B vitamins - B-6, B-9 (folate), and B-12 - are commonly thought to reduce cancer risk, among other benefits. Worryingly, the exact opposite may be true if they are taken at high levels over long periods of time.
Over recent years, a number of studies have looked for links between lung cancer and B vitamins. To date, results have been inconclusive - this is partly because the trials were rarely randomized, they investigated only short periods of supplementation, and only small numbers of lung cancer cases were involved in the analysis.
However, one of the latest investigations found a 21 percent increase in overall cancer risk with supplementation of B-12 and B-9. This increase in risk was predominantly due to a rise in lung cancer risk.
Lung cancer and vitamin B revisited
Recently, a group of researchers from multiple institutions set out to probe this association in the most detailed study of its kind to date.
Scientists from the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at the University Comprehensive Cancer Center (OSUCCC) in Columbus, OH, joined forces with the Fred Hutchinson Cancer Research Center in Seattle, WA, and National Taiwan University in Taipei.
Their combined work is the first prospective, observational study to examine links between long-term high doses of B-6 and B-12 supplements and lung cancer risk. The study was headed up by Theodore Brasky, Ph.D. - from the OSUCCC - and their results are published this week in the Journal of Clinical Oncology.
In all, data from 77,118 people were reviewed. The participants were from the Vitamins And Lifestyle cohort, which was set up to evaluate vitamin and mineral supplements and their relationship with cancer over the longer-term.
All participants enrolled in the state of Washington between 2000 and 2002, when they were aged 50 to 76. Each individual gave information regarding their use of vitamin B supplements over the previous 10 years.
When Medical News Today spoke with Dr. Brasky, he said, "Unlike most other studies (particularly at the time), we obtained information on supplement frequency of use, duration of use, and dose commonly used in the 10 years prior to the beginning of the study."
Before analysis, the data were controlled for several factors, including smoking, race, age, education, body size, personal history of cancer or chronic lung disease, alcohol consumption, family history of lung cancer, and use of anti-inflammatory drugs, which may have anti-cancer effects.
Heavy vitamin B use raises lung cancer risk
The results showed that high doses of vitamins B-6 and B-12 (well above standard supplement dosage) over a 10-year period increase the risk of lung cancer in male smokers. No relationship was found with vitamin B-9 (folate) or in women.
Male smokers taking 20 milligrams of vitamin B-6 per day for 10 years were three times more likely to go on to develop lung cancer, while male smokers taking 55 micrograms of vitamin B-12 per day for 10 years were around four times more likely to develop the disease.
Although the conclusions are concerning, Dr. Brasky is quick to explain, "These are doses that can only be obtained from taking high-dose B vitamin supplements, and these supplements are many times the U.S. Recommended Dietary Allowance."
MNT asked Dr. Brasky whether he was surprised by the findings. He responded, "I don't think we were surprised by the direction of the association both because of the context of prior literature as well as the general idea that there are often U-shaped associations between nutrition and disease." He also explained his thoughts on the size of effect.
"As far as the magnitude of the association, I think you could characterize our reaction as concerned; especially if you consider how common these supplements are. That said, our findings were specific to men who smoked."
Theodore Brasky, Ph.D.
He went on to explain that the "use of combustible tobacco is a far more important factor in lung cancer development in both men and women." Vitamins B-6 and B-12 may just "hasten or increase the likelihood of lung carcinogenesis among male smokers."
Why B vitamins influence cancer risk is not known for sure, but some believe that it is related to how B vitamins interact with the so-called one-carbon-metabolism pathway. This pathway is important for maintaining DNA integrity and regulating gene expression.
B vitamins are involved in this pathway, but, at higher doses, the pathway may be compromised, promoting carcinogenesis.
The results are likely to spark further studies looking at similar interactions. In fact, Dr. Brasky is already working on other analyses to confirm these findings. Although they picked out an effect in a subset of the population - older adult males that smoke - because B vitamin supplements are so widely available and minimally regulated, the subject warrants further scrutiny.