Commentary: Beyond beta-carotene-antioxidants and cardiovascular disease

In 1989 in an article entitled ‘Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity’ that appeared in the New England Journal of Medicine Daniel Steinberg et al. highlighted the potentially important role of oxidation of low-density lipoprotein (LDL)-cholesterol in atherogenesis.1 This laboratory work led epidemiologists to examine the association between intake of antioxidants (substances that might stop the oxidation of LDL-cholesterol such as beta-carotene) in the diet of free-living humans and subsequent cardiovascular disease.

Observational studies reported a significantly lower risk of cardiovascular death in those who ate diets rich in beta-carotene. In a meta-analysis the pooled relative risk reduction was 31% (95% CI : 41–20%, P < 0.0001) when those with high beta-carotene intake or serum beta-carotene levels were compared with those with low intakes or levels.2 Several trials of beta-carotene, which had been set up to examine the effect of antioxidants on cancer incidence then reported their results in the mid 1990s. The randomized trials did not confirm the beneficial association seen in observational studies. Instead, they reported a moderate adverse effect of beta-carotene supplementation with a relative increase in the risk of cardiovascular death of 12% (95% CI : 4–22%, P = …