Seventy-three male smokers who had bronchial squamous metaplasia (identified in one or more sputum samples) were randomly assigned to receive, in double-blind fashion, either placebo or 10 mg/day of folic acid plus 500 mcg/day of hydroxocobalamin (vitamin B12). After 4 months there was a significantly greater reduction of atypical cells in the supplemented group than in the placebo group.

Comment: Bronchial squamous metaplasia is a frequent forerunner of bronchogenic carcinoma. It has been suggested that certain components of cigarette smoke may inactivate folic acid, resulting in localized folic acid deficiency that renders the bronchial epithelium more susceptible to neoplastic transformation. Lower serum folate and vitamin B12 levels have been found in smokers, compared with non-smokers. Furthermore, plasma folate levels were lower in smokers with potentially premalignant bronchial squamous metaplasia than in smokers without metaplasia. These results suggest that supplementation with folic acid and B12 may help reduce the risk of lung cancer in cigarette smokers. Of course, quitting smoking would be of much greater benefit.

Heimburger DC, et al. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. JAMA 1988;259:1525-1530