Wrong approaches in vitamin research

“As soon as Linus Pauling claimed that the megadoses of vitamin C could prevent the metastasis of cancer, many researchers began to focus on how micronutrients could be used to prevent chronic diseases. Since then, many observational studies have indicated that antioxidant nutrients, especially vitamins C and E and beta-carotene, may help protect against cardiovascular diseases and cancer. It has been shown that antioxidants have a preventive effect, particularly in the earlier stages of atheroscle-rosis and carcinogenesis. People with a deficiency (i.e. participants with low concen-trations of antioxidants in the blood) and people with a greater need for antioxidants have particularly benefitted from supplementation. Thanks to conducting trials on animals and cell cultures, researchers have been able to investigate the consequences of poor protection against the destructive, disease-promoting effects of reactive oxygen radicals. These trials have helped provide an explanation for the results of the epidemiological studies: Clearly, the body's own internal syn-thesis of antioxidant enzymes is not always sufficient to build up a resistance against the oxidation caused by free radicals.

All the more disappointing are the results of randomized controlled trials that aimed to prevent the conse-quences of oxidative stress via targeted antioxidant supplementation; there should have been correspon-dingly fewer instances of cardiovascular diseases and cancer. However, this was not the case: In almost all of these studies, no differences were observed between the placebo and treatment groups. Only certain groups were shown to benefit from supplementation. In order to explain the obvious discrepancy between the observational and intervention studies, one would need to check whether prior knowledge had also been used to inform the structure and design of the randomized controlled trials. The observational studies showed that an inadequate supply of antioxidants and correspondingly low blood levels (which attested to an insuffi-cient antioxidant intake) were linked with an increased risk of cardiovascular disease and cancer. For the large intervention studies, an analysis of the blood levels of placebo-group participants clearly showed that almost all of the groups had a sufficient nutrient intake (1). There were two exceptions: the Linxian trials (2), in which the participants, who benefitted from an increase in their antioxidant intake, were clearly undersup-plied, and the study conducted on people with a gene variant that clearly demonstrated their greater need for vitamin E due to their polymorphism (3).

Since the participants in the vast majority of these cases had evidently not been randomized according to their vitamin status at the beginning of the study, these studies can only answer one question: whether administering pharmacologically higher doses to a person with an already sufficient vitamin intake can bring health benefits. The results of these studies clearly show that this does not apply to the general population. Furthermore, participants were mostly selected based on their already having a health problem, and the researchers were trying to prevent reoccurrences through intervention. Whether this is achievable, however, cannot be confirmed by epidemiology. Meta-analyses were also conducted to try and get more out of these already questionable studies, but this endeavor failed.

Micronutrient supplementation can therefore only have preventive effects against diseases that result from a long-term inadequate supply of nutrients. However, this does not mean that other population groups may, for whatever reason (e.g. a genetic disposition), have a greater need for nutrients and could therefore also benefit from supplementation. But, in cases of inadequate supply, it should be clarified whether pre-existing health issues cause the person to have a greater need or whether this need is due to an unbalanced diet. In any case, intake amounts should match official recommendations ¬– studies have shown that overdoses either have no greater effect or are possibly even damaging to the health. How cardiovascular diseases and cancer develop is also a very complex process, and so a lack (or excess) of essential dietary components is just one of many trigger factors.

It would be ideal if each person’s micronutrient supply situation could be investigated with regular blood tests. The health risks of an inadequate supply could then be identified and corrected early on. That said, the benefits of such investigations must also be weighed up against the costs.”

Based on: Moser U. Vitamins: wrong approaches. Symposium: ‘100 years of vitamins – Past, present, future: Micronutrients – Macro impact’. November 2012. Basel, Switzerland.

1. Moser U. Antioxidanzien in der Prävention von Herz-Kreislauf-Krankheiten und Krebs: Randomisierte klinische Interventionsstudien. Schweizerische Zeitschrift für Ernährungsmedizin. 2010; 5/10:21–23.
2. Blot W. J. et al. The Linxian trials: mortality rates by vitamin-mineral intervention group. Am J Clin Nutr. 1995; 62(6):1424–1426.
3. Blum S. et al. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics. 2010; 11(5):675–684.