Effects of omega-3 polyunsaturated fatty-acid supplementation on neuropathic pain symptoms and sphingosine levels in Mexican-Americans with type 2 diabetes

Abstract

PurposeTo determine whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs) reduces neuropathic pain symptoms in Mexican-Americans with type 2 diabetes.MethodsForty volunteers with type 2 diabetes enrolled in the “En Balance-PLUS” program, which provided weekly nutrition–diabetes education and daily supplementation with 1,000 mg docosahexaenoic acid (DHA)–200 mg eicosapentaenoic acid over 3 months. The study assessed self-reported neuropathic pain symptoms pre/postintervention using the short-form McGill Pain Questionnaire (SF-MPQ), monitored clinical laboratory values at baseline and 3 months, and performed baseline and 3-month metabolomic analysis of plasma samples.ResultsA total of 26 participants self-reported neuropathic pain symptoms at baseline. After 3 months of omega-3 PUFA supplementation, participants reported significant improvement in SF-MPQ scores (sensory, affective, and visual analogue scale; P<0.001, P=0.012, and P<0.001, respectively). Untargeted metabolomic analysis revealed that participants in the moderate–high SF-MPQ group had the highest relative plasma sphingosine levels at baseline compared to the low SF-MPQ group (P=0.0127) and the nonpain group (P=0.0444). Omega-3 PUFA supplementation increased plasma DHA and reduced plasma sphingosine levels in participants reporting neuropathic pain symptoms (P<0.001 and P<0.001, respectively). Increased plasma DHA levels significantly correlated with improved SF-MPQ sensory scores (r=0.425, P=0.030). Improved SF-MPQ scores, however, did not correlate with clinical/laboratory parameters.ConclusionThe data suggest that omega-3 PUFAs dietary supplementation may reduce neuropathic pain symptoms in individuals with type 2 diabetes and correlates with sphingosine levels in the plasma.

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“…57,58 As discussed above, unlike studies related to cardiovascular disease, in diabetes the role of omega-3 polyunsaturated fatty acids/fish oil as a potential treatment for complications including diabetic peripheral neuropathy, have not been adequately studied. 54,[59][60][61] Data in Table 2 indicate that the levels of omega-3 polyunsaturated fatty acids appearing in the serum of obese and diabetic rats with diet supplementation of menhaden oil can be achieved in human subjects taking 4 g of fish oil capsules per day. 62,63 In a study by Laidlaw and Holub, the omega-3 polyunsaturated fatty acid levels in serum increased from 5.6% to 14.4% after taking 4 g of fish oil (each 1 g capsule contained 35% EPA and 25% DHA and capsule supplementation was adjusted to provide the intended average daily intake of 4 g) for 4 weeks and the eicosapentaenoic acid to arachidonic acid ratio increased from 0.12 to 0.88.…”

New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism

“…Diabetic neuropathy, of the three complications, most closely associates with dyslipidaemia [16]. Obesity induced by a diet rich in saturated fatty acids is associated with the development of diabetic neuropathy in individuals with type 2 diabetes [72] and, as with diabetic retinopathy, PUFA supplementation ameliorates symptoms of diabetic neuropathy [73]. This clinical finding is strongly supported by the preclinical work of Yorek and colleagues (reviewed in [74]), that shows clinical benefit of PUFA treatment in multiple rodent models of diabetic neuropathy.…”

Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy?

“…Beyond mechanistic and animal studies, SPMs have also been tested as analgesics in humans with various pain-related conditions ( Table 1 ), such as chronic headaches [ 166 ], migraines [ 167 ], joint discomfort [ 15 , 168 ], sickle cell disease [ 169 ], diabetic neuropathy [ 170 ], and various rheumatic diseases [ 15 , 171 , 172 , 173 , 174 , 175 ]. Firstly, supplementation with certain doses of ω-3 PUFAs appears to produce an increase in circulating anti-inflammatory mediators in humans [ 176 ].…”

“…Similarly, in a randomized, double-blind, placebo-controlled trial fish oil with ω-3 PUFA reduced symptoms of pain and stiffness significantly after nine weeks of treatment were observed [ 168 ]. In the “En Balance-Plus” study, an interventional study designed to assess the efficacy of dietary ω-3 PUFA in diabetic patients, significant reductions in pain-related neuropathy symptoms were reported after three months [ 170 ]. A randomized, parallel-group, 12-weeks trial with a diet high in ω-3 fatty acids and low in ω-6 PUFA demonstrated a reduction in pain frequency, intensity, and psychological distress in patients with chronic headaches [ 166 ].…”