Comments by carlsonbjj
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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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      I wonder if this applies to nasal spray as well, as I know there is less systemic absorption.

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        super male vitality

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            Great article. Thanks for sharing, @carlsonbjj! I added a few more relevant tags.

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              Feel free to encourage Rhonda to tweet it! :)

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                tag your article next time! good read

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                  You might want to include tags so that people can search your links more easily.

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                    can anyone give me an ELI5 on this and its implications? neuroscience is greek to me.

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                      Lots of interesting goodies in this one, @carlsonbjj!

                      A synopsis of some of the more salient points for you, @rhonda

                      The microbiome affecting the blood-brain barrier:

                      Exposure of GF adult mice to the fecal microbiota from pathogen-free donors decreased BBB permeability and increased the expression of tight junction proteins (Braniste et al., 2014). Moreover, monocolonization of the intestine of GF adult mice with short chain fatty acid (SCFA)-producing bacterial strains normalized BBB permeability whilst sodium butyrate was associated with increased expression of occludin in the frontal cortex and hippocampus (Braniste et al., 2014). This study strengthens the hypothesis that the BBB may also be vulnerable to changes in the gut microbiota. […]

                      Disrupted microbiome affecting susceptibility to stress in adulthood and altering the development of the HPA axis:

                      It is plausible that subtle alterations in microbiota acquisition or maintenance in early life may act as a vulnerability factor, impacting on (neuro)endocrine and (neuro)immune signaling pathways of the brain-gut-microbiota axis, disruption of which may subsequently predispose to stress-related disorders in adulthood (Borre et al., 2014). Notably, animals devoid of a microbiota exhibit reduced levels of anxiety but an exaggerated neuroendocrine response to stress (Sudo et al., 2004). The most pronounced impacts of the microbiota may occur early in life during critical neurodevelopmental phases (Borre et al., 2014). It is evident that the gut microbiota is required for the normal development of the hypothalamic pituitary adrenal (HPA) axis and that there is a certain period in early life when colonization must occur to ensure normal development of this critical stress signaling pathway (Sudo et al., 2004; Moloney et al., 2014).

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                        Although GF mouse model isn’t a great correlate for real life.

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                        @carlsonbjj I have been gathering some trending data via ubiome. Going to order a few more of these while they are on sale…thanks!

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                          what is your opinion on this company? Are they mostly in it for the profits or will they make a big dent in microbiome research, or both?

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                            @carlsonbjj I think that lithium may affect cell membrane fluidity the same way DHA does. I’m currently researching this.

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                              I drink a fair amount of san pellegrino mineral water. I think 1 liter has 200 mcgs of lithium. Trader Joes has good prices

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                                Interesting had no idea was in san pellegrino.

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                                  Yup, here is the ingredients list on the right of the page: http://en.wikipedia.org/wiki/San_Pellegrino

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                              @carlsonbjj I’m conflicted about this as taking supplemental C and E immediately after workout may negate the ROS that is important to activate PGC1 alpha and mitochondrial biogenesis.

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                                but this doesn’t happen when taken more than 4 or so hours afterwards?

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                                  That’s not clear to me…need to figure out more of the kinetics .

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                                  This is a review of the same studies that I discuss in my rebuttal to multivitamins are bad video. Beta carotene given to smokers and folic acid given to people with polyps on colon. I discuss in my video. @Rachelgrob

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                                    Fantastic, thank you!!

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                                  I have a friend with mild autism. He did a urine test and had high levels of casomorphin and gliadorphin. He has avoided wheat and milk and it has helped him some.

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                                    the video at the end is hilarious, given the article

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                                      Glad they are looking at copper too.

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                                        I subscribed to the headspace app after seeing all of these studies on meditation. Seems like a good habit, cost-effective, etc.

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                                          @carlsonbjj “The issues are rising in importance, since 40% of all adults and 70% of all children take one or more antibiotics every year…” OMG. I had no idea that half the country takes antibiotics once a year. Also, many people can’t afford to eat organic and are eating meat loaded with antibiotics which is, undoubtedly, affecting the ecosystem in the gut. I’ve been doing research on the gut microbiome and will be doing a couple of vids on them very soon.

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                                            I wonder how long-lasting the damage to the intestinal epithelium is.

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                                              Gearing up to do some podcasts on the gut…One prob is after wiping out microbes, it is really hard to get new ones into the mucin…usu they just flow through and is why probiotics have to continually be taken…trying to figure way around this.