The effect of β-carotene supplementation on total mortality in male smokers depends on the smoking background and on the levels of vitamin C and E intakes according to a study published in Journal of Nutrition Science, read the article here.

An earlier, influential and highly-cited meta-analysis on diverse antioxidants pooled the results of 47 randomized trials and had calculated that antioxidants increased total mortality by 5% (JAMA 2007;297:842). However, antioxidants are a very heterogeneous group and there is no justification to consider that all antioxidants are so similar as to justify a statement that the 5% effect is valid for every antioxidant across-the-board. Instead, different antioxidants should be studied separately, and even for any single antioxidant, it is unlikely that there will be a uniform effect that applies to all people worldwide.

Previously, the effect of β-carotene supplementation on pneumonia was shown to vary over the large-scale Alpha-Tocopherol Beta-Carotene (ATBC) Study on 29,133 Finnish male smokers. Among those men who started to smoke at the age of 21 years or over, and smoked 21 cigarettes/day or more, β-carotene supplement increased the risk of pneumonia by 4-fold. However, this subgroup covered only 7% of the study participants. β-Carotene did not influence the risk of pneumonia in the remaining 93% of the study participants.

Dr. Harri Hemilä from the University of Helsinki, Finland, hypothesized that the effect of β-carotene on total mortality may be most prominent in the same subgroup of the ATBC Study in which it increased the risk of pneumonia. Consistent with this hypothesis, β-carotene increased mortality in the same subgroup by 56%. Within this subgroup, there was strong evidence of further heterogeneity, which indicated that vitamin C and vitamin E modified the effect of β-carotene supplementation.

The 20 mg per day dose of β-carotene used in the ATBC Study was particularly large as it increased the serum β-carotene level 17-fold compared with the baseline levels. Evidently, much less harm would be expected from much lower β-carotene doses that do not cause such great increases in serum β-carotene levels. In addition, the observed interactions between β-carotene and vitamins C and E should not be extrapolated to the general population, because the interaction was seen in a small subgroup of the study population.

The global market of β-carotene is a billion-dollar business. β-Carotene is available as single nutrient supplement and it is also included in various multivitamin supplement combinations. Further research on the potential harms from β-carotene supplementation is justified so that the specific groups of people who might be at risk of the harm can be instructed to avoid high-dose supplementation.

The heterogeneity of the β-carotene effect on mortality found in Hemilä’s study is a strong counterargument to the earlier influential meta-analysis published in 2007 that pooled diverse antioxidants into the one single 5% effect, and which assumed that the single effect applies to all antioxidants.

Dr Hemilä concludes that “several controlled trials have indicated that the administration of vitamin E and vitamin C may be beneficial in certain special contexts. The clinical importance of those findings is not clear. However, those findings should not be dismissed on the basis that a decade-old meta-analysis erroneously claimed that all antioxidants increase mortality on average by 5%. Smokers should avoid high doses of β-carotene.”