Metformin and Vitamin B12: Do You Need a Supplement?

Yes. In a 4.3-year trial of 390 insulin-treated adults with type 2 diabetes, metformin lowered vitamin B12 by 19% more than placebo, and deficiency was 7.2 percentage points more common¹. The UK medicines regulator now calls B12 deficiency a common metformin side effect, affecting up to 1 in 10 people².

The fix is to test your level rather than guess, and to treat a low result with a supplement or injection while you stay on metformin^{2, 3}. Most other supplements are compatible. Berberine lowers glucose and can add to metformin's effect, and goldenseal modestly lowered metformin levels in one human study, so tell your prescriber about either^{4, 5}. For the general evidence, see our pages on vitamin B12 and B12 deficiency.

Yes, in a way that grows with dose and time, although most people on metformin never become frankly deficient. The strongest evidence is the placebo-controlled trial above: B12 fell by 19% (95% CI 14% to 24%) with 850 mg of metformin three times a day, and the number needed to harm for deficiency was 13.8 over 4.3 years¹. The other evidence points the same way:

• Pooled studies: a meta-analysis of 31 studies found 2.09 times the risk of B12 deficiency with metformin and serum B12 lower by 63.7 pmol/L, depending on dose and duration⁶. An earlier analysis of 29 studies in 8,089 patients found an odds ratio of 2.45⁷.
• Long-term follow-up: in the Diabetes Prevention Program, 4.3% of metformin users had low B12 at 5 years versus 2.3% on placebo. At 13 years the gap (7.4% versus 5.4%) was no longer statistically significant. Low or borderline B12 was more common with metformin at both points, and each year of use raised the odds of deficiency by 13%⁸.
• Everyday populations: among US adults aged 50 or older with type 2 diabetes, 5.8% of metformin users were B12 deficient versus 2.4% of non-users⁹.
• People without diabetes: in 492 non-diabetic, high-risk breast cancer patients, median B12 after 6 months was 320 pmol/L on metformin versus 380 pmol/L on placebo (baseline medians were 390 and 370)¹⁰.

The metformin label reports that about 7% of patients with previously normal B12 dropped to subnormal levels in trials lasting 29 weeks, and that the change is rapidly reversible with supplements or by stopping the drug¹¹.

Low blood B12 is not always illness. The meta-analysis found no significant overall link between metformin and anemia or neuropathy⁶, and in the Diabetes Prevention Program anemia was more common with metformin but did not differ by B12 status⁸. Yet in the 390-person trial, metformin raised methylmalonic acid, a marker of B12 shortage inside tissues, and that rise was tied to worse neuropathy scores. Better glucose control offset it, so the net effect on neuropathy was not significant¹².

Levels start to fall within months, but frank deficiency usually takes years. Four trials lasting 6 weeks to 3 months found B12 lower by an average of 57 pmol/L¹³. In non-diabetic patients, median B12 fell from 390 to 320 pmol/L within 6 months of metformin, while it stayed near 370 to 380 pmol/L on placebo¹⁰. In the Diabetes Prevention Program, deficiency appeared in 4.3% of users by year 5⁸.

Risk rises with a higher dose, a longer course and other B12 risk factors, according to the regulator². B12 deficiency symptoms can take several years to appear¹⁴, which is why testing matters more than waiting for symptoms.

The regulator describes the mechanism as multifactorial: altered gut motility, bacterial overgrowth and reduced uptake of B12 in the small intestine². One proposed pathway is that metformin disrupts calcium-dependent uptake of the B12 and intrinsic factor complex in the ileum, the last part of the small intestine¹⁵. In 14 adults with type 2 diabetes switched to metformin, serum B12 and its active carrier form (holotranscobalamin) fell, and oral calcium reversed the drop in holotranscobalamin¹⁵.

A 2024 crossover pilot in 7 healthy adults tracked a labelled B12 dose. Absorption was 42.6% alone, 30.8% with 850 mg of metformin and 46.4% with metformin plus 500 mg of calcium¹⁶. Both studies are small, and the authors say calcium as a preventive strategy needs more study¹⁶.

The label notes that people with inadequate B12 or calcium intake or absorption seem more likely to develop low B12¹¹. That is a reason to meet your calcium needs from food, such as the options in our calcium-rich foods guide, not a reason to start high-dose calcium on your own. A review in Advances in Nutrition adds that a low blood level does not prove functional deficiency, which is why extra markers are used¹⁷.

Fatigue and neurological changes lead the list, followed by megaloblastic anemia, a sore swollen tongue (glossitis), palpitations and low blood counts¹⁴. Numbness and tingling in the hands and feet can occur, even without anemia¹⁴.

This overlaps with diabetic neuropathy, so symptoms alone cannot tell you the cause. The regulator advises testing B12 in metformin users who present with megaloblastic anemia or new-onset neuropathy². Our pages on peripheral neuropathy and anemia cover the other causes.

Not automatically, but you should know your level. Guidelines ask for monitoring, not blanket supplements. The metformin label says to measure blood counts yearly and B12 every 2 to 3 years¹¹. The 2026 American Diabetes Association standards say to "monitor and replete as appropriate"³. The UK regulator advises testing people with symptoms and considering periodic checks when risk factors are present².

A 2022 systematic review of 7 trials in 506 metformin-treated adults found that B12 supplements raised serum B12 in all 5 trials that measured it, and noted that no guideline then recommended routine supplementation¹⁸. A review in Advances in Nutrition suggests a middle path: monitor B12 and supplement once blood markers or clinical signs turn abnormal¹⁷.

Three situations favour acting sooner^{2, 14}:

• Symptoms: new numbness or tingling, unusual fatigue or anemia.
• Long or high-dose use: the regulator links risk to higher doses and longer treatment.
• Other B12 risk factors: older age, stomach or bowel conditions or surgery, pernicious anemia, a vegan or some vegetarian diets, low-normal B12 at baseline, and medicines that impair absorption, including proton pump inhibitors, H2 blockers such as cimetidine, and colchicine.

A serum B12 test comes first. Most laboratories call values below 200 or 250 pg/mL (148 or 185 pmol/L) subnormal, and a methylmalonic acid (MMA) test can confirm deficiency when B12 sits between 150 and 399 pg/mL¹⁴. An MMA above 0.271 micromol/L suggests deficiency, but kidney impairment and older age also raise it¹⁴. The 390-person trial defined deficiency as below 150 pmol/L and "low" as 150 to 220 pmol/L¹.

Because serum B12 alone can mislead, a review in Advances in Nutrition favours measuring at least 2 of 4 markers: total B12, holotranscobalamin, homocysteine and MMA¹⁷. Ask which markers your result used.

We found no trial that compared B12 forms head to head in metformin users, so no form is proven best. The trials below used methylcobalamin or hydroxocobalamin, while cyanocobalamin is the most common form in supplements¹⁴. What the metformin trials gave:

• 1,000 mcg a day by mouth for 12 months: in 90 adults who had taken metformin for at least 4 years and had diabetic neuropathy, methylcobalamin raised B12 from 232 to 777 pmol/L and improved nerve conduction, vibration sensing and pain scores, while the placebo group worsened¹⁹.
• 1,000 mcg a day under the tongue for 3 months: in 34 adults on metformin with B12 below 220 pmol/L, this beat a single 1 mg hydroxocobalamin injection at 3 months (372 versus 252 pmol/L). The two were similar at 6 months²⁰.
• Oral versus injection in general: a Cochrane review of 3 trials in 153 people found oral doses of 1,000 to 2,000 mcg a day normalised B12 about as well as injections, though the evidence was low quality²¹.
• Multivitamin amounts: the adult recommended intake is 2.4 mcg a day¹⁴, and a typical multivitamin has about 6 mcg. In US survey data, B12-containing supplements were not linked to less deficiency among people with diabetes, unlike those without diabetes, so those amounts may not be enough⁹.

B12 has no tolerable upper intake level because toxicity is low even at high doses¹⁴. The dose for a confirmed deficiency, and whether you need injections, is your clinician's call. Keep taking metformin while the deficiency is treated².

How should you take B12 with metformin?

We found no study showing that B12 must be spaced from metformin, and B12 is not in the label's interaction table. Metformin itself is taken with meals¹¹.

Does B12 fix neuropathy in metformin users?

Possibly, but the evidence is unclear. The systematic review of 7 trials found a significant improvement in neuropathy symptoms in 2 studies and no significant effect in 1¹⁸. The 1-year trial above is the clearest positive result; it enrolled people with B12 below 400 pmol/L¹⁹.

B12 is the one vitamin the American Diabetes Association flags for metformin users³. The others below have weaker or indirect evidence:

• Vitamin B12: test, then replace if low, as above.
• Folate and B-group vitamins: in a meta-analysis of 12 randomised trials, metformin raised homocysteine by 2.02 micromol/L when no folic acid or B vitamins were given, and lowered it by 0.74 micromol/L when they were. Overall, metformin did not significantly change homocysteine (+0.40 micromol/L, p = 0.10), and homocysteine is a marker, not an outcome²². See our folate page.
• Calcium: adequate intake matters for B12 absorption, as covered above¹¹.
• Niacin (vitamin B3): the label lists nicotinic acid, a form of niacin, among drugs that tend to raise blood glucose and may weaken glycemic control¹¹. See vitamin B3.

Can you take metformin and vitamins at the same time? The label's interaction table does not list B12, folate, calcium or magnesium¹¹, so the usual answer is yes, with the niacin caveat above.

Mostly yes, but the caveats differ. None of these appear in the label's interaction table¹¹, so the guidance below comes from smaller studies.

Berberine and goldenseal

Berberine lowers glucose in a way that adds to metformin. In a pilot of 36 adults with newly diagnosed type 2 diabetes randomised to berberine or metformin (0.5 g three times a day), HbA1c fell from 9.5% to 7.5% in the berberine group, similar to metformin. Across the pilot's two studies, 34.5% of berberine-treated patients had transient digestive effects²³. A meta-analysis of 14 trials in 1,068 people found that berberine plus an oral drug beat the drug alone, though study quality was low⁴.

The effect on metformin levels is mixed. In cells and in rats given intravenous metformin, berberine blocked the OCT1 and OCT2 transporters that move metformin and raised metformin exposure²⁴. In mice, oral berberine alone did not change metformin levels²⁵. Goldenseal, which contains berberine, lowered metformin exposure by about 20% at low metformin doses (500 to 750 mg) and by 0% at high doses (2,000 to 2,550 mg) in adults with type 2 diabetes. Overall, the change was not clinically meaningful, though the authors still suggest cautioning patients⁵. Tell your prescriber before starting, and see our berberine and goldenseal pages.

Inositol

The combination has been tested, in women with polycystic ovary syndrome (PCOS). A meta-analysis of 6 trials in 388 women lasting 3 to 6 months found that adding inositol to metformin improved cycle regularity (risk ratio 1.56) and hirsutism scores, with no significant difference in fasting glucose, HOMA-IR or BMI²⁶. The data are limited to PCOS. See myo-inositol and myo-inositol for PCOS.

Magnesium

Low magnesium (below 1.7 mg/dL) has been reported with metformin, possibly from digestive losses and uptake into cells, but chronic use also appears to lower urinary magnesium loss. The evidence is a case plus a narrative review, so it is limited²⁷. In a 16-week trial in 63 adults with type 2 diabetes and low magnesium (taking glibenclamide, not metformin), at the end of the trial HOMA-IR was 3.8 with magnesium chloride versus 5.0 with placebo, and fasting glucose was 8.0 versus 10.3 mmol/L²⁸. A blood test is the only way to know if you are low. See magnesium.

Apple cider vinegar

A meta-analysis of 7 controlled trials in type 2 diabetes found that apple cider vinegar lowered fasting glucose by 21.9 mg/dL and HbA1c by 1.53 points, with no effect on HOMA-IR. The abstract does not break results out by metformin use²⁹. See apple cider vinegar.

Other glucose-lowering supplements

A pharmacist-oriented review of 10 natural products with antidiabetic effects (including alpha-lipoic acid, chromium, magnesium, bitter melon, cinnamon and fenugreek) warns that they can add to the hypoglycemia caused by conventional medicines³⁰. Metformin alone carries little hypoglycemia risk³. For ashwagandha, turmeric, CoQ10 and melatonin we did not review metformin-specific safety data, so ask a pharmacist to check them against your prescription.

Metformin's boxed warning is lactic acidosis, a rare but serious build-up of lactate. Symptoms in reported cases included malaise, muscle pain, breathing difficulty, sleepiness and abdominal pain¹¹. The label lists these risk factors, and some matter for supplement and medicine choices¹¹:

• Kidney disease: metformin must not be used when eGFR is below 30 mL/min/1.73 m2, and starting it is not recommended at an eGFR of 30 to 45^{11, 3}. Kidney impairment also raises MMA, which can confuse a B12 test¹⁴.
• Liver disease, age 65 or older, and low-oxygen states: the label lists hepatic impairment, age 65 years or more and hypoxic states such as acute heart failure as risk factors, and advises avoiding metformin in hepatic disease¹¹.
• Contrast imaging and surgery: both are listed risk factors, so tell the team you take metformin¹¹.
• Acid-suppressing drugs and colchicine: proton pump inhibitors, H2 blockers and colchicine can also impair B12 absorption, so they stack with metformin's effect^{2, 14}.
• Insulin or sulfonylureas: metformin may increase hypoglycemia risk with these, and a lower dose of insulin or the sulfonylurea may be needed¹¹.
• Carbonic anhydrase inhibitors: topiramate, zonisamide, acetazolamide and dichlorphenamide may raise the risk of lactic acidosis, so more frequent monitoring is advised¹¹.
• Drugs that reduce metformin clearance: ranolazine, vandetanib, dolutegravir and cimetidine can raise metformin exposure¹¹.
• Alcohol: it potentiates metformin's effect on lactate metabolism, so excessive intake should be avoided¹¹.

A short plan for people taking metformin, based on the guidance above^{11, 2}:

1. Check your last test. The label schedule is B12 every 2 to 3 years, sooner with symptoms.
2. Ask for a B12 test now if you have numbness, tingling, unusual fatigue or anemia.
3. If B12 is low, ask whether oral 1,000 to 2,000 mcg a day or injections suit you²¹, and keep taking metformin.
4. Before adding a supplement, tell your prescriber about berberine, goldenseal or anything that lowers glucose, especially on insulin or a sulfonylurea.
5. Cover calcium from food rather than guessing at doses.

Food is one source of B12 (the adult recommended intake is 2.4 mcg a day¹⁴); see our vitamin B12 foods guide. If you also take tirzepatide, our tirzepatide and B12 guide covers that drug's B12 question.

Supplements in this guide

• Vitamin B12
• Berberine
• Myo-Inositol
• Magnesium
• Folate (Vitamin B9)
• Calcium

We searched the research literature on metformin and B12, calcium absorption, B12 treatment and supplement interactions, then read the abstracts of 26 journal records and the full text of the MHRA drug safety update, the 2026 American Diabetes Association standards table, the NIH Office of Dietary Supplements B12 fact sheet and the FDA metformin label. We prioritised randomised trials and meta-analyses. Most B12 evidence is observational or comes from trials where B12 was a secondary outcome, and supplement-interaction data are thin, with some from cells and animals. We did not review ashwagandha, turmeric, CoQ10 or melatonin interactions. An independent reviewer checked the draft against its sources, and we corrected the issues it found before publishing. Researched 30 October 2026.

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