{ "dataset": "medication-nutrient-depletion-matrix", "title": "Medication -> Nutrient Depletion Matrix — depletion magnitude, repletion form, and live cost per day", "sourcePage": "https://verifiedsupplementdata.com/medications/", "license": "CC BY 4.0", "licenseUrl": "https://creativecommons.org/licenses/by/4.0/", "attribution": "Verified Supplement Data (2026), Medication-Nutrient Depletion Matrix", "dateModified": "2026-07-14", "methodology": "Each drug-nutrient depletion is anchored to a randomized trial or meta-analysis (magnitudes reflect RCT/meta values, not the top of a cross-sectional range). \"repletionForm\" is the specific form that corrects the depletion (e.g. calcium citrate, not carbonate, on a PPI). cheapestCostPerDayUSD is the lowest cost-per-day third-party-verified product in the VSD catalog, joined from live pricing. Every PMID was independently verified against NCBI for existence, topical relevance, and absence of retraction (2026-07-14). evidence: strong = consistent RCT/meta; moderate = observational/mixed RCT; limited = small/single/inconsistent.", "disclaimer": "Educational information, not medical advice. Never stop a prescribed medication over nutrient depletion. Consult your prescriber.", "columns": [ "drug", "drugClass", "drugSlug", "nutrient", "magnitude", "magnitudeDetail", "mechanism", "evidence", "repletionForm", "repletionDose", "confirmatoryTest", "cheapestCostPerDayUSD", "buyUrl", "note", "pmids" ], "units": { "cheapestCostPerDayUSD": "USD/day" }, "rowCount": 9, "rows": [ { "drug": "Metformin", "drugClass": "Diabetes medicine", "drugSlug": "metformin", "nutrient": "Vitamin B12", "magnitude": "Lowers B12 about 19% over ~4 years. Roughly 1 in 9 long-term users ends up low.", "magnitudeDetail": "In a placebo-controlled trial, metformin lowered blood B12 by 19% over 4.3 years (de Jager, PMID 20488910). A meta-analysis found about 10.7% of users become deficient (Niafar, PMID 25502588). In the DPPOS trial, 4.3% were low at 5 years vs 2.3% on placebo, and each extra year of use added ~13% to the risk (PMID 26900641). A national survey put the odds of deficiency about 2.9x higher (PMID 22179958).", "mechanism": "Metformin blocks the spot at the end of your small intestine where B12 is normally absorbed. That step needs calcium, and metformin gets in the way.", "evidence": "strong", "repletionForm": "A regular oral B12 tablet (cyanocobalamin is the best-tested; methylcobalamin is fine too)", "repletionDose": "1,000-2,000 mcg a day", "confirmatoryTest": "Ask for a blood B12 test. If it comes back \"low-normal\" but you have symptoms, ask to add an MMA or \"active B12\" test — these catch a shortage that a normal B12 reading can miss (PMID 32089757).", "cheapestCostPerDayUSD": 0.11, "buyUrl": "https://verifiedsupplementdata.com/go/nature-made-b12-sublingual-1000/", "note": "A plain swallowed B12 tablet works fine — even though metformin blocks the gut, about 1% of a high dose still soaks in on its own (a 2,000 mcg pill matched B12 shots in a trial, PMID 9694707). Sublingual (under-the-tongue) and \"methyl\" B12 are sold as better, but they are not proven better than a plain tablet. The American Diabetes Association says long-term metformin users should get their B12 checked now and then, especially at higher doses or with tingling or anemia.", "pmids": [ "20488910", "25502588", "26900641", "22179958", "10977010", "9694707", "29543316", "32089757" ] }, { "drug": "Statins", "drugClass": "Cholesterol medicine", "drugSlug": "statins", "nutrient": "Coenzyme Q10", "magnitude": "Measurably lowers CoQ10 in your blood.", "magnitudeDetail": "A meta-analysis of controlled trials found statins significantly lower CoQ10 levels in the blood (PMID 30414615).", "mechanism": "Your body makes CoQ10 and cholesterol on the same assembly line. Statins shut down part of that line to lower cholesterol, and CoQ10 drops along with it.", "evidence": "moderate", "repletionForm": "CoQ10 (either ubiquinone or ubiquinol)", "repletionDose": "100-200 mg a day", "confirmatoryTest": "No blood test needed. People just try CoQ10 for a few weeks to see if muscle aches ease up.", "cheapestCostPerDayUSD": 0.34, "buyUrl": "https://verifiedsupplementdata.com/go/doctors-best-coq10-200-bioperine/", "note": "The drop in CoQ10 is real, but whether a supplement fixes muscle aches is mixed: one trial found no help (PMID 25545331), another found less mild-to-moderate aching (PMID 25375075), and a 2025 review weighs both (PMID 41158831). Also: statins do NOT lower vitamin D — that is a common myth (PMIDs 29067242, 36416841).", "pmids": [ "30414615", "17560286", "25545331", "25375075", "41158831", "29067242", "36416841" ] }, { "drug": "PPIs", "drugClass": "Acid-reflux medicine", "drugSlug": "ppis", "nutrient": "Magnesium", "magnitude": "Long-term use can lower magnesium (the FDA warned about this in 2011).", "magnitudeDetail": "A meta-analysis of observational studies links PPI use to higher risk of low magnesium (PMID 31689852). The risk is highest after more than a year of use and when combined with water pills (diuretics). A 2024 review calls the link real but a bit inconsistent (PMID 35652564).", "mechanism": "PPIs interfere with the channels your gut uses to pull in magnesium (PMID 26981439).", "evidence": "moderate", "repletionForm": "Magnesium glycinate (gentle, absorbs well)", "repletionDose": "200-400 mg a day", "confirmatoryTest": "A blood magnesium test (note: blood can look normal even when your body stores are low).", "cheapestCostPerDayUSD": 0.18, "buyUrl": "https://verifiedsupplementdata.com/go/bulksupplements-magnesium-glycinate/", "note": null, "pmids": [ "31689852", "26981439", "35652564" ] }, { "drug": "PPIs", "drugClass": "Acid-reflux medicine", "drugSlug": "ppis", "nutrient": "Vitamin B12", "magnitude": "Long-term use is linked to low B12.", "magnitudeDetail": "A large study (JAMA) linked 2+ years of PPI use to a higher chance of low B12 (PMID 24327038), and a meta-analysis confirms the link (PMID 37060552).", "mechanism": "Your stomach needs acid to free B12 from food. PPIs cut that acid, so less B12 gets released (PMID 25083257).", "evidence": "moderate", "repletionForm": "Any oral B12 (a supplement does not need stomach acid)", "repletionDose": "500-1,000 mcg a day", "confirmatoryTest": "A blood B12 test, plus an MMA test if the result is borderline.", "cheapestCostPerDayUSD": 0.11, "buyUrl": "https://verifiedsupplementdata.com/go/nature-made-b12-sublingual-1000/", "note": null, "pmids": [ "24327038", "37060552", "25083257" ] }, { "drug": "PPIs", "drugClass": "Acid-reflux medicine", "drugSlug": "ppis", "nutrient": "Calcium", "magnitude": "Blocks calcium carbonate (the common cheap form). Calcium citrate still absorbs fine.", "magnitudeDetail": "A randomized study showed PPIs cut absorption of calcium carbonate, which needs acid to dissolve (PMID 15989913); low stomach acid does the same (PMID 4000241). PPI use is also tied to a higher fracture risk (PMID 21483462).", "mechanism": "Calcium carbonate needs stomach acid to dissolve. Calcium citrate does not, so it still absorbs on a PPI.", "evidence": "moderate", "repletionForm": "Calcium CITRATE (switching the form is the key move)", "repletionDose": "As needed alongside your diet", "confirmatoryTest": "Not usually tested — the practical fix is simply switching the form.", "cheapestCostPerDayUSD": 0.17, "buyUrl": "https://verifiedsupplementdata.com/go/citracal-maximum-plus/", "note": "The key point: fix this by switching the FORM to calcium citrate, not by taking more calcium carbonate.", "pmids": [ "15989913", "4000241", "21483462" ] }, { "drug": "PPIs", "drugClass": "Acid-reflux medicine", "drugSlug": "ppis", "nutrient": "Iron", "magnitude": "Long-term use is linked to low iron.", "magnitudeDetail": "A large study links PPI use to iron deficiency (PMID 30141278), and a meta-analysis backs it up (PMID 35255801).", "mechanism": "Acid helps your gut absorb iron, and PPIs also raise a hormone (hepcidin) that blocks iron. Both push iron down (PMID 31669099).", "evidence": "moderate", "repletionForm": "Iron bisglycinate (gentler on the stomach than iron sulfate)", "repletionDose": "Only if a blood test confirms you are low", "confirmatoryTest": "Get a ferritin and transferrin-saturation test first — do not take iron without a confirmed shortage.", "cheapestCostPerDayUSD": 0.1, "buyUrl": "https://verifiedsupplementdata.com/go/now-iron-36-ferrochel/", "note": "Only take iron if a test confirms you are low. Too much iron is harmful.", "pmids": [ "30141278", "35255801", "31669099" ] }, { "drug": "PPIs", "drugClass": "Acid-reflux medicine", "drugSlug": "ppis", "nutrient": "Vitamin C", "magnitude": "Lowers how much vitamin C you absorb from food.", "magnitudeDetail": "PPIs reduce how much vitamin C your body takes in and lower the amount in your stomach fluid (PMIDs 16167970, 19262546).", "mechanism": "With less stomach acid, vitamin C changes into a form that is harder to absorb.", "evidence": "moderate", "repletionForm": "Plain vitamin C (a supplement easily makes up the difference)", "repletionDose": "250-500 mg a day if your diet is low", "confirmatoryTest": "Not usually tested; eating fruits and vegetables normally covers it.", "cheapestCostPerDayUSD": 0.07, "buyUrl": "https://verifiedsupplementdata.com/go/now-c-1000-bioflavonoids/", "note": null, "pmids": [ "16167970", "19262546", "25083257" ] }, { "drug": "Birth control (estrogen)", "drugClass": "Estrogen birth-control pill", "drugSlug": "birth-control", "nutrient": "Folate, B6 & B12", "magnitude": "Linked to slightly lower folate, B6, and B12 (weaker evidence).", "magnitudeDetail": "Pill users show higher homocysteine and lower folate, B6, and B12 in observational data (PMID 15013271), and reviews describe changed nutrient needs on the estrogen pill (PMID 23852908).", "mechanism": "Estrogen shifts how the body handles B vitamins. The effect is small and varies from study to study.", "evidence": "limited", "repletionForm": "Methylfolate plus B12 — a methylated B-complex is the easy option", "repletionDose": "A basic daily dose; 400-800 mcg methylfolate", "confirmatoryTest": "Not usually needed — most relevant if you might become pregnant (folate) or have symptoms.", "cheapestCostPerDayUSD": 0.11, "buyUrl": "https://verifiedsupplementdata.com/go/life-extension-optimized-folate/", "note": "Folate matters most if pregnancy is possible. B6 and zinc are also mentioned, but the evidence is thinner and we do not list a tested product for them.", "pmids": [ "15013271", "23852908" ] }, { "drug": "Birth control (estrogen)", "drugClass": "Estrogen birth-control pill", "drugSlug": "birth-control", "nutrient": "Magnesium", "magnitude": "May slightly affect magnesium (weak evidence).", "magnitudeDetail": "Older research describes a link between magnesium and estrogen (PMID 8409107); how much this matters for today's low-dose pills is unclear.", "mechanism": "Estrogen can shift where magnesium goes in the body; direct proof of a real shortfall is weak.", "evidence": "limited", "repletionForm": "Magnesium glycinate", "repletionDose": "200-300 mg a day", "confirmatoryTest": "Not usually tested.", "cheapestCostPerDayUSD": 0.18, "buyUrl": "https://verifiedsupplementdata.com/go/bulksupplements-magnesium-glycinate/", "note": null, "pmids": [ "8409107" ] } ] }