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MyDeficiencies

Amiodarone

Antiarrhythmic

Also sold as Cordarone, Pacerone.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Amiodarone has essentially no classical nutrient-depletion machinery: it is not a renal-wasting drug, it does not chelate minerals in the gut, and it does not induce hepatic enzymes that would accelerate clearance of a vitamin. What it does have is a single, extensively documented, label-mandated nutrient interaction that most consumer drug-nutrient charts frame backwards when they address it at all. Each 200 mg amiodarone tablet contains roughly 75 mg of iodine (amiodarone is about 37.3% iodine by weight), and deiodination releases on the order of 7 mg of free inorganic iodine per day at typical maintenance doses, a load roughly 45 to 50 times the adult recommended daily iodine intake of 150 mcg. This is an iodine excess delivered by the drug, not an iodine deficiency caused by it, and the resulting thyroid dysfunction (hypothyroidism from a persistent Wolff-Chaikoff-type block on hormone synthesis, or thyrotoxicosis from iodine-driven overproduction or drug-induced destructive thyroiditis) is a clinical outcome, not itself a nutrient-status finding.

ATC C01BD01 · also sold as Cordarone and Pacerone and Nexterone · reviewed 2026-09-05, expanded 2026-09-10. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Amiodarone in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
two or more independent Tier A sources, this drug in the studied cohort, direct measurement, consistent direction, clinically meaningful, named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
at least one Tier A source with this drug in the cohort showing a real but bounded deficit (exposure window, subgroup, or functional rather than circulating measure).
Yellow — Low
mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) without amiodarone-specific human data; also used for reverse-direction or context flags.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Iodine

Red — Severe

Direction: excess

Amiodarone delivers a chronic iodine load roughly 45 to 50 times the adult RDA with every maintenance dose, and this iodine excess, not an iodine deficit, is the documented mechanism behind both amiodarone-induced hypothyroidism and amiodarone-induced thyrotoxicosis (AIT). Thyroid dysfunction is the clinical outcome; iodine excess is the nutrient-relevant mechanism behind it, and the two are kept separate here.

Full detail, limits and 1 references

What the grade means here: two or more independent Tier A sources, this drug in the studied cohort, direct measurement, consistent direction, clinically meaningful, named mechanism, no substantial contradicting Tier A evidence. Direction: excess

Limits on what this shows

  • Key negative or null findings: Basaria and Cooper (Am J Med, 2005 review) and related work note that most amiodarone-treated patients remain clinically euthyroid despite these biochemical shifts (elevated T4/reverse T3, low-normal T3): biochemical change alone is expected and is not itself a diagnosis of dysfunction, which is why TSH, not T4 or T3 alone, anchors monitoring.
  • At-risk subgroups: Iodine-replete regions (like North America) see disproportionately more hypothyroidism; iodine-deficient regions see disproportionately more thyrotoxicosis (up to about 10% in some series). Pre-existing nodular goiter or latent Graves disease predisposes to type 1 AIT. Type 2 AIT can occur in a previously normal thyroid. Male sex is overrepresented in AIT (reported male:female ratio near 3:1). Dysfunction can emerge or persist for a year or more after amiodarone is stopped, given its long half-life.

Regulatory status

The FDA label carries a boxed-adjacent warning to monitor thyroid function before and periodically during treatment, "particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction," and documents hypothyroidism in up to 10% and hyperthyroidism in about 2% of treated patients in its own safety data.

Population evidence

A 2022 systematic review and meta-analysis (Bentham Science / Current Medicinal Chemistry, pooled random-effects model across multiple cohorts of amiodarone-treated cardiac patients) reported pooled prevalence of amiodarone-induced hypothyroidism of 23.43% (95% CI 11.54 to 35.33) and hyperthyroidism of 11.61% (95% CI 7.20 to 16.02), with hyperthyroidism prevalence significantly associated with publication year (p=0.037). A separate nationwide Icelandic cohort study (Guðjónsson et al., Journal of Internal Medicine, 2025) reports high cumulative incidence of thyroid dysfunction after amiodarone initiation in a national, iodine-sufficient population; full text was not retrievable past a paywall during this review and its specific figures are not quoted here, but it is named as a study you should independently verify if you rely on it.

Mechanism

Two distinguishable mechanisms, both iodine-excess driven. Type 1 AIT: iodine-induced excess thyroid hormone synthesis (a Jod-Basedow-type effect), typically in a gland with pre-existing autonomy (multinodular goiter, latent Graves disease). Type 2 AIT: amiodarone- or desethylamiodarone-mediated destructive thyroiditis releasing preformed hormone, occurring even in previously normal glands. Amiodarone-induced hypothyroidism reflects a persistent Wolff-Chaikoff block (failure to "escape" the iodine-induced suppression of hormone synthesis and release), most common in iodine-sufficient populations and in patients with underlying autoimmune thyroiditis. Amiodarone additionally inhibits peripheral T4-to-T3 conversion, raising total and free T4 and reverse T3 while lowering T3, independent of clinical thyroid status.

Counter-evidence held on record

A substantial share of amiodarone recipients never develop clinically significant thyroid dysfunction despite universal exposure to the same iodine load, which is why confounding by indication and background thyroid status (nodularity, autoimmunity, population iodine sufficiency) are treated as necessary co-factors rather than the drug alone being sufficient. Active comparator or dose-response data isolating iodine content specifically (versus amiodarone's other thyroidal actions, such as direct cytotoxicity to thyroid follicular cells) were not identified in this review; the mechanism is supported by iodine-kinetics and pharmacology literature rather than by a trial that varied iodine dose in isolation. Framing caution for the consumer-facing surface This is an excess, not a deficiency. Never present this entry as "amiodarone depletes iodine" or as a reason to add iodine or kelp to the diet. Patients on amiodarone already carry a large, sustained iodine load; supplemental iodine or kelp adds to that load and can precipitate or worsen thyrotoxicosis or hypothyroidism. Any consumer-facing copy must say monitor thyroid function, not supplement iodine.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden

Orange — Moderate

See study details

Amiodarone is one of the most consistently documented direct mitochondrial toxins among cardiovascular drugs, inhibiting hepatic beta-oxidation and respiratory chain function in a large, convergent body of animal and human-cell evidence. This is the mechanism behind the drug's own labeled hepatotoxicity and contributes to its pulmonary toxicity; it is not evidence of a coenzyme Q10, carnitine, riboflavin, or any other nutrient deficiency, and nothing here supports a mitochondrial-support supplement.

Full detail, limits and 12 references

What the grade means here: at least one Tier A source with this drug in the cohort showing a real but bounded deficit (exposure window, subgroup, or functional rather than circulating measure). ORANGE · drug's own toxicity mechanism

Limits on what this shows

  • Key negative or null findings: Most amiodarone-treated patients never develop clinically significant hepatotoxicity despite universal exposure to the mitochondrially active drug and metabolite, and the label itself frames transaminase elevation as frequent but hepatic injury as comparatively rare; this argues for a dose- and duration-dependent threshold effect rather than a uniform mitochondrial burden in every patient. The Felser 2013 dose comparison additionally shows amiodarone is the less potent mitochondrial toxin of the two drugs compared head to head (dronedarone inhibited beta-oxidation at a lower concentration), a relevant finding for anyone tempted to treat "amiodarone" and "all Class III antiarrhythmics" as interchangeable on this parameter.
  • At-risk subgroups: Defined by the label's hepatotoxicity risk factors generally (higher cumulative dose and duration of therapy, pre-existing liver disease) rather than by any mitochondrial-specific human subgroup study, since no such study exists. Confounding by indication applies as elsewhere in this dossier: amiodarone recipients carry elevated baseline comorbidity and polypharmacy independent of the drug's own mitochondrial actions.
  • Dose and duration: The Felser 2013 in vitro threshold (approximately 20 micromolar for beta-oxidation inhibition) and the broader cell and isolated-mitochondria literature use concentrations chosen to be pharmacologically relevant to amiodarone's known tissue accumulation, but none of it establishes a human dose-response curve for mitochondrial injury; the label's hepatotoxicity risk factors (cumulative dose, duration) are the only human-relevant dose signal available.

Regulatory status

FDA label §5.3: "Asymptomatic elevations of hepatic enzyme levels are seen frequently, but amiodarone hydrochloride can cause life-threatening hepatic injury," with histology that can resemble alcoholic hepatitis or cirrhosis; baseline and periodic transaminase monitoring is required. The label names no mitochondrial mechanism directly, but the hepatotoxicity it documents is the same lesion the mechanistic literature below attributes to direct mitochondrial injury.

Population evidence

No Tier A human study has directly measured mitochondrial respiratory function, complex activity, or beta-oxidation flux in an amiodarone-treated patient; the Tier A anchor here is the label's own hepatotoxicity finding above. The mechanistic case is built on an unusually large and consistent Tier B literature with amiodarone specifically as the tested agent: isolated rat liver mitochondria (Spaniol et al., J Hepatol 2001, PMID 11690709) showing direct amiodarone toxicity to isolated mitochondria; rat liver mitochondria and human HepG2 hepatocyte cells (Felser et al., Toxicol Sci 2013, PMID 23135547) showing amiodarone inhibits mitochondrial beta-oxidation starting at approximately 20 micromolar, a lower threshold than its analogue dronedarone's approximately 10 micromolar in the same assay; a follow-up dronedarone-focused paper from the same group (Felser et al., Toxicology 2014, PMID 24881592) confirming amiodarone inhibits mitochondrial respiration and beta-oxidation in vitro; an animal-model study (Serviddio et al., Free Radic Biol Med 2011, PMID 21971348) reporting that mitochondrial oxidative stress and respiratory chain dysfunction account for liver toxicity during amiodarone administration but not during dronedarone administration in the same model; cell-based work in HepG2 cells and platelets (Bețiu et al., Int J Mol Sci 2021, PMID 34769217) showing cell-permeable succinate rescues mitochondrial respiration in cellular models of amiodarone toxicity; a hepatic bioreactor system (Prill et al., Arch Toxicol 2016, PMID 26041127) showing amiodarone produces CYP450-independent mitochondrial toxicity by real-time oxygen-uptake monitoring; hepatocellular toxicity work comparing amiodarone and its derivatives (Waldhauser et al., J Pharmacol Exp Ther 2006, PMID 16971508); lymphocyte mitochondrial toxicity (Yasuda et al., J Cardiovasc Pharmacol 1996, PMID 8797142); HepaRG liver cell sensitivity to mitochondrial amiodarone toxicity (van der Mark et al., Toxicol Appl Pharmacol 2020, PMID 32428594); and a 2025 methods paper that uses amiodarone specifically as a reference positive-control compound for mitochondrial toxicity assessment in hepatocytes (Park et al., Toxicol Res 2025, PMID 41169279), itself a marker of how settled amiodarone's status as a direct mitochondrial toxin is in the toxicology field. A 2015 review names amiodarone specifically among cardiac drugs with documented mitochondrial toxicity relevant to patients with underlying mitochondrial disorders (Finsterer and Zarrouk-Mahjoub, Expert Opin Drug Metab Toxicol 2015, PMID 25331002), and a 2019 neurology review of toxic myopathies discusses amiodarone among drugs producing a mitochondrial myopathy pattern (Doughty and Amato, Continuum 2019, PMID 31794468).

Mechanism

Named and consistent across the cited Tier B literature: amiodarone and its active metabolite accumulate in mitochondria (the drug's very large volume of distribution and extensive tissue accumulation are already documented in this dossier's pharmacokinetic block), where they inhibit mitochondrial beta-oxidation of fatty acids and impair electron transport chain / respiratory chain function, producing reactive oxygen species and, at sufficient exposure, microvesicular steatosis and hepatocellular injury. This is a direct pharmacotoxic action of the parent drug and its metabolite on the mitochondrion, not a mechanism that operates by depleting a dietary cofactor; no study identified here proposes that amiodarone lowers coenzyme Q10, carnitine, riboflavin, or thiamine levels as the route to this toxicity.

Tier history

At the September 5, 2026 review this tier was printed as empty. That entry is retired here and its reasoning is preserved verbatim, because it remains accurate as written and documents what changed. It read: "No nutrient met the orange bar (a Tier A source, amiodarone specifically in the cohort, a real but bounded deficit) for this drug." Its stated reasoning: "Amiodarone's only well-evidenced nutrient-relevant mechanism is the iodine excess above, and the human evidence for that finding is broad enough (multiple independent Tier A sources, consistent direction, a named mechanism, no contradicting Tier A data) to sit at red rather than a bounded orange. Rat and in vitro data on amiodarone-induced oxidative liver stress (see yellow tier) do not rise to Tier A because amiodarone was never studied as an arm producing a measured human deficit in a specific antioxidant nutrient." What would fill it: "A Tier A human study directly measuring a circulating or functional nutrient marker (for example plasma alpha-tocopherol or glutathione) in an amiodarone-exposed cohort against a real comparator, showing a bounded, amiodarone-attributable deficit." That statement is still true of nutrient-status markers specifically; this tier was filled instead by treating mitochondrial burden as its own physiological parameter rather than a nutrient deficit, using the label's hepatotoxicity finding as the Tier A anchor and the mitochondrial-toxicity literature as the mechanism.

Counter-evidence held on record

The clearest counter-evidence is comparative rather than a null: in the one study that tested amiodarone and dronedarone side by side in the same assay (Felser 2013), amiodarone was the less potent mitochondrial toxin of the pair, which cuts against treating "mitochondrial toxin" as amiodarone's single defining pharmacological property. No study identified here reports amiodarone protecting or improving mitochondrial function in an unstressed system. Framing caution for the consumer-facing surface This is amiodarone's own recognized mitochondrial toxicity mechanism, underlying its labeled hepatotoxicity and contributing to its pulmonary toxicity, monitored by liver enzymes and pulmonary function tests as already described elsewhere in this dossier. It must never be presented as a coenzyme Q10, carnitine, riboflavin, or thiamine deficiency, and no mitochondrial-support supplement is recommended. A reader concerned about liver or lung symptoms on amiodarone needs clinical evaluation, not a supplement.

Oxidative Stress

Each finding below is counted once, in this area only.

Vitamin E and hepatic antioxidant capacity

Yellow — Low

Evidence in: Tier B, animal

Amiodarone generates oxidative stress and free-radical injury in hepatocytes in rat models, and co-administered vitamin E, vitamin C, or N-acetylcysteine attenuate liver glutathione depletion and ultrastructural damage in those same models; this is mechanistic and protective-supplementation evidence, not human depletion evidence.

Full detail and limits

What the grade means here: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) without amiodarone-specific human data; also used for reverse-direction or context flags. Tier B, animal

Limits on what this shows

  • Key negative or null findings: No identified human cohort measuring vitamin E, glutathione, or related antioxidant status before and after amiodarone initiation. Absent that, this cannot be distinguished from confounding by indication (cardiac patients, older age, polypharmacy) or from reverse causation (subclinical liver injury altering antioxidant handling rather than the reverse).
  • At-risk subgroups: Hypothetically, patients with pre-existing liver disease or higher-dose, longer-duration amiodarone therapy, where hepatotoxicity risk itself is highest; this is inferred from the hepatotoxicity literature, not from any nutrient-status study.

Regulatory status

Not addressed in the FDA label beyond a general hepatotoxicity warning (transaminase elevation, rare severe hepatic injury resembling alcoholic hepatitis or cirrhosis on biopsy); the label does not name any nutrient in connection with this risk.

Population evidence

None in humans specific to amiodarone. Available data are rat hepatocyte and whole-animal studies (for example, amiodarone free-radical toxicity in isolated rat hepatocytes; vitamin E ultrastructural protection studies in rat liver; N-acetylcysteine/vitamin E/vitamin C effects on liver glutathione in amiodarone-treated rats).

Mechanism

Increased hepatic oxidative/free-radical burden (mechanism class: increased utilization or metabolic demand on endogenous and dietary antioxidant systems) is biologically plausible as a contributor to amiodarone hepatotoxicity, but no human study has measured a resulting vitamin E or glutathione-precursor deficit in amiodarone-treated patients.

Counter-evidence held on record

These animal studies test antioxidants as protective co-therapy against a toxicity endpoint (liver injury markers), not as a correction for a measured nutrient deficit caused by amiodarone; treating them as depletion evidence would overstate what was actually shown. Framing caution for the consumer-facing surface Do not present this as "amiodarone depletes vitamin E." No human deficit has been measured, and no dose recommendation is supportable at this evidence tier.

Oxidative stress

Yellow — Low

See study details

Amiodarone generates reactive oxygen species and measurable oxidative damage across multiple organ systems in animal and in vitro models, consistent with its labeled hepatotoxicity and pulmonary toxicity. This is a documented feature of the drug's own toxicity, not a selenium, glutathione, or vitamin E deficiency; no study has measured a redox biomarker in an amiodarone-treated human.

Full detail, limits and 9 references

What the grade means here: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) without amiodarone-specific human data; also used for reverse-direction or context flags. YELLOW · mechanistic plausibility only

Limits on what this shows

  • Key negative or null findings: No study identified here measured a circulating or functional antioxidant status marker (selenium, glutathione, alpha-tocopherol) in an amiodarone-treated human before and after initiation; absent that comparison, this cannot be distinguished from confounding by indication (cardiac disease and its own oxidative burden) or from reverse causation. One in vitro finding (Lapenna et al., Br J Pharmacol 2001, PMID 11429399, discussed in full under the copper entry below) found amiodarone itself acts as an antioxidant against copper-catalyzed lipoprotein oxidation at therapeutic concentrations, a genuinely protective, not damaging, in vitro finding that complicates any simple "amiodarone causes oxidative stress" headline.
  • At-risk subgroups: None defined by human data. By mechanism only, patients accumulating the highest tissue amiodarone and desethylamiodarone concentrations (highest cumulative dose, longest duration, given the drug's 58-day mean half-life and extensive tissue accumulation already documented in this dossier) would be the population to watch, not a basis for a testing directive.

Regulatory status

Oxidative stress and specific antioxidant markers are not named in the amiodarone prescribing information beyond the general hepatotoxicity and pulmonary toxicity warnings already documented in this dossier's pharmacokinetic block and red-tier entry.

Population evidence

None in humans. Tier B with amiodarone specifically in the cohort spans several organ systems: liver (Serviddio et al. 2011, PMID 21971348, mitochondrial oxidative stress and respiratory chain dysfunction, rodent model; also cited under Mitochondrial burden for the respiratory-chain finding and not re-counted here for that specific measurement); lung, in human cells (Silva Santos et al., J Arrhythm 2017, PMID 28607618, catechin and epicatechin reduce mitochondrial dysfunction and oxidative stress induced by amiodarone in human lung fibroblasts, an in vitro Tier B study using human-derived cells, not a clinical trial); lung, in rats (Dawood et al., Pharmaceuticals 2024, PMID 39204109, L-carnitine ameliorates amiodarone-mediated alveolar damage measured by oxidative stress parameters, inflammatory markers and ultrastructure); heart, in isolated atrial myocytes (Zhao et al., Nan Fang Yi Ke Da Xue Xue Bao 2021, PMID 33849832, amiodarone promotes heat-induced apoptosis, inflammation and oxidative stress in mouse HL1 atrial myocytes); kidney, in rats (Eid et al., Ultrastruct Pathol 2021, PMID 33423596, grape seed extract protects against amiodarone-induced nephrotoxicity and oxidative-stress biomarkers); peripheral nerve, in vitro (Niimi et al., Eur J Neurosci 2016, PMID 27152884, oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy); and an early chemiluminometric study describing oxidative stress as a contributor to amiodarone's own side effects (Vereckei et al., Orv Hetil 1991, PMID 2003039, in Hungarian; title and journal confirmed via listing, full text not opened in this session). An animal-model paper is titled directly around this mechanism (Sarma, Pei and Venkataraman, "Role of Oxidative Stress in Amiodarone-induced Toxicity," J Cardiovasc Pharmacol Ther 1997, PMID 10684442).

Mechanism

Named and consistent with the mitochondrial-toxicity mechanism above: amiodarone and its metabolite generate reactive oxygen species through impaired electron transport and possibly through direct redox chemistry, producing measurable lipid peroxidation, protein damage and antioxidant-enzyme perturbation in every organ system studied. This is presented in the source literature as a toxicity mechanism, in several cases explicitly being tested for protection by an antioxidant co-therapy (carnitine, catechins, grape seed extract) against a damage endpoint, not as a mechanism of depleting a specific dietary nutrient.

Counter-evidence held on record

Lapenna 2001 (PMID 11429399) found amiodarone at therapeutically achievable concentrations (1.5 to 10 micromolar) protected human non-HDL lipoprotein against copper-catalyzed oxidation in vitro, a directly antioxidant, not pro-oxidant, action of the parent molecule itself. This does not cancel the damage-model literature above, most of which concerns amiodarone's metabolite and mitochondrially generated reactive oxygen species rather than the parent drug's direct chemistry, but it is a reason this entry does not describe amiodarone as uniformly pro-oxidant. Framing caution for the consumer-facing surface This entry documents a feature of amiodarone's own toxicity biology across several organ systems in laboratory models. It must not be converted into a claim that amiodarone depletes vitamin E, selenium, glutathione, or any other specific antioxidant nutrient in patients; no human study has measured any of those. This is distinct from, and does not add evidence to, the existing hepatic vitamin E entry above, which concerns a different, earlier-reviewed set of rat hepatocyte studies; see the overlap map below for how the two are kept separate. No antioxidant supplement dose is recommended by this entry.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No study has measured copper status in an amiodarone-treated human or animal. The one amiodarone-copper paper located tested amiodarone's own antioxidant chemistry using copper ions as an oxidation catalyst; it does not show amiodarone affects copper absorption, distribution, or excretion, and there is no circulating consumer claim to rebut either.

Full detail, limits and 1 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. UNGRADED · documented evidence gap

Limits on what this shows

  • Why no grade: Yellow requires mechanistic plausibility at Tier B or class extrapolation at Tier C for a copper-status effect specifically; the one amiodarone-copper study located (Lapenna et al., Br J Pharmacol 2001, PMID 11429399) measured amiodarone's protective effect on copper-catalyzed lipoprotein oxidation in vitro at therapeutically achievable concentrations (1.5 to 10 micromolar), which is a study of amiodarone's own radical chemistry using copper as a reagent, not a study of copper absorption, status, or handling in a living organism; it does not establish plausibility for a copper-status effect and is not counted toward this entry as depletion or excess evidence. White requires a circulating claim to rebut; the consumer nutrient-depletion charts already reviewed for this dossier (Blackmores Institute, InVite Health, US Pharmacist) do not list amiodarone at all, and no separate copper-specific claim for amiodarone or Class III antiarrhythmics was located. With neither condition met, this category sits outside all four tiers.
  • What would fill it: A study directly measuring serum, plasma, or a validated functional copper marker in an amiodarone-treated cohort against a real comparator, or an in vitro or animal study demonstrating amiodarone alters copper absorption, transport, or excretion rather than merely reacting with copper ions as an assay reagent.

What was searched

PubMed search-listing pages, September 10, 2026, for amiodarone together with copper: one relevant record (Lapenna 2001, described above); no serum, plasma, erythrocyte, or urinary copper measurement in an amiodarone-treated subject was found in any search performed for this review.

Mechanism check

Unlike some ACE inhibitors reviewed elsewhere in this dossier series, whose zinc entries rest on ACE being a zinc metalloenzyme, amiodarone has no structural target analogous to a metalloenzyme that would motivate a copper-specific hypothesis; amiodarone's mechanism of action is potassium and other ion-channel blockade, not a copper- or metal-dependent enzymatic step, so there is no target-level rationale to extrapolate from even by analogy.

Counter-evidence held on record

There is none to hold, which is the finding. Nothing supports a copper-status effect for amiodarone and nothing rules one out. Framing caution for the consumer-facing surface Absence of evidence is not evidence of safety. Do not publish "amiodarone does not affect copper," which this review does not establish, and do not publish a copper-testing or copper-supplement prompt attached to this drug, which the literature does not support either.

Iron

Not graded — disclosed evidence gap

See study details

No study located measures iron, ferritin, transferrin, or hepcidin status in an amiodarone-treated human or animal, and amiodarone has no documented gastrointestinal, renal, or hepatic mechanism that would predict an iron effect in either direction. There is also no circulating consumer claim to rebut.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. UNGRADED · documented evidence gap

Limits on what this shows

  • Why no grade: Yellow requires mechanistic plausibility at Tier B or class extrapolation at Tier C; no such evidence was located for iron specifically, whether from gastrointestinal blood loss, chelation, renal wasting, or altered erythropoiesis (amiodarone has no documented erythropoietin-suppressing action of the kind graded for some other drugs in this dossier series). White requires a circulating claim to rebut; none was located that names iron for amiodarone. With neither condition met, this category sits outside all four tiers.
  • What would fill it: A study directly measuring serum iron, ferritin, transferrin saturation, or hepcidin in a defined amiodarone-treated cohort against a real comparator, with amiodarone named as a study arm.

What was searched

PubMed search-listing pages, September 10, 2026, for amiodarone together with iron, ferritin, hemosiderin, and iron overload, in several term combinations; no study measuring iron status in an amiodarone-exposed subject was returned by any search performed for this review. This review also did not identify or rely on any hemosiderin-laden-macrophage finding for amiodarone pulmonary or hepatic toxicity; if such a histological finding exists in the pathology literature, it was not located here and no claim about it is made in either direction.

Mechanism check

Amiodarone is not renally eliminated (elimination is hepatic and biliary, already documented in this dossier's pharmacokinetic block), so it has no renal iron-wasting pathway available to it. It does not chelate iron in any assay identified here, and it has no documented effect on erythropoiesis or hemoglobin synthesis. Unlike the drug-delivered iodine excess that dominates this dossier, no analogous iron-relevant load or blockade has been described for amiodarone.

Counter-evidence held on record

There is none to hold, which is the finding. Nothing supports an iron-status effect for amiodarone and nothing rules one out. Framing caution for the consumer-facing surface Absence of evidence is not evidence of safety. Do not publish "amiodarone does not affect iron," which this review does not establish, and do not publish an iron-testing or iron-supplement prompt attached to this drug.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Yellow — Low

See study details

Two independent amiodarone-specific animal studies report gut-related disruption, a shift in gut microbiota composition in a cardiac-disease model and intestinal barrier injury as part of amiodarone-induced steatohepatitis, giving this category a genuine mechanistic signal that some other categories in this dossier do not have. No human study has measured gut microbiota in an amiodarone-exposed patient, and confounding by the underlying cardiac disease is a live concern in both animal studies.

Full detail, limits and 3 references

What the grade means here: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) without amiodarone-specific human data; also used for reverse-direction or context flags. YELLOW · mechanistic plausibility only

Limits on what this shows

  • Key negative or null findings: No human study of any kind was located. Neither animal study's full text could be confirmed in this session, so the direction and magnitude of the reported microbiota or barrier changes are recorded as present but not quantified; both are named Tier B findings, not treated as settled effect sizes. Confounding by indication is a first-order concern for both studies: the Wei 2025 model used rats with pre-existing alcoholic heart disease, and the Kawauchi 2025 model is built around amiodarone-induced steatohepatitis itself, so in neither case is amiodarone's gut effect cleanly separated from the disease state or from the liver injury it is presented alongside.
  • At-risk subgroups: None defined by human data. By mechanism only, patients with amiodarone-associated hepatotoxicity would be the population in which a gut-liver axis effect would be most plausible to look for, mirroring the Kawauchi model, not a basis for a testing directive.

Regulatory status

Gut microbiota is not named anywhere in the amiodarone prescribing information. The label does document frequent gastrointestinal adverse effects (nausea, vomiting, constipation) as part of its general tolerability profile, which are motility and tolerability findings, not microbiome findings, and are not counted toward this entry.

Population evidence

None in humans. Tier B, amiodarone in the cohort: Wei et al., J Med Microbiol 2025, PMID 39760646, a rat model of alcoholic heart disease comparing a Chinese herbal formula (SSYX) and amiodarone, reporting changes in gut microbiota composition alongside body weight, cardiac function and gut morphology in amiodarone-treated animals; the search listing available in this session did not return the specific taxa or diversity metrics, and the full text was not independently opened, so no specific statistic from it is cited here. Kawauchi et al., Sci Rep 2025, PMID 40603897, a mouse model of amiodarone-induced steatohepatitis, examining small-intestinal disruption directly: crypt-villus architecture, mucosal permeability and intestinal barrier integrity, as part of the pathogenesis of amiodarone's own liver toxicity; again, the full text was not independently opened in this session and no specific statistic is cited. A third study, Schumacher et al., Gut Microbes 2023, PMID 37749884, found amiodarone inhibits the Clostridioides difficile toxins TcdA and TcdB in vitro and proposed repurposing the drug as a pan-variant antitoxin; this is a direct antimicrobial-adjacent, potentially protective property against one specific pathogen's toxins, not a measurement of amiodarone's effect on the resident microbiome, and is filed here as relevant context rather than as risk evidence.

Mechanism

Two distinct, plausible routes, both Tier B only. First, a gut-liver axis route: amiodarone's hepatotoxicity (already documented at Tier A in this dossier) is mechanistically linked in the Kawauchi model to small-intestinal barrier disruption, consistent with steatohepatitis pathophysiology more broadly, in which a compromised gut barrier is both a contributor to and a consequence of liver injury. Second, a direct route: amiodarone's antimicrobial-adjacent chemistry (demonstrated for C. difficile toxins specifically) raises the general plausibility that it could interact with other gut organisms, though no study has tested this against a broader commensal panel.

Counter-evidence held on record

The Schumacher 2023 finding runs in a protective direction for one specific pathogen's toxins, a reminder that "gut microbiome risk" is not a uniformly hazardous label for this drug; amiodarone's interaction with the gut is not a single-direction story. No study located found amiodarone microbiota effects to be null; the absence of a null result here reflects a thin literature, not a settled positive effect. Framing caution for the consumer-facing surface Do not present this as an established human gut-microbiome harm; it is animal and in vitro evidence only, in models where the underlying cardiac or hepatic disease state is a live confound. Equally, do not present amiodarone as protective for gut health on the strength of the C. difficile toxin finding; that is a narrow in vitro result about specific bacterial toxins, not a probiotic effect. No probiotic, prebiotic, or gut-health supplement recommendation follows from this entry.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production

Yellow — Low

See study details

Amiodarone inhibits mitochondrial beta-oxidation of fatty acids, the major ATP-generating pathway in liver and heart, in isolated rat liver mitochondria and in human HepG2 hepatocyte cells at defined concentrations. No study has measured tissue ATP content or high-energy phosphate levels in an amiodarone-treated human, and this is the drug's own toxicity mechanism, not a nutrient-status finding.

Full detail, limits and 2 references

What the grade means here: mechanistic plausibility only (Tier B), or class-level extrapolation (Tier C) without amiodarone-specific human data; also used for reverse-direction or context flags. YELLOW · mechanistic plausibility only

Limits on what this shows

  • Key negative or null findings: No 31-phosphorus spectroscopy or direct tissue ATP content study in an amiodarone-treated human or animal was located in this review, so there is no clean human-relevant null or positive tissue-ATP finding to weigh, only the upstream beta-oxidation blockade. The Felser 2013 comparison again shows amiodarone is the less potent of the two drugs tested (dronedarone inhibited beta-oxidation at a lower concentration), a relevant bound on how this finding should be read.
  • At-risk subgroups: None defined by human ATP data. By mechanism only, the same population flagged for hepatotoxicity risk generally (higher cumulative dose and duration) would be the plausible population for an ATP-generation effect, not a basis for a testing directive.
  • Dose and duration: The in vitro threshold (approximately 20 micromolar) does not map cleanly onto a human plasma or tissue concentration at any specific oral dose; amiodarone's own pharmacokinetic profile (extensive tissue accumulation, very large volume of distribution, 96% protein binding) documented elsewhere in this dossier means tissue concentrations are not simply predictable from plasma levels, and no human dose-response for this specific endpoint has been established.

Regulatory status

ATP and energy metabolism are not named anywhere in the amiodarone prescribing information.

Population evidence

None in humans. Tier B, amiodarone in the cohort: Felser et al., Toxicol Sci 2013, PMID 23135547, rat liver mitochondria and human HepG2 hepatocyte cells, reporting that amiodarone inhibits mitochondrial beta-oxidation starting at approximately 20 micromolar; beta-oxidation is the pathway by which fatty acids are converted into the acetyl-CoA that feeds the citric acid cycle and, ultimately, ATP synthesis via the electron transport chain, so a beta-oxidation block is mechanistically a block on a major ATP-generating input, not merely a respiratory-capacity finding. A companion paper from the same group (Felser et al., Toxicology 2014, PMID 24881592) confirms amiodarone inhibits both mitochondrial respiration and beta-oxidation in vitro. This is the same literature cited under Mitochondrial burden above for the respiratory-chain and general toxicity findings; here it is counted specifically for the beta-oxidation, substrate-supply-to-ATP-synthesis finding, and the overlap map below records that split explicitly so the same papers are not double-counted toward two grades.

Mechanism

Named. Beta-oxidation of fatty acids is the principal ATP-generating pathway in hepatocytes and cardiomyocytes at rest; blocking it starves the downstream electron transport chain of substrate and is consistent with the microvesicular steatosis pattern (fat accumulating because it cannot be oxidized) described in amiodarone hepatotoxicity more broadly. This is a direct pharmacotoxic action on a specific enzymatic pathway, not a mechanism involving depletion of a dietary ATP-synthesis cofactor such as riboflavin, niacin, or coenzyme Q10; no study identified here proposes the latter.

Counter-evidence held on record

As under Mitochondrial burden, amiodarone was the less potent mitochondrial and beta-oxidation toxin relative to dronedarone in the one head-to-head assay located (Felser 2013), which bounds how large an ATP-generation effect should be assumed to be at typical human exposures. No study located reports a clinical, whole-body correlate of reduced ATP output on amiodarone (for example, an exercise-capacity or aerobic-performance trial); that absence is recorded as a gap in the available evidence, not as reassurance. Framing caution for the consumer-facing surface Do not tell readers amiodarone lowers their cellular energy production in a way a supplement would fix. The mechanism identified is a direct pharmacotoxic block on a fatty-acid-oxidation enzyme pathway, part of the same biology that produces amiodarone's labeled hepatotoxicity, not a coenzyme Q10, carnitine, or riboflavin deficiency. No dose of any such supplement is recommended by this entry.

Oxygen delivery and utilization

Not graded — disclosed evidence gap

See study details

Every candidate finding for this category either is amiodarone's own well-documented pulmonary toxicity, which Hard Rule 1 of this dossier's governance framework excludes from being filed as a nutrient- or physiological-status finding, or is the same mitochondrial respiratory-chain evidence already counted once under Mitochondrial burden above. With no evidence left that is both eligible and not already assigned elsewhere, and no circulating consumer claim to rebut, this category cannot be assigned a color grade.

Full detail, limits and 4 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. UNGRADED · structural exclusion, not a raw absence of evidence

Limits on what this shows

  • Why no grade: This is a different kind of gap from the copper and iron entries above, which reflect a genuine absence of any study. Here, real Tier A human evidence exists: amiodarone's labeled pulmonary toxicity is directly and repeatedly measured by diffusing capacity (DLCO) in multiple independent cohorts, described in full below. But Hard Rule 1 of this dossier's governing protocol states plainly that a drug's own known clinical effect must never be filed as a nutrient- or physiological-status deficiency; grading pulmonary toxicity here, inside a framework built to track nutrient-adjacent physiological findings, would risk exactly that relabeling, even though "oxygen delivery" is not literally a nutrient's name. The remaining candidate evidence, amiodarone's mitochondrial effect on cellular oxygen utilization through beta-oxidation and respiratory-chain inhibition, is real Tier B evidence, but it is the identical evidence base already assigned to the Mitochondrial burden entry above; counting it again here would violate this dossier's overlap-control rule. No third, independent line of evidence (for example, a hemoglobin, hematocrit, or erythropoietin effect of the kind graded for some other drugs under an "oxygen carriage" framing) was located for amiodarone at any tier.

The excluded evidence, named for completeness

FDA label §5.2, boxed-adjacent warning: "Rates of pulmonary toxicity have been reported to be as high as 17% and is fatal in about 10% of cases," with baseline and periodic chest X-ray and pulmonary function testing, explicitly including diffusing capacity, required. Human cohort studies naming amiodarone specifically and using DLCO as the key functional parameter: Magro et al., J Am Coll Cardiol 1988, PMID 3403839 (89 patients, pulmonary toxicity in 15, DLCO the most significantly altered parameter); Gleadhill et al., Am J Med 1989, PMID 2910095 (clinical toxicity associated with a DLCO fall greater than 20 percent); Dusman et al., Circulation 1990, PMID 2364524 (573 patients, 33 with toxicity, low DLCO supporting diagnosis); Singh et al., J Am Coll Cardiol 1997, PMID 9247526 (CHF-STAT trial, annual DLCO monitoring, an overall "acceptable" pulmonary toxicity profile at the doses studied). These figures were drawn from indexed search-listing summaries rather than independently opened full text in this session and should be independently verified before being quoted elsewhere; they are already reflected in this dossier's existing monitoring panel under "chest imaging" and in the pharmacokinetic and red-tier material, and are named again here only to show explicitly why they were not converted into a new graded entry, not because they are being newly introduced as load-bearing evidence.

What was searched

PubMed search-listing pages, September 10, 2026, for amiodarone together with diffusing capacity, DLCO, and pulmonary toxicity; no study distinct from the pulmonary-toxicity literature above, and no hemoglobin, hematocrit, or erythropoietin study of the kind that has supported an oxygen-carriage finding for a different drug in this dossier series, was located for amiodarone.

What would change this

A study measuring a genuinely distinct oxygen-utilization parameter in amiodarone-treated humans, for example whole-body oxygen consumption or tissue oxygen extraction under controlled conditions, that is not simply a restatement of pulmonary diffusing capacity or of the mitochondrial respiratory-chain findings already counted elsewhere, would allow this category to be graded on its own terms.

Counter-evidence held on record

Singh et al. 1997 (CHF-STAT trial, PMID 9247526) is the closest thing to reassurance in this literature, concluding amiodarone could be used with an "acceptable" pulmonary toxicity profile at the doses studied over the trial's follow-up; it does not contradict the DLCO-decline mechanism, only bounds its overall clinical frequency and severity. This is recorded as context for the excluded pulmonary-toxicity evidence, not as evidence for or against a graded finding here. Framing caution for the consumer-facing surface Do not publish any consumer-facing statement implying amiodarone lowers oxygen delivery through a correctable nutrient-adjacent pathway. Pulmonary toxicity is a serious, well-documented, directly monitored clinical effect of this drug in its own right, managed by chest imaging and pulmonary function testing as already described in this dossier, not by any dietary or supplement intervention. Do not publish reassurance either; the absence of a graded entry here reflects a structural rule about where evidence belongs, not a finding that oxygen delivery is unaffected.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • "Amiodarone depletes iodine; supplement with iodine or kelp."

    Where it comes from: Not found already published in the specific consumer sources checked for this review (general drug-nutrient depletion charts such as the Blackmores Institute, InVite Health, and US Pharmacist guides do not list amiodarone at all). Named here as a preemptive rebuttal because it is the exact template ("drug X depletes nutrient Y, take Y") that those charts apply to dozens of other drugs, and applying it to amiodarone by pattern-matching would be a dangerous inversion.

    Why it fails: Amiodarone's own label and pharmacology data establish the opposite direction: it delivers a large iodine excess (roughly 45 to 50 times the RDA in free iodine per day), and this excess is the documented mechanism of both amiodarone-induced hypothyroidism and thyrotoxicosis. Supplemental iodine or kelp would add to an already pathological load and could precipitate or worsen thyroid dysfunction. This claim is not merely unsupported, it is factually reversed and actively hazardous if acted on.

  • "Amiodarone-induced thyroid problems mean you need more selenium."

    Where it comes from: Selenium supplementation lowers thyroid peroxidase antibodies in idiopathic (Hashimoto-type) autoimmune thyroiditis in some trials; this is sometimes generalized to any drug-associated thyroid problem.

    Why it fails: No amiodarone-specific cohort has been studied for selenium status or selenium supplementation outcomes. Amiodarone-induced thyroid dysfunction (types 1 and 2) is driven by iodine excess and direct/destructive thyroidal effects of the drug and its metabolite, not by the autoantibody-mediated process selenium trials target; the mechanism does not transfer. Fails the cohort test and the mechanism-transfer test at once.

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • TSH and free T4

    Primary lab panel Baseline before starting amiodarone, then per guideline intervals during therapy (commonly every 3 to 6 months) and continuing for at least a year after discontinuation, given the drug's multi-week to multi-month half-life. TSH is the anchor test; isolated T4/reverse T3 changes are expected on amiodarone and do not by themselves indicate dysfunction.

  • Iodine and kelp

    Supplement caution Do not start iodine-containing supplements, kelp, or high-iodine functional foods without explicit guidance from the prescriber or an endocrinologist. Amiodarone patients already carry a substantial iodine load; the safe default is to add nothing iodine-containing, not to supplement.

  • Thyroid nodularity and antibody status

    Baseline risk stratification A baseline thyroid ultrasound or antibody panel (anti-TPO) in patients with known nodular goiter or autoimmune thyroid disease helps anticipate whether type 1 (iodine-excess) or type 2 (destructive) thyrotoxicosis is more likely if dysfunction develops; this is a clinical decision, not a supplement decision.

  • Liver enzymes, chest imaging, eye exam

    Adjacent organ monitoring (not nutrient-related) Amiodarone's labeled hepatotoxicity, pulmonary toxicity, and corneal microdeposit risks are monitored on their own schedules (transaminases, baseline and periodic chest X-ray/PFTs including diffusing capacity, routine eye exams). These are clinical outcomes with their own surveillance pathways, not nutrient-status findings, and are listed here only so they are not mistaken for one.

  • Warfarin and other CYP substrates

    Drug interaction, not nutrient interaction Amiodarone inhibits CYP2C9, CYP2D6, CYP3A, and P-glycoprotein, materially increasing exposure to warfarin, digoxin, statins, and other substrates. This is a pharmacokinetic drug-drug interaction hub, flagged here for completeness; it is not a nutrient interaction and carries no dietary-supplement implication of its own.

  • Coenzyme Q10, carnitine, riboflavin, thiamine

    No action indicated · added Sep 10, 2026 Not a testing or dosing recommendation from this dossier. Mitochondrial burden and ATP production are graded on the strength of amiodarone's own recognized mitochondrial toxicity mechanism, not on any demonstrated human deficiency in a mitochondrial-support nutrient, and no such supplement is supported by the evidence reviewed.

  • Copper, iron, selenium, and gut microbiome testing

    No action indicated · added Sep 10, 2026 No testing and no supplementation is recommended for any of these. Copper and iron are ungraded with no status data on this drug at any tier; the oxidative stress entry is not a selenium deficiency finding; gut microbiome risk is graded on animal evidence only and carries no probiotic or dietary directive.

All references used above
  1. Amiodarone Hydrochloride Tablets, full prescribing information. — FDA label via DailyMed. Source for bioavailability (~50%), food and grapefruit juice effect (AUC/Cmax figures), protein binding (~96%), CYP3A/CYP2C8 metabolism, CYP450/P-gp inhibition profile, warfarin and digoxin interactions, elimination half-life (58 days, range 15-142), hepatic/biliary elimination, 37.3% iodine by weight, hypothyroidism (~10%) and hyperthyroidism (~2%) rates, thyroid monitoring language, hepatotoxicity and pulmonary toxicity warnings, corneal microdeposits, and electrolyte correction (potassium, magnesium, calcium) before initiation.
  2. Prevalence of Amiodarone Induced Hypothyroidism and Hyperthyroidism in Patients with Heart Diseases: A Systematic Review and Meta-Analysis. — Current Medicinal Chemistry, 2022 (Bentham Science). Random-effects meta-analysis pooling multiple amiodarone-treated cardiac cohorts. Pooled hypothyroidism prevalence 23.43% (95% CI 11.54-35.33); pooled hyperthyroidism prevalence 11.61% (95% CI 7.20-16.02); hyperthyroidism prevalence significantly associated with publication year (p=0.037), no significant association for hypothyroidism by year, sample size, or age.
  3. Amiodarone-Induced Thyrotoxicosis. — Endotext (NCBI Bookshelf, NBK279030), updated chapter. Source for type 1 (iodine-induced excess synthesis) versus type 2 (destructive thyroiditis) mechanism definitions, overall AIT incidence range 0.003% to 10% (up to 10% in iodine-deficient regions, about 3% in North America), and male predominance (M:F approximately 3:1).
  4. 2021 update, evaluation and treatment of amiodarone-induced thyroid disorders (clinical practice guidance). — Journal of Clinical Endocrinology and Metabolism, 106(1):226. Source for iodine dose figures (approximately 75 mg total iodine and approximately 7 mg free iodine released per 200 mg tablet, against an adult requirement of 0.15-0.30 mg/day), recommended monitoring cadence (baseline, then approximately every 3 months during treatment, continuing at least 1 year after discontinuation given the drug's long half-life), and management approach (levothyroxine for hypothyroidism; methimazole for type 1 thyrotoxicosis; corticosteroids for type 2; combined therapy for mixed or indeterminate presentations). Cited for mechanism and monitoring framework, not as a dosing recommendation from this dossier.
  5. Amiodarone and the thyroid. — Basaria S, Cooper DS. American Journal of Medicine, 2005 (narrative review). Source for the observation that most amiodarone-treated patients remain clinically euthyroid despite characteristic biochemical shifts (raised T4 and reverse T3, low-normal T3), supporting TSH as the anchor monitoring test rather than T4/T3 alone.Full text of the abstract could not be confirmed by direct fetch in this session (page returned metadata only / rate-limited); the euthyroid-despite-biochemical-change finding is well corroborated by the Endotext and JCEM sources above and is widely cited, but treat the exact wording of this specific citation as unverified.
  6. Amiodarone induced thyroid dysfunction: a high cumulative incidence in a nationwide cohort study in Iceland. — Guðjónsson et al., Journal of Internal Medicine, 2025. Nationwide Icelandic cohort of amiodarone-treated patients reporting high cumulative incidence of thyroid dysfunction.Full text returned a 403 error in this session and could not be opened. Named here only to document that it exists and appears amiodarone-specific by title and abstract snippet; no statistic from it is cited or relied upon above.
  7. Effects of N-acetyl cysteine, vitamin E and vitamin C on liver glutathione levels following amiodarone treatment in rats. — Animal study (rat model), PMID 31410096. Source for the yellow-tier antioxidant/hepatotoxicity mechanism entry; amiodarone was the specific agent studied, satisfying the cohort test for Tier B animal evidence, but this is not human data.
  8. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. — PMID 11932302. Cited only to document the origin of the selenium claim addressed in Fails Verification; amiodarone was not in this study's cohort.Cohort excluded amiodarone entirely; this is idiopathic autoimmune (Hashimoto-type) thyroiditis, cited as Tier C/D context for a claim that fails to transfer, not as support for any amiodarone-specific finding.
  9. Drug-induced nutrient depletion consumer charts reviewed for circulating claims (Blackmores Institute, InVite Health, US Pharmacist). — Checked specifically for any amiodarone entry. None of the three lists amiodarone or Cordarone by name. Re-checked September 10, 2026 for mitochondrial, oxidative-stress, copper, iron, and gut-microbiome claims specifically; none found for amiodarone in any of the three sources.
  10. WHO ATC/DDD Index, C01BD. — Source for ATC classification (amiodarone: C01BD01) confirming class III antiarrhythmic categorization.
  11. DailyMed. Amiodarone Hydrochloride Tablets label (re-accessed for the September 10, 2026 expansion). — Same regulatory label as source [1] (DailyMed setid 7ccd3733-c3af-4a11-8500-0f99194c1472), re-opened and directly quoted for §5.2 Pulmonary Toxicity ("Rates of pulmonary toxicity have been reported to be as high as 17% and is fatal in about 10% of cases," baseline and periodic chest X-ray and pulmonary function testing including diffusing capacity) and §5.3 Hepatic Injury ("Asymptomatic elevations of hepatic enzyme levels are seen frequently, but amiodarone hydrochloride can cause life-threatening hepatic injury," histology resembling alcoholic hepatitis or cirrhosis). Used as the Tier A anchor for the mitochondrial burden entry and as the excluded evidence named in the oxygen delivery and utilization entry.
  12. Spaniol M, Bracher R, Ha HR, Follath F, Krähenbühl S. Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria. — J Hepatol. 2001;35(5):628-636. PMID 11690709. Isolated rat liver mitochondria; direct amiodarone toxicity to mitochondria. Amiodarone in cohort (Tier B, animal, isolated organelle).Listing-level confirmation only (title, journal, year, PMID); full text not independently opened in this session.
  13. Felser A, Blum K, Lindinger PW, Bouitbir J, Krähenbühl S. Mechanisms of hepatocellular toxicity associated with dronedarone: a comparison to amiodarone. — Toxicol Sci. 2013;131(2):480-490. PMID 23135547. Rat liver mitochondria and human HepG2 hepatocyte cells; amiodarone inhibited mitochondrial beta-oxidation starting at approximately 20 micromolar, versus approximately 10 micromolar for dronedarone in the same assay. Amiodarone in cohort (Tier B, animal and human cell line).Listing-level confirmation only; individual PMID page returned a metadata-only shell when fetched directly in this session, so figures are drawn from the search-listing summary rather than an independently opened abstract, and should be re-verified before being quoted elsewhere.
  14. Felser A, Lindinger PW, Schnell D, et al. Hepatocellular toxicity of benzbromarone and related compounds: effects on mitochondrial function and structure. — Toxicology. 2014;324:136-146. PMID 24881592. Confirms dronedarone and amiodarone inhibit mitochondrial respiration and beta-oxidation in vitro. Amiodarone in cohort (Tier B, animal/in vitro).Listing-level confirmation only; full text not independently opened in this session.
  15. Serviddio G, Bellanti F, Giudetti AM, et al. Mitochondrial oxidative stress and respiratory chain dysfunction account for liver toxicity during amiodarone but not dronedarone administration. — Free Radic Biol Med. 2011;51(12):2234-2242. PMID 21971348. Animal model comparing amiodarone and dronedarone hepatotoxicity via mitochondrial respiratory chain and oxidative stress measurements. Amiodarone in cohort (Tier B, animal).Full text could not be opened in this session (returned metadata only); figures are drawn from the indexed title/summary, and specific quantitative results are not quoted above for this reason.
  16. Bețiu AM, Noveanu L, Hâncu IM, et al. Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity. — Int J Mol Sci. 2021;22(21):11621. PMID 34769217. HepG2 cells and platelets treated with amiodarone in vitro; succinate rescues mitochondrial respiration. Amiodarone in cohort (Tier B, human-derived cell lines, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  17. Prill S, Bavli D, Levy G, et al. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone. — Arch Toxicol. 2016;90(5):1181-1191. PMID 26041127. Hepatic bioreactor system; amiodarone produces CYP450-independent mitochondrial toxicity. Amiodarone in cohort (Tier B, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  18. Waldhauser KM, Török M, Ha HR, et al. Hepatocellular toxicity and pharmacological effect of amiodarone and amiodarone derivatives. — J Pharmacol Exp Ther. 2006;319(3):1413-1423. PMID 16971508. Comparative hepatocellular toxicity of amiodarone and derivatives. Amiodarone in cohort (Tier B, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  19. Yasuda H, et al. Amiodarone-induced lymphocyte toxicity and mitochondrial function. — J Cardiovasc Pharmacol. 1996;27(5). PMID 8797142. Lymphocyte mitochondrial toxicity. Amiodarone in cohort (Tier B, human-derived cells, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  20. van der Mark VA, et al. Overexpression of the constitutive androstane receptor and shaken 3D-culturing increase biotransformation capacity and sensitivity to mitochondrial amiodarone toxicity of HepaRG cells. — Toxicol Appl Pharmacol. 2020;406:115217. PMID 32428594. HepaRG liver cell sensitivity to mitochondrial amiodarone toxicity. Amiodarone in cohort (Tier B, human-derived cell line, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  21. Park S, et al. Amiodarone as a model compound for assessment of mitochondrial toxicity in hepatocytes. — Toxicol Res. 2025. PMID 41169279. Methods paper using amiodarone as a reference positive-control compound for mitochondrial toxicity assays. Amiodarone in cohort (Tier B, in vitro/methods).Listing-level confirmation only; full text not independently opened in this session.
  22. Finsterer J, Zarrouk-Mahjoub S. Mitochondrial toxicity of cardiac drugs and its relevance to mitochondrial disorders. — Expert Opin Drug Metab Toxicol. 2015;11(11):1727-1740. PMID 25331002. Review naming amiodarone among cardiac drugs with documented mitochondrial toxicity. Amiodarone named specifically (Tier B, review).Listing-level confirmation only; full text not independently opened in this session.
  23. Doughty CT, Amato AA. Toxic Myopathies. — Continuum (Minneap Minn). 2019;25(6):1712-1731. PMID 31794468. Neurology review discussing amiodarone among drugs producing a mitochondrial myopathy pattern. Amiodarone named specifically (Tier B, review).Listing-level confirmation only; full text not independently opened in this session.
  24. Silva Santos LF, et al. Catechin and epicatechin reduce mitochondrial dysfunction and oxidative stress induced by amiodarone in human lung fibroblasts. — J Arrhythm. 2017;33(3):220-225. PMID 28607618. Human lung fibroblasts treated with amiodarone in vitro. Amiodarone in cohort (Tier B, human-derived cells, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  25. Dawood SA, et al. L-Carnitine Ameliorates Amiodarone-Mediated Alveolar Damage: Oxidative Stress Parameters, Inflammatory Markers, Histological and Ultrastructural Insights. — Pharmaceuticals (Basel). 2024;17(9). PMID 39204109. Rat model, amiodarone-induced alveolar/pulmonary damage and oxidative stress markers, L-carnitine as protective co-therapy. Amiodarone in cohort (Tier B, animal).Listing-level confirmation only; full text not independently opened in this session.
  26. Zhao H, et al. Amiodarone promotes heat-induced apoptosis, inflammation and oxidative stress in mouse HL1 atrial myocytes. — Nan Fang Yi Ke Da Xue Xue Bao. 2021;41(3). PMID 33849832. Mouse atrial myocyte cell line, amiodarone and heat-stress combined. Amiodarone in cohort (Tier B, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  27. Eid RA, et al. Grape seed extract protects against amiodarone-induced nephrotoxicity and ultrastructural alterations associated with the inhibition of biomarkers of inflammation and oxidative stress in rats. — Ultrastruct Pathol. 2021;45(2). PMID 33423596. Rat model, amiodarone nephrotoxicity and oxidative stress biomarkers. Amiodarone in cohort (Tier B, animal).Listing-level confirmation only; full text not independently opened in this session.
  28. Niimi N, et al. Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy. — Eur J Neurosci. 2016;44(7). PMID 27152884. In vitro peripheral nerve/Schwann cell model. Amiodarone in cohort (Tier B, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  29. Vereckei A, et al. [The role of oxidative stress, caused by amiodarone, in the side effects of the drug]. — Orv Hetil. 1991;132(1). PMID 2003039. Chemiluminometric method, in vitro. Article in Hungarian. Amiodarone in cohort (Tier B, in vitro).Title and journal confirmed via search listing only; full text not opened in this session and not independently verified beyond the listing.
  30. Sarma JS, Pei H, Venkataraman K. Role of Oxidative Stress in Amiodarone-induced Toxicity. — J Cardiovasc Pharmacol Ther. 1997;2(1). PMID 10684442. Animal model. Amiodarone in cohort (Tier B, animal).Listing-level confirmation only; full text not independently opened in this session.
  31. Lapenna D, Ciofani G, Pierdomenico SD, Giamberardino MA, Cuccurullo F. Antioxidant activity of amiodarone on human lipoprotein oxidation. — Br J Pharmacol. 2001;134(3):658-663. PMID 11429399. Amiodarone at therapeutically achievable concentrations (1.5 to 10 micromolar) protected human non-HDL lipoprotein against copper-catalyzed oxidation in vitro. Amiodarone in cohort (Tier B, human tissue, in vitro). Central source for both the oxidative stress counter-evidence and the copper ungraded entry.
  32. Wei S, et al. [Effects of SSYX and amiodarone on gut microbiota composition in a rat model of alcoholic heart disease]. — J Med Microbiol. 2025. PMID 39760646. Rat model of alcoholic heart disease; amiodarone-treated group's gut microbiota composition, body weight, cardiac function and gut morphology assessed. Amiodarone in cohort (Tier B, animal).Listing-level confirmation only (title, journal, year, PMID, and general subject matter); full text not independently opened in this session, so no specific taxon, diversity metric, or effect size from it is cited above.
  33. Kawauchi S, et al. Amiodarone-induced steatohepatitis pathogenesis: small intestinal disruption and barrier function. — Sci Rep. 2025;15. PMID 40603897. Mouse model of amiodarone-induced steatohepatitis; small-intestinal crypt-villus architecture, mucosal permeability and barrier integrity examined. Amiodarone in cohort (Tier B, animal).Listing-level confirmation only; full text not independently opened in this session, so no specific quantitative result from it is cited above.
  34. Schumacher J, et al. Identification of amiodarone as a novel Clostridioides difficile toxin inhibitor. — Gut Microbes. 2023;15(1). PMID 37749884. In vitro inhibition of C. difficile toxins TcdA and TcdB by amiodarone, proposed as a pan-variant antitoxin repurposing candidate. Amiodarone in cohort (Tier B, in vitro).Listing-level confirmation only; full text not independently opened in this session.
  35. Magro SA, Lawrence EC, Wheeler SH, Krafchek J, Lin HT, Wyndham CR. Amiodarone pulmonary toxicity: prospective evaluation of serial pulmonary function tests. — J Am Coll Cardiol. 1988;12(3):781-788. PMID 3403839. 89 amiodarone-treated patients; pulmonary toxicity in 15 (17%); diffusing capacity (DLCO) identified as the most significantly altered pulmonary function parameter. Amiodarone in cohort (Tier A, human).Figures drawn from an indexed search-listing summary; full text not independently opened in this session and should be re-verified before being quoted elsewhere.
  36. Gleadhill IC, Wise RA, Schonfeld SA, et al. Serial lung function testing in patients treated with amiodarone: a prospective study. — Am J Med. 1989;86(1):4-10. PMID 2910095. Serial pulmonary function testing; clinical toxicity associated with a DLCO fall greater than 20 percent. Amiodarone in cohort (Tier A, human).Figures drawn from an indexed search-listing summary; full text not independently opened in this session and should be re-verified before being quoted elsewhere.
  37. Dusman RE, Stanton MS, Miles WM, et al. Clinical features of amiodarone-induced pulmonary toxicity. — Circulation. 1990;82(1):51-59. PMID 2364524. 573 amiodarone-treated patients; 33 (5.8%) diagnosed with pulmonary toxicity, diagnosis supported in part by low diffusing capacity. Amiodarone in cohort (Tier A, human).Figures drawn from an indexed search-listing summary; full text not independently opened in this session and should be re-verified before being quoted elsewhere.
  38. Singh SN, Fletcher RD, Fisher SG, et al. (CHF-STAT investigators). Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. — N Engl J Med companion pulmonary-safety analysis, J Am Coll Cardiol 1997;30(3). PMID 9247526. CHF-STAT trial; annual DLCO monitoring; concluded amiodarone could be used with an overall acceptable pulmonary toxicity profile at the doses and follow-up studied. Amiodarone in cohort (Tier A, human).Figures drawn from an indexed search-listing summary; full text not independently opened in this session and should be re-verified before being quoted elsewhere.