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Updated October 10, 2026 · 7 min read

Vitamin B12:
who is at risk and how to treat it

Vitamin B12 supports red blood cells and nerves, and the body cannot make it. Deficiency is common, becomes more frequent with age, and is treatable, but its symptoms are vague and easy to put down to something else. This article covers who is at risk, how we test, and what the research says about taking B12 by mouth or by injection.

Who is at risk

B12 deficiency becomes more frequent with age, and the Cochrane review of oral and intramuscular B12 starts from that point (Wang 2018). Three situations are worth checking in particular.

Acid-reducing medicines. In a case-control study from Kaiser Permanente Northern California, people with two or more years of proton pump inhibitor use had higher odds of a B12 deficiency diagnosis (odds ratio 1.65). H2 blockers were linked as well, with an odds ratio of 1.25 (Lam 2013). This is observational, so it shows an association, not that the drug caused the deficiency.

Metformin. In a secondary analysis of the Diabetes Prevention Program Outcomes Study, 4.3% of people on metformin had low B12 at year 5, against 2.3% on placebo. Counting borderline levels, the figures were 19.1% and 9.5%. The authors state that routine B12 testing in people on metformin should be considered (Aroda 2016).

Vegan diets and other settings

In a review of studies of vegetarians, higher deficiency rates were reported among vegans than among vegetarians (Pawlak 2013). A 2026 Brazilian expert consensus names atrophic gastritis and bariatric surgery, together with older age, as settings where deficiency is common (Delphi 2026).

How the test is read

Testing is recommended when signs and symptoms suggest deficiency, and when risk factors make deficiency reasonably likely. Total serum B12 is typically the first test. If the result is unclear, methylmalonic acid or homocysteine may be checked, though both can rise for reasons other than B12 (Australian Prescriber 2026).

Oral or injection

Three randomized trials with 153 adults compared the two routes over three to four months. In two of them, 1,000 µg a day by mouth raised serum B12 with no clinically relevant difference from intramuscular injection. The evidence is low quality, and no trial measured symptoms, quality of life or how people felt (Wang 2018).

A 2026 systematic review of 13 studies found that several comparisons showed similar or better blood responses with oral dosing. Its authors say the choice of route should weigh patient preference, tolerability and access, and they note that evidence for sublingual dosing is particularly limited (EClinicalMedicine 2026).

Methylcobalamin and cyanocobalamin

Our B12 injections use methylcobalamin, which is compounded by a licensed U.S. pharmacy and is not FDA-approved. We found no trial in people that compares methylcobalamin with cyanocobalamin, so the choice of form is not supported by head-to-head evidence.

What this does not say

  • Low B12 is one possible cause of tiredness among many. A shot does not replace a full review of the history and labs.
  • The trials are small or short, and most measure blood levels rather than how people feel.
  • The metformin and acid-reducer findings are associations from observational or secondary analyses. They are reasons to test, not proof of cause.
  • Compounded products have not been reviewed by the FDA for safety, efficacy or quality.

How we use this

We test before we treat, and we treat what the test confirms. We do not present B12 injections as a cure for tiredness or as a fat burner.

If you take metformin or an acid reducer, your physician can check your level and explain what the result means for you.

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Sources

  1. 1.Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Wang H et al. Cochrane Database Syst Rev. 2018. Cochrane Database of Systematic Reviews
  2. 2.Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Lam JR et al. JAMA. 2013;310(22):2435-2442. JAMA
  3. 3.Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. Aroda VR et al. J Clin Endocrinol Metab. 2016;101(4):1754-1761. Journal of Clinical Endocrinology and Metabolism
  4. 4.How prevalent is vitamin B(12) deficiency among vegetarians? Pawlak R et al. Nutr Rev. 2013;71(2):110-117. Nutrition Reviews
  5. 5.Vitamin B12 deficiency: testing and treatment. Australian Prescriber. 2026. Australian Prescriber
  6. 6.Vitamin B12 replacement strategies: a Brazilian Delphi consensus. EClinicalMedicine. 2026. EClinicalMedicine
  7. 7.Comparative efficacy of vitamin B12 supplementation routes in adults with replacement indication: a systematic review. EClinicalMedicine. 2026. EClinicalMedicine

All research