Vitamin B12Cyanocobalamin / methylcobalamin · 4 claims

Deficiency causes fatigue, cognitive changes, anaemia and nerve damage, and it is one of the most common nutritional deficiencies globally, with prevalence estimates from 1.5% to 15%. Replacement corrects it, by any of the routes tested.

In people who are not deficient, nothing happens. In a controlled trial, healthy adults with normal baseline B12 took 3 mg/day of cyanocobalamin for two weeks. Serum levels rose as expected, from a median 355 to 961 pmol/L (p=0.020) — and there was no change in any measured sleep or wake parameter, with no correlation between B12 level and any of them.

That is the whole shape of B12 as a supplement. It is a correction, not an enhancement.

• RCTLack of association between serum vitamin B12 and nocturnal sleep parameters following cyanocobalamin supplementation in healthy adults 3 mg/day for two weeks; levels rose, sleep did not change
• CohortIntramuscular cyanocobalamin treatment in patients with corpus atrophic gastritis and vitamin B12 deficiency 213 patients · ~70% corrected at 20,000 mcg/year

Low B12 is a recognised consequence of metformin treatment, and the resulting symptoms — fatigue, mood change, cognitive change — overlap with things easily attributed to diabetes itself.

A one-year randomised, double-blind, placebo-controlled trial enrolled 90 people with type 2 diabetes who had been on metformin for at least four years and had both peripheral and autonomic neuropathy, all with B12 below 400 pmol/L, and tested oral methylcobalamin at 1000 mcg/day.

An unexpected practical note from the same literature: oral calcium supplementation has been shown to reverse metformin-induced B12 malabsorption, because the absorption defect is calcium-dependent.

• RCTVitamin B12 supplementation in diabetic neuropathy: a 1-year randomized, double-blind, placebo-controlled trial 90 patients on metformin ≥4 years; methylcobalamin 1000 mcg/day
• RevAnalysis of vitamin B12 levels in metformin and PPI use for quality improvement Absorption fractions and the calcium reversal finding

A systematic review and meta-analysis examined chronic proton pump inhibitor use, beyond six months, against two biomarkers of B12 status across six studies, 1,587 cases and 2,272 controls.

Standardised mean differences were 0.01 for serum B12 (95% CI −0.14 to 0.16, p=0.92) and 0.05 for total homocysteine (−0.02 to 0.11, p=0.17). No association between chronic PPI use and B12 deficiency on either marker.

The authors are appropriately careful: with so few studies using multiple biomarkers, they say it is difficult to recommend routine monitoring in low-risk patients on long-term PPIs, and call for future work using at least two markers. That is different from proving no effect exists — but it is a long way from the confident claim in circulation.

• MetaAssociation between long-term proton pump inhibitor therapy and vitamin B12 status: systematic review and meta-analysis 6 studies, 1,587 cases and 2,272 controls

A study of 312 patients with B12 deficiency compared intramuscular cyanocobalamin against sublingual methylcobalamin. Median levels rose from 177 to 447 ng/L at six weeks in the injection group, and 172 to 438 ng/L in the sublingual group. There were no significant between-group differences, and both achieved levels above 300 ng/L.

Broader reviews put it the same way: all three routes have fairly equal efficacy, with intramuscular typically preferred specifically in malabsorption or where neurological symptoms are present.

The related marketing claim that methylcobalamin is inherently superior to cyanocobalamin is asserted more often than it is demonstrated. The head-to-head above compared sublingual methylcobalamin with injected cyanocobalamin and found neither better.

• RCTEvaluation of a new sublingual methylcobalamin dosage regimen for childhood vitamin B12 deficiency 312 patients · no significant between-group differences
• RevRoute comparison and clinical preference in malabsorption All three routes of fairly equal efficacy