ArticleNutrients2022
Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy.
Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The efficacy and safety of Chinese herbal medicine in the treatment of painful diabetic neuropathy: A systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Omega-3 Fatty Acids Attenuate Neuropathic Pain by Modulating Ferroptotic Stress, Selenoamino Acid Metabolism, and Lipid Remodeling.Antioxidants (Basel, Switzerland) · 2026Article
- Type 5 diabetes mellitus: nutritional-imprinted β-cell insufficiency, diagnostic gaps, and emerging therapeutic strategies.Frontiers in endocrinology · 2026Review
- Diabetic Peripheral Neuropathy: New Diagnostics and Treatment Perspectives.Drugs & aging · 2026Review
- Adipose Tissue and Central Nervous System Crosstalk: Roles in Pain and Cognitive Dysfunction.Biomedicines · 2025Review
- Review
- Managing Burning Mouth Syndrome with Omega-3 Fatty Acids: A Clinical Trial of Pain Relief and Quality of Life Improvement.Journal of pharmacy & bioallied sciences · 2025Article
- Influence of Fatty Acid Desaturase Enzyme-1 Gene (FADS-1) Polymorphism on Serum Polyunsaturated Fatty Acids Levels, Desaturase Enzymes, Lipid Profile, and Glycemic Control Parameters in Newly Diagnosed Diabetic Mellitus Patients.International journal of molecular sciences · 2025Article
- Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy.Nutrients · 2025Article
- Metabolomics in Pathogenic Pathways and Targeted Therapies for Diabetic Neuropathy: A Comprehensive Review.Metabolites · 2025Review
- The global and regional burden of diabetic peripheral neuropathy.Nature reviews. Neurology · 2025Review
- Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy.Communications medicine · 2024Article
- Article
- Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy.Inflammopharmacology · 2024Review
- New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.Nutrition & diabetes · 2024Article
- Polyunsaturated fatty acids and diabetic microvascular complications: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.BMC medicine · 2023Article
- Neuroprotection with Bioactive Compounds.Nutrients · 2023Article
- Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin.Biological trace element research · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOmega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN.
methodsForty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping.
resultsThe data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (
conclusionThe reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.
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Registered trials
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