Ketone supplementation dose-dependently lowers postprandial blood glucose, lipid and ghrelin levels in individuals with type 2 diabetes: a randomised crossover study.

Ketone monoester (KE) supplementation reduced postprandial glucose incremental AUC by 36% compared with placebo in individuals with type 2 diabetes.

• Study 1 included 14 participants with type 2 diabetes treated with metformin monotherapy or lifestyle intervention alone.
• The iAUC for glucose decreased by 36% (95% CI 14, 57) with KE compared with placebo.
• Participants received 30 g of KE 30 min before a mixed meal test in a randomised, participant-blind crossover design.
• The primary outcome was the incremental AUC (iAUC) for glucose.

Ketone salts (KS) supplementation reduced postprandial glucose incremental AUC by 22% compared with placebo.

• The iAUC for glucose decreased by 22% (95% CI 1, 44) with KS compared with placebo.
• Participants received 30 g of KS 30 min before a mixed meal test.
• Study 1 used a three-arm crossover design comparing KE, KS, and placebo in 14 participants.
• Both the lower bound of the CI for KS (1%) suggests a borderline statistically significant effect.

Both KE and KS supplementation lowered postprandial non-esterified fatty acid (NEFA) and ghrelin concentrations.

• Reductions in postprandial NEFA were observed with both ketone supplements compared with placebo.
• Postprandial ghrelin concentrations were lowered by both KE and KS.
• These effects were observed in Study 1 (n=14) following a mixed meal test.
• KE additionally reduced postprandial triglycerides in Study 1 (n=14).

KE dose-dependently lowered the incremental AUC of glucose during an OGTT, with the strongest effect when ingested 30 or 60 minutes before the test.

• Study 2 included 10 participants investigated on six separate occasions.
• Doses tested were 0 g, 10 g, 20 g, and 40 g of KE administered 30 min, 60 min, or immediately before an OGTT.
• The strongest glucose-lowering effect was observed when KE was ingested 30 min or 60 min before the OGTT.
• A dose-dependent relationship was observed between KE dose and reduction in postprandial glucose iAUC.

No serious adverse events occurred with ketone supplementation, though transient mild gastrointestinal symptoms were reported.

• Gastrointestinal symptoms included nausea and diarrhoea.
• These symptoms were described as transient and mild.
• No serious adverse events were recorded across both studies.
• Both studies were conducted at Aarhus University Hospital, Denmark.

The study design employed two separate randomised, participant-blind crossover trials in individuals with type 2 diabetes managed without insulin.

• Participants had type 2 diabetes treated with either metformin monotherapy or a lifestyle intervention alone.
• Study 1 was registered as NCT05263401 and Study 2 as NCT05581043.
• The primary investigator randomly assigned the intervention order.
• Both studies were conducted at Aarhus University Hospital, Denmark.
• Funding was provided by the Novo Nordisk Foundation, the Health Research Foundation of Central Denmark Region, and the Aase Einar Danielsen Foundation.