Mebendazole

Limits on what this shows

• Null and negative findings: No human blood-cell, muscle or liver mitochondrial measurement after mebendazole was found. Hepatic enzyme elevation is a toxicity outcome and its mitochondrial basis is not stated in the labels or the glioma paper summary [1][2][24].
• At-risk subgroups: Not defined. Label toxicity risk groups are higher dose, longer courses and hepatic impairment.

Direction

Possible drug-caused organelle stress (excess burden signal) in tumor cells that divide rapidly; not a nutrient deficiency (Hard Rule 2). No nutrient is implicated.

Regulatory status

Label mechanism (section 12.4): interference with helminth tubulin formation, impairing glucose uptake; no mammalian mitochondrial content in the sections read [1][2].

Population evidence

None in humans. Gupta 2025 [21] (Cells; OVCAR3 and OAW42 human ovarian cancer lines, in vitro; open-access full text read in part through a summarizer, text ended partway through Results): mebendazole disrupted mitochondrial membrane potential dose-dependently after 48 h (Rhodamine 123 flow cytometry at 0.312, 0.625 and 1.25 micromolar in OVCAR3 and 0.156, 0.312 and 0.625 micromolar in OAW42), with increased cytochrome C, Bax and cleaved caspases and decreased Bcl-2. A paper on mebendazole and fungal energy production (Paracoccidioides) returned a reCAPTCHA and was not opened.

Exposure comparison

By my arithmetic (molar mass about 295 g/mol): Emverm plasma mebendazole at 100 mg twice daily does not exceed 0.03 microgram/mL, about 0.10 micromolar total [2]; the Vermox fed Cmax of 56.2 ng/mL is about 0.19 micromolar total [1]; the glioma trial's mean trough at 200 mg/kg/day was 261 ng/mL, about 0.88 micromolar total [24]. With 90 to 95% protein binding [1], unbound levels are far lower. The cell-line effects therefore sit within range only for total concentration at oncology-trial doses (about 12 g/day for a 60 kg adult, versus 200 mg/day on the Emverm label, by my arithmetic), not for deworming regimens.

Mechanism

Tubulin-targeted cytotoxicity leading to mitochondrial apoptosis in cancer cells [21]. Uncoupling by mebendazole was not shown in anything opened.

Counter-evidence held on record

Counter-evidence Cancer cell lines are not normal tissue and the paper tests anticancer activity. The concentrations overlap only high-dose oncology exposure. The same group of Tier B results is not human evidence. Framing caution A mechanistic signal only. Fatigue or low energy in a person taking mebendazole is not evidence of mitochondrial damage from this entry. No nutrient or supplement is suggested.

Limits on what this shows

• Null and negative findings: No human malondialdehyde, glutathione or antioxidant-enzyme study with mebendazole was retrieved in the channels tried. The authors of [19] describe the mebendazole effect as mild.
• At-risk subgroups: Not defined.

Direction

Excess oxidant load (drug-caused stress signal in rodents), not depletion of a dietary antioxidant (Hard Rule 2).

Regulatory status

No oxidative-stress statement in either label [1][2].

Population evidence

None in humans. Locatelli 2004 [19] (Redox Rep; adult male Wistar rats, mebendazole or albendazole 40 mg/kg for 2, 4, 8 or 10 days; abstract reconstructed from an OpenAlex record): liver SOD, catalase, glutathione reductase and glutathione S-transferase activities, TBARS, reduced and oxidized glutathione and serum nitric oxide were measured; both drugs induced oxidative stress with higher TBARS and lower antioxidant defenses, albendazole being a strong ROS/RNS generator and mebendazole a low and transient one; per-enzyme direction not given in the record. Tolstoj 2007 [20] (Parasitol Res; albino rats, Trichinella-infected versus parasite-free; abstract page partial): examined lipid peroxidation in blood after mebendazole; dose and markers not on the page read.

Exposure comparison

By my arithmetic (rat-to-human body-surface scaling divisor about 6.2), 40 mg/kg in a rat corresponds to roughly 6.5 mg/kg in a person, about 390 mg for a 60 kg adult. That is about twice the 200 mg/day Emverm regimen and below the 500 mg single Vermox dose [1][2], but rodents received it daily for up to 10 days and liver exposure is not comparable to plasma figures.

Mechanism

ROS/RNS generation and glutathione-system changes in rodent liver; not established in humans.

Counter-evidence held on record

Counter-evidence Short rodent courses in healthy or parasite-infected animals. Infection itself changes host redox balance, so human data would be confounded by the parasite. Abstract-level reads only. Framing caution A mechanistic signal only. This entry gives no basis for antioxidant supplements.

Limits on what this shows

• Null and negative findings: No iron, ferritin or protoporphyrin result showing a fall attributable to mebendazole was found. The measured results are improvement in the heaviest-infection group [7], a marginal ferritin rise (P=0.07) [7], a ferritin decline in all groups including controls [11], and null effects [9].
• At-risk subgroups: Children and pregnant women in hookworm-endemic areas, where anemia is driven by infection, diet and inflammation.

Direction

Reverse or neutral, and a disease effect: the infection causes blood loss; the drug has no iron-binding or iron-absorption mechanism in either label. Not a depletion (Hard Rule 2). Kept independent of Copper (Hard Rule 7).

Regulatory status

No mention of iron, ferritin or hemoglobin as a drug effect in either label; iron deficiency anemia appears only in section 8.1 as a risk of untreated maternal helminth infection; magnesium stearate is an excipient [1][2].

Population evidence

Stoltzfus 1998 [7] (cluster-randomized, Zanzibar, 2,924 schoolchildren, mebendazole 500 mg): average annual protoporphyrin change -5.9 micromol/mol heme in controls versus -23.5 in the thrice-yearly group (P under 0.001); ferritin +2.8 versus +4.5 micrograms/L (P=0.07); hemoglobin and anemia unchanged; effects larger with more than 2,000 hookworm eggs/g. Le Huong 2007 [9] (425 anemic children, 2x2 factorial): deworming showed no effect on hemoglobin, iron status or IgE; iron-fortified noodles raised ferritin by 16.3 micrograms/L (the iron effect, not a mebendazole effect). Stoltzfus 2004 [8]: iron raised ferritin; the page read did not give a mebendazole effect on iron indices. Shield 1981 [11] (PNG men, 128-man subgroup): at baseline egg counts were inversely correlated with hemoglobin and serum ferritin; after 6 months serum ferritin fell in all groups, more in controls than in treated groups, treated groups not significantly different from each other. Smith and Brooker 2010 [6]: adding iron to benzimidazoles showed no evident extra benefit (SMD 0.09 versus 0.04), and the review notes hemoglobin is insensitive to 20 to 30% decreases in iron stores, so other iron-store indicators may be more sensitive.

Mechanism

Indirect: removal of blood-feeding hookworm. None for mebendazole acting on iron itself.

Counter-evidence held on record

Counter-evidence Ferritin is an acute phase protein and was falling in controls in [11]; [7] was marginal (P=0.07) and its benefit concentrated in heavy infection. [6] could not pool ferritin. Mebendazole did not clear hookworm in [12]. Framing caution This entry describes an infection effect that deworming only partly reverses. It is not an iron depletion by the drug, and iron supplementation decisions belong with a clinician based on laboratory testing.

Limits on what this shows

• Null and negative findings: No source opened measured serum copper, ceruloplasmin or urinary copper after mebendazole.
• At-risk subgroups: Not defined.

Direction

Undetermined. In vitro complexation could, in principle, affect the drug's availability (nutrient to drug, Hard Rule 4) or luminal copper handling; neither was tested. Not a depletion claim. Kept independent of Iron (Hard Rule 7).

Regulatory status

Neither label mentions copper or any trace mineral interaction [1][2].

Population evidence

None in humans or animals after dosing. Azam 2011 [27] (J Sci Res; in vitro conductometric titration, Job's plots and Ardon's spectroscopic method in water at 37 C and several pH values; abstract-level): mebendazole forms a stable 1:1 complex with Cu(II) (stability constant not in the abstract) and less stable complexes with Cr(III); 1:3 and 1:4 species not ruled out. Kashan 2015 [28] (case-control, 37 Giardia and 50 Enterobius children with matched controls, drug not reported): infected children had lower serum copper (Enterobius 145.55 versus 176.26 micrograms/dL; Giardia 143.65 versus 176.26), zinc and magnesium; this is an infection effect, the study gave no treatment, and the control means were identical in both comparisons, which the page-reading tool flagged as an inconsistency.

Mechanism

Metal binding by the benzimidazole-carbamate structure in vitro; relevance to body copper is not shown. Mebendazole is poorly absorbed (label), which limits any systemic copper interaction; this is my inference.

Counter-evidence held on record

Counter-evidence Aqueous chemistry at undefined concentrations does not show a physiologic effect. The infection-linked copper finding [28] concerns children with parasites, not a drug exposure, and cannot be attributed to mebendazole. Framing caution Chemistry only, no evidence of copper loss or excess in anyone taking mebendazole. No copper supplement or avoidance is suggested, and no separation interval can be derived from an in vitro complexation paper.

Limits on what this shows

• At-risk subgroups: None defined. Effects depended on infection status.

Direction

Mixed and small; a composition shift with unknown consequences, not a nutrient deficiency. Worm clearance is a major competing explanation.

Regulatory status

Diarrhea, abdominal pain, flatulence, nausea, vomiting and anorexia are listed adverse reactions; no microbiome statement in either label [1][2].

Population evidence (mebendazole in the cohort)

Yang 2017 [16] (PLoS Negl Trop Dis; Taichung, Taiwan; 109 first and fourth graders, 30 pinworm-negative and 79 pinworm-infected; infected children re-sampled 2 weeks after a single 100 mg mebendazole dose; no untreated infected control; abstract read via DOAJ and a second record): microbiota diversity rose after infection and peaked after treatment; Fusobacteria lower, Actinobacteria higher; Bifidobacterium increased; intestinal secretory IgA was lower in infected children and rose in about half after treatment; higher pre-treatment Salmonella was associated with no SIgA rise. Numerical effect sizes and p-values were not in the abstract record.

CLASS EXTRAPOLATION (cohort test)

Martin 2018 [17] (double-blind placebo-controlled, Indonesia, albendazole every 3 months for 1.5 years, 150 subjects by pyrosequencing) and Schneeberger 2022 [18] (Laos, 80 patients, albendazole alone n=41 or albendazole plus ivermectin n=39) were opened at abstract level. Mebendazole was NOT in either cohort; both are Tier C for mebendazole and capped at yellow. [17]: albendazole overall did not significantly affect microbiome composition; differences appeared in those who stayed infected (largely Bacteroidetes). [18]: pre-treatment enterotype predicted cure with the combination (for example T. trichiura OR 0.03, P=0.0002 for enterotype 1 versus 3), with no enterotype association in the albendazole-alone arm; that is a microbiome-to-drug-outcome direction, not a drug effect on the microbiome.

Mechanism

Not established. Candidate explanations in the sources are worm removal and immune change [16][17]; a direct drug effect has not been separated from them.

Counter-evidence held on record

Counter-evidence [16] is uncontrolled and short (2 weeks), and children were infected at baseline. Class studies [17][18] concern a different drug, and [17] found no overall drug effect. Earlier albendazole studies referred to in the sibling albendazole dossier were not opened here. Framing caution A modest compositional shift, not dysbiosis and not a reason to take probiotics or any supplement. Do not infer harm from this entry.

Limits on what this shows

• At-risk subgroups: Marrow toxicity: higher doses, longer courses, chronic liver disease [1][2][25]. Anemia benefit: heavy hookworm infection and young children [7][8].

Direction

Reverse or neutral for the disease-clearance effect (anemia from hookworm blood loss improves only when the worm is cleared). Separately, marrow suppression is the drug's own toxicity (Hard Rule 2): an outcome, not a nutrient-style deficit. No hemoglobin deficit tied to a measured nutrient was found.

Regulatory status

Both labels: agranulocytosis and neutropenia reported with higher doses or longer durations than recommended for soil-transmitted helminths; monitor blood counts in those cases (section 5.2). Postmarketing: agranulocytosis, neutropenia, hepatitis, abnormal liver tests, glomerulonephritis. No incidence is given [1][2]. The Vermox label does not use the term bone marrow suppression.

Population evidence

Smith and Brooker 2010 [6] (systematic review and meta-analysis, 14 randomized trials, benzimidazole trials stratified by drug; read via PMC full text through a summarizer and a second OpenAlex abstract): mebendazole alone was tested in 3 trials (Stoltzfus 1998 and 2004, Le Huong 2007) and had no apparent effect on hemoglobin (no numeric estimate given); albendazole alone +1.89 g/L (95% CI 0.13 to 3.63); all benzimidazoles pooled SMD 0.05 (95% CI -0.02 to 0.12). Stoltzfus 1998 [7] (cluster-randomized schools, Zanzibar, mebendazole 500 mg, n=1,002 control, 952 twice-yearly, 970 thrice-yearly): no effect on annual hemoglobin change or anemia prevalence; severe anemia (hemoglobin under 70 g/L) RR 0.77 (95% CI 0.39 to 1.51) twice yearly and 0.45 (0.19 to 1.08) thrice yearly; effects on moderate-to-severe anemia significantly greater in children with more than 2,000 hookworm eggs/g. Stoltzfus 2004 [8] (randomized, double-blind, 2x2 factorial, 459 children aged 6 to 71 months, 500 mg every 3 months for 12 months): mebendazole reduced moderate anemia in children under 24 months (adjusted OR 0.41, 95% CI 0.18 to 0.94); iron had no effect on hemoglobin. Le Huong 2007 [9] (randomized 2x2, 425 anemic Vietnamese children aged 6 to 8, 6 months): deworming had no effect on hemoglobin or iron status. Larocque 2006 [10] (double-blind randomized, 1,042 pregnant women on 60 mg iron daily, mebendazole 500 mg single dose): third-trimester anemia 33.0% versus 32.3% (P=0.815). Shield 1981 [11] (345 PNG men, 128-man subgroup followed 6 months on mebendazole, parenteral iron or both): hemoglobin improved in all treated groups but not controls; arm-level numbers not in the abstract record. Stoltzfus 2001 [12] (614 Pemba children): mebendazole reduced Ascaris and Trichuris infections but not hookworm infections.

Marrow and hepatic toxicity (outcomes)

Case report [25]: chronic liver disease patient on high-dose mebendazole for hepatic hydatid cyst developed marrow aplasia at day 18, reversed after stopping; the authors counted it as the sixth reported case and suggested dose-relatedness and liver disease as contributors. Fifteen patients with inoperable hydatid disease on a 6-week high-dose course: one reversible neutropenia [29] (record read without title or journal). Phase 1 glioma trial [24] (24 patients, mebendazole 25 to 200 mg/kg/day as reported by the summarizer): grade 3 ALT or AST elevation in 4 patients (16.7%) at 200 mg/kg/day, three grade 3 hematologic events of unspecified type, anemia not reported. Animal: 50 mg/kg/day for 5 to 6 days caused leukopenia, thrombocytopenia and marrow aplasia in 5 pademelons, 4 of which died or were euthanised [26].

Mechanism

Hookworm causes intestinal blood loss; clearing it stops the loss. This is a disease effect. Mebendazole has no oxygen-carrying, erythropoietic or iron-binding mechanism in either label. The marrow mechanism is not stated in the labels.

Counter-evidence held on record

Counter-evidence Meta-analytic and trial evidence for mebendazole is mostly null for hemoglobin [6][7][9][10]; the one positive anemia result is in a subgroup of a factorial trial [8]. The Cochrane review of deworming in children [13] (45 trials; mass treatment hemoglobin MD -0.02 g/dL, 95% CI -0.08 to 0.04, 7,057 participants) did not name drugs in the abstract record read, so it is Tier C context only. Mebendazole did not clear hookworm in [12], which may explain weaker hemoglobin effects than albendazole; that explanation is mine and was not tested in the sources. Framing caution Not an oxygen-delivery deficiency and not a drug-caused anemia. Do not read this entry as a reason to take or avoid mebendazole or any iron product. Blood counts are monitored for drug toxicity at high doses or long courses.

Limits on what this shows

• Null and negative findings: No human lactate, ATP, creatine kinase or energy-expenditure outcome after mebendazole was retrieved. Dizziness, anorexia and abdominal pain are label adverse events and are clinical outcomes, not ATP findings [1][2].
• At-risk subgroups: Not defined.

Direction

Intended pharmacologic effect on the parasite (Hard Rule 2: not a human deficiency). Possible off-target effect on mammalian cell energy metabolism at high concentration; an excess burden signal, not a nutrient shortfall.

Regulatory status

Section 12.4 (both labels): interference with tubulin formation disrupts glucose uptake and digestive and reproductive functions in the helminth. The labels do not use the word ATP [1][2].

Population evidence

None in humans. da Silva 2023 [22] (Toxicol Appl Pharmacol; gastric cancer cells; abstract record via BVS): mebendazole altered glucose uptake, LDH activity and ATP production and changed mRNA of SLC2A1, HK1, GAPDH and LDHA; concentrations and the direction of the ATP change were not in the record read. Maali 2020 [23] (Jurkat T-cell line, in vitro): at the IC50 of about 10 micromolar, glucose uptake fell about 13.9%; ATP, mitochondrial function and ROS were not measured.

Mechanism

Parasite: loss of glucose uptake after tubulin disruption (label). Mammalian cells: reduced glucose uptake and glycolytic gene changes in cancer lines [22][23]; mammalian ATP depletion by mebendazole was not demonstrated in anything opened.

Counter-evidence held on record

Counter-evidence The parasite finding is the drug's purpose. The mammalian findings are cancer cell lines, one without concentrations in the record read. Concentrations in [23] are about 50 times the fed Cmax of a 500 mg dose by my arithmetic (10 micromolar versus about 0.19 micromolar total). Framing caution Do not read the label's glucose-uptake mechanism as a risk of ATP deficiency in the person taking the drug.