Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy
Abstract
Background: Omega-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. Methods: Forty 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. Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post…
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