Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer.

Design: prospective cohort (VITAL). Participants: 77,126 men and women aged 50-76 years from Washington State; baseline 24-page questionnaire; outcome: incident lung cancer identified via Seattle-Puget Sound SEER registry; follow-up through December 31, 2005 (mean 4.05 years); 521 cases; Analysis used Cox regression with age as the time variable; left truncation; robust standard errors; adjustments for smoking (years smoked, pack-years, pack-years squared) and sex; Exclusions: prior lung cancer at baseline; exposure measured as 10-year average supplement use.

10-year average daily intake of oral supplements: multivitamins (pills/week), vitamin C (mg/day), vitamin E (mg/day), and folate (mg/day); duration prior to baseline: 10 years.

Long-term use of supplemental multivitamins, vitamin C, and folate was not associated with a decreased risk of lung cancer. Supplemental vitamin E showed a small, dose-dependent increase in risk, strongest among current smokers and for NSCLC; HR 1.05 per 100 mg/day (95% CI 1.00–1.09; P=0.03); after adjusting for dietary vitamin E, HR 1.04 (95% CI 1.00–1.09; P=0.08). For NSCLC, HR 1.07 per 100 mg/day (95% CI 1.02–1.12; P=0.01). At 400 mg/day for 10 years, risk ≈28% higher. Current smokers in the highest vitamin E dose category had HR 1.59 (95% CI 1.05–2.41). No significant associations for vitamin C or folate with overall risk; authors conclude that these supplements are unlikely to reduce lung cancer risk, and supplemental vitamin E may increase risk; counsel patients against using these supplements to prevent lung cancer.

Observational design with potential residual confounding; self-reported supplement use may lead to exposure misclassification; predominantly white cohort with fewer current smokers, limiting generalizability; limited power to detect small risk differences (≥30%); nonrandomized.