Ketone ester-what’s in a name? Ambiguity begets uncertainty

Consumption of a “ketone ester” drink has resulted in either a significant improvement (Cox et al., 2016) or a significant impairment (Leckey et al., 2017) in cycling time trial performance. Results from the Cox and Leckey testing prompted a commentary by (Stubbs et al., 2018) potentially explaining the observed differences in outcome. While both groups tested “ketone esters”, the Cox group tested (R) 3-hydroxybutyl (R) 3-hydroxybutyrate while the Leckey group tested (R,S) 1,3-butanediol acetoacetate diester. The structural differences are apparent in their more formal names. The bulk of literature reports to date, involve the study of these two compounds although three additional “ketone ester” molecules have, more recently, been described. The study of ketone esters is not limited to the field of endurance athletics and physiology. Heart failure (Yurista et al., 2021), cognitive impairment (Newport et al., 2015), protection from ionizing radiation (Curtis et al., 2016), cancer treatment (Seyfried et al., 2011), sepsis (Weckx et al., 2022) and lifespan (Veech et al., 2017) are among research areas where the study of ketone esters has garnered interest. In addition to their function as an alternative fuel to glucose, in most organs, for the purpose of generating ATP, ketone bodies, particularly βHB have many signaling and epigenetic contributions (Newman and Verdin, 2017). Similarities, and differences, in exogenous ketones, and their metabolites, have been neatly summarized by (Evans et al., 2022), (Poff et al., 2020), and (Falkenhain et al., 2022) among others. Given the breadth of research interest, synthesis of novel “ketone esters” is certain to continue as research outcomes more clearly target specific chemical structures. Esters offer a convenient means of elevating circulating ketone levels without a concomitant acid or salt load. However, inclusion of generic terms, such as “ketone ester”, while brief and structurally correct, sow confusion in the minds of readers, particularly for those considering their use. The number of offerings begs for a simplified means of identifying each compound, to accompany the standard nomenclature, in lieu of “ketone ester”, much as NAD is understood to be shorthand for nicotinamide adenine dinucleotide. One method of identification may be to reference a patent number wherein the compound is described. Using patent numbers, while brief, are problematic as patents are written broadly, and in a deliberately obfuscatory manner, in order to describe a host of related compounds, thus defeating the purpose of clear identification of individual molecules. A second abbreviated naming option would be to reference, in some manner, the first report of a molecule’s use in the published literature. This option, while possibly not properly crediting the “inventor” would at least acknowledge the first published use of the molecule. Yet another option would be to form a standing committee, or commission, of researchers invested in the field, established for the purpose of formulating a set of naming rules or guidelines that would result in the clear and unambiguous assignment OPEN ACCESS