Beta-Hydroxybutyrate: A Supplemental Molecule for Various Diseases.

β-hydroxybutyrate (BHB) is a ketone body that serves as an alternative energy source for various tissues, including the brain, heart, and skeletal muscle. As a metabolic intermediate and signaling molecule, BHB plays a crucial role in modulating cellular and physiological processes. Notably, BHB supplementation offers a novel and promising strategy to induce nutritional ketosis without the need for strict dietary adherence or causing nutritional deficiencies. This review article provides an overview of BHB metabolism and explores its applications in age-related diseases. This review conducted a comprehensive search of PubMed, ScienceDirect, and other relevant English-language articles. The main findings were synthesized, and discussed the challenges, limitations, and future directions of BHB supplementation. BHB supplementation holds potential benefits for various diseases and conditions, including neurodegenerative disorders, cardiovascular diseases, cancers, and inflammation. BHB acts through multiple mechanisms, including interactions with cell surface receptors, intracellular enzymes, transcription factors, signaling molecules, and epigenetic modifications. Despite its promise, BHB supplementation faces several challenges, such as determining the optimal dosage, ensuring long-term safety, identifying the most effective type and formulation, establishing biomarkers of response, and conducting cost-effectiveness analyses. BHB supplementation opens exciting avenues for research, including investigating molecular mechanisms, refining optimization strategies, exploring innovation opportunities, and assessing healthspan and lifespan benefits. BHB supplementation represents a new frontier in health research, offering a potential pathway to enhance well-being and extend lifespan.