Omega-3 fatty acids and inflammatory processes: from molecules to man
Open accessAbstract
Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte–endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.
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These structural changes promote nitric oxide (NO) bioavailability and reduce endothelial expression of adhesion molecules such as VCAM-1 and ICAM-1, limiting monocyte adhesion and vascular inflammation.
“These structural changes promote nitric oxide (NO) bioavailability and reduce endothelial expression of adhesion molecules such as VCAM-1 and ICAM-1, limiting monocyte adhesion and vascular inflammation [98].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [98]
The section ‘Omega-3 fatty acids, inflammatory signalling and inflammatory proteins’ reports reduced VCAM-1 and ICAM-1 expression on cultured endothelial cells and monocytes. The References section also lists a study of reduced monocyte adhesion to endothelial cells. Neither passage establishes that the cited structural changes cause these effects, and the paper passages found do not address NO bioavailability; page numbers were not supplied. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLong-chain omega-3 fatty acids, especially EPA and DHA, influence the activity of genes related to metabolism and inflammation.
“Longchain omega-3 fatty acids—especially eicosapentaenoic acid and docosahexaenoic acid—modulate the expression of genes involved in metabolism and inflammation139”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [139]
Suboptimal omega-3 levels affect the resolution phase of inflammation.
“having suboptimal omega-3 levels139, which impacts the resolution phase of inflammation”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [139]
Omega-3 PUFAs reduce inflammation.
“Omega-3 PUFAs modulate inflammation.”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [24]
Omega-3 PUFAs take part in producing eicosanoids, prostaglandins, resolvins, protectins, and leukotrienes.
“They are involved in production of eicosanoids, prostaglandins, resolvins, protectins, and leukotrienes”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [24]
Higher EPA and DHA concentrations in cell membranes reduce arachidonic acid available for making proinflammatory eicosanoids.
“Increased cellular membrane concentrations of EPA and DHA decrease the availability of arachidonic acid as a substrate for the synthesis of proinflammatory eicosanoids”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [24]
EPA and DHA regulate T cell function.
“EPA and DHA regulate T cell function”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [24]
EPA lowers expression of the cyclooxygenase-2 gene.
“EPA decreases expression of the cyclooxygenase-2 gene”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [24]
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n-3 Polyunsaturated Fatty Acids and Their Derivates Reduce Neuroinflammation during Aging
Joffre, C., Dinel, A., Chataigner, M., Pallet, V., & Layé, S. (2020) · Nutrients · doi:10.3390/nu12030647 · Cited by 74 · see citing works
Omega-3 fatty acids from fish by-products: Innovative extraction and application in food and feed
Rodrigues, M., Rosa, A., ALMEIDA, A. A., Martins, R., Ribeiro, T. B., Pintado, M., Gonçalves, R. F. S., Pinheiro, A. C., Fonseca, A. J. M., Maia, M. R. G., et al. (2024) · Food and Bioproducts Processing · doi:10.1016/j.fbp.2024.02.007 · Cited by 73 · see citing works
Abdel‐Wareth, A. A. A., Williams, A. N., Salahuddin, M., Gadekar, S., & Lohakare, J. (2024) · Frontiers in Veterinary Science · doi:10.3389/fvets.2024.1382163 · Cited by 78 · see citing works
- Authors
- Calder, P. C.
- Affiliations
- Southampton General Hospital (GB)
- Corresponding author
- Calder, Philip C.
- ORCID
- Calder, Philip C.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2017-09-12
- Volume
- 45
- Issue
- 5
- Pages
- 1105-1115
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W2754394790
- Cited by
- 1,456
- References
- 87
- Citations by year
- 2026: 250 · 2025: 255 · 2024: 179 · 2023: 140 · 2022: 141 · 2021: 170 · 2020: 167 · 2019: 97 · 2018: 52 · 2017: 3 · 2015: 1
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Keywords
- omega-3 fatty acids, omega-6 fatty acids, inflammation, eicosapentaenoic acid, docosahexaenoic acid, fish oil, resolvins, protectins, maresins, eicosanoids, arachidonic acid, leukotrienes, prostaglandins, inflammatory cytokines, nuclear factor-kappaB, PPARγ, lipid rafts, cell membrane phospholipids, rheumatoid arthritis, atherosclerosis, critically ill patients, anti-inflammatory mechanism
- MeSH terms
- Anti-Inflammatory Agents, Clinical Trials as Topic, Dietary Fats, Unsaturated, Docosahexaenoic Acids, Humans, Inflammation, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Cytokines, Fatty Acids, Omega-6
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