Benefits
Correcting Low B12 Status
In a randomized trial in 50 people with low B12 after gastric bypass surgery, 1,000 mcg a day of oral methylcobalamin normalized B12 levels in everyone, matching hydroxocobalamin injections over 6 months. A Cochrane review found high oral B12 doses as effective as injections for blood and nerve responses in deficiency, based on 2 small trials.
Homocysteine Metabolism
Vitamin B12 is the cofactor for methionine synthase, which converts homocysteine to methionine. Supplements containing B12 lower homocysteine, but according to NIH, trials found that B12 alone or with other B vitamins had no effect on heart attacks or death rates in people at risk of or with heart disease.
Neurological Function
Vitamin B12 is required for the development, myelination and function of the central nervous system, and deficiency can cause numbness and tingling and, in some cases, dementia. In older adults, however, trials of B12 alone or with folic acid and vitamin B6 for 1 to 2 years had no effect on cognitive function, according to NIH. The benefit applies to correcting low B12, not to boosting normal cognition.
Energy Metabolism
Vitamin B12 takes part in energy metabolism, and fatigue is one symptom of deficiency. NIH reports that B12 supplementation appears to have no effect on athletic performance or endurance in people with sufficient B12 status, so extra B12 is not an energy booster unless levels are low.
Vegetarian and Vegan Diets
Natural food sources of vitamin B12 are limited to animal foods, so vegans and vegetarians have a higher risk of deficiency. NIH notes that fortified foods and B12 supplements can substantially reduce that risk. Methylcobalamin is one of several supplement forms that can be used.
Older Adults and Absorption
Low B12 is common in older adults, especially those with atrophic gastritis, which affects 8 to 9% of people aged 65 and older and reduces the stomach acid and intrinsic factor needed to absorb B12 from food. Free B12 from supplements is absorbed normally in that case. NIH reports no difference in effect between oral and sublingual forms.
Mechanism of action
Methionine Synthase Cofactor
Methylcobalamin is the cofactor for methionine synthase, which converts homocysteine to methionine. Methionine is used to make S-adenosylmethionine (SAMe), a methyl donor for almost 100 substrates including DNA, RNA, proteins and lipids.
Methylmalonyl-CoA Mutase (Adenosylcobalamin)
The other active form, adenosylcobalamin, is the cofactor for L-methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in propionate metabolism. Raised methylmalonic acid in blood is a marker of low B12.
All Forms Convert to the Same Active Forms
Supplemental methylcobalamin, adenosylcobalamin, hydroxocobalamin and cyanocobalamin are reduced to a core cobalamin molecule inside cells, and the methyl group of methylcobalamin is cleaved off. The cell then makes methylcobalamin and adenosylcobalamin in a ratio not influenced by the form swallowed.
Absorption at High Doses
Intrinsic factor absorbs about half of small doses (1 to 2 mcg), but only about 2% of a 500 mcg dose and 1.3% of a 1,000 mcg dose are absorbed. This is why high oral doses can correct deficiency even when absorption from food is poor. NIH reports no evidence that absorption differs by supplement form.
Clinical trials
Randomized controlled trial comparing daily oral methylcobalamin 1,000 mcg with intramuscular hydroxocobalamin injections for 6 months. (Schijns et al. 2018, Am J Clin Nutr)
50 adults with low serum B12 after Roux-en-Y gastric bypass surgery (23 oral, 27 injection).
B12 normalized in every participant and did not differ between groups. Methylmalonic acid and homocysteine fell within both groups, with no difference between groups at 6 months.
Cochrane systematic review of randomized trials comparing oral with intramuscular vitamin B12 in people with B12 deficiency. (Vidal-Alaball et al. 2005, Cochrane Database Syst Rev)
2 trials, 108 participants recruited and 93 followed for 90 days to 4 months.
High oral doses (1,000 and 2,000 mcg) were as effective as injections for short-term blood and neurological responses. The authors described the evidence as coming from limited studies.
Systematic review of 7 randomized controlled trials (1954 to 2004), 4 using methylcobalamin and 3 a B-complex including B12. (Sun et al. 2005, Acta Neurol Taiwan)
People with diabetic peripheral neuropathy.
Pain and tingling improved in the trials, and methylcobalamin improved autonomic symptoms in 3 studies, but effects on vibration sense and nerve conduction were inconsistent. Five of the 7 trials were of poor quality, and the authors called for better trials.
24-week multicenter randomized double-blind placebo-controlled trial of a combination of L-methylfolate 3 mg, methylcobalamin 2 mg and pyridoxal-5'-phosphate 35 mg (Metanx). (Fonseca et al. 2013, Am J Med)
214 adults with type 2 diabetes and peripheral neuropathy.
The primary outcome, vibration perception threshold, did not change. Symptom scores improved at weeks 16 and 24 and homocysteine fell by 2.7 micromol/L versus a 0.5 rise on placebo. Methylcobalamin was one of three ingredients, so its own effect cannot be separated.