studies with antioxidants have again provided negative results with regard to a reduced risk of cancer and mortality (1, 2, 3). The very latest studies on the prevention of prostate cancer (1, 2) have attracted particular attention, and we are already reading about how useless antioxidants are. In this regard we would like to refer you to a comment in JAMA (4), which very clearly addresses the problems of such intervention studies with individual components of a balanced diet. In addition to an elementary weakness of both studies due to their failure to screen PSA, Dr Gann points to the following essential connection: “It may be time to give up the idea that the protective influence of diet on prostate cancer risk – which is clearly observed in migrant studies and in populations transitioning to a Western diet - can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men.” He goes on to describe attempts to make certain molecules responsible for a protective effect as a reductionist point of view, and also casts doubt on the usefulness of placebo-controlled Phase 3 studies in this connection.
In doing so he summarises in a few words the extremely complex problems that are encountered by studies on nutritional intervention:
• Beginning of the intervention: in all the papers named above the subjects were already at least 50 (i.e. 55 or 70) years old at the beginning of the intervention. In this age group it must be assumed that precancerous and other subclinical diseases are already present in many cases which increase the risk of disease and mortality accordingly. Thus one can hardly talk about primary prevention with micronutrients, although this would actually be the main potential of nutritional intervention.
• Duration of the intervention: although the period of five to 10 years alone is remarkable for a study, it is still inadequate with regard to the pathogenesis of chronic diseases, i.e. the nature of primary prevention (moreover, the SENECA study gives no details of how long the nutritional intervention lasted).
• Choice of substances used: it can be seen that more recent studies are conducted with more or less physiological doses, and not with very high doses as before (400 IU vit. E., 500mg vit. C, 200µg selenium). However, the number of substances used remains very limited (e.g. vitamin E + selenium alone or in combination, vitamins C + E alone or in combination; the SENECA study investigated the most different combinations) and is not at all related to a healthy diet with its mixture of innumerable active nutrients.
With regard to these problems we would like to refer you to P. Prock’s contribution at the ENA conference in Rimini in October 2006 (5). The question of which study design can be used to investigate nutritional intervention reliably remains unsolved.
1. Lippman SM et al.: Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT), JAMA. 2008 Dec 9. [Epub ahead of print], PMID: 19066370
2. Gaziano JM et al.: Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial., JAMA. 2008 Dec 9. [Epub ahead of print], PMID: 19066368
3. Brzozowska A et al.: Supplement use and mortality: the SENECA study., Eur J Nutr. 2008 Apr;47(3):131-7. Epub 2008 Apr 14., PMID: 18414768
4. Gann PH: Randomized Trials of Antioxidant Supplementation for Cancer Prevention - First Bias, Now Chance—Next, Cause;, JAMA. 2009;301(1):(doi:10.1001/jama.2008.863).
5. Prock P: The Science behind Supplements (Abstract), ENA-conference, Rimini in Oktober 2006