High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations

Patients with cancer have been reported to show elevated plasma concentrations of vitamin B12, thus causing uncertainties regarding safety of vitamin B12. We conducted a systematic literature search and a scoping review of human studies published in PubMed between January 2005 and March 2022, to investigate the association between vitamin B12 (concentrations of B12 biomarkers, intake, and genetic determinants) and cancer. Except for liver cancer, the association between plasma vitamin B12 concentrations and cancer was not consistent across the studies. Vitamin B12 intake from food, or food and supplements, showed even less consistent associations with cancer. There was no evidence for temporality, coherence, or a biologically meaningful dose-response relationship between plasma vitamin B12 concentrations and cancer. Genetically determined high plasma vitamin B12 was likely to be associated with cancer. Available randomized controlled trials have used a high dose of multivitamin supplements and cancer was the unplanned outcome, thus the causality of B12 in cancer cannot be judged based on these trials. Additionally, low plasma vitamin B12 concentrations were common in patients with cancer. Therefore, there is not sufficient evidence to assume that high plasma vitamin B12, high B12 intake, or treatment with pharmacological doses of vitamin B12, is causally related to cancer. Low vitamin B12 status in patients with cancer needs to be diagnosed and treated in order to prevent the hematological and neurological sequela of the deficiency.