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Review
. 2023 Jul:63:102730.
doi: 10.1016/j.redox.2023.102730. Epub 2023 May 3.

Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review

Amanda Rundblad  1 , Viviana Sandoval  2 , Kirsten B Holven  3 , José M Ordovás  4 , Stine M Ulven  5
Affiliations
Review

Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review

Amanda Rundblad et al. Redox Biol. 2023 Jul.

Abstract

Cardiovascular disease (CVD) is a leading cause of death worldwide. Supplementation with the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with lower CVD risk. However, results from randomized controlled trials that examine the effect of omega-3 supplementation on CVD risk are inconsistent. This risk-reducing effect may be mediated by reducing inflammation, oxidative stress and serum triglyceride (TG) levels. However, not all individuals respond by reducing TG levels after omega-3 supplementation. This inter-individual variability in TG response to omega-3 supplementation is not fully understood. Hence, we aim to review the evidence for how interactions between omega-3 fatty acid supplementation and genetic variants, epigenetic and gene expression profiling, gut microbiota and habitual intake of omega-3 fatty acids can explain why the TG response differs between individuals. This may contribute to understanding the current controversies and play a role in defining future personalized guidelines to prevent CVD.

Keywords: Epigenetics; Gene expression; Genotype; Gut microbiota; Omega-3 fatty acids; Triglycerides.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kirsten B Holven reports grants the three last 3 from Amgen, Sanofi, Kaneka and personal fees from Amgen, Sanofi, Pronova, outside the submitted work.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
A) EPA and DHA alter gene expression of genes involved in antioxidant response, detoxification and inflammation by activating NFE2L2 and inhibiting NFKB via activation of PPARs, inhibition of TLR4 signaling and through inhibition via GPR 120. Moreover, EPA and DHA alter expression of genes involved in lipid metabolism by activating PPARs and inhibiting expression and nuclear translocation of SREBP1. B) EPA and DHA reduce plasma TG levels by reducing VLDL synthesis and de novo lipogenesis by inhibiting DGAT. Additionally, EPA and DHA increase fatty acid β-oxidation, reduce hepatic delivery of NEFA, and increase hepatic PL synthesis rather than TG. Illustrations from Servier Medical Art. Abbreviations: apoB-100, apolipoprotein-100, apo-CIII, apolipoprotein-CIII, DAG, diacylglycerol, DGAT, diacylglycerol O-acyltransferase, FA, fatty acid, GRP120, G-protein coupled receptor 120, HSL, hormone sensitive lipase, LPL, lipoprotein lipase, MAG, monoacylglycerol, NEFA, non-esterified fatty acids, NFKB, nuclear factor-kappa B, NFE2L2, NFE2 like bZIP transcription factor 2, PPAR, peroxisome proliferator-activated receptor, PL, phospholipids, SREBP, sterol regulatory element binding protein, TG, triglyceride, TLR4, toll-like receptor 4, VLDL, very low-density lipoprotein.
Fig. 2
Fig. 2
A) Individual variation in TG response to omega-3 supplementation. B) Baseline TG concentration is on average higher among those who respond to omega-3 supplementation by lowering TG concentrations. Dashed lines indicate mean baseline TG in non-responders (green) and responders (purple). Figure shows individual data from participants receiving omega-3 supplementation in two different randomized controlled trials [14,77]. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 3
Fig. 3
The TG response to omega-3 supplementation is associated with several genotypes, including genotype associations that are dependent on food intake. Abbreviations are explained in the list of abbreviations.
See this image and copyright information in PMC

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