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    While I always appreciate a critical view on supplements, I have to say that this is a really crappy paper that shouldn’t give you a bad feeling about or even keep you from taking B vitamin supplements - at least unless you are a smoker.

    1. It has severe methodological issues. Post-hoc analysis are problematic as they open the data to interpretation bias. The more subgroubs and end points you look at, the more likely some significant association will pop up purely due to chance. In this case, Brasky looked at such a variety of both subgroups and endpoints, that this is very likely indeed. What most mainstream media reports on his paper conveniently ignore is that he only found a positive association between B6 and B12 intake and certain types of lung cancers in male smokers - none in woman, none in non-smokers.
    2. The associations he found are not only inconsistent with the existing literature on B vitamins and cancer risk, but also, to some degree, self-contradictory. If vitamins B6 and B12 would fuel lung-cancer growth in smokers, there would be no plausible biochemical reason for this effect to be gender-specific (after all, lung cancer is not a hormone-related cancer), yet Brasky found no association in women (see point 1). Moreover, a RCT arm of the data he analyzed, the Physician’s Health Study II, found a significantly reduced risk of cancer in men taking a multivitamin that contained a rather high dose of vitamin B12 (Centrum Silver, 25 mcg B12).
    3. In contrast to the RCT arm, he entirely relies on self-reported, observational data about supplement intake. Apart from reliability issues with such data, there is the possibility of an ill-user effect, e.g. heavy smokers who already felt their lung-health deteriorating because of their habit may have been inclined to take high-dose supplement in a futile effort to counter the harm of smoking.
    4. Brasky, the lead author, is a known troll with an anti-supplement bias, who is seeking media attention by publishing this kind of “studies”. In 2013 he published a paper, showing a similarly spurious, biochemically implausible positive association between fish oil intake and prostatate cancer risk. Although this paper was harshly criticized by accomplished researchers in the field (see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828934/), it generated worldwide media attention and many wildly generalizing, sensationalist headlines - precisely because of the fact that it went against all previous knowledge on the subject, as if by intention. Seems he can’t stop doing it…

    My take? Although the results are likely due to chance, and the way papers like this are promoted in the media really drives me mad, the associations, which are far from evidence, at least warrant some further investigations allowing for more definite conclusions. Until then, smokers (and only smokers!) may be well-advised not to take high dose B-vitamins, just in case. They are much better adviced, however, to quit smoking.

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      Your first point is incorrect. There was a link between b6 and b12 intake and lung cancer in male non-smokers

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        IRRC that link was not statistically significant - only when he looked and smokers and non-smokers together, it became significant.

        Anyway, I have done some digging into the literature and finally found a study that clearly falsifies Brasky’s hypothesis:

        https://jamanetwork.com/journals/jama/fullarticle/186130

        A RCT in 12,064 mycordial infartion survivors, half of them taking 1 mg(!) of B12 daily (plus 2 mg of folic acid) for a mean follow-up of 6.7 years. No benefits for any of the primary endpoinds. BUT:

        “By contrast, with more than 1300 incident cancers during up to 7 years of treatment with 2 mg folic acid and 1 mg vitamin B12 daily, SEARCH provides no evidence of adverse effects on cancer at any particular site including […] lung cancer in 116 (1.9%) vs 122 (2.0%) (RR, 0.95; 95% CI, 0.74-1.23)”.

        Mind you, this is a RCT, the only kind of study that can actually establish a cause-effect relationship in humans. It was large and long-term. With a B12 dose 20 times as high as the dose range where Brasky’s data massage of an observatory study relying on self-reported(!) supplement intake found a sharply increased risk of lung cancer.

        This is what bothers me about Brasky. Had he done his homework and was he an intellectual honest researcher, he would simply have published his results without fuss, cautiosly mentioning the conflicting and unconclusive evidence and encourging further research into a possible mechanistical between supplemental B12 and lung cancer to either validate or falsify his hypothesis - instead of going full-blown PR, passing correlation off as causation (to generate sensationalist media headlines) and - probably needlessly - scaring thousands people about the supplements they are taking.

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      Dr Brasky has a history of reporting negatively on supplement issues and can manipulate the media with his press releases. He does infer an increased risk on non smoking men but it is vaguely implied in the release. Furthermore, relied on “patient reports” (for ten years) and “statistical methods”…which allowed these conclusions, although many confounders. Later in the release it changes language in quotes from unqualified link to “may cause an increased risk…….” and also states that “doses are much higher than anyone would really take in ten years….” or something to that effect. This is crap. Furthermore, we don’t know of actual serum B12 in these individuals……does it matter ?…..I would think so. What about the relative risk of a lung cancer versus the known downstream problems with chronic B12 deficiency, such as in PA?