Serum B Vitamin Levels and Risk of Lung Cancer

Vitamin B6 and the amino acid methionine appear to be associated with a decreased risk of lung cancer, a large prospective cohort study found.

The cohort study, which included more than 500,000 patients from 10 countries, found those patients with the highest serum levels of vitamin B6 had a 56% reduced risk of lung cancer compared with those with the lowest levels, Paul Brennan, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues reported in the June 16 issue of the Journal of the American Medical Association.

Higher methionine levels were also associated with a reduced relative risk of 48%.

Deficiencies in B vitamins are thought to increase the likelihood of DNA damage and subsequent gene mutations, the researchers said, which means they may have a potentially important role in inhibiting cancer development.

To investigate whether these compounds might be associated with risk of lung cancer, the researchers analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study which included 519,978 patients enrolled between 1992 and 2000.

A total of 385,747 had given blood samples.

By 2006, the IARC researchers identified 899 cases of lung cancer among the study cohort, and these patients were matched with 1815 controls.

After controlling for smoking, the researchers found a lower risk of lung cancer among patients who had the highest serum levels of vitamin B6 compared with those with the lowest levels (OR 0.44, 95% CI 0.33 to 0.60, P<0.000001).

The same pattern was also seen for serum methionine (OR 0.52, 95% CI 0.39 to 0.69, P<0.000001).

There were "similar and consistent" decreases in lung cancer risk for never, former, and current smokers for both serum B6 and methionine levels, the authors reported.

The researchers also saw a moderately lower risk for higher levels of serum folate, although this was apparent only for former and current smokers (OR 0.68, 95% CI 0.51 to 0.90, P=0.001).

There were no trends for serum vitamin B2, vitamin B12, or homocysteine levels.

Finally, having above-median levels of serum methionine and B6 was associated with a lower overall risk of lung cancer (OR 0.41, 95% CI 0.31 to 0.54), and that was also true among individual groups of never, former, and current smokers.

The researchers said their findings are consistent with the results of large cohort trials that found a lower risk of colorectal cancer with higher levels of vitamin B6, although they note that the evidence is limited for other cancer types.

Yet they cautioned that in two large randomized controlled trials, folate did not reduce risk of colorectal cancer. In fact, there was some evidence of an increased risk of adenocarcinomas.

"It is unlikely that further intervention trials of B vitamins would be advisable," they wrote. But these results do indicate that the "timing of folate supplementation may be essential, with folate being beneficial in primary prevention of colorectal neoplasia, but potentially harmful in the presence of established cancer."

They also added that in terms of lung cancer prevention, any additional evidence about causality regarding B vitamins shouldn't take away from public health efforts to reduce the number of smokers.

They concluded that "clarifying the role of B vitamins and related metabolites in lung cancer risk is likely therefore to be particularly relevant for former smokers and never smokers."

Dietary sources of B6 include beans, grains, meats, poultry, fish, and some fruits and vegetables. Sources of methionine include animal proteins, nuts, and vegetable seeds.

Len Horovitz, MD, a pulmonary specialist at Lenox Hill Hospital in the Bronx, N.Y., who was not involved in the study, said that "optimizing B6 levels to reduce lung cancer risk is seemingly straightforward, and probably a good idea if not taken to excess."

But he cautioned that the "precise dose is unclear." High doses, for example, may be damaging, as was seen in previous trials of antioxidants in lung cancer, including beta carotene.

"One message about taking any supplements to reduce risk," he said, "is that the appropriate dose needs to be found, and that more is not necessarily better."

Limitations of the study included its retrospective design, measurement of serum B vitamin levels from a single blood sample taken at study recruitment, which the authors noted, differences in serum levels and vitamin intake as noted in food frequency questionnaires, and differences in serum levels of vitamin B6 between cases and controls for which there may be multiple explanations.