Omega-3 Fatty Acids Improve Functionality of High-Density Lipoprotein in Individuals With High Cardiovascular Risk: A Randomized, Parallel, Controlled and Double-Blind Clinical Trial

Abstract

Omega-3 (ω-3) fatty acids have been extensively studied for primary and secondary prevention of cardiovascular health, but their ability to modulate HDL functionality remains unclear. The purpose of this study was to investigate the role of ω-3, rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA), on HDL functionality. For that, 147 individuals with high cardiovascular risk were randomized in ω-3 (1 g of fish oil each - 370 mg of EPA and 230 mg of DHA, 3 times per day total EPA+DHA = 1,800 mg) or ω-6 groups (1 g of sunflower oil each - 760 mg of linoleic acid, 3 times per day; total linoleic acid = 2,280 mg). Fasting blood samples were collected at baseline time and after 8 weeks of follow-up and, and the lipid profile and glucose metabolism were evaluated from plasma. From HDL, the fatty acid profile, apolipoproteins (Apo AI, CII and CIII), paraoxonase-1 (PON1), cholesteryl ester transfer protein (CETP), subfractions and antioxidant activity were investigated. Omega-3 improved large HDL (HDL = 28.7%) and reduced small HDL (HDL10 = −10.6%) and the non-esterified fatty acids in HDL (NEFAs-HDL) level (−16.2%). A significant reduction in CETP activity was observed in the ω-3group (Δ ω-6 = 3.60 pmol/ul/h and Δ ω-3 = −1.99 pmol/ul/h; p = 0.044). The antioxidant capacity estimated by Lag time analysis did not change after the ω-3intervention. Changes in PON1 and Apo AI were inversely associated with increased incorporation of EPA (AOR = 0.446; IC = 0.200–0.994) and DHA (AOR = 0.351; IC = 0.150–0.821) in HDL, respectively. Cardioprotective profile obtained by pooled fatty acids analysis was related to a decrease in Apo CIII (r = −0.638; p = 0.002) and CETP (r = −0.341; p = 0.012) and an increase in Apo CII (r = 0.448; p = 0.042) and PON1 (r = 0.388; p = 0.003). In conclusion, omega-3 was effective in the reduction of cardiovascular risk associated with HDL functionality by size improvement and changes in its lipid, antioxidant and enzyme composition.

Eicosapentaenoic and Docosahexaenoic Acid Supplementation Increases HDL Content in n-3 Fatty Acids and Improves Endothelial Function in Hypertriglyceridemic Patients

“…Our results showed a significant increase in EPA and DHA as components of lipids carried by HDLs. Such increments were similar to that observed in the plasma of patients with high cardiovascular risk treated with 1800 mg/d of n-3 as fish oil, and who reached 220.3% and 68.3% of EPA and DHA increase in plasma, respectively [ 15 ]; this study also demonstrated a modification of HDL subclasses induced by n-3 supplementation. Conversely, we did not observe any change in HDL size distribution or in lipids of HDL subclasses, probably because our study group was more homogeneous in terms of risk factors than the previous report [ 15 ].…”

“…Moreover, DHA may contribute to the increase the anti-inflammatory properties of HDLs since this fatty acid, as well as EPA, are precursors of resolvins (inflammation-resolving mediators) via the lipoxygenase pathway [ 24 ]. Finally, it cannot be discarded that the reduction in some other n-6 fatty acids in HDL may also contribute to the beneficial effects of n-3 supplementation [ 15 ]. This issue needs to be addressed in further studies.…”

“…In this context, high-density lipoproteins (HDLs) have been described as lipoproteins with beneficial effects on endothelial function [ 12 , 13 , 14 ], probably associated with their EPA and DHA content [ 15 ]. HDLs are heterogeneous complexes of proteins and lipids that have been proposed to protect against cardiovascular disease through different mechanisms, including the reverse transport of cholesterol (RTC) [ 16 ].…”

Protective and therapeutic potentials of HDL and ApoA1 in COVID-19 elderly and chronic illness patients

“…This may be responsible for the worse morbidity of their COVID‐19 course owing to lack of these resolution factors (Pal et al 2020 ). EPA- and DHA-linked HDL improves it antioxidant and enzyme functions (Cartolano et al 2022 ).…”

Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers

“…In addition to the emerging measures of healthspan, reports also suggest that fish oils exert beneficial health effects via the modulation of lipid profiles, primarily through triglycerides (Tg), but also through modification of high-and low-density lipoproteins (HDL and LDL, respectively), though results for the latter are less consistent [17][18][19][20][21][22][23].…”