N-3 fatty acid supplementation mediates lipid profile, including small dense LDL, when combined with statins: a randomized double blind placebo controlled trial

Lipids Health Dis. 2022 Sep 1;21(1):84. doi: 10.1186/s12944-022-01686-y.

ABSTRACT

BACKGROUND: Epidemiological and clinical evidence suggests that high-dose intake of omega 3 fatty acids (n-3 FA) have a favorable role in altering serum triglycerides (TG) and non-high density lipoprotein cholesterol (non-HDL-C) when combined with statins in hyperlipidemic patients. Their efficacy in altering low-density lipoprotein cholesterol (LDL-C) particle size is yet to be established.

AIM: This study evaluated the effects of supplementing 4 g/day Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on serum blood lipids, including small, dense LDL-C particle concentration, in hyperlipidemic patients receiving stable statin therapy.

METHODS: In this randomized, placebo-controlled, double-blind parallel group study, 44 patients on statin therapy for > 8 weeks with non-HDL-C concentrations above 130 mg/dL were randomized into two groups. For 8 weeks, together with their prescribed statin, the intervention group received 4 g/day EPA + DHA (3000 mg EPA + 1000 mg DHA in ethyl ester form) and the placebo group received 4 g/day olive oil (OO). Measurements of serum non-HDL-C, TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C (including large – LDL I; intermediate – LDL II; and small – LDL III subclasses), very-low-density lipoprotein cholesterol (VLDL-C) concentration, were taken at baseline and post-intervention. Dietary intake was assessed with a weighed intake, 3-day food diary at week 4. Primary outcome measures were percent change in LDL III, non-HDL-C and LDL particle number.

RESULTS: At the end of treatment, the median percent change in serum LDL III concentration was significantly greater in the n-3 FA group plus atorvastatin compared to placebo (- 67.5% vs – 0%, respectively; P < 0.001). Supplementation with n-3 FA plus atorvastatin led to significant reductions in serum non-HDL-C (- 9.5% vs 4.7%, P < 0.01), TG (- 21.5% vs 6.2%, P < 0.001) and VLDL-C (- 36.9% vs 4.0%, P < 0.001) and TC (- 6.6% vs 2.1%, P < 0.001). Between the groups, no significant difference in percent change in the serum concentration of LDL-C, HDL-C, as well as in the LDL I and LDL II subclasses was observed.

CONCLUSION: In this group of hyperlipidemic patients on a stable statin prescription, OM3 plus atorvastatin improved small dense LDL concentrations, non-HDL-C, VLDL-C and TG to a greater extent than atorvastatin alone. Further studies are warranted in this area.

TRIAL REGISTRATION: This trial was retrospectively registered on 23 May 2019 on ClinicalTrials.gov with ID: NCT03961763.

PMID:36050695 | PMC:PMC9434850 | DOI:10.1186/s12944-022-01686-y