The recent article by Hone-Blanchet et al. [1] reports substantial reductions in both GABA and glutamate concentrations following ingestion of a ketone ester known to elevate D-beta-hydroxybutyrate (D-βHB) levels. A striking aspect of their results is that GABA levels appeared to fall by roughly 50% over 30 min following ketone ingestion. This is such a large reduction that it raises the question of whether it is physiologically plausible, especially given that there is no mention of adverse cognitive or functional consequences of this change. It is essential to exclude the possibility that these findings might be contaminated by measurement error.

One indication of possible measurement error is the unusually high coefficient of variation (CV) of pre-ingestion GABA values. As calculated from Figures 2A, 2B, 2G, and 2H, the CV values range from 17% to 47%, with an average of 28%. Supplemental Tables 1 and 3 indicate an even higher average CV of 34% for pre-ingestion GABA. Similarly, Figures 2A and 2B portray baseline GABA levels as varying over a three- to four-fold range, which is not physiologically credible in healthy adults. In contrast, a large multi-site study reported average within-site CVs of 9.5% and 18.8% for edited GABA+ and macromolecule-suppressed GABA respectively [2]. The GABA values reported by Hone-Blanchet et al. are estimated from spectra acquired with a STEAM sequence and appear to include a relatively high degree of noise variance.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD