Vitamin B12

Non-negotiable for plant-based diets and older adults — deficiency is quiet until it's neurological.

Overall grade: Grade A
Last revised: Jul 10, 2026; 3
graded outcomes: 0
references listed

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A structured monograph in Prometheus's bundled library. Its grades are the monograph's own reading of the evidence, not a peer-reviewed review.

3 at grade A · 1 at grade C · 1 at grade D — 5 graded rows

What is known

Each outcome with its grade (how strong the evidence is, A to D), the size of the effect where the entry records one, and how often studies agree.

Outcome	Grade	Effect size	Agreement
Correcting deficiency / anemiaDefinitional	Evidence grade A	Large	high
Neuropathy (early deficiency)Reversible if caught early	Evidence grade A	Moderate	high
Energy in replete peopleNo effect without deficiency	Evidence grade D	Trivial	high

Correcting deficiency / anemiaEvidence grade A
Definitional
Largehigh
Neuropathy (early deficiency)Evidence grade A
Reversible if caught early
Moderatehigh
Energy in replete peopleEvidence grade D
No effect without deficiency
Trivialhigh

Conditions

How the entry reads its effect on diagnosed conditions: the direction first, then the grade. Never a substitute for the person who treats you.

Pernicious / macrocytic anemia ImprovesEvidence grade AStandard treatmentGrade A
Cognitive decline No clear effectEvidence grade CCorrects deficiency-linked decline onlyGrade C

What is uncertain

Read off the same rows as above. Nothing here is added that the entry does not itself record.

Thin evidence: Energy in replete people (grade D).
Caution with Folate (B9): High folate masks the anemia of B12 deficiency while nerve damage continues — check B12 directly.
Watch with Folate (B9): High folate masks the anemia of B12 deficiency while nerve damage continues — check B12 directly.

Interactions

Documented pairings with supplements and medicines. A medicine on this list is a conversation for whoever prescribes it.

Folate (B9)Caution
High folate masks the anemia of B12 deficiency while nerve damage continues — check B12 directly.
MetforminDepletes a nutrient
Long-term metformin lowers B12 in up to a third of users — test annually.
PPIsDepletes a nutrient
Acid suppression starves the absorption pathway over years.

The evidence in words

What it is

B12 is a water-soluble vitamin found almost exclusively in animal foods. It is essential for red-blood-cell formation, DNA synthesis, and the myelin sheath around nerves. Because the liver stores years' worth, deficiency develops slowly and can be missed until it causes anemia or irreversible nerve damage.

How it works

B12 is a cofactor for two enzymes: methionine synthase (regenerating methionine and folate, tying it to homocysteine and methylation) and methylmalonyl-CoA mutase. Absorption is a multi-step process requiring stomach acid and intrinsic factor — which is why acid-suppressing drugs and gastric/ileal disease impair it.

What the evidence shows

Grade A for treating and preventing deficiency; supplementation reliably corrects the anemia and, if caught early, the neuropathy. In replete people it does nothing extra — the energy-boost marketing is deficiency-correction dressed up. Vegans, long-term metformin or PPI users, and older adults with low absorption should supplement or test proactively, because the neurological damage from prolonged deficiency can be permanent.

How to use it

For maintenance in vegans, 50–250 µg/day oral (or 1,000 µg a few times weekly) works because passive absorption covers a fraction of large doses. Confirmed deficiency with neurological signs is a medical matter and often treated with injections. Methylcobalamin and cyanocobalamin are both effective.

Safety & interactions

Exceptionally safe with no established toxicity; excess is excreted. The real danger is under-treatment. High-dose folate can mask the anemia of B12 deficiency while nerve damage progresses — test B12 status, don't just chase the blood count. metformin — Long-term metformin lowers B12 in up to a third of users — test annually. ppi — Acid suppression starves the absorption pathway over years. Folate (B9) — High folate masks the anemia of B12 deficiency while nerve damage continues — check B12 directly.

Bottom line

If you eat little or no animal food, or take metformin or a PPI long-term, supplement B12 or test — the downside of deficiency (permanent nerve damage) is far worse than the trivial cost of prevention.

How it is used

As the entry records it, from the studies it summarises. Not a recommendation for you — doses that suit a trial population may not suit you.

Vegan maintenance: 50–250 µg/day, or 1,000 µg 2–3×/week.
Deficiency: Medical management; often injections initially.

Entries that share this one's tags or conditions.

Vitamin B12 for Cognitive declineEvidence grade C — Corrects deficiency-linked decline onlyEvidence grade C
Vitamin B12 for Correcting deficiency / anemiaEvidence grade A — DefinitionalEvidence grade A
Vitamin B12 for Energy in replete peopleEvidence grade D — No effect without deficiencyEvidence grade D
Vitamin B12 for Neuropathy (early deficiency)Evidence grade A — Reversible if caught earlyEvidence grade A

Sources

This entry lists no references of its own.

Last revised Jul 10, 2026. A grade is this entry's reading of the evidence, not medical advice.