Ketone supplementation for 14 days may improve glycemic control and vascular function in adults with obesity, according to study results published in The Journal of Clinical Endocrinology and Metabolism.

Previous studies showed that ketone body β-hydroxybutyrate may have a significant impact on metabolic control, inflammation, oxidative stress, and cardiovascular function. A ketone monoester (KME) drink containing β-hydroxybutyrate may protect against postprandial hyperglycemia.

The objective of the current study was to determine the impact of KME on postprandial glucose, systemic inflammation, and vascular function in adults with obesity.


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The randomized crossover study included 14 adults with obesity (mean age, 56 years; mean body mass index, 32.8 kg/m2). The participants were randomly assigned to consume KME containing 12 gm β-hydroxybutyrate, or placebo, prior to each meal for 2 weeks.

Researchers used continuous glucose monitoring to assess postprandial glucose levels and flow-mediated dilation (FMD) of the right brachial artery to measure endothelial function. They assessed plasma inflammatory markers before and after the intervention and administered questionnaires to assess feelings of hunger and fullness following the meals. They gave wrist-worn devices to participants to track their physical function.

Premeal ketone supplementation reduced 2-hour postprandial glucose area under the curve by 8% compared with placebo (mean difference, -54.6 mmol/L x 120 minutes; 95% CI, -94.4 to 14.8 mmol/L; g = 0.735, P = .011), reduced 24-hour mean glucose (-0.41 mmol/L, 95%CI, -0.25 to -0.58; g=0.686, P = .0001), and reduced continuous overall net glycemic action (-0.37 mmol/L, 95% CI, -0.181 to -0.562; g=0.577, P = .001), compared with placebo.

There was a significant increase in brachial artery FMD with KME, from 6.2% to 8.9% (+2.7%, 95% CI, 0.98-4.4; g=1.05, P =.0004), while in the placebo group there was no change in brachial artery FMD.

Lipopolysaccharide-stimulated monocyte caspase-1 activation was significantly lower following KME supplementation compared with placebo (P = .004), but there were no changes in circulating cytokines.

The ketone supplement was well tolerated and adherence was high over the 14-day period.

The study had several limitations of note. Because volunteers without overt insulin resistance or impaired glucose tolerance were enrolled, the results may not be applicable to patients with prediabetes or type 2 diabetes. No data were available on the effect of ketone supplementation on cardiovascular risk, and glucose levels were measured in interstitial fluid, which can be affected by changes in subcutaneous blood flow.

“These findings provide important evidence for the therapeutic potential of ketone supplementation for protecting and improving cardiometabolic health,” wrote the researchers.

Reference

Walsh JJ, Neudorf H, Little JP. 14-days of ketone supplementation lowers glucose and improves vascular function in obesity: a randomized crossover trial. Published online December 26, 2020. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa925