High dose vitamin B supplements linked to lung cancer in smokers

A report published in the Journal of Clinical Oncology shows that male smokers who took high dose vitamin B6 and B12 supplements – often marketed as energy boosters and present in energy drinks – had three to four times the risk of developing lung cancer, compared to men who did not take the vitamin B supplements. The same effect was not seen in women.

“High dose supplements should not be taken for lung cancer prevention and in fact may increase risk of the disease in men,” the authors conclude.

But while the study shows a worrisome link, it also has weaknesses. “It could be an association by chance,” says Adrian Esterman, a biostatistician at the Sansom Institute of the University of South Australia.

Even the primary author does not believe the data should be interpreted to mean there is a causal link. “I can’t tell you that the link is causal; it’s important to me that the study is replicated,” says Theodore Brasky, now at Ohio State University.

Vitamin B supplements are marketed as boosting energy. Often they come at extraordinarily high doses. The recommended daily allowance for vitamin B6 for men is only about one and a half milligrams, and for vitamin B12, it’s less than two and a half micrograms per day. “But if you look at these supplement bottles, they’re being sold in pill form at up to 5,000 micrograms per dose, which is much, much higher than the daily recommended amount,” said Brasky. “Energy drinks like Monster can carry up to 80 times the RDA of B vitamins.”

When it comes to the science, the reports on taking supplements of B vitamins are mixed. For instance, in 2010 a large European study called EPIC found that higher blood levels of B6 were associated with a lower risk of lung cancer. On the other hand, a 2009 Norwegian study that gave high doses of vitamin B supplements to patients with pre-existing heart disease for up to 39 months found that it raised the risk of lung cancer. In this case, the vitamins used were folate (B9) and Vitamin B12.

The study on which this report is based specifically set out to explore the links between various types of supplements – vitamins, minerals and herbal extracts – and cancer.

Known by its acronym VITAL (vitamins and lifestyle), it involved sending questionnaires to people across 13 counties in Washington State during the period 2000–2002. Some 77,118 participants aged between 50 and 76 were asked to detail their diets and use of supplements over the previous ten years. Their personal data was also recorded including age, education, gender, ethnicity, height and weight, medical history and history of smoking.

The researchers also had access to a cancer registry that serviced the same area. They followed the group for six years.

The main findings were that men who had taken a high dose of vitamin B6 greater than 20 mg per day for ten years (the recommended daily allowance is 1.7mg/day) were at an 80% higher risk of lung cancer.

When it came to Vitamin B12, those who had taken greater than 55 micrograms per day (RDA is 2.5 micrograms per day) were at a 98% greater risk of lung cancer.

Women did not show an increased risk.

Most of the risk was linked to men who were active smokers throughout the period. Their risk was three to four times higher if they were taking high-dose supplements.

So does this mean the vitamin supplements caused these cancers? Not necessarily.

Studies of this kind can easily create spurious associations. For instance, it could be that those people who took supplements had good reason to worry about lung cancer. Perhaps they were smokers or had a family history or perhaps their workplaces or residences put them at risk. These people would also be more motivated to volunteer for a study on supplements and cancer. 

Though the VITAL questionnaire attempted to dissect out possible confounding factors, it did not specifically ask about peoples’ workplace or domestic exposures to pollutants.

“The thing that worries me most is that the VITAL study was looking for an association between 13 types of vitamins and over 120 different types of cancer. This means that many associations found could be completely by chance,” says Esterman. “ And they did not collect data on passive smoking, or occupational exposure, so they could not adjust for two major potential confounding factors for lung cancer.”

Besides the limitations of the study, is there a plausible biological mechanism that would explain why excess use of B vitamins is linked to cancer?

The authors point to the fact that vitamin B6 and B12 are involved in the so-called “one carbon pathway” that is crucial for synthesizing and regulating DNA. Exposure to such high levels could disrupt the regulation of cell growth and lead to cancer. But if the effect is real, why was it not seen with women?

The authors suggest that male hormones might affect the way the B vitamins interact with the one carbon pathway.

So what’s to be drawn from this study?

“If I was a male smoker in this age range, I’d probably cut back – just in case,” says Esterman.

In any event, says Brasky, “It’s very easy to get all the vitamin B you need in this country, from eating meats, chickpeas and foods like cereal that are fortified with them, so there really is no reason to supplement your vitamin B intake at these levels, and certainly not for years on end.”