B12 and Lung Cancer

A recently-released study from the University of Washington found an increase in lung cancer among male smokers with a vitamin B12 intake of 55 µg per day or more (3). There was no increase in lung cancer among women, women smokers, or non-smoking men.

Because this study raises concern about vitamin B12 supplements for smokers, I’ve updated the VeganHealth.org article, Smokers and Cyanocobalamin. The article is short, so I’ve reproduced it here:

Because smokers receive cyanide from smoking, and vitamin B12 can actually be used to detoxify cyanide due to its strong affinity for the cyanide molecule, there’s a concern that perhaps cyanocobalamin will not be effective for smokers.

For example, hydroxocobalamin injections decreased blood cyanide levels by 59% in smokers (1.5-3 packs/day) and cyanide was eliminated in the urine as cyanocobalamin (1). In another study, smokers were found to excrete 35% more B12 than nonsmokers (2). But in another, serum B12 of smokers didn’t differ from nonsmokers, and the Institute of Medicine concluded that “The effect of smoking on the B12 requirement thus appears to be negligible (2).”

But most smokers have an intake of hydroxocobalamin, and other non-cyanocobalamin forms of B12, through animal foods, while vegan smokers do not have a non-cyanocobalamin source of B12 unless they seek out a supplement. There’s no research on B12 and vegan smokers, but I’m not aware of any who have had trouble warding off B12 deficiency.

Additionally, one prospective study found an increase in lung cancer with B12 supplements among male smokers for the highest intake group of 55–275 µg/day (3). Other research has not found an association with vitamin B12 in cancer, but it hasn’t been studied thoroughly among male smokers. However, an arguably better piece of evidence comes from a randomized, clinical trial that did not find an increase in cancer with increasing serum B12 levels (from 400 µg/day) in a population with a high rate of smoking (4).

At this time, there doesn’t seem to be enough evidence to warrant separate vitamin B12 recommendations for smokers.

References

1. Forsyth JC, Mueller PD, Becker CE, Osterloh J, Benowitz NL, Rumack BH, Hall AH. Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol. 1993;31(2):277-94.

2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.

3. Brasky TM, White E, Chen CL. Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. J Clin Oncol. 2017 Aug 22:JCO2017727735.

4. Ebbing M, Bønaa KH, Nygård O, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njølstad I, Refsum H, Nilsen DW, Tverdal A, Meyer K, Vollset SE. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18;302(19):2119-26.

8 Responses to “B12 and Lung Cancer”

  1. Daisy Says:

    Jack, I’m appalled at your response. This study finds a solid foundation between high doses of B12 and 6 and lung cancer and not just among smokers. Almost all B12 supplements are mega doses.

    From the link: “In contrast, use of vitamin B6 and B12 from individual supplement sources, but not from multivitamins, was associated with a 30% to 40% increase in lung cancer risk among men. When the 10-year average supplement dose was evaluated, there was an almost two-fold increase in lung cancer risk among men in the highest categories of vitamin B6 (> 20 mg/d; hazard ratio, 1.82; 95% CI, 1.25 to 2.65) and B12 (> 55µg/d; hazard ratio, 1.98; 95% CI, 1.32 to 2.97) compared with nonusers.”

    http://ascopubs.org/doi/abs/10.1200/JCO.2017.72.7735

  2. Jack Norris RD Says:

    Daisy,

    I read the article and corresponded with the author who wrote this to me:

    “Please note that the increased risk that we observed was more or less restricted to male current smokers. Thus, there is little cause for concern among men but rather men who smoke and who are taking high doses of B6/B12 (and that this risk is several times that of men who smoke who do not take high doses of B6/B12).”

  3. Ari Says:

    Hi Dr. jack norris

    is it the kind of b12 used in this studies cyanocobalamin? there is less risk for methylcobalamin and other b12 (bacause of cyanide)? i’m currently using 1000mcg of methylcobalamin a day (since i read in veganheatlh.org that 1000mcg is the ideal dose for methylcobalamin, cyanocobalamin just gave a lot of acne).

    Why in the study link they concluded one thing (there is risk for all men), and the author replied you another conclusion (that the risk is only among smoking men)?

    (also, i’m a woman, i’m just curious)

  4. Jack Norris RD Says:

    Ari,

    The article didn’t state, but since almost all B12 supplements are cyanocobalamin, it’s a safe bet that’s what most of them were in this study.

    > Why in the study link they concluded one thing (there is risk for all men), and the author replied you another conclusion (that the risk is only among smoking men)?

    The study says this:

    > There were too few patients among never smokers to evaluate associations. For vitamin B6 and B12, the HRs con- trasting the highest to the lowest categories of 10-year use were considerably stronger among current smokers versus recent or former smokers.

    So it might be safer to say that there’s no reason to assume this finding would be true in never smoking men.

  5. Allen Says:

    Hi Jack Norris,

    Does this finding pertain only to tobacco smokers? Would it have implications for someone taking b-12, who also smokes cannabis for chronic pain?

    Thanks for all your work. Take care.

  6. Jack Norris RD Says:

    Allen,

    I personally don’t think there’s an effect here caused by vitamin B12—I think this study is most likely a statistical anamoly. That said, I don’t feel confident about that and so caution may be warranted. I would have no idea if it translates to cannabis. It might be most prudent to stick with small amounts of B12 in your case.

  7. Greg M Says:

    The confusing part of this for many is the conflating of the various vitamin B12 molecules, most of which are available in supplement form. What is at issue is not B12 (cobalamin) supplementation, but supplementation with cyanocobalamin.

    Cobalamin is naturally in various forms in the body, bound to other different molecules. Without a attached subunit, it is susceptible to degradation and not really usable. Without getting into the big scope of vitamin B12 metabolism, suffice it to say that the two primary forms of B12/cobalamin in the body are: methylcobalamin and 5-deoxyadenosylcobalamin (aka adenosylcobalamin). Methylcobalamin is used in methyl group metabolism, including DNA synthesis, and adenosylcobalamin is used in the mitochondria as a co-factor in helping odd-chain fatty acids, some amino acids and cholesterol get metabolized into energy (into the Krebs cycle).

    There is one other form, hydroxocobalamin that is naturally made by bacteria (although synthesized commercially) , and which the body easily converts into methylcobalamin. So, what’s with the primary supplemented form (in the USA), cyanocobalamin? It is cobalamin, with a cyanide molecule cap on it. Cobalamin has a really strong affinity for hydrogen cyanide, to the point that hydroxocobalamin is a common treatment for cyanide poisoning (cyanide is a mitochondrial poison in high enough quantities).

    Bottom line is that the body can deal with a small amount of cyanide easily (it is found in some foods in small amounts). And cyanocobalamin is stable in storage, compared to other forms. So, inexpensive production coupled with stability is why it is a common form in the USA. In the end, it will get converted to either adenosyl or methylcobalamin in the body and the cyanide will get shifted onto another molecular sink for excretion (but maybe methylcobalamin, ironically).

    But when people smoke, the body is getting a non insignificant amount of hydrogen cyanide in the smoke (and in answer to the question, cannabis smoke has been shown to have even higher levels of hydrogen cyanide [as much as 6x more] as compared to tobacco smoke). As a primary detox sink for cyanide is the cobalamin group in the body, the question is raised whether taking cyanocobalamin allows the body to deal with the excess cyanide or not. Logically, it would seem that your body needs cobalamin that is not cyanide bound to fulfil that role, so, especially for smokers (of any kind) it may be important that you take a form of B-12 that is not cyanocobalamin. (There are products on the market with methylcobalamin, adenosylcobalamin and hydroxocobalamin, either individually or in combination. – although they are more expensive than cyano versions).

    By the way, here is a link to a good breakdown regarding tobacco vs cannibis smoke content. So much focus has been on the intoxicating affect of cannabis smoking, that the toxic potential of cannabis smoke content to the lungs and body has not been as much on the table. While it lacks meaningful amounts of nicotine, as with tobacco, there are still issues with tar, but also way higher levels of things like nitric oxide, ammonia and hydrogen cyanide.

    Resource:
    A Comparison of Mainstream and Sidestream Marijuana and Tobacco Cigarette Smoke Produced under Two Machine Smoking Conditions
    http://pubs.acs.org/doi/full/10.1021/tx700275p

  8. Jack Norris RD Says:

    Greg,

    Thank you for this thorough answer. I had considered whether cyanide would be the problem with cyanocobalamin for smokers, but the Agency for Toxic Substances and Disease Registry says “Cyanide has not been reported to cause cancer in people or animals.”

    https://www.atsdr.cdc.gov/PHS/PHS.asp?id=70&tid=19

    So B12 causing lung cancer due to the cyanide molecule doesn’t seem plausible.

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