(LB01-33-26) Differential Lipoprotein and Glycemic Responses to a 28-Day Controlled Ketogenic Diet by Body Mass Index: A Clinical Trial

Objectives: Interindividual variability in cardiometabolic responses to ketogenic diets (KDs), particularly low-density lipoprotein cholesterol (LDL-C) elevations, is poorly understood. This study evaluated the effects of a controlled KD on lipids/lipoproteins (LDL-C primary outcome), glycemic markers, and vascular function in adults with normal BMI compared to those with obesity.

Methods: This non-randomized, parallel, controlled feeding trial enrolled adults aged 25–45 years with LDL-C ≤100 mg/dL and either normal BMI (18.5–22 kg/m²) or obesity (30–35 kg/m²). Participants consumed a weight-maintenance KD (total daily energy as 75% fat, 18% protein, 5% net carbohydrate) for 28 days. Fasting blood draws, flow-mediated dilation (FMD), pulse wave velocity (PWV), and dual-energy X-ray absorptiometry were completed at baseline and endpoint. Between-group differences were evaluated using ANCOVA adjusted for baseline values, age and sex. Estimated marginal means and 95% confidence intervals were derived using emmeans in R (v4.3.1).

Results: Twenty-two adults completed the intervention (normal BMI: n=14, BMI 21.3 ± 1.3 kg/m², LDL-C 80.8 ± 19.6 mg/dL; obesity n=8, BMI 31.7 ± 1.6 kg/m², LDL-C 84.1 ± 18.7 mg/dL). LDL-C increased more in the normal BMI group than the group with obesity (22.1 mg/dL; 95% CI 5.0, 39.3), as did total cholesterol (34.4 mg/dL; 95% CI 17.6, 51.2) and non-HDL-C (29.6 mg/dL; 95% CI 9.4, 49.7). In contrast, reductions in glucose (−7.7 mg/dL; 95% CI −13.8, −1.6) and HOMA-IR (−0.9; 95% CI −1.4, −0.4) were greater in the normal BMI group. No between-group differences were observed for vascular outcomes, although moderate effect sizes favored normal BMI for FMD (−2.18%; 95% CI: −4.55, 0.20) and PWV (−0.39 m/s; 95% CI: −0.85, 0.06). Baseline body fat percentage was inversely associated with baseline-adjusted LDL-C (β = −1.22 mg/dL per % body fat; p = 0.021).

Conclusions: Responses to a KD differed by BMI group, with individuals with normal BMI exhibiting greater increases in LDL-C alongside greater improvements in glycemic markers. These findings provide novel evidence from a controlled feeding trial that adiposity is an important determinant of heterogeneity in lipid responses to KDs and support personalized approaches to carbohydrate-restricted diets.

Funding Sources: Department of Nutritional Sciences