Medicines That Lower Vitamins and Minerals: Metformin, PPIs, Diuretics and What to Test

Some common medicines lower a vitamin or mineral over months or years, and a few do the opposite and push potassium too high. This guide covers adults and sorts each pair by how well it is documented: on the drug's FDA-approved label, in an FDA safety communication, in pooled studies, or only in marketing.

Get tested before you supplement, and never change your medicine yourself. A blood test shows whether you are actually low; your clinician then sets the dose. Don't stop, skip or swap a prescribed medicine to avoid a "depletion": ask your prescriber or pharmacist.

The short version

• Metformin and vitamin B12: on the label, which says to check B12 every 2 to 3 years. Lower B12 in adults with type 2 diabetes or prediabetes, against placebo. A Grade A (de Jager 2010; Aroda 2016).
• Acid-reducing PPIs (omeprazole and others) and magnesium: an FDA safety communication and the label; low magnesium was more common in users than non-users in observational studies. C Grade C (Srinutta 2019).
• Thiazide water pills and potassium: lower potassium against other blood pressure medicines in 10 trials. A Grade A (Mukete 2013). Spironolactone, ACE inhibitors and ARBs do the opposite: potassium supplements and salt substitutes can push potassium dangerously high (spironolactone label).
• Statins and CoQ10: blood levels fall, but no harm from that fall has been shown (Banach 2015).

Does metformin deplete vitamin B12, magnesium or CoQ10?

Vitamin B12: on the label, grade A for lower levels (adults with type 2 diabetes or prediabetes, against placebo). The metformin label says it may lower B12 and tells prescribers to measure B12 every 2 to 3 years and blood counts yearly (DailyMed). In 390 insulin-treated adults with type 2 diabetes, 4.3 years of metformin left B12 19% lower than placebo, and deficiency was 7.2 percentage points more common (de Jager 2010). In the Diabetes Prevention Program, people with prediabetes on metformin more often had low B12 at 5 years (4.3% against 2.3%), and nerve damage turned up more often in metformin users whose B12 was low (Aroda 2016). Pooling 4 trials, B12 was 57 pmol/L lower after 6 weeks to 3 months (Chapman 2016). The test is the point, not stopping metformin: see does metformin lower vitamin B12? and vitamin B12 for energy.

Magnesium: grade C, an association only. In 929 people with type 2 diabetes in primary care, metformin use went with slightly lower blood magnesium, as did several other diabetes medicines (Waanders 2020). CoQ10 and vitamin D: marketing claims, not shown. No study in people has shown that metformin lowers either; the metformin and CoQ10 studies are animal and lab work.

Does omeprazole deplete magnesium, B12, iron or calcium?

Magnesium: FDA safety communication and label; grade C (observational studies). In 2011 the FDA warned that prescription proton pump inhibitors (PPIs), such as omeprazole, esomeprazole and pantoprazole, can cause low magnesium when taken for long periods, in most cases over a year. In about a quarter of the cases it reviewed, magnesium supplements alone did not fix the level and the PPI had to be stopped. It told prescribers to consider checking magnesium before and during long-term use, especially with digoxin or diuretics, and said over-the-counter PPIs used as the package directs carry very little risk (FDA 2011). Across 16 observational studies (131,507 people), 19.4% of PPI users had low magnesium against 13.5% of non-users (adjusted odds ratio 1.71), more so at high doses (Srinutta 2019).

Vitamin B12: on the label; grade C. The omeprazole label says daily use for more than 3 years may lead to B12 deficiency (DailyMed). Comparing 25,956 people diagnosed with B12 deficiency and 184,199 without, 2 or more years of PPIs (odds ratio 1.65) or H2 blockers such as famotidine (1.25) were more common in those with deficiency (Lam 2013); a 2023 review of 25 studies called the link small and inconsistent (odds ratio 1.42, 2,852 PPI users against 28,070 non-users) (Choudhury 2023).

Iron: grade C. The label notes that PPIs can cut absorption of medicines that need stomach acid, including iron salts. In a similar study, 2 or more years of PPIs went with iron deficiency (adjusted odds ratio 2.49), more at higher doses, and less after stopping (Lam 2017). See iron supplements.

Calcium and bones: on the label; grade C. The label warns that multiple daily doses for a year or longer may raise the risk of hip, wrist and spine fractures (DailyMed). Across 24 observational studies (about 2.1 million people), hip fractures were 20% more common in PPI users (risk ratio 1.20) (Poly 2019). Ask whether you still need the PPI and at what dose; see heartburn and reflux.

Which water pills and blood pressure medicines change potassium and magnesium?

Thiazide and loop diuretics lower potassium and magnesium: on the labels; grade A for potassium with low-dose thiazides (against other blood pressure medicines); loop diuretics: on the label. The hydrochlorothiazide label warns of low potassium, especially with brisk water loss or long use, and says thiazides raise magnesium loss in urine (DailyMed). The furosemide label adds steroids, large amounts of licorice and long laxative use as extra risks (DailyMed). In 10 trials (17,636 people), potassium fell 0.22 mmol/L on low-dose thiazides and rose 0.05 on other blood pressure drugs (Mukete 2013). Your prescriber checks this with blood tests and may prescribe potassium. Thiazides also hold on to calcium and can nudge blood calcium up (label above), so ask before adding calcium or high-dose vitamin D.

Spironolactone, ACE inhibitors and ARBs raise potassium: on the labels; grade C for harm. The spironolactone label says potassium supplements, potassium-based salt substitutes and ACE inhibitors or ARBs raise the risk of high potassium, which can be severe (DailyMed); the lisinopril label lists kidney problems and diabetes as well (DailyMed). After spironolactone use jumped in Ontario, hospital stays for high potassium in older people with heart failure on ACE inhibitors rose from 2.4 to 11.0 per 1,000, and deaths from 0.3 to 2.0 per 1,000 (Juurlink 2004). On these medicines, take no potassium pills or salt substitutes unless prescribed. See electrolyte supplements and can I take magnesium with blood pressure medicine?

Do statins lower CoQ10?

Statins lower the CoQ10 in your blood: across 8 placebo-controlled trial arms, by 0.44 µmol/L (Banach 2015). Whether this fall matters is unclear: trials of CoQ10 for statin muscle pain disagree: two reviews (6 and 7 trials) found no clear benefit (Banach 2015; Kennedy 2020), while a review of 12 trials (575 people) found less muscle pain (Qu 2018); see CoQ10 supplements and CoQ10.

Which epilepsy medicines affect vitamin D and folate?

Vitamin D and bone: on the phenytoin label; grade C (observational). The phenytoin label links long-term use with thinner bones and fractures, says it can lower vitamin D, and asks prescribers to consider bone-related blood tests (DailyMed). In 12 studies, people on carbamazepine had vitamin D levels 4.00 ng/mL lower on average (LoPinto-Khoury 2021); another review found lower vitamin D and calcium but no clear difference in bone density (Zhang 2020). Ask about testing; see epilepsy and vitamin D supplements.

Folate and pregnancy: on the valproate label. Valproate raises the risk of birth defects, including neural tube defects. The label says folic acid before conception and early in pregnancy lowers neural tube defects in the general population, but it is not known whether it lowers the risk with valproate, and that valproate must not be stopped suddenly because seizures can follow (DailyMed). If you could become pregnant on any seizure medicine, plan with your neurologist and your midwife or obstetric team before pregnancy.

When is a supplement part of the treatment?

• Methotrexate and folic acid: on the label; grade B. For rheumatoid arthritis, psoriasis and juvenile arthritis, prescribers usually add folic or folinic acid to cut side effects, as the label tells them to. In cancer treatment, the label says folate can make methotrexate work less well, so never take folic acid unless your oncology team says so (DailyMed). In 6 trials (624 people with rheumatoid arthritis), it meant fewer stomach side effects (risk ratio 0.74), fewer liver test rises (0.23) and fewer people stopping methotrexate (0.39), at moderate quality (Shea 2013). Take it only as your prescriber directs.
• Steroid tablets and bone: on the label. The prednisone label lists osteoporosis and spine fractures and says steroids raise calcium and potassium loss (DailyMed). For adults on steroids for more than 3 months, the American College of Rheumatology advises an early fracture-risk check (Humphrey 2023) and has recommended calcium and vitamin D, with a bone medicine at higher risk (Buckley 2017). See osteoporosis.
• Isoniazid and vitamin B6: on the label. The tuberculosis medicine can lower B6; nerve damage in the feet and hands is its most common toxic effect, and the label recommends B6 for people who are malnourished or prone to nerve damage, such as those with diabetes or heavy drinking (DailyMed). Take B6 only as your prescriber directs.
• GLP-1 medicines: eating much less can leave gaps; see supplements on GLP-1 medicines.

Which "depletion" claims aren't backed by evidence?

Charts online list dozens of drug-nutrient pairs. Even a 2018 review written partly by supplement-company staff (its conflict-of-interest statement says so) concluded that most pairs need better trials and that widespread supplementation is not recommended (Mohn 2018). Examples:

• Metformin "depletes CoQ10 or vitamin D": no study in people shows it (above).
• Birth control pills "deplete folate and B12": grade C, mostly not. A review found current low-dose pills do not clearly lower folate and do not affect functional B12 markers, though they may lower B6 levels (Wilson 2011).
• "Every statin user needs CoQ10": the blood-level fall is real, but whether topping it up eases statin muscle pain is unclear, because the reviews disagree (above); see CoQ10 supplements.

Safety and interactions

• Test, then treat. Ask which test fits your medicine (B12, magnesium, potassium, vitamin D, ferritin) and let your clinician set any dose.
• Potassium: no upper limit has been set, but in people whose kidneys clear it poorly, from kidney disease or medicines such as ACE inhibitors or potassium-sparing diuretics, extra potassium can be dangerous (NIH ODS).
• Magnesium: upper limit for adults, 350 mg a day from supplements and medicines, because higher doses cause diarrhea, nausea and cramps; take more only on your clinician's advice (NIH ODS; check your stack). With kidney disease, kidneys that don't clear magnesium can let it build up to dangerous levels (weakness, low blood pressure, heart rhythm problems), from supplements, antacids or laxatives; don't take magnesium supplements unless your kidney doctor advises it (NIH ODS); see supplements and your kidneys.
• Iron: keep iron tablets locked away from children, because an accidental overdose can kill a young child; take iron only if a test shows you are low and your clinician advises it (NIH ODS).
• Vitamin D: upper limit for adults, 4,000 IU (100 mcg) a day, because more can raise blood calcium; go higher only with blood tests or your clinician's advice (NIH ODS).
• Vitamin B6: upper limit for adults, 100 mg a day, because months of large doses can damage the nerves that carry feeling (NIH ODS).
• Folic acid: upper limit for adults, 1,000 mcg a day from supplements and fortified foods, because large amounts can hide the anemia of B12 deficiency while nerve damage goes on, which matters on metformin or PPIs (NIH ODS).
• Spacing: iron, calcium and magnesium can block some medicines; see can I take iron, calcium or magnesium with levothyroxine?

When to see a doctor

• Urgently: muscle spasms, tremor, an irregular heartbeat or a seizure on a PPI or water pill (possible low magnesium) (FDA 2011); weakness, cramps or a racing or irregular heartbeat on a water pill (possible low potassium) (DailyMed), or on spironolactone or an ACE inhibitor (possible high potassium).
• Soon: numbness or tingling in your hands or feet, memory changes, a sore tongue, or tiredness with pale skin or breathlessness on metformin or long-term acid reducers (possible B12 deficiency, which can cause anemia and nerve damage) (NIH ODS).
• Also soon: a bone broken in a minor fall on steroids, PPIs or seizure medicines; burning or numb feet on isoniazid.
• Before pregnancy: if you take a seizure medicine, see your neurologist and your midwife or obstetric team first.

Don't stop a prescribed medicine on your own; ask the prescriber or pharmacist. If you are pregnant or breastfeeding, ask your midwife or obstetric team. If you are under 18, ask a clinician.

FAQ

What vitamins does metformin deplete? Vitamin B12. It is on the label, which says to check B12 every 2 to 3 years, and in placebo-controlled trials of people with type 2 diabetes or prediabetes, B12 ended lower on metformin (grade A). No study in people shows metformin lowers CoQ10 or vitamin D.

Does omeprazole deplete magnesium? It can, usually after more than a year of prescription use. The FDA warned in 2011, and in about a quarter of its cases magnesium supplements alone did not fix the level. Observational studies link PPIs with low magnesium (grade C). Ask for a magnesium test.

Should I take a supplement to stop my medicine depleting nutrients? Not without a test. Get the blood test that fits your medicine; if you are low, your clinician sets the dose. Some supplements, such as potassium on spironolactone or ACE inhibitors, can be dangerous.

Do water pills lower potassium? Thiazide and loop diuretics can, and in 10 trials low-dose thiazides lowered potassium against other blood pressure medicines (grade A). Spironolactone does the opposite, so don't add potassium yourself.

Related pages

• Vitamin B12 · Vitamin B12 deficiency protocol · Magnesium · Potassium · Folic acid · Vitamin D · Calcium · Vitamin B6
• Type 2 diabetes · Reflux protocol · Epilepsy protocol · Osteoporosis
• Can I take berberine with metformin? · Electrolyte supplements · Vitamin D supplements · Iron supplements
• Check my stack · How we grade

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