Vitamin B6 and B12 Supplements Appear to Cause Cancer in Men

Energy. If you’re not taking vitamin B12, forget about having energy. As The Dr. Oz Show has recommended, “End your energy crisis with Vitamin B12.” The nice thing about sublingual pills is “you don’t need a doctor, you don’t need a prescription.”

And don’t get me started on metabolism. If you want to “supercharge your metabolism and energy levels,” Amazon can deliver you a tall bottle of B12 supplements by the end of the day. Your metabolic processes will be the envy of the neighborhood. (“Is Janice ... on something?” “Yes—B12!”)

These are the sort of vague marketing claims that have propelled the cobalt-based compounds sold as B12 into American hearts and minds and blood in ever-growing quantities. They are extrapolations from the fact that B12 deficiency causes anemia, and correcting that deficiency will alleviate symptoms of fatigue and weakness. But as the National Institutes of Health notes, “Vitamin B12 supplementation appears to have no beneficial effect on performance in the absence of a nutritional deficit.”

Nonetheless around 50 percent of people in the United States take some form of “dietary supplement” product, and among the most common are B vitamins. Worse than just a harmless waste of money, this usage could be actively dangerous. In an issue of the Journal of Clinical Oncology, published this week, researchers reported that taking vitamin B6 and B12 supplements in high doses (like those sold in many stores) appears to triple or almost quadruple some people’s risk of lung cancer.

This is a heavy claim about a very common substance, so it’s worth spending a minute on the methodology. Concerns about B-vitamin supplements and cancer have been percolating for years. They came up quietly in a large trial in Norway that concluded ten years ago. Starting in 1998, researchers assigned 6,837 people with heart disease to take either B vitamins or a placebo.

The researchers then watched as people died and contracted diseases in ensuing years—and the vitamin group raised concerns. In 2009, the researchers reported in the Journal of the American Medical Association that taking high doses of vitamin B12 along with folic acid (technically vitamin B9) was associated with greater risk of cancer and all-cause mortality.

The largest increase in cancer risk was in the lung. Still, the number of cases of lung cancer among these 6,837 Norwegians was relatively small—so the actual risk was difficult to quantify. But it was big enough to catch the attention of Theodore Brasky and Emily White, two researchers at the Fred Hutchinson Cancer Research Center in Seattle. White had been overseeing a cohort study that involved more than ten times as many people as the Norwegian trial, some 77,000 people across the state of Washington. The cohort is tracking their supplement intake as we speak, and it is also being followed for cancers by the National Cancer Registry.

The Washington study was specifically designed to examine the roles of “dietary supplements”—compounds known as vitamins, minerals, and non-vitamin non-mineral compounds like ginseng—in cancer risk. This was an ideal setup to look at the relationship between B vitamins and cancer, and see if it was indeed worthy of concern. So Brasky and White, along with Chi-Ling Chen at National Taiwan University, broke down this population by B-vitamin use and looked at cancers. Unfortunately their findings were even more significant than the Norwegian trial.

Lung-cancer risk among men who took 20 milligrams of B6 daily for years was twice that of men who didn’t. Among people who smoke, the effect appeared to be synergistic, with B6 usage increasing risk threefold. The risk was even worse among smokers taking B12. Using more than 55 micrograms daily appeared to almost quadruple lung-cancer risk.

There was no apparent risk among women—which is not to say it doesn’t exist, only that it wasn’t apparent.

Why or how would B vitamins increase a person’s risk of cancer?

I asked Brasky what he thought was going on. It’s all hypothetical, and he has no clear idea bout the sex discrepancy. What he does know is that  B vitamins all contribute enzymes and coenzymes to a metabolic pathway that breaks down folate in order to make the bases that comprise DNA. The pathway also regulates the expression of genes (by creating methyl groups that can essentially turn genes on and off). When we have too little of these B vitamins, this pathway can go wrong, leading to problems like incorporation of the wrong types of bases into DNA, which can cause breaks in the strands, and, in theory, lead to cancer.

Deficiency can also mean genes that should be inhibited are no longer inhibited, also potentially meaning cancer. Sufficiency of certain vitamins is important in cancer prevention, but avoiding excess appears to be similarly important.

Among smokers, who are already exposed to carcinogens, the effect of taking anything that impairs these cellular processes could be even more likely to lead to cancer.

The research team is quick to note that the doses of B vitamins in question are enormous. The U.S. Recommended Dietary Allowance for B6 is 1.7 milligrams per day, and for B12 it’s 2.4 micrograms. The high-risk group in the study was taking around 20 times these amounts.

That could seem nonsensical, except that these are the doses for sale at healthy-seeming places like Whole Foods and GNC. Many sellers offer daily 100-milligram B6 pills. B12 is available in doses of 5,000 micrograms.

I asked Brasky if his finding means that products like these should be more closely regulated—at least to require selling more reasonable doses, or to disclose risks, as is required for pharmaceuticals. Currently, supplements are absolved from this sort of requirement, or even to prove safety or efficacy before going to market. This is dictated by a 1994 law called the Dietary Supplement Health and Education Act (DSHEA).

“The law was created by industry lobbying to keep the FDA away from regulation, so the industry self-regulates,” said Brasky. But he deferred and said he hoped this article wouldn’t be about regulation. “I don’t want to pick a fight with the vitamin industry for any reason.”

So that falls to me. There are legitimate and important uses for B-vitamin supplements, but the emerging evidence suggests we’re best to treat them more like pharmaceuticals than like panaceas to be shoveled into us in pursuit of energy, metabolic fortitude, “cardioprotection,” “bone wellness,” or whatever way in which we’d like to be better.

The enduring theme in health is that more doesn’t mean better. What’s healthy for one person may be unhealthy for another. The fact of a product being sold without a prescription does not mean it is exempt, or that it’s good or even harmless. Any ingested bioactive substance will come with risks and benefits.

The current law gives consumers no reason to expect that risks will be listed on the labels of these products, or that health claims are accurate. A product like a high-dose B6 and B12 supplement hits shelves, and only decades later do researchers begin to understand the long-term health effects, who might benefit from taking it, and who might be harmed.