High serum vitamin B12 links to cancer and mortality
Cancer incidence increased with adjusted hazard ratios of 1.05 to 1.08 above the 400–600 pg/mL reference, while mortality showed a J-shaped pattern.
The Journal of Nutrition
In a retrospective study of 3,950,497 adults across 19 countries, researchers examined how serum vitamin B12 concentrations relate to cancer incidence and all-cause mortality over 10 years. They grouped participants into six baseline strata, using the 400 to 600 pg/mL range as the reference.
Overall cancer incidence increased modestly at concentrations above the reference stratum, with adjusted hazard ratios between 1.05 and 1.08. Deficiency-range concentrations showed no association with cancer incidence. All-cause mortality followed a J-shaped pattern, with elevations at both extremes. When excluding the first two years of follow-up, the cancer association above 1,000 pg/mL attenuated from an adjusted hazard ratio of 1.07 to 1.02. Mortality associations at deficiency-range concentrations showed the least attenuation.
Why it matters
Serum vitamin B12 is frequently monitored in clinical practice, yet extreme levels are linked to distinct long-term health risks. Clarifying whether elevated levels reflect reverse causation rather than direct harm informs the safe management of vitamin B12 therapy.
Caveats
The findings come from a retrospective observational cohort and cannot establish causality. In addition, the marked attenuation of the cancer association after excluding early follow-up years indicates that reverse causation likely explains part of the initial signal.
The paper
Tainan Municipal Hospital · Asia University
The Journal of Nutrition · 29 Sep 2026