| domain | strongest finding | evidence type/species | key quantitative datum | source/date/DOI |
|---|---|---|---|---|
| Human clinical syndrome | Acute ackee intoxication follows ingestion of unripe ackee and presents with vomiting, hypoglycemia, and CNS depression; severe cases may progress to seizures, coma, and death | Human clinical case/report | Onset reported within 6–48 h; death in severe cases may occur within 48 h; unripe fruit reported to contain hypoglycin A at about 100-fold higher concentration than ripe fruit | Latif & Luthra, 2017, DOI: 10.23937/2377-3634/1410073 (pqac-00000000, pqac-00000005) |
| Human historical pathology | Fatal human cases show multi-organ fatty degeneration, especially liver, with renal, pancreatic, cardiac, and pulmonary involvement | Human historical autopsy series | Severe cases described with onset within about 2 h; historical mortality estimates 80–90% in early reports | Scott, 1916, DOI: 10.1080/00034983.1916.11684104 (pqac-00000001, pqac-00000004, pqac-00000012) |
| Mechanism | Hypoglycin A is metabolized to MCPA-CoA, causing an acquired multiple acyl-CoA dehydrogenase deficiency and impaired fatty-acid oxidation/gluconeogenesis | Mixed evidence: human biochemical inference plus extrapolative rat/horse data | Extrapolative horse biomarker data: serum HGA 387.8–8493.8 μg/L; urine HGA 143.8–926.4 μg/L; controls less than 10 μg/L | Bochnia et al., 2015, DOI: 10.1371/journal.pone.0136785; Boemer et al., 2017, DOI: 10.1371/journal.pone.0182761 (pqac-00000006, pqac-00000007, pqac-00000010) |
| Analytical diagnostics | Exposure can be supported by measuring hypoglycin A and downstream metabolites or conjugates; acylcarnitine and organic-acid profiling are informative | Human analytical mention plus extrapolative horse biomarker data | Extrapolative horse MCPA-carnitine data: serum 0.17–0.65 mmol/L vs controls less than 0.01; urine 0.34–2.05 μmol/mmol vs controls less than 0.001 | Bochnia et al., 2015, DOI: 10.1371/journal.pone.0136785; Latif & Luthra, 2017, DOI: 10.23937/2377-3634/1410073 (pqac-00000000, pqac-00000006) |
| 2023 development | A derivatization-free UPLC-MS/MS method was validated for hypoglycin A, methylenecyclopropylglycine, and metabolites in milk and urine, improving surveillance capability | Extrapolative analytical method development | HGA limit of quantification in milk 1.12 μg/L; 68 milk samples from 35 farms showed no quantifiable toxin or metabolites | El-Khatib et al., 2023, DOI: 10.1007/s00216-023-04607-9 (pqac-00000008) |
| Treatment evidence | Best-supported management is early dextrose plus supportive care, including fluids, electrolyte correction, and monitoring of glucose, liver, and kidney injury | Human case evidence plus extrapolative mouse/rat evidence | Recovery may occur within about 1 week in nonfatal cases; no validated antidote identified | Latif & Luthra, 2017, DOI: 10.23937/2377-3634/1410073 (pqac-00000002, pqac-00000011) |
| Treatment limitations | Glycine, methylene blue, and carnitine have experimental rationale, but clinical efficacy in humans remains unproven | Mixed evidence; mouse/rat/horse evidence extrapolative | No controlled human trial identified; no ackee-specific interventional trial found in retrieved trial search | Latif & Luthra, 2017, DOI: 10.23937/2377-3634/1410073 (pqac-00000002) |
| Epidemiology and outbreaks | Disease clusters seasonally where ackee is consumed, with children disproportionately affected; modern epidemiologic data are sparse | Human historical evidence plus outbreak review snippets | Haiti 2000–2001 outbreak reported as 60 intoxication cases; older reports emphasize child predominance | Scott, 1916, DOI: 10.1080/00034983.1916.11684104 (pqac-00000004, pqac-00000012) |
| Food safety and prevention | Prevention depends on avoiding unripe or unopened ackee, removing seeds and membrane, and using regulated low-hypoglycin products | Human public-health and food-safety evidence | FDA import standard cited as hypoglycin A limit of 100 ppm for regulated products | Latif & Luthra, 2017, DOI: 10.23937/2377-3634/1410073 (pqac-00000000, pqac-00000005) |
| Animal models | Rat, mouse, horse, and related Sapindaceae toxin studies support mechanism and biomarker development, but remain extrapolative for human disease | Extrapolative animal evidence | Rat dose-response model exists; horse disease shows strong biomarker association with HGA exposure | Bochnia et al., 2015, DOI: 10.1371/journal.pone.0136785; Boemer et al., 2017, DOI: 10.1371/journal.pone.0182761 (pqac-00000006, pqac-00000007) |


*Table: This table summarizes the strongest available evidence for acute ackee fruit intoxication across clinical, mechanistic, diagnostic, epidemiologic, preventive, and animal-model domains. It prioritizes direct human evidence and clearly labels extrapolations from horse, rat, mouse, and other comparative studies.*