Vitamin B12 and Cancer: The Canary in the Coal Mine?
Yesterday, TalkingNutrition reported on how an adequate vitamin B12 status can improve health outcomes for babies during their first thousand days from conception to two years of age. Today, an article on the link between high vitamin B12 levels and cancer risk by Arendt and colleagues has been picked up as a nutrition news story by various online news providers such as Medical News Today, Everyday Health, SBS News Australia and the Huffington Post. The titles of these articles ranged from the mild “High Levels of Vitamin B12 May Be Linked To Increased Cancer Risk” to the more sensational “Vitamin B12 In The Blood May Indicate Risk Of Cancer.” Neither headline accurately reflect the authors’ conclusions in the original article. The second headline is especially puzzling as vitamin B12 is always in the blood and its absence would indicate severe deficiency or a problem with sample preparation.
The original article describes epidemiological research conducted in a large cohort in Denmark. The authors linked several population-wide databases to identify people who had their plasma cobalamin (vitamin B12) levels measured within a certain period of time, and linked this with cancer diagnosis. The authors excluded people who were being treated for vitamin B12 deficiency from their diagnosis. The authors also excluded people with low serum B12 levels, below 200 pmol/l. Despite uncertainty about appropriate cut-off points for serum B12 levels that indicate deficiency, this value is likely to remove people with clear deficiency from the analysis. For more discussion on the relationship between serum B12 and the functional marker of vitamin B12 deficiency, methylmalonic acid concentration, see Bailey et al. The remaining cohort was divided into three groups based on their vitamin B12 levels: 200-600 pmol/l (normal range, found in 94% of the cohort), 600-800 pmol/l (high-normal, found in 4% of the cohort), 800 pmol/l (high, found in 2% of the cohort).
Over an average of 3.5 years of follow-up, Arendt and co-workers found that there was an increased risk of cancer in people with vitamin B12 levels above 200 pmol/l, and the risk appeared to increase with increasing levels of vitamin B12 in the blood. This risk was only elevated in the first year after the vitamin B12 was measured, and for subsequent years (up to 5 years), there was no increased risk of cancer diagnosis in people with B12 levels up to the high-normal range. This result is rather puzzling, as cancer normally takes many years to develop (Cancer Research UK provides an excellent resource that describes how cancer arises from gradually acquired mutations). The study used a snapshot of individuals’ vitamin B12 status and linked it to cancer diagnosis within the short term. As cancer diagnosis was only elevated during a window of the first year after vitamin B12 status was measured and later decreased, whereas vitamin B12 stores in the body are sufficient to last for years, it would seem that factors related to active cancer development are likely to be responsible for the elevated levels of vitamin B12. High vitamin B12 levels may provide an indication that cancer is established. Modifiable factors related to vitamin B12 status such as dietary intake are not likely to be able to influence cancer risk based on this study’s results.
One finding was that cancers related to smoking and alcohol abuse were more likely to be found even up to 5 years after high vitamin B12 levels were measured. Alcoholics are more likely to have higher levels of vitamin B12, according to a study by Himmerich and co-workers, therefore high vitamin B12 levels and risk of cancer may result from alcohol abuse. Another possibility is that non-specific symptoms such as fatigue, anemia and unexplained weight loss may cause health-care providers to suspect both vitamin B12 deficiency and cancer, leading to a correlation between testing for cancer and vitamin B12.
The results do not support a causative role of vitamin B12 and cancer. Although high vitamin B12 levels could indicate an increased risk of cancer in the short-term, a prospective, longitudinal study that tracks vitamin B12 levels in a cross-section of the population are needed to confirm this result. It is also important to “hit the sweet spot” and avoid vitamin B12 deficiency. As vitamin B12 expert Professor Allen explains, vitamin B12 deficiency is found throughout the world and contributes to a preventable cause of illness for millions of people.
Arendt JF, Pedersen L, Nexo E, Sørensen HT. Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study. J Natl Cancer Inst. 2013 Nov 18. [Epub ahead of print] doi: 10.1093/jnci/djt315
Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009 Feb;89(2):693S-6S. doi: 10.3945/ajcn.2008.26947A. Epub 2008 Dec 30. http://www.ncbi.nlm.nih.gov/pubmed/19116323
Bailey RL, Durazo-Arvizu RA, Carmel R, Green R, Pfeiffer CM, Sempos CT, Carriquiry A, Yetley EA. Modeling a methylmalonic acid-derived change point for serum vitamin B-12 for adults in NHANES. Am J Clin Nutr. 2013 Aug;98(2):460-7. doi: 10.3945/ajcn.113.061234. Epub 2013 Jun 26. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142730
Herrmann W, Obeid R. Utility and limitations of biochemical markers of vitamin B12 deficiency. Eur J Clin Invest. 2013 Mar;43(3):231-7. doi: 10.1111/eci.12034. Epub 2013 Jan 18. http://www.ncbi.nlm.nih.gov/pubmed/23330849
Himmerich H, Anghelescu I, Klawe C, Szegedi A. Vitamin B12 and hepatic enzyme serum levels correlate in male alcohol-dependent patients. Alcohol Alcohol. 2001 Jan-Feb;36(1):26-8. http://www.ncbi.nlm.nih.gov/pubmed/11139412