Vitamin B12 and Medicines: Metformin, Acid Reducers and Others That Lower B12
Metformin, acid-reducing medicines and nitrous oxide can lower vitamin B12. What labels, trials and the NHS say, how B12 is monitored, and why not to stop a medicine on your own.
Content last updated . This page has not been medically reviewed.
Start here
Do not stop or change metformin, an acid reducer or any prescribed medicine because of this page. Talk to your prescriber or pharmacist first, because these medicines treat real conditions. Low vitamin B12 can cause symptoms such as extreme tiredness, pins and needles, memory problems and a sore tongue, and the NHS says some problems caused by deficiency can be irreversible, so see a clinician if you think you may be deficient. [1] Poison Help (US) is 1-800-222-1222 if anyone has swallowed too many vitamins or medicines; call 911 in an emergency.Medicines that can lower B12
The NHS says some medicines can lead to a reduction in the amount of vitamin B12 in the body, with proton pump inhibitors (PPIs), metformin and nitrous oxide as examples, and that your GP will be aware of them and monitor you if necessary. [2]| Medicine | What the source found | Strength of evidence |
|---|---|---|
| Metformin (US label) | The prescribing information says metformin may lower vitamin B12 levels, and to measure blood counts annually and vitamin B12 at 2 to 3 year intervals and manage any abnormalities. [3] It reports subnormal B12 in approximately 7% of patients in 29-week trials. [3] | Regulator labeling |
| Metformin (randomized trial) | In 390 insulin-treated people with type 2 diabetes, metformin for 4.3 years lowered B12 by a mean 19% versus placebo; the absolute risk of deficiency was 7.2 percentage points higher. [4] | Trial: blood levels |
| Metformin (long-term follow-up) | In the Diabetes Prevention Program, low B12 was more common with metformin at 5 years (4.3% vs 2.3%), and years of use were linked to higher risk. The authors said routine B12 testing should be considered. [5] | Trial follow-up |
| Metformin (pooled) | A 2016 meta-analysis of 26 papers found metformin use associated with B12 lower by 57 pmol/L, and called monitoring prudent. [6] | Association |
| PPIs and H2 blockers | In a large US case-control study, 2 or more years of PPI use (odds ratio 1.65) or H2 blocker use (1.25) was linked with B12 deficiency. [7] | Association (observational) |
| PPIs (US label) | A pantoprazole label says daily long-term acid-suppressing treatment over a long period (for example longer than 3 years) may lead to malabsorption of B12. [8] | Regulator labeling |
| Nitrous oxide | Listed by the NHS as a medicine that can reduce B12. [2] | Listed by NHS |
An association does not prove the medicine alone caused a low level, and a low blood level is not the same as symptoms. Study results come from specific groups and may not apply to you.
We could not read the American Diabetes Association Standards of Care or NICE guidance this session (both blocked automated access), so we make no statement about what those bodies advise.
What to do
- Ask your prescriber or pharmacist whether B12 monitoring suits your situation. The labels above describe monitoring intervals for metformin. [3]
- Report symptoms (see Start here) rather than guessing at a supplement.
- If a clinician finds low B12, treatment is theirs to choose; see Vitamin B12 deficiency and Vitamin B12 tests.
- Folic acid above 1 mg a day can mask B12 deficiency. [9]
Frequently asked questions
Does metformin cause B12 deficiency?
A trial found it lowers B12 and raises the risk of deficiency over years. [4] Monitoring is described on the US label. [3]
Do acid reflux medicines lower B12?
Observational data link long-term use to deficiency. [7] Do not stop one without talking to your prescriber.
Should I take a B12 supplement with metformin?
Ask your clinician. We found no source we could read that gives a rule for everyone. The label advises monitoring and managing abnormalities. [3]
What are the signs of low B12?
The NHS lists tiredness, pins and needles, a sore tongue, memory problems and more, and says to see a GP if you suspect it. [1]
Can other medicines affect folate too?
The NHS lists some anticonvulsants, colestyramine, sulfasalazine and methotrexate for folate. [2]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
How to read the evidence labels
Labels used on this page: evidence of effect on blood levels (trial), association (observational), regulator labeling, mixed and Proper evidence not found.
Who is at extra risk
References
- NHS (UK). Vitamin B12 or folate deficiency anaemia: Overview. Page last reviewed 20 February 2023. Read 2026-10-23.
- NHS (UK). Vitamin B12 or folate deficiency anaemia: Causes. Page last reviewed 20 February 2023. Read 2026-10-23.
- US prescribing information for metformin hydrochloride tablets (generic), DailyMed, National Library of Medicine. Revised 06/2026. Read 2026-10-23.
- de Jager J, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ 2010;340:c2181.
- Aroda VR, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016;101(4):1754-1761.
- Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab 2016;42(5):316-327.
- Lam JR, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013;310(22):2435-2442.
- US prescribing information for pantoprazole sodium delayed-release tablets (generic), DailyMed, National Library of Medicine. Label version effective 2026-10-13. Read 2026-10-23.
- NHS (UK). Vitamins and minerals: B vitamins and folic acid. Page last reviewed 3 August 2020. Read 2026-10-23.