# Omega-3 Polyunsaturated Fatty Acids in the Treatment of Diabetic Peripheral Neuropathy:  Is the source important?

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2022 · —

## Abstract

In 2015, 9.4% of the United States population had diabetes and statistically about 50% of these patients will or
already have developed diabetic peripheral neuropathy (DPN). This problem is even more critical in the
veteran health care population with nearly 25% of veterans having diabetes, primarily type 2. In veterans
diabetes is the leading cause of blindness, end-stage renal disease and non-trauma related amputations. The
only treatment for DPN is glycemic control, which is ineffective in subjects with type 2 diabetes. Thus, there is a
critical need of a treatment for DPN. Our studies have demonstrated that treating diabetic rodents with DPN
with omega-3 polyunsaturated fatty acids (PUFA) derived from menhaden (fish) oil initiates nerve damage
repair and reverses DPN. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the predominate
omega-3 PUFA found in fish oil and are the precursors of E and D series resolvins, respectively, which have
anti-inflammatory and neuroprotective properties. We have shown that these metabolites alone elicit repair of
nerve damage caused by diabetes when administered endogenously in vivo. As we initiate plans to advance
omega-3 PUFA to a clinical trial for DPN there remains several questions to be addressed. One common
problem with the design of many of the previous clinical trials of omega-3 PUFA primarily for treatment of
cardiovascular disease were that they failed to determine the circulating levels of omega-3 PUFA or their
metabolites over the course of the study. For most of these studies it was unknown whether dosing was
sufficient to make a therapeutic change in the omega-3 index, defined as the sum of EPA and DHA as a
percentage of total fatty acids in red blood cells. Another poorly explored question has been what is the best
source or composition of omega-3 PUFAs that will provide the most favorable and safe outcome? This is
highlighted by the recent REDUCE-IT study that found that a 4 g daily dose of icosapent ethyl (ethyl ester of
EPA) to have a statistical benefit on reducing ischemic events in subjects with hypertriglyceridemia. Was the
significant outcome achieved in this study due to icosapent ethyl being a more effective source of omega-3
PUFA or use of a higher dose than many previous studies? We have shown that treating type 2 diabetic rats
with fish oil that achieved an omega-3 PUFA concentration in serum that was obtained in human subjects
treated with 4 g of fish oil per day is an efficacious treatment for DPN. However, is fish oil the best source of
omega-3 PUFA for the treatment of DPN or are the ethyl ester derivatives of EPA and/or DHA more
efficacious? Ethyl esters of EPA (Vascepa®) or the combination of EPA and DHA (Lovaza®) are
pharmaceutical compounds and represent a highly purified and concentrated source of EPA and DHA and void
of the less favorable compounds found in fish oil. Studies have shown that EPA and DHA and their metabolites
have different molecular targets. ...

## Key facts

- **NIH application ID:** 10447652
- **Project number:** 5I01RX003826-02
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Mark A. Yorek
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447652

## Citation

> US National Institutes of Health, RePORTER application 10447652, Omega-3 Polyunsaturated Fatty Acids in the Treatment of Diabetic Peripheral Neuropathy:  Is the source important? (5I01RX003826-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10447652. Licensed CC0.

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