Vegan Vitamin B12 Supplements and Lung Cancer

Table of Contents

On August 23, 2017, a long-term study was published online (Journal of Clinical Oncology) showing an association between an increased risk of lung cancer and long-term, high-dose use of vitamin B supplements in men. Due to the public discourse, we have taken a closer look at the study and would like to comment on it. For vegans, the intake of vegan vitamin B12 supplements is essential, so we would like to provide some clarity.

Study Structure and Hypothesis

The observational study from the University of Taiwan examined the association between long-term use of vitamin B supplements and the risk of lung cancer in 77,118 U.S. participants aged 50 to 76 years from the VITAL (Vitamins and Lifestyle) cohort.

The B vitamins studied were those that are important for the C1 metabolic pathway. This means that they are part of a biochemical mechanism that interacts with the amino acids homocysteine and methionine. If there is an imbalance, the development of cancer can be promoted. Relevant B vitamins include vitamin B6 (pyridoxine/-al), vitamin B9 (folic acid), and vitamin B12 (cobalamin). In addition to the vitamin intake, other parameters such as body mass index, eating habits (using a food frequency questionnaire), tobacco consumption, education, family history etc. were examined. The data are based on interviews or recordings of the participants from the last 10 years. The primary parameter to be studied was the average dosage consumed during this period. Based on previous studies, the researchers hypothesized that high-dose supplementation of these B-vitamins for several years may promote carcinogenesis (Kim, 2004; Ebbing et al., 2009).

Results

Overall, the participant groups exceeded the intake recommendations (Recommended Daily Allowance, RDA) according to current scientific knowledge.
No effect on lung cancer risk was observed for chronic use of multivitamin and folic acid supplements.
For high intakes of vitamin B6 (> 20 mg/day) and vitamin B12 (> 55 µg/day) over a 10-year period, an increased risk of lung cancer was observed only in men, especially in those who smoked. Overall, the risk was doubled. In men who smoked at the time of the study, the risk was tripled for vitamin B6 and almost quadrupled for vitamin B12 at the above doses. Doses below these levels did not result in a significantly increased risk.
For women, no increased risk was observed in this cohort (Brasky et al., 2017). This suggests sex differences, probably due to hormonal status. However, it is important to note that lung cancer is more common in men than in women.

Vitamin B12 Supplements in the Vegan Diet

Vitamin B12 is considered the most critical nutrient in a vegan diet, meaning that it is not obtained from food. Studies show that vegans who do not supplement this vitamin have inadequate blood levels (Gilsing et al., 2010; Herrmann et al., 2003), which underscore the importance of a supplementation. Vitamin B12 deficiency can lead to irreversible damage of the nervous system, folate deficiency, and impaired blood synthesis. The EFSA sets an Adequate Intake (AI) for cobalamin at 4 µg/day for adults (EFSA, 2015).

Recommendations for Vegans

Vegan B12 supplements are essential for a plant-based diet. Therefore, this study does not lead to a recommendation against their use; it is still strongly recommended. The results of this study suggest that men in particular should avoid high doses. The British Vegan Society recommends an intake of 10 µg per day, which is considered safe according to current scientific knowledge. However, if you take the vegan B12 supplement in tablet form or swallow it directly, passive diffusion through the mucous membranes is bypassed at such low doses, as this resorption mechanism is only possible at higher doses. With a daily intake of 55 µg, the maximum amount that is actively absorbed is 1.5 to 2 µg. If you are taking a liquid or sublingual supplement, passive diffusion occurs with a resorption rate of about 1%. This would be 0.55 µg, far from the minimum requirement and even further from the recommended 4 µg, which includes a safety margin (EFSA, 2015). The use of proton pump inhibitors interferes with the synthesis of intrinsic factor, which is the vitamin B12 shuttle for active absorption, leading to a decrease in absorption rate (O’Leary and Samman, 2010).

Other human studies have not shown a similar effect in healthy people. However, these studies were limited to a shorter period of time (EFSA, 2006). The European Food Safety Authority concludes that “long-term oral or parenteral administration of daily cobalamin doses between 1 and 5 mg given to patients with compromised cobalamin absorption did not reveal adverse effects.” (EFSA, 2015).

In 2019, a study was published that looked at serum vitamin B12 levels in people from several cohorts in a case-control study. They also performed what is called Mendelian randomization. This method can be used to determine whether there is a causal relationship between a risk factor and a disease. In this case, the scientists concluded that high vitamin B12 levels increase the risk of lung cancer (Fanidi et al., 2019). It is not known to what extent these results can be extrapolated to the general population. Furthermore, the reason for the higher serum levels is not clear. This means that the reverse conclusion, that high vitamin B12 intake via supplements increases the risk of lung cancer, cannot be drawn. Also important to note: holoTC levels are more accurate than serum levels for determining vitamin B12 status. However, in the studies that have been done, high serum levels have been associated with lung cancer. Based on current scientific knowledge, using the holoTC level to assess your vitamin B12 status does not indicate your risk of developing lung cancer.

Conclusion: Vitamin B12 Supplements in a vegan Diet

In summary, vegan vitamin B12 must be supplemented in a plant-based diet. Otherwise, sooner or later, a deficiency will occur, leading to serious adverse health effects.

The results of the study by Brasky and colleagues and the other existing scientific literature can emphasize the importance of sensible supplementation, but do not prove that taking vitamin B12 supplements is harmful to health. Finally, it is recommended to monitor your vitamin B12 blood levels (holoTC) and adjust your supplementation dose accordingly. In practice, this means

If you have adequate blood levels with low-dose vegan vitamin B12 supplementation, there is no need to choose high-dose supplements.

Literature

Brasky T.M., White E., Chen C.-L. Long-Term, Supplemental, One-Carbon Metabolism–Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. Journal of Clinical Oncology (2017). published online before print: 1-9.

Kim Y.-I. Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer? Cancer, Epidemiology, Biomarkers and Prevention (2004). Vol. 13(4): 511-519.

Ebbing M., Bønaa K.H., Nyga˚rd O., Arnesen E., Ueland P.M., Nordrehaug J.E., Rasmussen K., Njølstad I., Refsum H., Nilsen D.W., Tverdal A., Meyer K., Vollset S.E. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA (2009). Vol 302(19): 2119-2126.

EFSA (2015). Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12) | EFSA. https://www.efsa.europa.eu/en/efsajournal/pub/4150.

Fanidi, A., Carreras-Torres, R., Larose, T.L., Yuan, J.-M., Stevens, V.L., Weinstein, S.J., Albanes, D., Prentice, R., Pettinger, M., Cai, Q., et al. (2019). Is high vitamin B12 status a cause of lung cancer? Int J Cancer 145, 1499–1503.

Gilsing A.M.J., Crowe F.L., Lloyd-Wright Z., Sanders T.A.B., Appleby P.N., Allen N.E., Key T.J. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. European Journal of Clinical Nutrition (2010). Vol. 64: 933–939.

Herrmann W., Schorr H, Obeid R., Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. The American Journal of Clinical Nutrition (2003). Vol. 78: 131–136.

Deutsche Gesellschaft für Ernährung (DGE), Österreichische Gesellschaft für Ernährung (ÖGE), Schweizerische Gesellschaft für Ernährung (SGE) (2018); Referenzwerte für die Nährstoffzufuhr; 2. Auflage, 4. aktualisierte Ausgabe

EFSA. European Food Safety Authority. Tolerable Upper Intake Levels for Vitamins and Minerals. Scientific Committee on Food Scientific Panel on Dietetic Products, Nutrition and Allergies (2006): 1-480.

O’Leary F., Samman S. Vitamin B12 in Health and Disease. Nutrients (2010). Vol. 2: 299-316.

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