Vitamin B12 is required for myelin synthesis, the formation of the protective sheath around nerve fibres, for red blood cell production via its role in DNA synthesis, and for the metabolism of homocysteine, an amino acid associated with cardiovascular disease when elevated. B12 deficiency produces a spectrum of effects including megaloblastic anaemia, subacute combined degeneration of the spinal cord, peripheral neuropathy, cognitive decline, and psychiatric symptoms. Critically, neurological damage from B12 deficiency can be irreversible if the deficiency is prolonged.
The Reference Range Problem
The UK laboratory reference range for serum B12 typically starts at 180 to 200 nanomoles per litre, and values above this are reported as normal. However, research by Vogiatzoglou et al. and others has shown that neurological symptoms and cognitive decline associated with B12 insufficiency can occur at levels up to 400 nanomoles per litre. The functional marker of B12 adequacy at the tissue level, methylmalonic acid, is elevated in a significant proportion of people with serum B12 in the so-called normal range. An optimal serum B12 level is generally considered to be above 400 nanomoles per litre.
Who Is at Risk
The groups most at risk of B12 deficiency include vegans and strict vegetarians, as B12 is found almost exclusively in animal products. Adults taking proton pump inhibitors long-term, as gastric acid is required for B12 release from food proteins. Adults over 60, in whom atrophic gastritis and reduced intrinsic factor production impair absorption. Adults taking metformin, which reduces B12 absorption in the ileum. And those with conditions affecting the small bowel including coeliac disease, Crohn's disease, and previous gastric surgery.
Forms of B12 and Supplementation
Cyanocobalamin is the most commonly used supplemental form and is effective and inexpensive. Methylcobalamin, the active form used directly by the nervous system, is argued to be preferable for neurological applications, though the evidence for superior efficacy is not definitive. For those with absorption problems due to intrinsic factor deficiency or gastric atrophy, high-dose oral B12 of 1000 micrograms per day is absorbed through passive diffusion independently of intrinsic factor, making injections unnecessary in most cases despite common clinical practice.
- Vegans and strict vegetarians must supplement B12: no reliable plant food source provides sufficient B12
- If you take PPIs or metformin long-term, request B12 monitoring at least annually
- An optimal serum B12 is above 400 nmol per litre, not simply above the laboratory reference range
- High-dose oral B12 of 1000 micrograms per day is effective even with absorption problems through passive diffusion
- Request methylmalonic acid testing if you have neurological symptoms with a serum B12 in the normal range
Sources
- Vogiatzoglou, A., et al. (2008). Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology, 71(11), 826-832.
- Andrès, E., et al. (2004). Vitamin B12 malabsorption in general practice. Journal of Internal Medicine, 256(4), 286-295.