Researchers found the development of lung cancer appears to overwhelm any putative protective effects of prolonged use of vitamins C, E, and folate supplements.

by Judith Groch, Senior Writer, MedPage Today 

Seattle, WA, Feb. 29 —
The development of lung cancer appears to overwhelm any putative protective effects of prolonged use of vitamins C, E, and folate supplements, found researchers here.

Moreover, extended use of vitamin E supplements was associated with a small increased risk of lung cancer, more so in smokers, Christopher G. Slatore, M.D., of the University of Washington here, and colleagues reported in the first March issue of the American Journal of Respiratory and Critical Care Medicine.

The findings came from a prospective cohort of 77,126 men and women, ages 50 to 76, in Washington state who participated in the VITAL (VITamins And Lifestyle) study.

From October 2000 to December 2002, patients were identified through the Seattle-Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry.

In a mean of four years, 521 individuals developed lung cancer. Non-small-cell lung cancer accounted for 75% of the total.

After adjustment for smoking, age, and sex, after an average 10 years’ use, no benefit was found for any of the supplements (P=0.69 for trend).

But when modeled continuously, the researchers found that over 10 years, for every 100 mg/d of supplemental vitamin E, there was a small increased risk of lung cancer (HR 1.07, 95% CI 1.02 to 1.12, P=0.033).

This translated to a 28% increased risk of non-small-cell lung cancer at a vitamin E dose of 400 mg/d for 10 years, the investigators said.

The lung cancer risk of supplemental vitamin E was largely confined to current smokers. When analyzed by current smoking status, the researchers found an increased risk over 10 years for every 100 mg/d increase in vitamin E (HR 1.11, 95% CI 1.03 to 1.19, P<0.01), with an overall P value for interaction of 0.06. The risk was greatest for non-small-cell lung cancer.

Current smokers in the highest dose category (>215 mg/d) had a significantly increased risk of lung cancer (HR 1.59, 95% CI 1.05 to 2.41, P<0.001 for trend).

One possible mechanism for this effect is that although vitamin E is considered an antioxidant, it might act as a pro-oxidant, as well, the researchers said.

After adjusting for intake of vitamin E from food sources, the point estimate for supplemental vitamin E was unchanged (HR 1.04, 95% CI 1.00 to 1.09, P=0.08), although the results were no longer significant.

The risks for supplemental vitamin C and folate did not change substantially when adjusted for dietary intake.

Among the study limitations the researchers noted that residual confounding, such as education and BMI, might have biased the results, although after adjustment, the results did not change.

Other limitations included the fact that the cohort was mainly white and there were fewer current smokers than in the U.S. as a whole.

Future studies may focus on other components of fruits and vegetables that may explain the decreased risk of lung cancer associated with fruits and vegetables, Dr, Slatore said.

Meanwhile, he said, these results, in combination with other studies, should prompt clinicians to counsel patients that these supplements are unlikely to reduce the risk of lung cancer and vitamin E supplements may be harmful, especially for smokers.

In an accompanying editorial, Tim Byers, M.D., M.P.H., of the University of Colorado, wrote, “How could a beneficial effect of consuming fruits be consistent with adverse effects of a nutrient derived in large part from the same food group?”

The answer, he said, is that fruit contains not only vitamins but also many hundreds of other phytochemicals whose functions are not well understood.

Recommendations advising eating at least two servings of fruit each day would likely lead to a reduced risk for lung cancer as well as a reduced risk for other cancers.

However, Dr. Byers said, any benefit to smokers from increasing fruit intake would be more than offset if even a small proportion of smokers decided to continue tobacco use.

This study was supported by a grant from the National Cancer Institute. None of the study authors or Dr. Byers, the editorialist, reported a financial conflict of interest.

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Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Published: February 29, 2008


Primary source:

American Journal of Respiratory and Critical Care Medicine

Source reference:

Slatore CG, et al “Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer” Am J Respir Crit Care Med 2008; 177: 524-530.