© 2008 American Thoracic Society
Can Moderate Doses of Vitamin E Protect against Lung Cancer?To the Editor:The article by Dr. Slatore and colleagues indicates that vitamin E is unlikely to reduce the risk of lung cancer (1). Indeed, the authors report that vitamin E supplements might actually increase the risk. In this study, no statistically significant associations were found between 10-year lung cancer incidence and vitamin E at any dose level (Table 2). The lack of association persisted when the results were stratified by cancer morphology and smoking status. The only evidence that vitamin E might increase the risk of lung cancer appeared when the trend among vitamin E dose tertiles was considered in three ranges: low (<200 mg/d), moderate (42–215 mg/d), and high (>215 mg/d). Analysis indicated a slight increase in risk of 1.05 for each additional 100 mg/d dose. The trend toward increased risk at higher doses, though, depends on the noticeably low risk levels (HR, 0.80) observed in the moderate dose range. This surprisingly low HR applied equally among all morphologies (range, 0.68–0.84) and among all smoking categories (range, 0.68–0.86). While the HRs were not statistically significant, the unusually low risk values in the moderate dose range accentuate the trending curve observed among dose tertiles, which formed the basis for the reported finding of vitamin E's detrimental effect. The authors mention the "U-shape" of the curve from low to high dosage, and they conclude that the trend is "heavily influenced by subjects using high-dose vitamin E supplements." But it also would be correct to say that the observed trend is influenced by the low HR levels in the moderate dosage tertile. Interestingly, the finding of lower risks with moderate dosage of vitamin E is consistent with the recent meta-analyses of vitamin E's effect on all-cause mortality by Miller and colleagues and Bjelakovic and colleagues (2, 3). In fact, Miller and coworkers present a diagram of the dosage-risk curve (Figure 3, p. 43), indicating that the transition from a protective to a detrimental effect for vitamin E occurs at a dosage of approximately 150 IU/day (100.7 mg/d), which is in the middle of Slatore and coworkers' moderate dose tertile. These considerations call into question the interpretation of the dose trend observed in the Slatore study and the significance of the calculated incremental risk of 1.05 per 100 mg/day. Moreover, the possibility of a protective effect for moderate doses of vitamin E in the range of 100–200 IU/day is suggested by the data, which merits additional attention by researchers.
The Ohio State University College of Public Health FOOTNOTES Conflict of Interest Statement: A.E.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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