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.

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

super male vitality

this is great

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

i really like this guy

tag your article next time! good read

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

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

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).

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

So basically a low calorie keto diet?

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

@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.

(Beta Carotene and Folic acid)

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.

the video at the end is hilarious, given the article

Glad they are looking at copper too.

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

@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.