Proton Pump Inhibitors (PPIs)
Common brand names: Prilosec, Nexium, Protonix, Prevacid
Five nutrients listed against this medication. The most severe is marked critical.
At a glance
All five are marked well documented.
At a glance
- Magnesium (Glycinate)Critical · Well documented
- Vitamin B12Critical · Well documented
- ZincModerate · Well documented
- Vitamin CModerate · Well documented
- IronModerate · Well documented
Color shows how serious each listed effect is. The label beside it shows how strong the evidence is. The cards below explain each one and show its evidence.
Nutrients it can lower
A prescribing cascade is when the side effect of one drug is read as a new condition and a second product is started to treat it. In 2025 an international panel of experts in geriatric medicine and pharmacology published a list of 65 potentially inappropriate cascades. Two begin with a proton pump inhibitor: a PPI followed by a vitamin supplement after osteoporosis or fracture, and a PPI followed by a vitamin or mineral supplement after a deficiency. The depletions listed on this page are the first half of both sequences. The panel's concern is that the second product is added while the first drug goes unreviewed. The list is expert consensus, not a trial finding, and it does not say that repletion is wrong for any individual.
Rochon et al. (European Geriatric Medicine, 2025; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 40742670): international expert panel's list of 65 potentially inappropriate prescribing cascades.
Mechanism, PPIs reduce gastric acid needed for magnesium absorption in the duodenum. The FDA issued a black box warning in 2011 for hypomagnesemia in PPI users. Risk increases significantly after 1+ year of use.
Common signs, Muscle cramps, tremors, cardiac arrhythmia, hypertension, fatigue, anxiety
Observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. study of older inpatients (Sr Care Pharm, 2022; PMID 36461136): PPI use was associated with hypomagnesemia, consistent with the FDA's 2011 warning on PPI-induced low magnesium.
Magnesium bisglycinate was used at 300–400 mg daily. With long-term PPI use, serum magnesium is commonly monitored every 6 months.
Mechanism, B12 absorption requires gastric acid to cleave it from food proteins. PPIs suppress acid production, dramatically reducing food-bound B12 absorption. Crystalline B12 in supplements bypasses this.
Common signs, Cognitive decline, peripheral neuropathy, fatigue, elevated homocysteine An amino acid in the blood that rises when vitamin B12, folate or B6 are low.
Lam et al. (JAMA, 2013; PMID 24327038): 2+ years of PPI use was associated with roughly a 65% higher risk of vitamin B12 deficiency.
Methylcobalamin 1,000–2,000 mcg sublingual daily is a range in common use, not from a trial cited on this row. Lam reports B12 deficiency associated with acid-suppressant use and tested no repletion dose, form or route.
Mechanism, Gastric acid is required for zinc ionization and absorption. PPI use reduces zinc bioavailability The share of a dose that reaches the bloodstream in a form the body can use. by 40–50%.
Common signs, Immune suppression, wound healing delay, taste/smell changes, skin issues
Sturniolo et al. (J Am Coll Nutr, 1991; PMID 1894892): inhibition of gastric acid secretion reduced zinc absorption in man.
Zinc 15–30 mg daily with food is a range in common use, not from a trial cited on this row. The cited paper measured zinc absorption under acid suppression and tested no repletion dose or form.
Mechanism, Ascorbic acid (Vitamin C) in the stomach is converted from dietary sources partly via acid-dependent mechanisms. PPI users show lower gastric and serum Vitamin C.
Common signs, Immune impairment, oxidative stress, slower tissue repair
Henry et al. (Aliment Pharmacol Ther, 2005; PMID 16167970): a short course of omeprazole reduced plasma vitamin C in healthy volunteers, independent of dietary intake.
Vitamin C 500–1,000 mg daily is a range in common use, not from a trial cited on this row. The cited paper reports reduced bioavailability of dietary vitamin C on a proton pump inhibitor; it tested no supplemental dose and no buffered form.
Mechanism, Non-heme iron (from plants) requires an acidic environment for conversion to absorbable ferrous form. PPI use impairs this conversion.
Common signs, Fatigue, anemia, cold intolerance, cognitive fog
Hutchinson et al. (Gut, 2007; PMID 17344278): a PPI suppressed absorption of dietary non-haem iron from a test meal, confirming the acid-dependent absorption mechanism.
Serum ferritin is commonly monitored. Where iron is supplemented, ferrous bisglycinate is often chosen as better tolerated and more absorbable than ferrous sulfate. In a 2026 study of 2.3 million adults aged 66 and over in Ontario, 11.9% of people who started an iron supplement were started on a laxative afterward, the highest incidence the study reports. The study records the order in which prescriptions were filled, not that iron caused each one (Rochon et al., BMJ, 2026; PMID 42727946).
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Disclosure
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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