Benefits
Normal red blood cell formation
B12 is needed to make red blood cells, and deficiency causes megaloblastic anemia with fatigue, weakness and pale skin. Injections are the usual treatment, but a Cochrane review of three trials in 153 people, cited by NIH, found 1,000 to 2,000 mcg a day by mouth normalized blood B12 about as well as injections, though the evidence was of low quality.
Normal nerve function
In a 1-year trial in 90 metformin users with nerve damage and B12 below 400 pmol/L, 1,000 mcg a day of methylcobalamin improved nerve conduction, vibration sense, pain and quality of life versus placebo. In 201 people aged 75 and over with moderately low B12 but no symptoms, 1 mg a day for a year did not change nerve function.
Homocysteine lowering
B12 helps convert homocysteine to methionine. In a 5-year trial in 5,522 people with vascular disease or diabetes, folic acid, B6 and B12 lowered homocysteine but did not reduce the combined rate of cardiovascular death, heart attack and stroke; strokes alone were fewer, while hospital stays for unstable angina were more common.
Energy metabolism (deficiency-related tiredness)
B12 is a cofactor in energy metabolism, and fatigue is a common sign of deficiency. NIH notes that supplements appear to give no benefit for performance or endurance in people with adequate B12, and a pooled review of 16 trials found only one trial on fatigue, too few to analyze. Expect a difference only if your levels are low.
Infant development: a Nepal trial
In 600 marginally stunted Nepalese infants aged 6 to 11 months, a year of B12 improved blood markers of B12 status but did not improve neurodevelopment, growth or hemoglobin compared with placebo. B12 deficiency in pregnancy and breastfeeding can still harm infant development, so status matters for mothers on vegan diets.
Memory and thinking in older adults
Deficiency can cause cognitive changes, but supplementing older adults with low or borderline B12 showed no significant benefit: 24 weeks in 195 people, 12 months in 201 and 27 months in 271 older adults with diabetes. A meta-analysis of 16 trials in 6,276 people without advanced neurological disease found no effect on cognition or depressive symptoms.
Bone health
In the 2-year B-PROOF trial in 2,919 people aged 65 and over with high homocysteine, 500 mcg of B12 plus folic acid did not reduce osteoporotic fractures overall (hazard ratio 0.84, not significant). More cancers were reported in the supplement group (63 versus 42), a finding the trial was not designed to test.
Mechanism of action
Red blood cell formation and DNA synthesis
B12 is a cofactor for methionine synthase, which works with folate in making DNA. In deficiency, folate becomes trapped in a form the body cannot use, DNA synthesis slows and red blood cells come out large and immature (megaloblastic anemia).
Nerve function and myelin
B12 is also a cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. In deficiency, methylmalonic acid builds up and nerve function and myelin can be damaged; neurological symptoms can appear without anemia.
Homocysteine metabolism
Methionine synthase converts homocysteine to methionine, so B12 deficiency raises homocysteine. B vitamins lower homocysteine, but in the HOPE-2 trial that did not reduce the combined rate of cardiovascular death, heart attack and stroke.
Energy metabolism
The succinyl-CoA made with B12's help feeds into the citric acid cycle. This is why deficiency can cause fatigue; it does not mean extra B12 boosts energy in people with adequate levels.
Absorption
B12 in food is bound to protein and released by stomach acid, then absorbed with intrinsic factor in the lower small intestine. B12 in supplements is already free, so people who absorb food B12 poorly can often absorb supplemental B12. Only about 2% of a 500 mcg dose is absorbed.
Clinical trials
Double-blind, randomized, placebo-controlled trial of 1 mg crystalline B12 a day by mouth for 12 months in 7 general practices in South East England (Dangour et al. 2015, Am J Clin Nutr)
201 people aged 75 and over with moderately low serum B12 (107 to 210 pmol/L) and no anemia; 191 provided outcome data.
Serum B12 rose and homocysteine fell 17%, but there was no effect on the primary nerve outcome, on any other nerve or motor measure, or on cognitive function. The trial does not support benefits from correcting moderate deficiency without symptoms.
Randomized placebo-controlled trial of methylcobalamin 1,000 mcg a day for 27 months (Kwok et al. 2017, Clin Nutr)
271 non-demented outpatients with diabetes aged 70 or older with plasma B12 of 150 to 300 pmol/L.
Methylmalonic acid and homocysteine fell, but at 27 months there was no significant difference from placebo in cognitive decline (CDR) or neuropsychological test scores.
Double-blind, placebo-controlled trial of 1,000 mcg B12, 1,000 mcg B12 plus 400 mcg folic acid, or placebo for 24 weeks (Eussen et al. 2006, Am J Clin Nutr)
195 people aged 70 and older with mild B12 deficiency.
Supplementation corrected the mild deficiency but did not improve any cognitive domain; memory improved more in the placebo group than in the B12-alone group.
Prospective, double-blind, placebo-controlled trial of oral methylcobalamin 1,000 mcg a day for 1 year (Didangelos et al. 2021, Nutrients)
90 people with type 2 diabetes on metformin for at least four years, with peripheral and autonomic nerve damage and B12 below 400 pmol/L.
B12 rose from about 232 to 777 pmol/L. Sural nerve conduction velocity and amplitude, vibration perception, pain score and quality of life improved versus placebo; cardiovascular autonomic tests did not improve significantly.
Randomized, double-blind trial at three centers in Pakistan comparing 1,000 mcg a day of Sucrosomial B12 with locally sold oral B12 products for 7 days (Memon et al. 2024, Front Nutr)
Healthy adults with low-normal serum B12 (200 to 300 pg/mL).
Serum B12 rose faster and higher with the Sucrosomial product than with the conventional oral products at each center. A 7-day blood-level study, not a test of symptoms or health outcomes.
Double-blind, randomized, placebo-controlled trial of 500 mcg B12 plus 400 mcg folic acid a day for 2 years; both arms also got 600 IU vitamin D3 (van Wijngaarden et al. 2014, Am J Clin Nutr)
2,919 people aged 65 and over with high homocysteine (12 to 50 micromol/L).
Osteoporotic fractures occurred in 4.2% on supplements and 5.1% on placebo (hazard ratio 0.84, 95% CI 0.58 to 1.21), not a significant difference. Incident cancer was reported more often with supplements (63 versus 42), which the trial was not designed to assess.
Randomized placebo-controlled trial of folic acid 2.5 mg, B6 50 mg and B12 1 mg a day for an average of five years (Lonn et al. 2006, N Engl J Med)
5,522 people aged 55 or older with vascular disease or diabetes.
Homocysteine fell, but the combined rate of cardiovascular death, heart attack and stroke did not differ (18.8% versus 19.8%, relative risk 0.95). Stroke alone was less common (relative risk 0.75) and hospital stays for unstable angina more common (1.24).
Randomized, double-blind, placebo-controlled trial of daily B12 for 12 months (Strand et al. 2020, PLoS Med)
600 marginally stunted infants aged 6 to 11 months in Nepal.
B12 improved blood markers of B12 status but did not improve neurodevelopment, growth or hemoglobin compared with placebo.