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Report of a Preliminary Randomized, Double-blind Intervention Trial

Douglas C. Heimburger, MD; C. Bruce Alexander, MD; Robert Birch, PhD; C. E. Butterworth, Jr, MD; William C. Bailey, MD; Carlos L. Krumdieck, PhD, MD

JAMA. 1988;259(10):1525-1530.

Abstract
To test whether changes in folate and vitamin B₁₂ nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, we conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 µg of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B₁₂. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B₁₂ used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B₁₂ by smokers.

(JAMA 1988;259:1525-1530)

Author Affiliations
From the Departments of Nutrition Sciences (Drs Heimburger, Butterworth, and Krumdieck), Medicine (Drs Heimburger and Bailey), Pathology (Dr Alexander), and Biostatistics and Biomathematics (Dr Birch) and the Comprehensive Cancer Center (Drs Heimburger, Birch, and Krumdieck), University of Alabama at Birmingham; and the Birmingham Veterans Administration Medical Center (Drs Alexander and Bailey). Dr Birch is now with the Biological Therapy Institute, Franklin, Tenn.

Footnotes
Reprint requests to the Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294 (Dr Krumdieck).

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