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Cancer Epidemiology Biomarkers And Prevention

Vitamin A (retinol) and its analogues (retinoids) are of great interest to scientists as possible agents for the chemoprevention of cancer in high-risk populations. Concerns have been raised, however, about possible adverse effects of these agents, even when administered at doses below those ordinarily associated with toxicity. Several reports have associated the use of vitamin A analogues with clinically significant elevations in serum triglyceride levels. It is not clear, however, whether retinol itself can produce this undesirable effect. As part of an ongoing major trial of retinol and [beta]-carotene, researchers have examined the effect of long-term retinol supplementation on serum triglyceride levels.

In the [beta]-Carotene and Retinol Efficacy Trial (CARET), 1,845 subjects at high risk of lung cancer (because of smoking and/or asbestos exposure) have received supplements of 25,000 IU/day of vitamin A or placebo for up to eight years. (The subjects also received 15 or 30 mg of [beta]-carotene or placebo.) Repeated measurements of serum triglyceride levels showed only a very small, clinically unimportant increase in the vitamin A group, which developed promptly after the initiation of supplementation. The effect was statistically significant only because of the very large number of participants in the study. The increase in serum triglycerides due to vitamin A supplementation was not progressive and was independent of[beta]-carotene supplementation.

These results indicate that vitamin A supplementation at a dose of 25,000 IU/day is not associated with undesirable increases in serum triglyceride levels. Since moderate doses of vitamin A analogues such as isotretinoin have been associated with triglyceride elevations, these findings suggest that retinol may have a safety advantage over its analogues.

Gilbert S Omenn, Gary E Goodman, Mark Thornquist, and John D Brunzell, Long-Term Vitamin A Does Not Produce Clinically Significant Hypertriglyceridemia: Results from CARET, the [beta]-Carotene and Retinol Efficacy Trial, Cancer Epidemiology, Biomarkers & Prevention 3(8):711-713 (Dec 1994) [Reprints: Gilbert S Omenn, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, MP-859, Seattle WA 98104]

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