A Toxicological Convergence Hypothesis for the English Sweating Sickness (1485–1551)

The English Sweating Sickness (1485–1551) remains a historical enigma. Its sudden onset, profuse sweating, irregular recurrence, elite selectivity, geographic confinement, and abrupt disappearance resist conventional infectious explanations. This manuscript proposes that the syndrome may represent an **acute combined toxic exposure event** driven by **toxicological convergence**: fungal mycotoxins amplified by plant-derived toxins within the climatic and cultural context of Tudor England. Humid summers during the early Little Ice Age plausibly increased fungal contamination of stored foods (trichothecenes, aflatoxins, ergot alkaloids). Concurrently, aristocratic cuisine and household remedies may have relied on preserved meats and potent local herbs—henbane, belladonna, wormwood, pennyroyal, and yew—introducing tropane alkaloids, thujone, pulegone, and taxines. In combination, these agents could produce a cascade involving gastrointestinal barrier disruption, impaired hepatic detoxification, neuroautonomic dysregulation, intense sweating, electrolyte derangement, arrhythmia, and rapid collapse. This framework aims to reconcile major anomalies of the outbreaks more coherently than single-cause hypotheses and is testable using modern biomolecular archaeology (e.g., LC–MS/MS analysis of dental calculus, bone collagen, and cooking residues). Reinterpreting Sweating Sickness as toxicological convergence offers a research program bridging historical medicine, toxicology, and climate studies.