Summary
Diabetic neuropathy affects up to 50% of diabetes patients and refers to damage to the nerves that is related to diabetes-related excessive blood sugar levels. The symptoms of diabetic neuropathy include numbness, tingling, and pain, most commonly in the legs and feet. Research has shown that in the context of diabetic neuropathy, omega-3 fatty acids such as DHA can help against nerve damage, neuropathic pain symptoms and inflammation.

Introduction
Diabetes is characterised by dysregulation of blood sugar levels as the result of insulin dysfunction, though the origin of this insulin dysfunction differs between type 1 and type 2 diabetes. A common complication in both types of diabetes is diabetic neuropathy, a type of nerve damage that is related to excessive blood sugar levels. Although this damage is most common in the legs and feet, it can occur in many other parts of the nervous system. This contributes to the large variety of symptoms associated with diabetic neuropathy. The most prevalent symptoms are numbness, tingling sensations, and pain in the legs, feet, arms, and hands. In more severe cases, diabetic neuropathy can lead to muscle weakness, loss of balance and coordination, and impaired organ function. The condition can be assessed clinically using measures such as corneal nerve fiber length (CNFL) as well as patient-reported symptom scales such as the Short-Form McGill Pain Questionnaire (SF-MPQ).

Although the driving factor of diabetic neuropathy is chronic hyperglycaemia (high blood sugar), inflammation and oxidative stress play an important role in the progression of nerve damage. Omega-3 fatty acids DHA and EPA, have anti-inflammatory properties and support neuronal health and function. Research has indicated that supplementation with Omega-3 fatty acids can help patients with diabetic neuropathy. The studies highlighted below show that DHA and EPA can play a positive role in countering nerve fiber damage, reducing pain, and targeting the inflammatory and metabolic pathways that underlie diabetic neuropathy. 

Research Findings
Britten-Jones and colleagues conducted a trial to evaluate the effects of omega-3 fatty acid supplementation on peripheral nerves in type 1 diabetes (Britten-Jones et al., 2021). A group of forty-three participants with type 1 diabetes was divided in halves and were given either 1,800 mg/day of fish oil or a placebo of 600 mg/day olive oil for 180 days. The primary outcome was the change in corneal nerve fiber length (CNFL) from baseline to day 180. The CFNL is indicated in the total length of corneal nerve fibres (in mm) within a pre-defined area of the cornea (in mm²). At the end of the supplementation period, the estimated relative increase in CNFL in the omega-3 group compared with placebo was 2.70 mm/mm². The Omega-3 Index also increased relative to placebo by 3.3%. The authors concluded that long-chain omega-3 supplements imparted corneal neuroregenerative effects in persons with type 1 diabetes in their trial. This indicates a meaningful role for DHA and EPA in modulating peripheral nerve health in the context of diabetic neuropathy.  

Durán and colleagues investigated the effects of omega-3 PUFA supplementation on neuropathic pain symptoms and plasma metabolites in individuals with type 2 diabetes (Durán et al., 2019). Forty participants with type 2 diabetes enrolled in the "En Balance-PLUS" program, which provided weekly nutrition and diabetes education alongside daily supplementation with 1,000 mg DHA and 200 mg EPA for three months. Of the 40 participants, 26 self-reported neuropathic pain symptoms at baseline. After three months of supplementation, participants reported significant improvements across all dimensions of the aforementioned SF-MPQ, including sensory scores, affective scores, and visual analogue scale ratings. Participants in the moderate-to-high pain group had the highest relative plasma sphingosine levels at baseline. Sphingosine is a metabolite that is central in pathways associated with chronic pain and neuropathy; the authors found that high levels of plasma sphingosine were positively correlated with pain severity in their study. Omega-3 PUFA supplementation increased plasma DHA levels and significantly reduced plasma sphingosine levels in participants reporting neuropathic pain. Notably, increased plasma DHA levels were significantly correlated with improved sensory pain scores. The authors concluded that omega-3 PUFA supplementation may reduce neuropathic pain symptoms in individuals with type 2 diabetes, and that this effect correlates with changes in sphingosine levels in the plasma.

In a follow-up study on the same cohort, Durán and colleagues further examined the metabolic mechanisms by which omega-3 PUFA supplementation may reduce neuropathic pain in type 2 diabetes (Durán et al., 2022). Using blood plasma collected at baseline and after three months of supplementation with 1,000 mg DHA and 200 mg EPA, the researchers analyzed metabolic pathway changes. The results showed that metabolites in the blood plasma shifted significantly toward a more anti-inflammatory state following supplementation. The authors concluded that the reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation. As inflammation and oxidative stress is causally related to diabetic neuropathy, DHA and EPA may have beneficial potential in this condition. 

Conclusion
Diabetic neuropathy is a prevalent complication of diabetes with severe consequences to quality of life, affecting up to half of all individuals with the condition. The nerve damage it causes can range from painful sensory symptoms to serious functional impairments, significantly reducing quality of life. No definitive cure exists, and current management is largely focused on glycaemic control and symptom relief. Research into the role of DHA and EPA in diabetic neuropathy has provided encouraging evidence for the potential of nutritional intervention. Clinical trials have shown that omega-3 PUFA supplementation can increase small fiber nerve regeneration in individuals with type 1 diabetes, suggesting that these fatty acids can halt and even reverse nerve damage (check in relation to first source). In individuals with type 2 diabetes, supplementation with DHA and EPA has been shown to significantly reduce self-reported neuropathic pain symptoms, with the degree of improvement correlating with increases in plasma DHA levels. Taken together, these findings highlight DHA as a promising dietary intervention to support peripheral nerve health and reduce the burden of diabetic neuropathy.

References
Britten-Jones, A. C., Kamel, J. T., Roberts, L. J., Braat, S., Craig, J. P., MacIsaac, R. J., & Downie, L. E. (2021). Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial. Diabetes, 70(8), 1794–1806. https://doi.org/10.2337/db21-0136

Durán, A. M., Beeson, W. L., Firek, A., Cordero-MacIntyre, Z., & León, M. D. (2022). Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy. Nutrients, 14(4). https://doi.org/10.3390/nu14040761

Durán, A. M., Salto, L. M., Câmara, J., Basu, A., Paquien, I., Beeson, W. L., Firek, A., Cordero-MacIntyre, Z., & De León, M. (2019). Effects of omega-3 polyunsaturated fatty-acid supplementation on neuropathic pain symptoms and sphingosine levels in Mexican-Americans with type 2 diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 109–120. https://doi.org/10.2147/DMSO.S187268