(P09-07-26) Increases in Apolipoprotein B Correlate With Changes in Circulating Ketone Concentrations at the Onset of Isoenergetic Ketogenic Diets

Objectives: Ketogenic diets increase apolipoprotein B (apoB) concentrations and atherogenic lipoproteins despite fat loss after 4 weeks. We explored acute changes in apoB and lipoprotein profile after 5 days of isoenergetic ketogenic diet and association with plasma ketones.

Methods: This is an interim analysis of a randomized crossover trial investigating ketogenic diet with or without nicotinamide riboside (NR) supplementation. Participants (n=21 [10 female], mean±SD age 34±9 y, body mass index 34.4±13.4 kg/m²) completed two 14-d visits in a random order with or without NR, with 9-d of standard American diet (std; 50% carbohydrates, 35% fat) followed by 5-d of isoenergetic ketogenic diet (keto; 5% carbohydrate, 80% fat). Investigators remain blinded to supplement condition. Fasting plasma total ketones, apoB, and lipoprotein particle concentrations were quantified using NMR spectroscopy and triglyceride (TG) concentrations measured by Abbott Architect during std and after 5-d of keto. Data were analyzed using linear mixed-effects models: timepoint (std, keto) and visit (1, 2) as fixed effects, participant as a random effect. We report estimated mean differences (95% CI) for keto vs std and Pearson correlation coefficients between Δketones and ΔapoB within visits.

Results: From std to 5-d of keto, ketones increased by 3.3 (2.7 to 3.9) mmol/L (P < 0.001). ApoB increased by 18 (13 to 24) mg/dL (P < 0.001) from a pooled mean±SD value of 94±19 mg/dL on std. Triglyceride-rich lipoprotein particle concentrations increased by 57 (17 to 97; P=0.006) nmol/L, and total LDL particle concentrations increased by 252 (90 to 415; P=0.003) nmol/L, from pooled mean±SD values of 72±38 and 1395±415 nmol/L respectively on std. Changes in TG were 2 (-22 to 27; P=0.86) mg/dL. There were strong positive correlations between Δketones and ΔapoB (v1 r=0.85, v2 r=0.81, both P < 0.001).

Conclusions: Isoenergetic ketogenic diet is associated with rapid increases in apoB concentrations and remodeling of atherogenic lipoproteins after first 5-d. Increases in apoB are correlated with increases in ketones, suggesting early lipoprotein remodeling is associated with the magnitude of ketogenesis.

Funding Sources: This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) within the National Institutes of Health (NIH).