Exogenous Ketones as Therapeutic Signaling Molecules in High-Stress Occupations: Implications for Mitigating Oxidative Stress and Mitochondrial Dysfunction in Future Research.

High-stress occupations (ie, firefighters, military personnel, police officers, etc.) are often plagued by cardiometabolic diseases induced by exposure to chronic stressors. Interrupted sleep cycles, poor dietary patterns, lack of physical activity, and smoke exposure along with simultaneous psychological stressors promote chronic low-grade inflammation and excessive oxidative stress. Collectively, these data suggest that practical interventions which might mitigate the underlying pathologies of these cardiometabolic diseases are warranted. Ketones, specifically R-βHB, modulates intracellular signaling cascades such as the cellular redox ratios of NAD⁺/NADH, the activity of NAD dependent deacetylases SIRT1 and SIRT3, and promotes a robust mitochondrial environment which favors reductions in oxidative stress and inflammation. To date, the literature examining R-βHB as a signaling metabolite has mostly been performed from endogenous R-βHB production achieved through nutritional ketosis or cell culture and mouse models using exogenous R-βHB. To the authors knowledge, only 1 study has attempted to report on the effects of exogenous ketones and the mitigation of oxidative stress/inflammation. Therefore, the scope of this review is to detail the mechanisms of R-βHB as a signaling metabolite and the role that exogenous ketones might play in mitigating diseases in individuals serving in high-stress occupations.