Multivitamins Do Not Reduce Risk for Lung Cancer, and Vitamin E May Raise It

February 29, 2008 — The long-term use of supplemental multivitamins does not reduce the risk of developing lung cancer, and high doses of vitamin E may even raise the risk, particularly in smokers. These conclusions from a large, prospective study tie in with previous research, say the investigators.

Together, these findings “should prompt clinicians to counsel patients that these supplements are unlikely to reduce the risk of lung cancer and may be detrimental,” say Christopher G. Slatore, MD, from the University of Washington in Seattle, Washington, and colleagues. They report the new findings in the March 1 issue of the American Journal of Respiratory and Critical Care Medicine.

“Vitamin pills are widely used with the idea that supplementing our diet with extra vitamins must be a good thing,” comments Tim Byers, MD, MPH, from the University of Colorado in Aurora, Colorado, in an accompanying editorial. “However, almost every time we take a hard look at objective evidence regarding nutritional supplements, the balance tips away from benefit and toward harm.”

“Over the past two decades, we have been repeatedly disappointed in the ability of vitamin supplements to reduce risk for cancers at several sites, including the stomach, colorectum, breast, and lung. Foods that are rich in vitamins seem to be associated with a reduced risk of cancer, but vitamins packaged as pills clearly do not have the same effect,” Dr. Byers writes.

Vitamin E Increased Risk

Dr. Slatore and colleagues analyzed data from the VITamins And Lifestyle (VITAL) study conducted in Washington State and calculated hazard ratios (HRs) for lung cancer according to self-reported average daily use of multivitamins during a 10-year period. They also examined use of vitamin C, vitamin E, and folate. The team found 521 cases of lung cancer among the 77,721 participants, and after adjusting for smoking, age and sex, they found no inverse association with any supplement.

However, there was a small increase in the risk for lung cancer associated with vitamin E (HR, 1.05 for every 100-mg/day increase in dose; P = .033). This risk was largely confined to current smokers (HR, 1.11; P < .01) and was greatest for non–small-cell lung cancer (HR, 1.07; P = .004). “This risk translates into a 28% increased risk of lung cancer at a dose of 400-mg/day for 10 years,” the researchers write.

“Our results show a possible U-shaped association, with subjects using a medium dose for 10 years having a decreased risk whereas those using a high dose for 10 years showed an increased risk,” they comment. “One possible mechanism is that, although vitamin E is considered an antioxidant, it might act as a prooxidant as well.”

These results with high-dose vitamin E are reminiscent of findings from previous trials of beta-carotene, Dr. Byers comments in the editorial. These were prompted by early observations that fruit and vegetables seemed to lower the risk for lung cancer, but supernutritional levels of beta-carotene (just below the dose at which skin is noticeably orange) were shown to increase the risk for lung cancer, beginning as soon as 2 to 3 years after supplementation.

“How could a beneficial effect of consuming fruits be consistent with an adverse effect of a nutrient that is derived in a large part from that same food group?” Dr. Byers asks. The likely answer is that “processes involved in biologic systems end up being far more complex than we had previously thought. Fruits contain not only vitamins but also many hundreds of other phytochemical compounds whose functions are not well understood.”

However, even advice on eating more fruit is not straightforward, he comments. The World Cancer Research Fund and the American Cancer Society both recommend eating at least 2 servings of fruit each day, and this would likely lead to a reduction in the risk for lung cancer in addition to several other cancers as well as cardiovascular disease. However, among smokers, any benefit from eating more fruit would be more than offset if even a small proportion of smokers decided to continue with smoking instead of changing their diet, Dr. Byers writes. Nevertheless, a doubling or tripling of fruit intake among survivors of lung cancer could offer important extra benefits in maintaining body weight and improving well-being while the effects on prognosis of lung cancer are assessed.

The researchers and Dr. Byers have disclosed no relevant financial relationships.

Am J Respir Crit Care Med. 2008;177:470-471, 524-530.

Clinical Context

Cigarette smoking is thought to be the primary reason for 90% of all lung cancers, so smoking cessation is obviously the best strategy for the prevention of this cancer. However, there is limited evidence that other preventive strategies are significantly effective across large populations. There is no consensus to recommend the routine use of radiographic studies to screen at-risk patients for lung cancer. The use of vitamin supplements has generally not been associated with a decreased risk for lung cancer, despite the fact that consumption of fruits and vegetables seems to be beneficial in reducing this risk. In fact, consumption of beta-carotene supplements has actually been associated with an increased risk for lung cancer.

Many previous studies of supplements in the prevention of lung cancer examined the issue as a dichotomous variable: study subjects had either used or had not used supplements. The current study uses a large patient cohort to examine not only if the use of supplements affects the risk for lung cancer, but also whether there is a dose-response relationship between supplements and lung cancer.


About this entry