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

Abstract

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.

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis

“…Fifth, all the metabolic traits were investigated in the fasted state only. It is conceivable that the indirect effects of postprandial plasma glucose [ 41 , 42 ], lipid profile [ 43 , 44 ] and incretins [ 42 , 45 , 46 ] on the association between liver fat and IPFD may differ from those in fasted state. Further mediation analyses may consider exploring metabolic traits in a postprandial state.…”

Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue

“…A recent small randomized controlled trial (RCT) with a crossover design alleviated concerns about whether acute ketosis might have an adverse effect on plasma lipid profile by studying 18 adults (12 men, 6 women) with prediabetes, who, following an overnight fast, ingested a single dose of ketone monoester β-hydroxybutyrate (KEβHB) drink or placebo drink [ 83 ]. A considerable increase of blood β-OHB from 0.2 to 3.5 mmol/L ( p < 0.001) was noted within 30 min.…”

Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management

“…The CETUS randomized controlled trial (as part of the COSMOS program) investigated the acute effects of oral ketone monoester on a range of metabolic parameters in individuals with new-onset prediabetes after acute pancreatitis. The ingestion of D-β-hydroxybutyrate-(R)-1,3 butanediol led to markedly elevated circulating levels of β-hydroxybutyrate and resulted in significantly reduced levels of triglycerides and glucose [ 98 , 99 ]. The pharmacological developments described above are well in line with the growing appreciation of intra-pancreatic fat deposition (as the local source of lipids in the pancreas), not merely general obesity, in diseases of the pancreas [ 100 ].…”