The Bog Bilberry Enigma: A Phytochemical and Ethnopharmacological Analysis of Vaccinium uliginosum L. Fruits in Regard to Their Alleged Toxicity

<i>Vaccinium uliginosum</i> (bog bilberry) is widely consumed in North America and Asia but has been historically avoided in many parts of Europe due to its alleged poisonous effects. We aimed to address this discrepancy in a systematic way with a combined phytochemical and ethnopharmacological approach, using UHPLC and UHPSFC for the chemical analysis, model organisms <i>Caenorhabditis elegans</i> and human liver cells GFP-Huh-7 for the bioactivity and toxicity testing, as well as fermentation experiments. Phytochemical analysis revealed minimal differences in the metabolite pattern between European and North American samples, with no evidence of toxic alkaloids or harmful secondary metabolites. Extracts exhibited no strongly toxic effects in the tested concentrations, neither in vitro (cell viability) nor in vivo (<i>C. elegans</i>). Berries infected by <i>Monilinia megalospora</i> showed altered flavonoid and anthocyanin contents but no increased toxicity. Notably, bog bilberries demonstrated a fermentation potential superior to <i>Vaccinium myrtillus,</i> resulting in an alcohol content of 4.8-5.8% ABV in unsweetened juices, thus potentially explaining historical accounts of inebriation. In conclusion, direct toxicity derived from these fruits is unlikely, but the alcohol content due to fruit fermentation is a plausible explanation for the folklore names ("drunk, inebriating berry"). However, additional factors such as human error, individual intolerance, or endophytic activity need to be considered.