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Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

ABSTRACT: BACKGROUND:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and different cardiovascular effects, and commonly used fish oil supplements have considerably varied EPA/DHA ratios. AIMS:We compared the effects of fish oil supplements with different EPA/DHA ratios on lipoprotein metabolism. METHODS:In a double-blind, randomized cross-over study, normolipidemic adults (n = 30) consumed 12 g/day of EPA-rich (EPA/DHA: 2.3) or DHA-rich (EPA/DHA: 0.3) fish oil for 8-weeks, separated by an 8-week washout period. RESULTS:Both fish oil supplements similarly lowered plasma TG levels and TG-related NMR parameters versus baseline (p < 0.05). There were no changes in plasma cholesterol-related parameters due to either fish oil, although on-treatment levels for LDL particle number were slightly higher for DHA-rich oil compared with EPA-rich oil (p < 0.05). Both fish oil supplements similarly altered HDL subclass profile and proteome, and down regulated HDL proteins related to inflammation, with EPA-rich oil to a greater extent. Furthermore, EPA-rich oil increased apoM abundance versus DHA-rich oil (p < 0.05). CONCLUSIONS:Overall, fish oil supplements with varied EPA/DHA ratios had similar effects on total lipids/lipoproteins, but differences were observed in lipoprotein subfraction composition and distribution, which could impact on the use of EPA versus DHA for improving cardiovascular health.

SUBMITTER: Yang ZH

PROVIDER: S-EPMC7146314 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

Yang Zhi-Hong ZH Amar Marcelo M Sampson Maureen M Courville Amber B AB Sorokin Alexander V AV Gordon Scott M SM Aponte Angel M AM Stagliano Michael M Playford Martin P MP Fu Yi-Ping YP Yang Shanna S Mehta Nehal N NN Remaley Alan T AT

Nutrients 20200312 3

<h4>Background</h4>Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and different cardiovascular effects, and commonly used fish oil supplements have considerably varied EPA/DHA ratios.<h4>Aims</h4>We compared the effects of fish oil supplements with different EPA/DHA ratios on lipoprotein metabolism.<h4>Methods</h4>In a double-blind, randomized cross-over study, normolipidemic adults (n = 30) consumed 12 g/day of EPA-rich (EPA/DHA: 2.3) or DHA-rich (EPA/DHA: 0.3) fish ...[more]

PMID: 32178279

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Project description:Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies.We conducted a review, using systematic methodology, of studies in humans assessing the mechanisms of action of EPA and DHA on apolipoprotein B-containing lipoproteins, including TG-rich lipoproteins and low-density lipoproteins (LDLs). A systematic search of PubMed retrieved 55 articles, of which 30 were used in the review; 35 additional arrticles were also included.In humans, dietary DHA is retroconverted to EPA, while production of DHA from EPA is not observed. Dietary DHA is preferentially esterified into TGs, while EPA is more evenly esterified into TGs, cholesterol esters and phospholipids. The preferential esterification of DHA into TGs likely explains the higher turnover of DHA than EPA in plasma. The main effects of both EPA and DHA are decreased fasting and postprandial serum TG levels, through reduction of hepatic very-low-density lipoprotein (VLDL)-TG production. The exact mechanism for reduced VLDL production is not clear but does not include retention of lipids in the liver; rather, increased hepatic fatty acid oxidation is likely. The postprandial reduction in TG levels is caused by increased lipoprotein lipase activity and reduced serum VLDL-TG concentrations, resulting in enhanced chylomicron clearance. Overall, no clear differences between the effects of EPA and DHA on TG levels, or on turnover of TG-rich lipoproteins, have been observed. Effects on LDL are complex and may be influenced by genetics, such as APOE genotype.EPA and DHA diminish fasting circulating TG levels via reduced production of VLDL. The mechanism of reduced VLDL production does not involve hepatic retention of lipids. Lowered postprandial TG levels are also explained by increased chylomicron clearance. Little is known about the specific cellular and biochemical mechanisms underlying the TG-lowering effects of EPA and DHA in humans.

Project description:IntroductionAlmegaPL® is an oil rich in polar-lipid (> 15% w/w) derived from the microalga Nannochloropsis, that contains exclusively eicosapentaenoic acid (EPA > 25% w/w), without the DHA that is present in all other natural sources of omega-3. Previous findings from a randomized controlled clinical trial demonstrated the ability of AlmegaPL® supplementation to reduce cholesterol levels.MethodsIn this post-market cohort study, we built upon previous findings and targeted the actual end-users of the supplement. Participants were recruited from a new subscriber database of AlmegaPL® capsules (1000-1100 mg/day) to capture the complexity of real-world clinical and consumer settings. Changes in circulating triglycerides (TG), remnant cholesterol (RC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), high-sensitivity C-reactive protein (hs-CRP), glucose and glycated hemoglobin (HbA1c) were monitored at baseline, Month 3, and Month 6 of supplementation using the at-home Baseline Heart Health Testing Kit by Imaware® (Houston, TX, USA).ResultsParticipants, who had, on average, normal TG level at baseline (1.62 ± 0.60 mmol/L), experienced a significant and progressive decrease in TG at Month 3 (8.0%; -0.13 ± 0.59 mmol/L; p < 0.001) and Month 6 (14.2%; -0.23 ± 0.64 mmol/L; p < 0.001) (primary outcome). Furthermore, after 6 months of supplementation, TC and non-HDL-cholesterol decreased by 5.0% (-0.26 ± 0.98 mmol/L; p < 0.001) and 5.5% (-0.21 ± 0.86 mmol/L; p < 0.001) respectively, primarily driven by a 14.9% reduction in RC (-0.11 ± 0.29 mmol/L; p < 0.001).DiscussionConsistent with our previous clinical trial, the decrease in RC was not coupled to an increase in LDL, which seems to be a benefit associated with EPA-only based formulations. In addition, this study demonstrated the AlmegaPL® capacity to maintain already healthy TG levels by further inducing a 14.9% decrease. Collectively, these findings highlight AlmegaPL® uniqueness as a natural over-the-counter option for EPA-only polar lipid that appears particularly effective in maintaining blood lipid levels in a generally healthy, normolipidemic population.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05267301.

Project description:IntroductionLong chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia.Subjects and methodsIn the present study, we compared oxylipin patterns of 10 hyperlipidemic (cholesterol >200mg/dl; triglyceride >150mg/ml) and 10 normolipidemic men in response to twelve weeks of LC n-3 PUFA intake (1.14g DHA and 1.56g EPA). Levels of 44 free hydroxy, epoxy and dihydroxy FAs were analyzed in serum by LC-MS. Additionally, oxylipin levels were compared with their parent PUFA levels in erythrocyte membranes; a biomarker for the individual PUFA status.ResultsDifferences in the oxylipin pattern between normo- and hyperlipidemic subjects were minor before and after treatment. In all subjects, levels of EPA-derived oxylipins (170-4800pM) were considerably elevated after LC n-3 PUFA intake (150-1400%), the increase of DHA-derived oxylipins (360-3900pM) was less pronounced (30-130%). The relative change of EPA in erythrocyte membranes is strongly correlated (r≥0.5; p<0.05) with the relative change of corresponding epoxy and dihydroxy FA serum levels. The effect on arachidonic acid (AA)-derived oxylipin levels (140-27,100pM) was inconsistent.Discussion and conclusionsThe dietary LC PUFA composition has a direct influence on the endogenous oxylipin profile, including several highly biological active EPA- and DHA-derived lipid mediators. The shift in oxylipin pattern appears to be dependent on the initial LC PUFA status particularly for EPA. The finding that also levels of other oxylipins derived from ALA, LA or AA are modified by LC n-3 PUFA intake might suggest that at least some of the effects of EPA and DHA could be mediated by a shift in the entire oxylipin profile.

Dataset Information

Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

Publications

Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

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