EVALUATION OF THE SAFETY AND TOLERABILITY OF EXOGENOUS KETOSIS INDUCED BY ORALLY ADMINISTERED FREE BETA-HYDROXYBUTYRATE IN HEALTHY ADULT SUBJECTS

Abstract

ABSTRACTBeta-hydroxybutyrate (D-BHB) is a metabolite with intrinsic signalling activity that has gained attention as a potentially clinically useful supplement. There are available supplements for inducing ketosis: ketone salts, ketone esters, and medium-chain triglycerides. Even when all of them raise the beta-hydroxybutyrate in the blood and all are safe and well tolerated, they significantly differ in their safety profile, their palatability, and their price. A fourth and potentially interesting option is to use biologically identical beta-hydroxybutyrate, while it is already commercially available in the United States (American Ketone LLC) and Greater China (MedPHA Ltd). However, its safety and tolerability had not yet been documented in the scientific literature. We evaluated the safety and tolerability of orally administered Free D-BHB in a gender and age-balanced sample of 24 asymptomatic and overtly healthy adults. No participant showed acid-base abnormalities or electrolyte abnormalities. Secondary symptoms were reported after only 6.2% of all drink takes and none of the reports described the symptom as “severe”. The most frequently reported secondary effects (19/720 or 2.6%) were gastrointestinal discomfort, headache (7/720 or 1%), and loss of appetite (7/720 or 1%). No correlation between weight-adjusted dose and frequency of secondary symptoms was observed. Free D-BHB was a safe and well-tolerated intervention for inducing sustained exogenous ketosis. Being bio-identical, salt-free, and lacking intermediate metabolites, this form of supplementation could have a larger safety spectrum than salt or alcohol-based exogenous ketones. More research is warranted to assess its clinical efficacy in those clinical scenarios in which achieving ketosis rapidly could be beneficial.KEY MESSAGESWhat is already known on this topic-Ketogenic supplements could be useful therapeutic tools in certain time-sensitive circumstances. A previously unexplored but attractive option is using bio-identical D-BHB.What this study adds-Diluted Free D-BHB is a safe and well-tolerated intervention for inducing sustained exogenous ketosis.How this study might affect research, practice, or policy-Being bio-identical, salt-free, further research is warranted on the potential clinical uses of Free-BHB.