{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:17:31Z","timestamp":1785827851251,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Interventions that induce ketosis simultaneously lower blood glucose and the explanation for this phenomenon is unknown. Additionally, the glucose\u2010lowering effect of acute ketosis is greater in people with type 2 diabetes (T2D). On the contrary, L\u2010alanine is a gluconeogenic substrate secreted by skeletal muscle at higher levels in people with T2D and infusing of ketones lower circulating L\u2010alanine blood levels. In this study, we sought to determine whether supplementation with L\u2010alanine would attenuate the glucose\u2010lowering effect of exogenous ketosis using a ketone ester (KE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This crossover study involved 10 healthy human volunteers who fasted for 24\u00a0h prior to the ingestion of 25\u00a0g of <jats:sc>d<\/jats:sc>\u2010\u03b2\u2010hydroxybutyrate (\u03b2HB) in the form of a KE drink (\u0394G<jats:sup>\u00ae<\/jats:sup>) on two separate visits. During one of the visits, participants additionally ingested 2\u00a0g of L\u2010alanine to see whether L\u2010alanine supplementation would attenuate the glucose\u2010lowering effect of the KE drink. Blood L\u2010alanine, L\u2010glutamine, glucose, \u03b2HB, free fatty acids (FFA), lactate and C\u2010peptide were measured for 120\u00a0min after ingestion of the KE, with or without L\u2010alanine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>The KE drinks elevated blood \u03b2HB concentrations from negligible levels to 4.52\u00a0\u00b1\u00a01.23\u00a0mmol\/L, lowered glucose from 4.97\u00a0\u00b1\u00a0SD 0.39 to 3.77\u00a0\u00b1\u00a0SD 0.40\u00a0mmol\/L, and lowered and L\u2010alanine from 0.56\u00a0\u00b1\u00a0SD 0.88 to 0.41\u00a0\u00b1\u00a0SD 0.91\u00a0mmol\/L. L\u2010alanine in the KE drink elevated blood L\u2010Alanine by 0.68\u00a0\u00b1\u00a0SD 0.15\u00a0mmol\/L, but had no significant effect on blood \u03b2HB, L\u2010glutamine, FFA, lactate, nor C\u2010peptide concentrations. By contrast, L\u2010alanine supplementation significantly attenuated the ketosis\u2010induced drop in glucose from 28%\u00a0\u00b1\u00a0SD 8% to 16%\u00a0\u00b1\u00a0SD 7% (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The glucose\u2010lowering effect of acutely elevated \u03b2HB is partially due to \u03b2HB decreasing L\u2010alanine availability as a substrate for gluconeogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.300","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T07:24:05Z","timestamp":1637133845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Exogenous <scp>d<\/scp>\u2010\u03b2\u2010hydroxybutyrate lowers blood glucose in part by decreasing the availability of L\u2010alanine for 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