Dietary Macronutrients and Circulating Nonesterified Fatty Acids: A Secondary Analysis of the OMNI Heart Crossover Trial

J Nutr. 2022 Dec;152(12):2802-2807. doi: 10.1093/jn/nxac187. Epub 2023 Feb 10.


Background: Nonesterified fatty acids (NEFAs) play key roles in the pathophysiology of diabetes and cardiovascular disease.

Objectives: We sought to determine whether macronutrient content differences affect NEFA concentrations in a randomized crossover trial.

Methods: Total NEFAs were measured from postintervention specimens of participants in the OMNI Heart trial (Optimal Macronutrient Intake Trial to Prevent Heart Disease). OMNI Heart compared 3 healthful diets to evaluate their effect on systolic blood pressure and serum LDL cholesterol: carbohydrate-rich diet (58% carbohydrate); protein-rich diet (25% protein), about half from plant sources; and a diet rich in unsaturated fatty acids (21% unsaturated fat), predominantly monounsaturated. The trial included 164 participants who consumed the 3 diets, each for 6 wk. Data were analyzed from the 156 participants with unthawed serum available from the week 6 visit for all diet periods. We used ANCOVA and generalized estimating equations (GEEs) to compare serum NEFA concentrations across the 3 diet periods.

Results: The mean ± SD age of study participants was 52.9 ± 10.6 y and mean BMI was 30.3 ± 6.1 kg/m2. Fifty-five percent of participants were women and 55% were African American. Comparisons of adjusted mean serum NEFA concentrations after each diet intervention identified no statistically significant differences (58% carbohydrate: 0.144 ± 0.083 mEq/L; 25% protein: 0.143 ± 0.076 mEq/L; 21% unsaturated fat: 0.143 ± 0.084 mEq/L; ANCOVA, P = 0.99). Likewise, we observed no significant serum NEFA concentration difference by diet in adjusted GEE models. In adjusted models, serum NEFA concentrations were positively associated, as anticipated, with female sex and higher BMI.

Conclusions: In this randomized crossover trial, we observed nearly identical serum NEFA concentrations after each of 3 healthful diets, regardless of macronutrient content.

Keywords: OMNI Heart; dietary intake; macronutrients; nonesterified fatty acids; obesity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cross-Over Studies
  • Diet
  • Dietary Carbohydrates
  • Dietary Fats*
  • Fats, Unsaturated
  • Fatty Acids
  • Fatty Acids, Nonesterified*
  • Female
  • Humans
  • Male
  • Nutrients


  • Fatty Acids, Nonesterified
  • Dietary Fats
  • Dietary Carbohydrates
  • Fats, Unsaturated
  • Fatty Acids