Lansoprazole

Limits on what this shows

• Key null findings: The adipocyte result runs opposite to inhibition ([19]). No human electron-transport, membrane potential or biogenesis data found.
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the label sections read.

Population evidence

Tier B, no human cohort. [16] Lansoprazole kills intracellular M. tuberculosis by targeting cytochrome bc1 after sulfoxide reduction to lansoprazole sulfide; the abstract states it spares the human H+/K+-ATPase and gives no data on human mitochondrial bc1. [17] Screen of 727 FDA-approved drugs: lansoprazole metabolite(s) interact with complex III in Candida auris, with a 1.7-log CFU reduction in a mouse kidney burden when combined with amphotericin B. [18] H. pylori respiration inhibited dose-dependently, rotenone-like substrate pattern. [19] In mice, lansoprazole raised energy expenditure and increased thermogenic gene expression and mitochondrial respiration in primary adipocytes via PHOSPHO1 inhibition.

Mechanism

Named in microbes (cytochrome bc1 / complex III). Absent for human mitochondria: no study opened tests human cells or tissue for bc1 inhibition.

Counter-evidence held on record

Microbial targets with metabolite-dependent activation do not establish a human effect; the mouse study's dose is not stated in the abstract. Do not present this as human mitochondrial toxicity, and do not present the mouse result as a metabolic benefit.

Limits on what this shows

• Key null findings: The in-vitro concentration in [21] (10^-4 M) is not related to plasma exposure in any source opened.
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the label sections read.

Population evidence

Tier B, in vitro. [20] In endothelial cells and macrophages lansoprazole increased HO-1 mRNA and ferritin protein and decreased NADPH-mediated ROS formation; the radical-scavenging effect diminished with an HO inhibitor. [21] Lansoprazole at 10^-4 M significantly inhibited the roughly twofold rise in oxygen-derived free radical production of human neutrophils exposed to H. pylori extract, and tissue myeloperoxidase fell after treatment in biopsies. [17] In Candida auris, complex III interaction increased oxidative stress within fungal cells.

Mechanism

Named for the protective effect (HO-1 induction through a pathway blocked by the PI3K inhibitor LY294002, [20]). No systemic antioxidant-capacity or lipid-peroxidation data in lansoprazole users were found.

Counter-evidence held on record

The drug's own chemistry appears protective in vitro; no source shows depletion of antioxidants. This is a reverse-direction mechanistic finding. It is not evidence that lansoprazole is an antioxidant therapy, and no antioxidant supplementation is implied.

Limits on what this shows

• Key null findings: No difference in iron/ferritin deficiency by PPI type [12]. No lansoprazole study of iron status was retrieved. The Gastroenterology cohort on PPI and iron deficiency [28] had no retrievable abstract.
• At-risk subgroups: People relying on non-haem iron or oral iron salts (label pH-dependence). In haemochromatosis the effect lowered phlebotomy need [13].

Regulatory status

Label section 7 (7/2023 extract) lists iron salts among agents whose absorption depends on gastric pH and is reduced by lansoprazole; this is a drug-affects-nutrient direction [1]. The label gives no separation interval in the extract read.

Population evidence

Class-level, Tier C [13]: 7 haemochromatosis patients needed 2.5 L vs 0.5 L blood removed per year before vs during PPI therapy; in 14 phlebotomised patients with normal iron stores, 7 days of PPI lowered area under the serum iron curve, percentage recovery of a 14.5 mg dietary iron dose, and peak serum iron and ferritin. The PPI used is not named in the abstract. A 37-patient pilot of long-term PPI users vs 30 unmatched controls measured iron but the abstract gives no iron direction [14]. In a 255-patient cross-sectional study, ferritin below 30 ng/mL did not differ significantly by PPI type (33/101 omeprazole, 29/61 esomeprazole), with no lansoprazole figure in the abstract and no non-user group [12].

Mechanism

Present, class A: gastric acid supports non-haem iron absorption [13]. Not tested in a lansoprazole cohort.

Cohort test

[13] fails for this drug (lansoprazole not shown in the cohort), so it is Tier C class extrapolation, capped at yellow.

Counter-evidence held on record

Reduced absorption is not an iron deficiency; in iron-overload disease it was the beneficial direction. Anemia is an outcome and is handled under oxygen delivery, not as iron deficiency (Hard Rule 2). Do not read this as a reason to take iron; supplementation could be the hazard in iron-overload states. No dose is given. Surfaces only as a monitoring prompt.

Limits on what this shows

• Key null findings: No copper deficit measured in a PPI cohort in sources opened.
• At-risk subgroups: None identified.

Regulatory status

Copper is not mentioned in the label sections read.

Population evidence

Tier C [14]: 37 long-term PPI users vs 30 controls (unmatched for age): serum zinc and copper higher in PPI users; numerical values are not in the abstract and the PPIs are not named. A 2015 J Neurol Sci article titled "PPIs as possible risk factor for copper deficiency myelopathy" appears in a PubMed listing; its abstract and text could not be retrieved, so it is not relied on [see Sources note].

Mechanism

None named in any source opened.

Cohort test

Fails (lansoprazole not shown); Tier C, capped at yellow. Kept independent of Iron (Hard Rule 7).

Counter-evidence held on record

The one measurement opposes a depletion claim; its design (unmatched controls, class-level) limits it. This entry is revisit-flagged because the myelopathy report was not accessible. Higher serum copper is not an excess-risk claim either. Neither copper supplementation nor restriction is implied.

Limits on what this shows

• Key null findings: None retrieved for lansoprazole.
• At-risk subgroups: Hospitalized patients for C. difficile per label.

Regulatory status

Label 5.3: PPI therapy "may be associated with an increased risk of Clostridium difficile-associated diarrhea", especially in hospitalized patients [1][2]. This is an infection outcome, not a measurement of microbiome composition.

Population evidence

Tier C [15]: 1,815 individuals in three cohorts, 211 PPI users; significant decrease in Shannon diversity, 20% of taxa altered, Rothia p = 9.8 x 10^-38; increases in Enterococcus, Streptococcus, Staphylococcus and Escherichia coli. The abstract does not name the PPIs, so lansoprazole is not verified in the cohort. Lansoprazole-based H. pylori triple-therapy trials of gut microbiota exist (titles seen: Helicobacter 2016, Int J Antimicrob Agents 2007, Lancet Infect Dis 2019) but include antibiotics and were not opened; they are not usable as lansoprazole-alone evidence.

Mechanism

The abstract names no mechanism; the observed pattern is oral bacteria over-represented in stool. Not tested in a lansoprazole-only cohort in sources opened.

Cohort test

Fails (lansoprazole not shown); Tier C class extrapolation, capped at yellow.

Counter-evidence held on record

Cross-sectional association; confounding by indication, age and co-medication is not excluded; no nutrient consequence has been shown. Not a nutrient-deficiency claim; probiotics or other products are not recommended by this dossier.

Limits on what this shows

• Key null findings: None retrieved.
• At-risk subgroups: None defined; hemolysis was idiosyncratic.

Regulatory status

Not addressed in the label sections read.

Population evidence

Tier B [22]: a man treated only with lansoprazole developed jaundice and fatigue; haemoglobin fell from 14.0 to 3.3 g/dL, direct Coombs test positive, IgG antibody to lansoprazole detected; recovered within three weeks after transfusion and corticosteroids (1996 case; abstract only). Tier C [14]: 37 long-term PPI users vs 30 healthy controls (mean age 57.1 vs 39.3): red cell count 4.24 vs 4.7 x 10^6/ul and haemoglobin 12.5 vs 14.3 g/dl (both p<0.001); PPIs not named in the abstract.

Mechanism

For [22], drug-dependent IgG-mediated hemolysis (immune, not nutritional). For [14], no mechanism shown; the authors suggest iron deficiency without demonstrating it. No arterial oxygenation or tissue oxygen delivery data were found.

Counter-evidence held on record

Controls in [14] were about 18 years younger and unmatched, and anemia is an outcome (Hard Rule 2). A single case cannot establish frequency, and the patient also received antibiotics five days later. Anemia in a lansoprazole user is not evidence of iron or B12 deficiency without direct measurement; sudden jaundice or dark urine is a prescriber-level issue.

Limits on what this shows

• Key null findings: No human or mammalian ATP, phosphocreatine or energy-charge data found.
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the label sections read.

Population evidence

Tier B [18]: lansoprazole and AG-1789 "dose-dependently inhibited cellular respiration by an endogenous substrate and decreased the ATP level in Helicobacter pylori cells"; 50% inhibitory concentrations for respiration were close to MICs for growth. The mouse adipocyte study reports increased mitochondrial respiration with no ATP result in the abstract [19].

Mechanism

Present in bacteria (respiratory-chain inhibition); absent for human cells in sources opened.

Counter-evidence held on record

Bacterial finding; the mammalian result [19] points the other way. Fatigue from B12 or magnesium status is a separate question handled in those entries. Not a statement that lansoprazole lowers energy output in people.