In double-blind trials, synthetic beta-carotene supplementation has led to an increased risk of lung cancer in smokers,^1,2 though not in groups consisting primarily of nonsmokers.³ Smokers should avoid synthetic beta-carotene supplements, including the relatively small amounts found in many multivitamins.

The researchers who conducted the lung cancer trials have been criticized for not having used the natural form of beta-carotene.⁴ Preliminary evidence suggests that natural beta-carotene supplementation results in better antioxidant activity⁵ and anticancer activity in humans⁶ than does supplementation with synthetic beta-carotene. Nonetheless, much less is known about natural beta-carotene and questions remain about its potential efficacy.⁷ The effect of natural beta-carotene supplementation on lung cancer risk has yet to be studied.

The strong association between increased intake of beta-carotene from food and a reduced risk of lung cancer⁸ does not necessarily mean that supplementation with natural beta-carotene supplements would reduce the risk of lung cancer. Dietary beta-carotene may be a marker for diets high in certain fruits and vegetables that contain other anticancer substances that may be responsible for the protective effects. Until more is known, some doctors advise smokers to avoid all forms of beta-carotene supplementation—even natural beta-carotene.

Selenium has been reported to have diverse anticancer actions.^9,10 Selenium inhibits cancer growth in animals.¹¹ Low soil levels of selenium (probably associated with low dietary intake), have been associated with increased cancer incidence in humans.¹² Blood levels of selenium have been reported to be low in patients with many cancers,^{13,14,15,16,17,18,19,20} including lung cancer.²¹ In preliminary reports, people with the lowest blood levels of selenium had between 3.8 and 5.8 times the risk of dying from cancer compared with those who had the highest selenium levels.^22,23

The strongest evidence supporting the anticancer effects of selenium supplementation comes from a double-blind trial of 1,312 Americans with a history of skin cancer who were treated with 200 mcg of yeast-based selenium per day or a placebo for 4.5 years and then followed for an additional two years.²⁴ Although no decrease in skin cancers occurred, a 50% reduction in overall cancer deaths and a 37% reduction in total cancer incidence was observed. A 46% decrease in lung cancer incidence and a 53% drop in deaths from lung cancer also occurred. These findings were all statistically significant.

Relatively high blood levels^25,26 and dietary levels²⁷ of vitamin E have been associated with a reduced risk of lung cancer. In a preliminary trial, nonsmokers who took vitamin E supplements had a 45% lower risk of lung cancer compared with nonsmokers who did not supplement with vitamin E.²⁸ While a double-blind trial reported that vitamin E supplementation had no effect on lung cancer risk,²⁹ the amount used—approximately 50 IU per day—may have been too low to have a significant effect.

Preliminary animal and test tube research suggests that conjugated linoleic acid might reduce the risk of cancers at several sites, including breast, prostate, colorectal, lung, skin, and stomach.^30,31,32,33

Folic acid and vitamin B12 work together in the body to help cells replicate normally. In a double-blind trial, smokers with precancerous changes in the lungs were given a placebo or the combination of 10,000 mcg of folic acid and 500 mcg of vitamin B12 per day for four months.³⁴ A significant reversal of precancerous changes occurred in those given vitamin supplements compared with those given the placebo.³⁴ No trials have investigated whether either vitamin given alone or the combination of both vitamins would help to treat people who already have lung cancer.

Numerous preliminary studies have shown an association between drinking green tea and a reduced risk of several types of cancer^35,36,37,38 including lung cancer.³⁹ In contrast, preliminary studies of black tea consumption have not found that it protected against any type of cancer.^40,41,42