August 22, 2017
3 min read

High vitamin B intake increases lung cancer risk among men

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Theodore Brasky

Men who reported long-term, high-dose supplementation with vitamins B6 or B12 appeared two to four times more likely than nonusers to develop lung cancer, according to results of a prospective, observational study.

Male smokers demonstrated the greatest risk.

Theodore Brasky, PhD, research assistant professor at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and colleagues adjusted their analysis for several factors, including smoking history, age, race, body size, alcohol consumption, personal history of cancer or chronic lung disease, family history of lung cancer and use of anti-inflammatory drugs.

“This sets all of these other influencing factors as equal, so we are left with a less confounded effect of long-term B6 and B12 super-supplementation,” Brasky said in a press release. “Our data show that taking high doses of B6 and B12 over a very long period of time could contribute to lung cancer incidence in male smokers. This is certainly a concern worthy of further evaluation.”

Vitamins B6 and B12 have been touted for their potential to accelerate metabolism and increase energy. There also has been speculation that these vitamins may reduce cancer risk.

Prior studies designed to assess the association between lung cancer risk and B vitamin intake have yielded inconsistent results. Randomized trials have been limited by short supplementation periods, as well as small numbers of incident lung cancer cases, according to study background.

Brasky and colleagues conducted what they described as the first prospective, observational study to examine the effects of long-term, high-dose vitamin B6 and B12 supplement use on lung cancer risk.

Researchers analyzed data from 77,118 participants in the Vitamins and Lifestyle (VITAL) cohort, a long-term prospective observational study designed to evaluate the potential associations between cancer risk and use of vitamin or other mineral supplements.

The study participants — who ranged in age from 50 to 76 years — were recruited from Washington state between 2000 and 2002. Upon enrollment, they reported their B-vitamin usage from the previous 10 years, as well as dosage information.

Brasky and colleagues linked the study cohort to a population-based SEER cancer registry that documented all incident cancers except nonmelanoma skin cancers diagnosed in a 13-county region of western Washington.

After mean follow-up of 6 years, researchers identified 808 incident invasive lung cancer cases in the cohort.

Analysis revealed no association among women between lung cancer risk and supplementation with vitamin B6 or vitamin B12.


Among men, vitamin B6 and B12 supplementation from individual supplement sources —not multivitamins — appeared associated with a 30% to 40% increase in lung cancer risk.

When researchers evaluated 10-year average supplement doses, results revealed a near-doubling of lung cancer risk among men in the highest categories of vitamin B6 supplementation (> 20 mg per day, HR = 1.82; 95% CI, 1.25-2.65) and vitamin B12 supplementation (> 55 µg per day, HR = 1.98; 95% CI, 1.32-2.97) compared with nonusers.

The increased risk persisted for all histologic subtypes of lung cancer except adenocarcinoma, for which researchers observed no association.

When Brasky and colleagues stratified results by smoking status, they determined the cohort included too few never-smokers to accurately evaluate potential associations in that group.

However, the differences in lung cancer risk between the highest and lowest categories of supplementation use appeared considerably greater among current smokers than recent smokers — defined as those who quit less than 10 years prior — or former smokers, defined as those who quit 10 or more years prior.

Current smokers who reported 10-year use of vitamin B6 at doses greater than 20 mg per day appeared nearly three times as likely to develop lung cancer as nonusers (HR = 2.93; 95% CI, 1.5-5.72).

Current smokers who reported 10-year use of vitamin B12 at doses greater than 55 µg per day appeared nearly four times as likely to develop lung cancer as nonusers (HR = 3.71; 95% CI, 1.77-7.74).

Although the associations weakened among recent and former smokers who reported the highest usage of both vitamins, the HRs for lung cancer risk in both groups remained greater than 1.

The researchers acknowledged limitations to their study, including the lack of information about cohort members’ environmental or lung cancer risk factors, as well as lack of serum B-vitamin measurements to assess prevalence of suboptimal intake or to complement their findings from self-reported intake.

In addition, the highest categories of supplementation reported in this study represent usage levels that can only be obtained from high-dose vitamin B supplements, Brasky said. This intake is many times the U.S. recommended dietary allowance and far exceeds dose levels of daily multivitamins.

“Nonetheless, half of the U.S. adult population uses one or more dietary supplements,” Brasky and colleagues wrote. “Our study found that consuming high-dose individual B6 and B12 vitamin supplements over a 10-year period is associated with increased lung cancer risk, especially in male smokers. ... The associations we observed provide evidence that high-dose B6 and B12 supplements should not be taken for lung cancer prevention and, in fact, may increase risk of this disease in men.” – by Mark Leiser

Disclosures: The NCI, NIH and Office of Dietary Supplements funded this study. The researchers report no relevant financial disclosures.