Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial.

Background: Ketone monoester β-hydroxybutyrate (KEβHB) ingestion has emerged as an effective method of inducing acute ketosis. Although evidence suggests that KEβHB can offer several therapeutic benefits, whether KEβHB affects lipid profile is still unknown.

Aims: The primary aim was to study the effect of KEβHB on plasma lipid profile in individuals with prediabetes. The secondary aim was to investigate the role of saturated fat intake in that effect.

Methods: This study was a randomized controlled trial with cross-over design. Following an overnight fast, 18 adults (six women and 12 men) with prediabetes (diagnosed based on the American Diabetes Association criteria) ingested a single dose of KEβHB drink or placebo drink. Blood samples were collected every 30 min, from baseline to 150 min. Outcome variables included changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, remnant cholesterol, triglycerides, and the triglycerides to HDL cholesterol ratio. The area under the curve (AUC) over 150 min was calculated for each outcome following ingestion of the drinks. Habitual saturated fat intake was ascertained using the EPIC-Norfolk food frequency questionnaire.

Results: Significant elevation of blood β-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 min. Acute ketosis resulted in significantly lower AUCs for remnant cholesterol (p = 0.022) and triglycerides (p = 0.022). No statistically significant differences in the AUCs for total cholesterol, HDL cholesterol, LDL cholesterol, and the triglycerides to HDL cholesterol ratio were found. The changes in remnant cholesterol and triglycerides were statistically significant in individuals with high, but not low, habitual saturated fat intake.

Conclusion: Acute ketosis had no untoward effect on plasma lipid profile. Moreover, it led to significantly reduced circulating levels of remnant cholesterol and triglycerides. This paves the way for investigating whether exogenous ketone supplementation reduces cardiovascular disease risk (via its actions on triglyceride-rich lipoproteins) in at-risk populations.  Trial registration: ClinicalTrials.gov, NCT03889210.