Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia—a randomized controlled feeding trial

• Published in: The American journal of clinical nutrition Vol. 115; no. 1; pp. 154 - 162
• Main Authors: Ebbeling, Cara B, Knapp, Amy, Johnson, Ann, Wong, Julia MW, Greco, Kimberly F, Ma, Clement, Mora, Samia, Ludwig, David S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2022; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Body Mass Index; cardiovascular disease risk factors; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Diet, Carbohydrate-Restricted - methods; Diet, Reducing - methods; dietary trial; Dyslipidemias - blood; Dyslipidemias - complications; Dyslipidemias - diet therapy; Female; Humans; Insulin - blood; Insulin Resistance; Intention to Treat Analysis; low-carbohydrate diet; macronutrients; Male; Middle Aged; obesity; Obesity - blood; Obesity - complications; Obesity - diet therapy; Original Research Communications; saturated fat; Treatment Outcome; Triglycerides - blood; Weight Loss; Young Adult; low-carbohydrate diet; cardiovascular disease risk factors; HDL-P; saturated fat; dietary trial; LPIR; Lp(a); CVD; Carb; HMW; TRL-P; hsCRP; LDL-P; macronutrients; obesity
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/nqab287

Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption.
This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance.
After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from 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). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis.
Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet.
A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.