Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort

Abstract

Purpose Inconsistent findings have been reported of a link between the use of one-carbon metabolism-related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplement use relative to cancer risk. Methods A total of 77,118 participants of the VITAL cohort, 50 to 76 years of age, were recruited between October 2000 and December 2002 and included in this analysis. Incident, primary, invasive lung cancers (n = 808) were ascertained by prospectively linking the participants to a population-based cancer registry. The 10-year average daily dose from individual and multivitamin supplements were the exposures of primary interest. Results Use of supplemental vitamins B₆, folate, and B₁₂ was not associated with lung cancer risk among women. In contrast, use of vitamin B₆ and B₁₂ from individual supplement sources, but not from multivitamins, was associated with a 30% to 40% increase in lung cancer risk among men. When the 10-year average supplement dose was evaluated, there was an almost two-fold increase in lung cancer risk among men in the highest categories of vitamin B₆ (> 20 mg/d; hazard ratio, 1.82; 95% CI, 1.25 to 2.65) and B₁₂ (> 55µg/d; hazard ratio, 1.98; 95% CI, 1.32 to 2.97) compared with nonusers. For vitamin B₆ and B₁₂, the risk was even higher among men who were smoking at baseline. In addition, the B₆ and B₁₂ associations were apparent in all histologic types except adenocarcinoma, which is the type less related to smoking. Conclusion This sex- and source-specific association provides further evidence that vitamin B supplements are not chemopreventive for lung cancer and may be harmful.

Fig A1.

Forest plot of previous studies of vitamin B₆ and lung cancer risk, stratified on exposure type.

Fig A2.

Forest plot of previous studies of vitamin B₁₂ and lung cancer risk, stratified on exposure type.