Taking supplements of the vitamin A precursor beta-carotene may increase the risk of colorectal cancer in smokers and drinkers, according to new research published this week.
The study, led by Dartmouth Medical School (DMS) in the US, comes days after the UK's Food Standards Agency issued a warning about the effects of high doses of beta-carotene. The agency recommends maximum daily supplementation of 7mg, considerably lower than that supported by the Health Food Manufacturer's Association (HFMA) - 20mg.
While beta-carotene, a powerful antioxidant, has been associated with cancer-fighting properties, there is also previous evidence to show that it has negative effects in smokers.
Dr John A. Baron, professor of medicine at DMS, and his colleagues found that for participants who smoked cigarettes and drank more than one alcoholic drink per day, beta-carotene doubled the risk of recurring adenomas, benign tumours that could lead to colorectal cancer. In non-smokers or non-drinkers however, beta-carotene supplementation was associated with a 44 per cent decrease in the risk of colorectal adenoma recurrence, compared to those subjects who received a placebo.
"The key point of the study was the supplements had different effects, depending on the smoking and drinking habits of the subjects," Baron said. "These findings illustrate the complexity that we face in designing safe and effective chemopreventive strategies for any cancer. A careful mix of animal studies, epidemiology and clinical trials is needed to continue to determine successful methods of preventing cancer," he said.
The examination of smoking and drinking on adenomas builds on two earlier clinical trials focused on lung cancer, which included large numbers of mainly cigarette smokers. They found that beta-carotene supplementation was associated with an increased risk of lung cancer, particularly among those who also drank alcohol. Supplement manufacturers have however pointed out that these trials used synthetic beta-carotene, and that the results are "irrelevant to natural beta-carotene" (comment from Solgar).
A third randomised trial, which enrolled mostly non-smokers, found no association between beta-carotene supplementation and risk of lung cancer, suggesting that cigarette smoking and alcohol intake were somehow associated with the adverse effects of beta-carotene.
The new study, published in the 21 May issue of the Journal of the National Cancer Institute, examined data on 864 people who had participated in the Antioxidant Polyp Prevention Study. The participants, who were polyp-free after having had previous polyps removed, were randomly assigned to receive either placebo or 25mg beta-carotene and/or vitamins C and E in combination (1000mg and 400mg respectively, or a placebo). Participants completed a questionnaire about their smoking habits and alcohol intake.
They were followed up with colonoscopy for adenoma recurrence one year and four years later.
The authors point out that the alcohol and smoking habits were reported by the subjects, so there is a potential for measurement error and association with other unknown lifestyle factors. Nonetheless, Baron and his co-authors conclude: "Supplementation [with beta-carotene] was beneficial among subjects who did not drink or smoke but, if anything, increased risk among those who drank and/or smoked."
For participants who smoked cigarettes and also drank more than one alcoholic drink per day, beta-carotene doubled the risk of adenoma recurrence, they reported.
While the study seems to confirm the potential benefits of the supplement for non-smokers, it does suggest that labelling or other measures may need to take account of possible at-risk groups. Further research may be needed to look into possible different actions of synthetic and natural versions of beta-carotene. Yesterday we reported that researchers are to investigate the possible negative effects of the carotenoid lycopene on smokers.