A Randomized Trial of ω-3 Fatty Acid Supplementation and Circulating Lipoprotein Subclasses in Healthy Older Adults

Abstract

Background: Omega-3 (n-3) PUFAs are recognized for triglyceride-lowering effects in people with dyslipidemia, but it remains unclear if n-3-PUFA intake influences lipoprotein profiles in older adults without hypertriglyceridemia.

Objectives: The objective was to determine the effect of n-3-PUFA supplementation on plasma lipoprotein subfractions in healthy older men and women in the absence of cardiovascular disease (CVD) or hypertriglyceridemia. This was a secondary analysis and considered exploratory.

Methods: Thirty young (20-35 y old) and 54 older (65-85 y old) men and women were enrolled in the study. Fasting plasma samples were collected. After baseline sample collection, 44 older adults were randomly assigned to receive either n-3-PUFA ethyl esters (3.9 g/d) or placebo (corn oil) for 6 mo. Pre- and postintervention plasma samples were used for quantitative lipoprotein subclass analysis using high-resolution proton NMR spectroscopy.

Results: The number of large, least-dense LDL particles decreased 17%-18% with n-3 PUFAs compared with placebo (<1% change; P < 0.01). The number of small, dense LDL particles increased 26%-44% with n-3 PUFAs compared with placebo (∼11% decrease; P < 0.01). The cholesterol content of large HDL particles increased by 32% with n-3 PUFAs and by 2% in placebo (P < 0.01). The cholesterol content of small HDL particles decreased by 23% with n-3 PUFAs and by 2% in placebo (P < 0.01).

Conclusions: Despite increasing abundance of small, dense LDL particles that are associated with CVD risk, n-3 PUFAs reduced total triglycerides, maintained HDL, reduced systolic blood pressure, and shifted the HDL particle distribution toward a favorable cardioprotective profile in healthy older adults without dyslipidemia. This study suggests potential benefits of n-3-PUFA supplementation to lipoprotein profiles in healthy older adults without dyslipidemia, which should be considered when weighing the potential health benefits against the cost and ecological impact of widespread use of n-3-PUFA supplements.This trial was registered at clinicaltrials.gov as NCT03350906.

Keywords: aging; docosahexaneoic acid; eicosapentaenoic acid; lipoproteins; nuclear magnetic resonance; triglyceride.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Cross-sectional comparisons of main plasma lipid parameters measured by NMR in young (n = 30) and older (n = 54) adults (left column), and the effects of 6 mo of placebo (n = 22, middle column) and n–3-PUFA supplementation (n = 22, right column) on triglycerides (A), esterified cholesterol (B), free cholesterol (C), phospholipids (D), apoA (E), apoB (F), and lipoprotein particle number (G). A total of 5 participants dropped out after randomization (2 placebo, 3 n–3 PUFA). Data are shown as mean ± SD. *Significant (P value < 0.05) differences between young and older adults observed at baseline. ΩSignificant differences between treatment groups found by ANCOVA.

FIGURE 2

Cross-sectional comparisons of plasma VLDL subfractions measured by NMR in young (n = 30) and older (n = 54) adults (left column), and the effects of 6 mo of placebo (n = 22, middle column) and n–3-PUFA supplementation (n = 22, right column) on triglycerides (A), esterified cholesterol (B), free cholesterol (C), and phospholipids (D). VLDL particles are numbered 1–4 in order of increasing density and decreasing size. A total of 5 participants dropped out after randomization (2 placebo, 3 n–3 PUFA). Data are shown as mean ± SD. *Significant (P value < 0.05) differences between young and older adults observed at baseline. ΩSignificant differences between treatment groups found by ANCOVA.

FIGURE 3

Cross-sectional comparisons of plasma LDL subfractions measured by NMR in young (n = 30) and older (n = 54) adults (left column), and the effects of 6 mo of placebo (n = 22, middle column) and n–3-PUFA supplementation (n = 22, right column) on triglycerides (A), esterified cholesterol (B), free cholesterol (C), phospholipids (D), apoB (E), and lipoprotein particle number (F). LDL particles are numbered 1–6 in order of increasing density and decreasing size. A total of 5 participants dropped out after randomization (2 placebo, 3 n–3 PUFA). Data are shown as mean ± SD. *Significant (P value < 0.05) differences between young and older adults observed at baseline. ΩSignificant differences between treatment groups found by ANCOVA.

FIGURE 4

Cross-sectional comparisons of plasma HDL subfractions measured by NMR in young (n = 30) and older (n = 54) adults (left column), and the effects of 6 mo of placebo (n = 22, middle column) and n–3-PUFA supplementation (n = 22, right column) on triglycerides (A), esterified cholesterol (B), free cholesterol (C), phospholipids (D), apoA-1 (E), and apoA-2 (F). HDL particles are numbered 1–4 in order of increasing density and decreasing size. A total of 5 participants dropped out after randomization (2 placebo, 3 n–3 PUFA). Data are shown as mean ± SD. *Significant (P value < 0.05) differences between young and older adults observed at baseline. ΩSignificant differences between treatment groups found by ANCOVA.