Albendazole

Limits on what this shows

• Null and negative findings: No human blood-cell, muscle or liver mitochondrial measurement after albendazole was found. Hepatic enzyme elevation (16% in hydatid disease) is a label toxicity, and its mitochondrial basis is not stated [1].
• At-risk subgroups: Not defined. Label risk groups for toxicity are liver disease and high-dose long cycles.

Direction

Possible drug-caused organelle stress (excess burden signal), not a nutrient deficiency (Hard Rule 2). No nutrient is implicated by these studies.

Regulatory status

Label mechanism is parasite beta-tubulin binding; no mammalian mitochondrial content in the label sections read [1]. A secondary source states albendazole binds parasite beta-tubulin much more tightly than mammalian beta-tubulin [6].

Population evidence

None in humans. McCracken and Stillwell 1991 [24] (Tier B; PubMed abstract, truncated by the fetch tool): albendazole reduced artificial-membrane resistance at below 0.1 micromolar and conducted protons at least an order of magnitude better than 2,4-dinitrophenol; from 1 to 40 micromolar albendazole lowered P/O ratios of rat liver mitochondria in a concentration-dependent way with beta-hydroxybutyrate as substrate. Castro 2016 [26] (Tier B): MCF-7 breast cancer cells at about 5 micromolar showed loss of mitochondrial membrane potential and a roughly 123% rise in ROS, both reversed by N-acetylcysteine.

Exposure comparison

By my arithmetic from [7] (parent Cmax 57.5 to 128.9 ng/mL, molar mass 265.33 [4]) parent albendazole peaks at about 0.22 to 0.49 micromolar total; sulfoxide peaks (830 to 1,580 ng/mL, molar mass about 281.3) at about 3.0 to 5.6 micromolar total, with about 70% protein bound [1]. The proton-conducting effect in artificial membranes occurred below 0.1 micromolar, and the mitochondrial and cell effects at 1 to 40 and about 5 micromolar sit above total parent peaks and within the range of total sulfoxide peaks; the in vitro work used parent drug, and unbound concentrations are lower.

Mechanism

Lipid-soluble proton conduction (uncoupling) in lipid bilayers and mitochondria [24]; oxidative injury in cultured cells [26].

Counter-evidence held on record

Counter-evidence Isolated-organelle and cancer-cell studies do not show a mitochondrial effect in treated patients. The abstract of [24] was truncated at 250 words by the fetch tool, so later conclusions were not read. Framing caution A mechanistic signal only. Fatigue or low energy in a patient taking albendazole 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 albendazole was retrieved. A PubMed listing for "albendazole oxidative stress" (65 results, page 1 of 10 read) returned animal, parasite, cancer-cell and veterinary records and no human treatment study [28]. A sheep study of albendazole and Strongyloides papillosus oxidative stress was seen only as a snippet and not opened.
• At-risk subgroups: Not defined.

Direction

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

Regulatory status

No oxidative-stress statement in the labels [1][2].

Population evidence

None in humans. Locatelli 2004 [25] (Tier B; Wistar rats, albendazole or mebendazole 40 mg/kg for 2, 4, 8 or 10 days; OpenAlex-reconstructed abstract): both drugs produced oxidative stress with higher TBARS and lower antioxidant defenses; albendazole was a strong ROS/RNS generator, mebendazole low and transient. The abstract record gave no direction per enzyme. Castro 2016 [26] (Tier B): in Ehrlich-tumor mice albendazole raised TBARS and protein carbonyl, raised CAT, SOD and GR activity and depleted reduced glutathione; in MCF-7 cells ROS rose about 123% at 5 micromolar and N-acetylcysteine reversed cytotoxicity and ROS. By my arithmetic (division by about 6.2 for rat body-surface scaling), 40 mg/kg in a rat corresponds to roughly 6.5 mg/kg in a person, which is within a factor of about 2.3 of the 15 mg/kg/day label dose for patients under 60 kg [1] (label dosing is divided and given for up to 28-day cycles).

Mechanism

ROS/RNS generation and glutathione depletion; not established in humans.

Counter-evidence held on record

Counter-evidence Animal doses were short courses in healthy or tumor-bearing rodents; the parasite itself also changes host redox balance, so human data would be confounded by infection. Framing caution A mechanistic signal only. This entry gives no basis for antioxidant supplements, which could also affect cancer-cell studies in unknown ways.

Limits on what this shows

• Null and negative findings: No iron, ferritin or transferrin result showing a fall after albendazole was found. The one albendazole-alone iron result retrieved (Chen 2016 [18]) is an improvement, and the authors attribute the 3-month ferritin rise partly to the inflammatory process induced by the drug's anthelmintic effect (ferritin is an acute phase protein) and partly to better iron absorption once parasites are cleared; they also note the trial was not strictly blinded, did not measure other micronutrients, and had hookworm recurrence in all arms. A PubMed listing for "albendazole serum ferritin children" returned six records, of which only [18] and [13] bear on albendazole with iron indices (and [13] cannot separate albendazole from praziquantel); the rest were observational, iron-supplement or mixed-drug designs [28].
• At-risk subgroups: Children and pregnant women in hookworm-endemic areas: anemia there is driven by infection, malnutrition 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 the label. Not a depletion (Hard Rule 2). Kept independent of Copper (Hard Rule 7).

Regulatory status

No mention of iron, hemoglobin (other than aplastic anemia) or any nutrient in the Edenbridge label (revised 7/2026) [2]; magnesium stearate appears only as an excipient. The Albenza label retrieved had no nutrient interaction [1].

Population evidence

Chen 2016 [18] (randomized trial, anemic Sichuan preschoolers aged 3 to 6 years with hemoglobin 80 to under 110 g/L and C-reactive protein under 10 mg/L; full text opened on the open-access Cambridge Core page, tables 1 to 3 are images and were not readable). Flow of participants: Methods state 216 recruited; Results state 209 randomized (70 control, 72 albendazole 400 mg, 67 albendazole plus vitamin A 60,000 micrograms); 23 dropped out (6, 10 and 7), leaving 186 analysed (64, 62, 60). The abstract figure of 209 is the randomized number and 186 is the analysed number; the 216 versus 209 mismatch is internal to the paper and is not explained there. Albendazole-alone arm (within-group change versus baseline, text values): ferritin rose to 39.1 micrograms/L at 3 months (6-month value not given in text); transferrin receptor-ferritin index rose to 1.79 at 3 months; total body iron rose to 10.1 mg/kg at 3 months; hemoglobin rose to 105.7 g/L at 3 months and 115.5 g/L at 6 months; soluble transferrin receptor did not change; retinol did not change; hookworm prevalence fell at 3 and 6 months (P under 0.05, counts in an unreadable table). Baseline values for these arms were in image tables and were not retrieved. The combination arm was higher than the albendazole-alone arm: ferritin 46.1 and 44.4 micrograms/L at 3 and 6 months, body iron 13.61 and 11.17 mg/kg, hemoglobin 114.2 and 116.8 g/L. Control arm: no significant change in any measure in the Results, although the Discussion states an overall hemoglobin increase and anemia decrease in the control arm, a conflict within the paper. The text reports no direct albendazole-alone versus control test. Bhargava 2003 [13]: serum ferritin improved in children treated for schistosomiasis (P=0.019), a praziquantel-linked finding, and ferritin rose with C-reactive protein, an inflammation confounder. Smith and Brooker 2010 [11]: no apparent additional benefit from combining benzimidazoles with iron supplementation. Torlesse 2001 [12] measured serum ferritin but the abstract gives no value.

Mechanism

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

Counter-evidence held on record

Counter-evidence Pooled hemoglobin gains are small (+1.89 g/L [11]) and heterogeneous; mass deworming shows no average hemoglobin benefit [14]. Ferritin is raised by inflammation, so ferritin changes in infected children are hard to read [13]; the authors of [18] themselves attribute part of the 3-month ferritin rise to drug-induced inflammation, and the control arm also showed a hemoglobin rise in their Discussion. Framing caution This entry describes an infection effect that albendazole 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

• Why no grade: Dual condition met: no Tier B or C source for albendazole and body copper, and no circulating claim linking albendazole to copper could be found within the channels tried. A disclosed gap, not a finding of safety. Kept independent of Iron (Hard Rule 7).

What was searched

PubMed listing "albendazole copper": 10 records on page 1, all copper nanoparticle or metal-complex pharmaceutics, veterinary or environmental studies (for example copper oxide nanoparticles with albendazole against hydatid protoscoleces, copper oxide wire particles in lambs, Cu(II) and Fe(III) Schiff-base complexes containing albendazole, earthworm toxicity of copper plus albendazole), plus a stability study where copper ions catalyzed oxidation of ricobendazole in aqueous solution; none measured copper status in a person or animal given albendazole [28]. Repair pass (2026-10-09): PubMed listing "albendazole ceruloplasmin OR serum copper" completed but the parser dropped the drug term, returning 2,345 general copper records with no albendazole record in the first 10 (page 1 only; not informative for the drug) [28]; two further phrasings ("albendazole serum trace elements zinc copper children", "albendazole zinc copper deworming") returned fetch errors, and "albendazole copper serum human" returned HTTP 429. Albendazole-copper chemistry seen in the first pass (metal complexes, copper-catalyzed ricobendazole oxidation, nanoparticle formulations) is in vitro pharmaceutics or veterinary and is not human; it was not used as Tier B evidence for body copper status. The Edenbridge label search for vitamins, minerals, iron, hemoglobin and albumin returned no mention, and copper was not separately queried [2]; the Albenza label sections summarized had no nutrient interaction [1]. Web search for consumer copper claims was not possible (budget exhausted).

Channel outcomes

PubMed: one clean albendazole-copper listing in the first pass, plus one repair-pass listing (serum copper, ceruloplasmin) that did not retain the drug term, two errored phrasings and one 429; WebSearch refused (shared budget exhausted); OpenAlex, Crossref and Europe PMC rate limited during the repair. No human copper measurement with albendazole in the cohort was found on any channel that completed. Genuine gap on the evidence seen; a clean albendazole-restricted ceruloplasmin or serum copper listing was not obtained, so a tooling-limited tail remains.

Limits on what this shows

• Null and negative findings: Martin 2018 [20] is the placebo-controlled null. Earlier studies described secondhand in [23] (for example an Ecuadorian school trial with no effect on composition and an Indonesian trial with no diversity change) were not opened.
• At-risk subgroups: None defined. Effects were larger or different in helminth-infected participants.

Direction

Mixed and small. Not a nutrient deficiency; a composition shift with unknown consequences. Clearance of the helminth itself is a major competing explanation.

Regulatory status

Diarrhea and abdominal pain are listed adverse events (abdominal pain 6% in hydatid disease); no microbiome statement [1][2].

Population evidence

Martin 2018 [20] (double-blind placebo-controlled trial, Indonesia, albendazole or placebo every 3 months for about 1.5 years, 150 people profiled by 16S sequencing): albendazole overall did not appear to affect gut composition directly; differences appeared only in people who stayed infected, mostly with Trichuris. Easton 2019 [21] (Kenya, albendazole 400 mg, uncontrolled before-after; 24 STH-infected and 21 uninfected followed to 3 months): Chao1 richness fell at 3 months in participants uninfected at baseline (P=0.026), which the authors suggest may be a direct drug effect; Clostridiales rose (P=0.0002) and Enterobacteriales fell (P=0.0004) after hookworm clearance. Dommann 2026 [22] (Cote d'Ivoire trial, 400 mg albendazole arm n=67 of 204 paired samples, Trichuris-infected, sampled at baseline and 2 to 3 weeks): PERMANOVA R-squared 0.0079 (P=0.032), phylum composition stable (P greater than 0.3), 2 species changed at q below 0.05 (Holdemanella porci abundance q=0.03; Prevotella copri prevalence q less than 0.001) and Streptococcus mitis prevalence at q=0.06; the authors call the shifts limited and probably indirect. Tikhonova 2026 [23] (Ethiopia, single 400 mg dose, 67 children followed one year, no untreated control): observed taxa fell (P less than 0.006) and evenness rose (Shannon P less than 0.015), with 12 to 13 genera increased; differences depended on baseline infection.

Mechanism

Not established. Candidate explanations in the sources are worm removal opening niches, immune changes and, for the uninfected-group richness fall, a direct drug effect [21][22][23].

Counter-evidence held on record

Counter-evidence No sampling gave a clinical outcome; no cohort had a worm-free, albendazole-versus-placebo arm with deep sequencing at long follow-up. [22] and [21] have no placebo arm, and [23] has no untreated control. 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

• Null and negative findings: The Cochrane review of deworming drugs in children [14] (45 trials; the 44 smaller trials involved about 67,672 participants) concluded that treating all children, infected or not, probably has little or no average effect on hemoglobin, weight, height or cognition; the benefit is confined to infected individuals. Lau 2020 [15] (23 studies of soil-transmitted helminth treatment in pregnancy; albendazole or mebendazole versus placebo): hemoglobin did not differ significantly (no numbers in the abstract). Whether albendazole was in every Cochrane trial was not confirmed in the record read, so [14] is used as context only.
• At-risk subgroups: Marrow toxicity: liver disease, hepatic echinococcosis and high-dose long cycles per the label. Hookworm-anemia benefit: infected individuals, pregnant women, heavy infection intensity [11].

Direction

Reverse (hemoglobin rises) for the disease-clearance effect. Separately, rare marrow suppression is the drug's own toxicity (Hard Rule 2): it is an outcome, not a nutrient-style oxygen-delivery deficit, and no hemoglobin deficit tied to a measured nutrient was found.

Regulatory status

Label: fatalities due to granulocytopenia or pancytopenia; blood counts at the start of each 28-day cycle and every 2 weeks, with higher risk in liver disease or hepatic echinococcosis; post-marketing aplastic anemia, bone marrow suppression and neutropenia. Treatment discontinuations were mainly leukopenia (0.7%) or hepatic abnormalities (3.8% in hydatid disease). No incidence for neutropenia is given in the label sections read [1][2]; a narrative review states albendazole can cause neutropenia at high doses [27] (Tier C, abstract only).

Population evidence

Smith and Brooker 2010 [11] (systematic review and meta-analysis; 14 randomized trials of benzimidazole treatment, stratified by drug): albendazole +1.89 g/L hemoglobin (95% CI 0.13 to 3.63), mebendazole no effect, albendazole plus praziquantel +2.37 g/L (1.33 to 3.50); anemia RR 0.87 for benzimidazoles alone and 0.61 with praziquantel; no added benefit of iron supplementation on top of benzimidazoles. Torlesse and Hodges 2001 [12] (longitudinal, Sierra Leone, 125 pregnant women, single 400 mg dose): first-to-third-trimester hemoglobin fell 6.6 g/L less with albendazole than control (P=0.0034); iron-folate effect 13.7 g/L, additive. Bhargava 2003 [13] (randomized, 1,115 Tanzanian schoolchildren; albendazole plus praziquantel versus placebo): hemoglobin +9.3 and +8.8 g/L in treated groups (P less than 0.001); albendazole could not be separated from praziquantel. Hamidu 2024 [16] (399 Ghanaian schoolchildren, albendazole 400 mg at baseline and month 6): proportion with normal hemoglobin rose over time (P less than 0.01); no control arm, and values were not in the abstract. Chen 2016 [18] (anemic Sichuan preschoolers, 62 analysed in the albendazole-alone arm): hemoglobin rose within the arm to 105.7 g/L at 3 months and 115.5 g/L at 6 months (baseline not retrieved; the paper's Discussion also reports a hemoglobin rise in the control arm, so the net drug effect is unclear).

Mechanism

Hookworm causes intestinal blood loss; clearing it stops the loss. This is a disease effect. Albendazole has no oxygen-carrying, erythropoietic or iron-binding mechanism in the label sections read. Marrow suppression has no mechanism stated in the labels.

Counter-evidence held on record

Counter-evidence A trial showing higher hemoglobin after albendazole does not show that albendazole raises hemoglobin in uninfected people; the Cochrane review points the other way for mass treatment [14]. Chakrabarti 2024 [17] (105,060 Indian individuals aged 1 to 19, cross-sectional) found lower odds of anemia in dewormed children (aOR 0.72, 95% CI 0.67 to 0.78), but the record read does not name the drug, so it is context only. 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 albendazole or any iron product. Blood-count monitoring is a label requirement for the drug's toxicity.

Limits on what this shows

• Null and negative findings: No human lactate, ATP, creatine kinase or energy-expenditure outcome after albendazole was retrieved. Post-marketing asthenia and rhabdomyolysis are label adverse events, which are clinical outcomes and not ATP findings [2].
• At-risk subgroups: Not defined.

Direction

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

Regulatory status

Label section 12.1: binding to beta-tubulin lowers parasite glucose uptake and depletes glycogen, and the resulting lack of glucose lowers ATP production in the parasite [1].

Population evidence

None in humans. McCracken and Stillwell 1991 [24]: in Hymenolepis diminuta a therapeutic dose of albendazole lowered ATP levels, the ATP/ADP ratio and adenylate energy charge; in rat liver mitochondria, 1 to 40 micromolar albendazole lowered P/O ratios (ATP made per oxygen atom). Concentration relevance to treated patients is discussed in the Mitochondrial burden entry.

Mechanism

Parasite: impaired glucose uptake after tubulin disruption (label), and in a secondary source inhibition of fumarate reductase and malate dehydrogenase at higher concentrations [4]. Mammalian: uncoupling [24]. Mammalian cells have far lower affinity for the drug target [6].

Counter-evidence held on record

Counter-evidence The parasite findings are the drug's purpose, and the mammalian findings rest on one 1991 abstract plus one cancer-cell study, none in humans. Framing caution Do not read the label's ATP statement as a risk of ATP deficiency in the person taking the drug.