Can vitamin B12 cause cancer?

A few studies warn of an allegedly increased risk of cancer due to high-dose vitamin B12 intake. We are aware of the original work on this topic and the discussion about it, which is used by some people to discredit dietary supplements in general and high-dose vitamin B12 products in particular. In the case of such a sensitive problem, an objective analysis of the existing data should be carried out before warnings are issued. Although such articles produce nice headlines, they often cannot withstand scientific evidence.

Are there any studies that have shown that vitamin B12 promotes the development of cancer?

First of all, it should be noted that no study has so far shown a causal relationship between high-dose vitamin B12 food supplements with the methylcobalamin form of B12 and cancer.

In a meta-analysis published in 2016 from 18 controlled and randomized studies with a total of 74,498 participants, no connection could be established between the consumption of vitamin B12 supplements and the cancer frequency in almost all types of cancer (1). Surprisingly, a reduction in the risk associated with vitamin B12 supplementation was found in skin cancer; no effect was observed in all other types of cancer. The doses of vitamin B12 in the different studies varied between 20 µg and 2000 µg, the number of patients in the individual studies between 100 and 12,000. The authors also examined a possible connection between cobalamin intake and the occurrence of cancer in individuals consuming more than 400 µg. In comparison with the second group, who consumed 400 µg vitamin B12 or less, no significant difference could be found.

One year later, a study on vitamin B12 and lung cancer risk attracted the media (2). The study was designed as an observational study, which is scientifically not conclusive for a causal relationship. Nevertheless, the study postulated - though only in male smokers - a connection between cobalamin intake and the increased incidence of lung cancer. Non-smokers and females showed no increased risk in this study.

How can one interpret these results and how were the data on the intake of vitamin B12 collected?

The participants in the study by Brasky et al. (2) were using surveys to describe their lifestyle habits over the past 10 years. Since many people do not even know what they ate the previous day, a large margin of error can be expected with this type of survey. Who can reliably remember their daily vitamin B12 intake over the past 10 years? In addition, no blood values for cobalamin were determined. The survey method was therefore unable to provide any answers for a possible deficiency in vitamin B12, which means that the question of a possible causality was not answered either. If there is actually a connection between the consumption of vitamin B12 supplements and lung cancer, an increased vitamin B12 status could also be the result from the existing cancer. Therefore, it would serve as a diagnostic marker in the sense of a reversed causality. According to another study by Collin et al. which showed a correlation between prostate cancer risk and vitamin B12 levels, this is the more likely conclusion (3). A connection between the total level of vitamin B12 and the occurrence of prostate cancer could be identified. However, there was no association between the active vitamin in the form of holo-TC and prostate cancer.If the ingested amount of vitamin B12 would promote the growth of cancer cells, then the study participants with the highest holo-TC values should have shown an increased risk of cancer. This, however, was not the case. Therefore, the results rather suggest that the increased serum levels of cobalamin were caused by the cancer and not vice versa.

In another study in 2018, the open questions about a possible causal relationship between vitamin B12 and cancer were to be clarified via a new design (4). The study investigated a possible connection between the cobalamin freely circulating in the serum and the risk of lung cancer, but definitely not the influence of a substitution of vitamin B12 supplements and the risk of lung cancer. The blood levels of B12 were measured on average 6.4 years before the lung cancer diagnosis. Depending on the subgroup of the study, the risk of lung cancer increased by up to 20% with higher B12 levels. However,increased serum B12 levels can have various other causes, such as insufficient binding of cobalamin to transport molecules, falsified measured values, or certain serious illnesses. Therefore, when trying to prove a correlation, the measurement of the usable cobalamin in the form Holo-TC should be preferres over the freely circulating B12 in the serum.

Reports of an increased risk of cancer from dietary supplements such as vitamin B12 worry many vegans. Because of these fears, they may stop using the dietary supplements that are essential for them and end up in a deficiency state with serious consequences. However, the current data do not give any evidence that high-dose vitamin B12 intakes of 500 µg daily would contribute to an increased cancer risk.

Basically, it is reasonable to substitute only as much vitamin B12 as necessary and as little as possible. The measured level of the usable cobalamin in the form of holo-transcobalamin (Holo-Tc) should serve as a recommended marker for a necessary substitution. If possible, it should be in the range of 35 - 50 pmol / l or above.

Nico Rittenau has summarized all these explanations very well in his video. You can watch it here: https://www.youtube.com/watch?v=wn2XjD9MnQQ.

References:

(1) Sui-Liang Zhang et al (2016). Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality, A PRISMA-compliant cumulative meta-analysis of randomized controlled trials. Medicine (Baltimore); 95(31):e3485.

(2) Brasky TM et al (2017). 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; 20, 35(30): 3440-3448.

(3) Collin SM et al (2010). Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev; 19(6): 1632-42.

(4) Fanidi A et al (2019). Is high vitamin B12 status a cause of lung cancer? Cancer Epidemiology; 145(6): 1499-1503.