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Omega-3 Polyunsaturated Fatty Acids (PUFAs) and Diabetic Peripheral Neuropathy: A Pre-Clinical Study Examining the Effect of Omega-3 PUFAs from Fish Oil, Krill Oil, Algae or Pharmaceutical-Derived Ethyl Esters Using Type 2 Diabetic Rats

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Omega-3 Polyunsaturated Fatty Acids (PUFAs) and Diabetic Peripheral Neuropathy: A Pre-Clinical Study Examining the Effect of Omega-3 PUFAs from Fish Oil, Krill Oil, Algae or Pharmaceutical-Derived Ethyl Esters Using Type 2 Diabetic Rats

Author
Eric Davidson , Oleksandr Obrosov ,Lawrence Coppey , andMark Yorek

1Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA

2Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA

3Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA

4Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA

* Author to whom correspondence should be addressed.
† These authors contributed equally to this work.
Biomedicines 2025, 13(7), 1607; https://doi.org/10.3390/biomedicines13071607
Submission received: 13 May 2025 / Revised: 24 June 2025 / Accepted: 26 June 2025 / Published: 30 June 2025
(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)
Abstract
Background and Objectives

We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs?

Methods
Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined.
Results
The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints.
Conclusions
We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective.
Keywords:
omega-3 polyunsaturated fatty acids; fish oil; peripheral neuropathy; eicosapentaenoic acid; docosahexaenoic acid
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