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

Cara B Ebbeling, Amy Knapp, Ann Johnson, Julia M W Wong, Kimberly F Greco, Clement Ma, Samia Mora, David S Ludwig, Cara B Ebbeling, Amy Knapp, Ann Johnson, Julia M W Wong, Kimberly F Greco, Clement Ma, Samia Mora, David S Ludwig

Abstract

Background: Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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://ichgcp.net/clinical-trials-registry/NCT02068885.

Keywords: cardiovascular disease risk factors; dietary trial; low-carbohydrate diet; macronutrients; obesity; saturated fat.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Study design.
FIGURE 2
FIGURE 2
Participant flow. PCP, primary care practitioner.
FIGURE 3
FIGURE 3
Change in LPIR, Lp(a), and LDL-C by diet group in the Framingham State Food Study. LDL-C increased in all groups, without difference by group, potentially reflecting adaptation to increased energy intake in the Test phase. The sample includedn = 53 in Low-Carb, n = 48 in Moderate-Carb, andn = 46 in High-Carb. Because data were missing for 2 participants in Moderate-Carb, the Lp(a) analysis included n = 46 for this group. Means were constructed and compared using unadjusted repeated measures ANOVA. A partial F test was used to assess overall significance of diet in the repeated measures model. Lp(a) was log-transformed for analysis. For visualization, percentage change (mean with SE) was calculated from data in Table 2 and Supplemental Table 5. LDL-C, LDL cholesterol; Lp(a), lipoprotein(a); LPIR, lipoprotein insulin resistance.

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