Effects of a Low-Carbohydrate Diet on Cardiometabolic Risk Factors During Weight-Loss Maintenance: A Randomized Controlled Feeding Trial

Abstract Objectives To compare effects of diets varying in carbohydrate (carb) and fat on plasma lipids and lipoprotein subfractions. Methods Participants (N = 164, 70% female, 18–65 y, BMI ≥ 25 kg/m2) achieved 10–14% weight loss on a run-in diet and then were randomized to 3 test diets for 20 weeks of weight-loss maintenance. Percentages of total energy from carb-fat-protein for high-, moderate-, and low-carb diets were 60-20-20 (HI), 40-40-20 (MOD), and 20–60-20 (LO). Relative amounts of added sugar (15% total carb) and saturated fat (35% total fat) were fixed across diets. Plasma was collected at START (post-weight loss) and END of trial. The primary outcome for this ancillary study was lipoprotein insulin resistance (LPIR) – a 6-component weighted score of triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P) (NMR spectroscopy, LabCorp). Other outcomes included large LDL-P concentration, triglycerides (TG), and cholesterol (HDL-C, LDL-C). Means (±SE) and END–START changes (mean [95% CI]) were constructed and compared from repeated measures ANOVA. Results Retention was 90% and 147 participants provided evaluable data, with no difference in body weight by diet after randomization. LPIR was 32.6 ± 1.5 at START. Change in LPIR differed by diet (P = 0.009): LO (−5.3 [−9.2, −1.5]), MOD (−0.02 [−4.1, 4.1]), HI (3.6 [−0.6, 7.7]). Diet effects favoring LO compared to HI were observed for large/very large TRL-P (P = 0.005), large HDL-P (P = 0.045), TG (P = 0.006), and HDL-C (P = 0.04). There were no mean differences between diets for particle sizes, LDL-P subfraction concentrations, and LDL-C (START: 79.3 ± 1.8 mg/dL; END–START: HI, 8.2 [4.2, 12.2]; MOD, 11.7 [7.8, 15.7]; LO, 10.0 [6.3, 13.7]). Conclusions With 3-fold higher saturated fat content (21% vs 7% total energy), a low- vs high-carb diet improved LPIR, a biomarker of diabetes risk, and several other components of the metabolic syndrome, with no adverse effects on LDL-P or LDL-C. These results from a large feeding study suggest that carb restriction may help prevent cardiometabolic disease independent of body weight. Funding Sources Nutrition Science Initiative (gifts from Arnold Ventures and Robert Lloyd Corkin Charitable Foundation), New Balance Foundation, Many Voices Foundation, Blue Cross Blue Shield.