ABSTRACT & COMMENTARY
Do B Vitamins Cause Lung Cancer? The answer is sex-, supplement-, and smoking-dependent REFERENCE
Brasky TM, White E, Chen CL. Long-term, supplemental, one-carbon metabolismrelated vitamin B use in relation to lung cancer risk in the vitamins and lifestyle (VITAL) cohort. J Clin Oncol. 2017;35(30):3440-3448. STUDY OBJECTIVE
To examine the relationship between longterm supplemental B vitamin intake and lung cancer risk DESIGN
Prospective cohort study in 13 counties around the Puget Sound in northwest Washington state (VITAL cohort) PARTICIPANTS
Men and women, aged 50 to 76 at baseline and covered by the Surveillance, Epidemiology, and End Results (SEER) program cancer registry, were recruited from 364,418 baseline questionnaires from October 2000 to December 2002. Individuals with a history of lung cancer at baseline, lung cancer diagnosis on death certificate with no date of diagnosis, lung lymphoma and in situ lung cancer were excluded; after exclusions, 77,118 were available for study. Cohort members were followed from baseline to December 31, 2007, a mean follow-up of 6 years. STUDY PARAMETERS ASSESSED
Diet was assessed by food frequency questionnaire of 120 foods and beverages adapted from the Women’s Health Initiative, and the following demographic and health-related characteristics were collected: height, weight, computed BMI, education, family history of lung cancer, medical history, and cigarette smoking history, including age of onset of daily smoking, current smoking habits, cumulative years of smoking, number of years since quitting, and categorization as never smoked, former smoker (quit ≥10 years ago), recent smoker (quit <10 years ago), or current smoker. Cohort members reported their regular intake (≥1 per week for ≥1 year) of multivitamin, individual vitamin supplements, and
mixtures in a closed-ended format including usual daily dose of B6, B9, and B12, use of a multivitamin formulation, and brand name. KEY FINDINGS
Participants who developed lung cancer tended to be older, male, and less educated at baseline. They also had a lower BMI, consumed less alcohol, were more likely to be current smokers at baseline, had greater pack years, and were more likely to have a positive history of chronic obstructive pulmonary disease (COPD) and cancer. Comparing men and women, women consumed more B vitamins from supplements (P<0.001), men tended to consume more B vitamins from diet (P<0.001), and women had lower overall B vitamin intake (food and supplements; P<0.001). Both groups exceeded the US recommended daily allowance (RDA) for each B vitamin. There was no correlation of lung cancer risk with B vitamins in women. In men, compared to nonusers, intake of individual B vitamin supplements was associated with increased lung cancer risk for B6 (hazard ratio [HR]: 1.84; 95% confidence interval [CI]: 1.01-3.36) and B12 (HR: 2.42; 95% CI: 1.49-3.95). The 10-year average daily dose for men in the highest to lowest categories of B6 intake (>20 mg/d; HR: 1.82; 95% CI: 1.25-2.65) and B12 (>0.55 mcg/d; HR: 1.98; 95% CI: 1.32-2.97) was greater for current smokers compared to recent smokers or former smokers. Among current male smokers, only B6 above 20 mg per day (HR: 2.93; 95% CI: 1.5 -5.72, P=0.04) and B12 above 55 mcg per day (HR: 3.71; 95% CI: 1.77 -7.74, P<0.01) were significant for lung cancer risk. There was no risk for lung cancer in former smokers who quit more than 10 years ago or less than 10 years ago. There were too few participants who had never smoked to evaluate associations. The association with increased use of B vitamins was similar across all histological subtypes of lung cancer except adenocarcinoma.
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Paul Richard Saunders, PhD, ND, DHANP PRACTICE IMPLICATIONS The relationship between B vitamins and cancer has been examined in a few prior studies. A randomized intervention study by Ebbing et al provided B vitamins to 6,837 patients with ischemic heart disease for 38 months, with another 39 months of follow-up. The study, which was conducted from 1998 to 2007, had 4 arms: 0.4 mg/d B12 plus 0.8 mg/d folic acid; 0.8 mg/d folic acid plus 40 mg/d B6; 40 mg/d B6 only; and placebo.1 Investigators found no effect of B6 on lung cancer. In the B12 plus folic acid arm, 10% developed cancer, while 8.4% of participants who did not receive that combination developed cancer (HR: 1.21; 95% CI: 1.03 -1.41, P=0.02). In this study, 40% were current smokers and 72% were current or former smokers. All-cause mortality was higher in the B12 with folic acid vs other treatments (16.1% vs 13.8%; HR: 1.18, P=0.01) and was mainly due to lung cancer. The cause of the increased cancer was unknown. The Hordaland Health Studies were surveys performed in Hordaland County, Norway during the 1990s. The surveys were used to explore homocysteine in about 7,000 residents.2 An analysis of B6 metabolism found that the 4-pridoxic acid/ pyridoxal + pyridoxal-5-phosphate ratio was a marker of B6 catabolism during inflammation and may be a marker of carcinogenesis. Smoking creates inflammation that can take