‘Statistical chance’: Academia and industry cast doubt on B vitamin-lung cancer links

By Stephen Daniells

- Last updated on GMT

© iStock/MrKornFlakes
© iStock/MrKornFlakes
An observational study reporting that long-term use of high-dose vitamin B6 and B12 supplements may more than triple the risk of lung cancer in male smokers, but experts are questioning the conclusions.

Analysis of data from the 77,000-participant VITamins And Lifestyle (VITAL) cohort study revealed that male smokers taking B6 at doses over 20 mg per day for 10 years were three times more likely to develop lung cancer. Additionally, male smokers taking B12 at doses over 55 micrograms per day for a decade were approximately four times more likely to develop the disease compared to non-users.

There was no increased risk of lung cancer found in women who took high-dose vitamin B6 and B12 supplements long-term, according to a paper published earlier this week in the Journal of Clinical Oncology.

The results – which show a correlation and not causation – are at odds with other data in the scientific literature, including a randomized clinical trial that found no link, and other observational studies that found a reduction​ in risk associated with vitamin B6.

“Statistical chance”

Experts from both academia and industry have responded negatively to the study’s conclusions and the headlines the study generated. For example, Cambridge University’s Prof Paul Pharoah told The Independent:“The most likely explanation for those findings is statistical chance.

“The authors have investigated many sub-groups … and they have focused on the results that are most significant. Previous randomized controlled trials have found little evidence of association for supplementation of these vitamins on lung cancer risk.

“In summary, this in an intriguing finding, but it cannot be considered definitive.  While it is possible that the findings are real, the most likely explanation is statistical chance.”

Limitations

Duffy MacKay, ND, Sr VP, scientific & regulatory affairs, for the industry’s Council for Responsible Nutrition, said consumers should resist the temptation to allow sensational headlines from this new study to alter their use of B vitamins, especially without further understanding of the nature of this study and a conversation with their healthcare practitioners.

Quit smoking

According to the CDC: 
“Cigarette smoking is the number one risk factor for lung cancer. In the US, cigarette smoking is linked to about 80% to 90% of lung cancers."

Dan Fabricant, PhD, president & CEO of the Natural Products Association & a former head of the FDA's Dietary Supplement Division, said: “People who want to avoid cancer should avoid using tobacco, because smoking causes lung cancer, not vitamin B.

"This study is flawed and ignores the potential for a host of other environmental factors and causes.  Millions of healthy individuals use vitamins and supplements, including vitamin B to support their lifestyles.”

“The numerous benefits of B vitamins from food and dietary supplements, including supporting cognition, heart health, and energy levels, are well-established, and this study in the ​Journal of Clinical Oncology doesn’t change those facts,” ​said Dr MacKay. “Additionally, this observational study doesn’t prove causality between B vitamins and lung cancer risk, and in actuality, has some significant limitations to consider.

“Those limitations include the dependence on the ability of the study population, ages 50–76 years old, to remember and accurately report what they consumed over a ten-year period prior to the start of the study. Further, the results of this study conflict with the results of previous studies, including a randomized control trial as well as two studies that measured vitamin B6 serum levels and demonstrated reduction in lung cancer risk. Due to the limitations and its misalignment with the greater body of scientific evidence, the study should be interpreted with caution.

“For consumers, the key takeaway from this study is that smokers have a higher risk of lung cancer than non-smokers. If you have concerns about lung cancer or B vitamins, we recommend talking with your doctor or other healthcare practitioner. We remind consumers that dietary supplements are intended to supplement, not replace, a healthy diet. They cannot—and will not—reverse the potential harm from unhealthy behavior, such as smoking.”

Study details

Vitamin B6 © iStock PhotographyFirm
A study published in JAMA in 2010 found that, based on data from almost 400,000 people (including current and former smokers), higher blood levels of vitamin B6 may reduce the risk of lung cancer by about 50%.Image © iStock/PhotographyFirm

Epidemiologists from The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), Fred Hutchinson Cancer Research Center and National Taiwan University are reported to be the first to use a prospective, observational study to assess at the effects of long-term high-dose B6/B12 supplement use and lung cancer risk. 

Participants in the VITamins And Lifestyle (VITAL) cohort study were aged between 50 and 76, and upon enrolling, they reported their B-vitamin usage over the past 10 years, including dosage information.

After crunching the numbers to adjust for different factors, the researchers found that taking high doses of B6 and B12 over a many years could contribute to lung cancer incidence rates in male smokers, said Theodore Brasky, PhD, who led the study at OSUCCC - James.

Brasky noted these findings related to doses that are well above those from taking a multivitamin every day for 10 years. The recommended daily allowance (RDA) for vitamin B6 for men is 1.3 mg per day for men aged 19-50, and 1.7 mg per day for older men. For B12, it is 2.4 micrograms per day.

“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. “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.”

Media coverage

Pyramid of evidence based medicine
Systematic reviews and meta-analyses sit at the very top of the pyramid of scientific evidence, making them the strongest forms of evidence.

The observational study has received widespread coverage in the mainstream media, with the results poorly represented in headlines, often with no mention whatsoever of the correlation being limited to male smokers​, such as:  Could high doses of vitamin B supplements raise lung cancer risk? (CBS News​)​; High doses of vitamin B tied to lung cancer risk, study says (CNN​)​; Clear link between heavy vitamin B intake and lung cancer (Science Daily​)​; Too much vitamin B could increase lung cancer risk in men, study says (USA TODAY​)​.

This is in stark contrast to the very limited media coverage of a meta-analysis of omega-3 and cardiac death risk published this week, which pooled data from 14 randomized, controlled trials (RCTs) totaling 71,899 people. Omega-3 supplements were found to reduce the risk of cardiac death by an average of 8%, while the risk reduction in people who had elevated triglycerides or LDL cholesterol was even higher at 17% (Journal of Clinical Lipidology).​ To read NutraIngredients-USA’s coverage of that meta-analysis, please click HERE​.

Source: Journal of Clinical Oncology
Published online ahead of print, doi: 10.1200/JCO.2017.72.7735
“Long-Term, Supplemental, One-Carbon Metabolism–Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort”
Authors: T.M. Brasky, et al. 

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