Beyond ethanol? 1,3-butanediol as a metabolically distinct functional beverage ingredient considering redox balance, mitochondrial resilience and neuroimmune effects: A narrative review

Background Ethanol consumption is strongly associated with oxidative stress, mitochondrial dysfunction, inflammation, and cardiometabolic disease, motivating the search for safer functional beverage alternatives. Among emerging candidates, 1,3-butanediol (1,3-BD) has gained interest due to its ability to increase circulating β-hydroxybutyrate (βHB) and induce nutritional ketosis. Scope and approach This narrative review compares the metabolic, mitochondrial, redox, neuroimmune, and translational physiological effects of ethanol and 1,3-BD. Mechanistic, preclinical, clinical, regulatory, and food-science evidence regarding metabolism, safety, and food-related applications of 1,3-BD are critically evaluated. Key findings and conclusions Although ethanol and 1,3-BD share initial hepatic enzymatic pathways, their downstream effects differ markedly. Ethanol promotes reductive stress, inflammation, lipogenesis, and mitochondrial dysfunction, whereas 1,3-BD-derived βHB supports NAD + restoration, AMPK/SIRT activation, mitochondrial biogenesis, improved oxidative efficiency, and attenuation of NF-κB/NLRP3 signaling. Importantly, most mechanistic evidence derives from studies of βHB, exogenous ketone esters, ketogenic diets, or fasting rather than from direct 1,3-BD intervention trials; the redox–mitochondrial benefits attributed to 1,3-BD are therefore largely inferred from βHB-mediated mechanisms advanced in preclinical models. Human and preclinical studies show that (R)-1,3-BD and related ketone esters can induce sustained, generally well-tolerated ketosis with mild euphoria and promising cardiometabolic and bioenergetic effects, although trials remain small, short, and predominantly open-label. Moreover, 1,3-BD occurs naturally in fermented foods and is regulated as a food additive and flavoring solvent (JECFA ADI 0–4 mg/kg; FDA 21 CFR §172.712). A GRAS notice for (R)-1,3-BD (FDA GRN 1165) was filed but voluntarily withdrawn in 2024, so (R)-1,3-BD does not currently hold FDA-affirmed GRAS status. Safety, however, is not uniformly benign: high-dose or chronic 1,3-BD exposure in animals has produced metabolic acidosis, body-weight loss, central nervous system depression, and hepatic inflammation and steatosis, while evidence on long-term safety, psychomotor performance, abuse liability, drug interactions, and real-world alcohol-substitution potential in humans remains limited. Overall, 1,3-BD should currently be viewed as a metabolically distinct functional beverage ingredient with promising redox-mitochondrial properties rather than a direct psychoactive replacement for ethanol.