Men who took high doses of vitamin B6 and B12 supplements had a higher risk of lung cancer, and the association was highest among current smokers, according to a study published Tuesday.
The study found a 30% to 40% increased risk of lung cancer among men taking these vitamins from individual supplements -- not from multivitamins or diet alone. But the effect seemed to be driven by current smokers who far exceeded the recommended daily amounts of the vitamins, according to study author Theodore Brasky, an epidemiologist in the division of cancer prevention and control at the Ohio State University College of Medicine.
"I think these results point to a synergism" between high-dose B vitamins, smoking and lung cancer risk among men, Brasky said.
Current male smokers taking the highest levels of vitamin B6 had triple the risk of lung cancer over six years, compared with those who didn't take supplements. For vitamin B12, that risk nearly quadrupled. These levels were more than 11 times the recommended daily amount of B6 and 23 times that of B12.
"If you look at B-vitamin supplement bottles ... they are anywhere between 50-fold the US recommended dietary allowance (to) upward of 2,100-fold," Brasky said. B12 injections have also become "in vogue" in recent years, he said.
In smaller quantities, these vitamins are involved in several vital processes in the body, including DNA replication. But many high-dose supplements, he said, claim to boost energy and provide other unproven benefits.
"That's marketing. That's not science," he said.
The study was limited to roughly 77,000 Washington state adults, ages 50 to 76. This included 139 cases of lung cancer among more than 3,200 current male smokers. Over 93% of participants were white.
There were too few cases of lung cancer among nonsmokers to include them in the full analysis. An increased risk of lung cancer was not seen among women or with the vitamin B9, also known as folate.
Other researchers have found different results. Some studies linked vitamin B6 with lower lung cancer risk, and another found that B12 had no impact on risk. The authors of the new study said that the discrepancy could be because some of these studies measure B vitamins in the blood and not through dietary surveys, like they did. Or it may be that lung cancer itself raises levels of these vitamins in the body.
"I think it's hard to say" why these studies contradict each other, said Elizabeth Kantor, an epidemiologist at Memorial Sloan Kettering Cancer Center who has studied dietary supplements and cancer risk. She was not involved in the latest research. "Is it the disease process that affects the blood levels? I think that the door remains open on that."
A focus on B vitamins may not be the most effective way to protect against lung cancer, experts warn.
"Combustible tobacco smoke is the No. 1 most important factor, not just only in lung cancer but in many cancers," Brasky said.
Cigarette smoking is a factor in 80% to 90% of lung cancers in the United States, according to the US Centers for Disease Control and Prevention. Smokers are 15 to 30 times more likely to get lung cancer or die from it than nonsmokers. Lung cancer kills more Americans than any other kind of cancer.
"When we're talking about what to be concerned about most: If you're a male smoker and you want to take B vitamins, you can stop smoking," Brasky said.
"Smoking is the most important thing here, and that's preventable."
To B or not to B?
"In the average person in this country, it's tough to be deficient" in B vitamins, Brasky said.
Those who are -- those with anemia or celiac disease, for example -- will feel tired and run down. For them, supplements might help.
But taking "megadoses" of these supplements doesn't do much for the average healthy person, Brasky said, nor does it cause immediate harm. The body tends to get rid of excess vitamin, he said.
"There's always this black box between what people say they eat or take and what is actually absorbed," said Regan Bailey, an associate professor of nutrition science at Purdue University and a former nutritional epidemiologist with the National Institute of Health's Office of Dietary Supplements. She also was not involved in the new study.
Stomach acid and digestion, Bailey said, are able to "rip out" B12 from food so that the body can absorb it. Some synthetic supplements, however, may be more easily absorbed.
Vitamin B12 is found in animal products like meat, eggs and milk. Americans get most of their B6 from fortified cereals, beef, chicken, fruits and starchy vegetables.
Too little of these vitamins is thought to carry cancer risk, too. Errors can happen when building new strands of DNA, causing them to break. And genes responsible for cell division may be thrown off by these changes, the study authors said.
In high concentrations, however, the exact relationship between the vitamins and lung cancer is unclear. If the vitamins are indeed responsible for increasing the lung cancer risk, Brasky said, another question would be whether B vitamins are hastening the development of a lung cancer that's already there or leading to new cancers.
Bailey warned that we are nowhere close to claiming that these high-dose supplements cause cancer. She added that the dietary survey the researchers used -- which calculated the average daily intake over the prior 10 years -- can be imprecise. But Brasky said that adults generally recall which supplements they've taken, allowing researchers to get a good idea of their average doses.
People mostly take dietary supplements because they think they will make them healthier, not because they are trying to add nutrients to their diet, Bailey showed in a 2013 study. And those who take vitamins may be hard to study, she said, because they fall into two very different categories.
"In my mind, people take supplements because they're sick and trying to get better or because they're healthy and want to stay that way," she said.
In a study in October, Kantor showed that about half of American adults have consistently taken dietary supplements over the years. The use of B12 grew 40% from 1999 to 2012, while the use of B6 dropped by a smaller amount.
"There might be one reason why somebody takes something, but it can have other effects on our bodies," Kantor said. "We don't know the whole host of effects."
The good news, Bailey said, is that most people aren't taking the single-vitamin, high-dose supplements that go far beyond recommended levels.
"Most people are taking multivitamins," she said, "and for that, there's really been no (cancer) association, which I think is a success story."
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