Vitamin B12 (cobalamin)
Corrects deficiency-driven fatigue and cognitive complaints in older adults, vegans, and long-term metformin users.
Why
Vitamin B12 deficiency is common with age (gastric atrophy reduces absorption), with strict plant-based diets, and on long-term metformin (the MHRA reclassified B12 deficiency as a common side effect in 2022). Deficiency presents as fatigue, paraesthesias, and cognitive slowing, often before haematological signs appear. The Eussen 2005 dose-finding RCT in older adults showed that very modest oral doses (the RDA of 2.5 µg) failed to normalise plasma markers, while doses of 647–1032 µg/day produced 80–90% of the maximum reduction in methylmalonic acid over 16 weeks.
How it works
Cofactor for methionine synthase (homocysteine → methionine) and methylmalonyl-CoA mutase. Required for myelin maintenance, DNA synthesis in haematopoiesis, and single-carbon metabolism in the CNS.
Expected onset · Energy and cognition often improve over 4–12 weeks; haematological correction by 8 weeks
How to take
Dosage
1,000 µg/day oral (cyanocobalamin or methylcobalamin) is a pragmatic correction dose, well above the Eussen 2005 plateau threshold of ~650 µg/day. Established deficiency may require intramuscular hydroxocobalamin under a clinician.
Timing
With or without food; daily
On the label
Cyanocobalamin and methylcobalamin both correct deficiency at adequate doses; the Eussen RCT used cyanocobalamin. Sublingual offers no proven advantage over oral.
Ideal for
Adults over 60, strict vegetarians/vegans, long-term metformin users, people with pernicious anaemia or post-gastric surgery.
Safety
Evidence
Eussen 2005 dose-finding RCT (n=120 older adults with mild B12 deficiency): 647–1032 µg/day oral cyanocobalamin produced 80–90% of the maximum reduction in plasma methylmalonic acid over 16 weeks; the 2.5 µg RDA was insufficient when absorption is impaired.
- Eussen et al., Arch Intern Med 2005, dose-finding RCT (n=120) of oral cyanocobalamin in mild B12 deficiency in older adults
- EFSA Scientific Opinion 2010, authorised health claims for B12 and reduction of tiredness/fatigue, normal neurological function, and homocysteine metabolism
- MHRA Drug Safety Update 2022, vitamin B12 deficiency now a recognised common side effect of metformin
Where to get it
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