Alcohol consumption and its association with Leber hereditary optic neuropathy: a systematic review

Introduction Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disorder leading to sudden, bilateral vision loss. Environmental factors such as alcohol consumption have been implicated, but evidence remains unclear. The objective of this study is to review the association between alcohol consumption, and clinical outcomes in LHON.Methods MEDLINE, Embase, and Scopus were searched (April 2025) for studies of LHON mutation carriers reporting alcohol exposure and LHON manifestation or conversion. Risk of bias was assessed with the Newcastle – Ottawa Scale.Results Five observational studies (1362 subjects) were included. Alcohol was measured as units/week, AUDIT-defined ‘excessive’ use, or drink-years, with variable ‘heavy’ thresholds. Two studies reported higher weekly intake in affected carriers: one reported higher cumulative and maximum intake in late-onset cases. One sibling case – control study reported lower odds of being affected among drinkers versus nondrinkers. In the largest cohort, affected carriers reported higher maximum intake, but alcohol was not independently associated with conversion after adjustment for smoking, whereas smoking remained significant. No study evaluated alcohol cessation.Conclusions Evidence is limited and inconsistent; heavy intake may be more common among affected carriers, but associations are sensitive to smoking adjustment. Prospective studies with standardized dose metrics and cessation analyses are needed.