What are documented case reports of alpha‑lipoic acid toxicity and what doses were involved?
Executive summary
Alpha‑lipoic acid (ALA) is widely used as an over‑the‑counter antioxidant and for diabetic neuropathy, and published clinical toxicology literature documents a very small number of serious intoxications—mostly in children but including recent adult fatalities—after acute ingestions measured in grams rather than the milligram doses commonly used therapeutically [1] [2] [3]. Reported toxic doses cluster around 6 g in several cases, with at least one reported pediatric fatality and a recent adult death after a 6 g ingestion, while other patients have survived larger ingestions up to 18 g [3] [4] [5].
1. What ALA is and how it’s normally dosed: safe ranges cited by reviews
Alpha‑lipoic acid is an antioxidant used orally for diabetic neuropathy and other indications; standard adult supplement doses typically range from about 200 mg to 2400 mg per day in studies and reviews, and many toxicology reviews state 200–2400 mg/day is considered safe for adults though pediatric safety is not established [2] [1] [6]. Regulatory assessments and toxicology summaries note experimental animal findings at high doses but emphasize that clinical overdose reports in humans are rare [7] [6].
2. Pediatric case reports: seizures, status epilepticus and a fatal 6 g ingestion
Multiple pediatric intoxication reports describe serious neurologic events—seizures, status epilepticus, vomiting, and unconsciousness—after single acute ingestions; WebMD and clinical reviews summarize cases in children from 14 months to 16 years who took doses up to 2400 mg as a single dose with seizures reported, and individual case reports in the literature document fatal and nonfatal outcomes after gram‑level ingestions in infants and adolescents [8] [2] [9]. A pediatric fatality linked to a 6 g ingestion has been cited in review articles and case series summaries [4] [5].
3. Adult case reports and first reported adult mortality after 6 g
Until recently most reported severe ALA intoxications were pediatric; case reports document a small number of adult overdoses, including a 42‑year‑old woman who intentionally ingested ten 600 mg tablets (6 g total, ~92.3 mg/kg) and developed refractory seizures, metabolic acidosis, multiorgan failure and died despite aggressive ICU measures—this was described as the first reported adult mortality from ALA toxicity [3] [10]. Conversely, other adult cases have survived acute ingestions of 6 g and even 18 g with supportive care, indicating variable outcomes at similar doses [3] [5].
4. Patterns of clinical toxicity and the implicated dose range
Across case reports the clinical phenotype of severe ALA overdose includes refractory seizures/status epilepticus, lactic/metabolic acidosis, rhabdomyolysis, thrombocytopenia, renal dysfunction and cardiovascular compromise consistent with mitochondrial failure; reported toxic ingestions that produced severe illness or death are on the order of grams—commonly ~6 g—though survival after 6 g and 18 g has been reported, so no single lethal threshold is established [3] [4] [11]. Toxicology reviews note that while routine adult dosing up to ~2400 mg/day has been used without side effects, there is no validated “safe” pediatric dose and the dose–response relationship for acute toxicity is poorly defined [2] [1] [11].
5. Mechanisms, uncertainties, and clinical implications
Authors propose mitochondrial dysfunction, lactic acidosis and possible pro‑oxidant effects at very high concentrations as mechanistic drivers of the observed multiorgan failure, but mechanistic understanding in humans remains limited and animal studies show organ‑level injury only at much higher exposures [12] [7]. The literature is small—reviews count fewer than ten reported severe human intoxications in decades—so clinicians are advised to treat severe ALA overdose aggressively and toxicologists caution that outcomes vary even at comparable ingested doses [4] [9]. Reported cases often lack complete toxicologic assay data or co‑ingestant exclusion, and systematic dose–response data are absent, which limits firm dose thresholds for harm [5].
6. Bottom line
Documented severe ALA toxicities are rare but real: the clinical case literature identifies gram‑level acute ingestions—commonly around 6 g—as repeatedly associated with seizures, metabolic collapse and, in at least two reported cases (one pediatric, one adult), death, while other patients have survived similar or higher ingestions with supportive critical care; absence of robust dose–response data and pediatric safety limits means caution is required around storage, labeling and pediatric access to concentrated formulations [3] [4] [2] [5].