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EPA + DHA supplementation reduces PMN activation in microenvironment of chronic venous leg ulcers: A randomized,
Jodi C McDaniel1, Laura Szalacha2, Michelle Sales1
1College of Nursing, The Ohio State University, Columbus, Ohio.
Abstract:
Sustained high levels of activated polymorphonuclear leukocytes (PMNs) and PMN-derived proteases in the microenvironment of chronic venous leg ulcers (CVLUs) are linked to chronic inflammation and delayed healing. Uncontrolled PMN activity eventually destroys newly developed tissue and degrades critical growth factors. The bioactive components of fish oil (n-3 eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have strong inflammation-resolving actions and have been shown to assuage PMN activity, but have not been tested in CVLU patients. This randomized controlled study compared the effectiveness of oral EPA + DHA therapy to a placebo for reducing PMN activation in CVLU microenvironments. At Days 0, 28, and 56, markers of PMNs (CD15) and activated PMNs (CD66b), and levels of PMN-derived proteases human neutrophil elastase and matrix metalloproteinase-8 were measured in CVLU fluid from patients receiving standard compression therapy and (1) EPA + DHA therapy (n = 16) or (2) placebo (n = 19). By Day 56, the EPA + DHA Group had a significantly lower percentage of CD66b+ cells in CVLU fluid compared to Day 0 (p = 0.02) and to Day 28 (p = 0.05). Importantly, there were downward trends in levels of both matrix metalloproteinase-8 and human neutrophil elastase over time in the EPA + DHA Group, which also demonstrated greater reductions in wound area by Day 28 (57% reduction) and Day 56 (76% reduction) than the Control Group (35% and 59%, respectively). Moreover, reductions in wound area had significant negative relationships with CD15+ cells in wound fluid at Days 28 (p = 0.008) and 56 (p < 0.001), and CD66b+ cells at Days 28 (p = 0.04) and 56 (p = 0.009). The collective findings provide supplemental evidence that high levels of activated PMNs in CVLU microenvironments inhibit healing, and suggest that EPA + DHA oral therapy may modulate PMN activity and facilitate healing of CVLUs when added to standard care regimens.
Insights
Oral fish oil supplements, rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), significantly reduced activated polymorphonuclear leukocytes (PMNs) in chronic venous leg ulcers (CVLUs). This suggests EPA+DHA therapy may improve CVLU healing when combined with standard care.
Area of Science:
- Wound healing research
- Inflammation biology
- Nutritional science
Background:
- Chronic venous leg ulcers (CVLUs) exhibit sustained inflammation due to activated polymorphonuclear leukocytes (PMNs) and their proteases.
- This uncontrolled PMN activity impedes tissue repair and degrades growth factors, delaying wound healing.
- Fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess anti-inflammatory properties and modulate PMN activity.
Purpose of the Study:
- To evaluate the efficacy of oral EPA+DHA therapy in reducing PMN activation in the microenvironment of CVLUs.
- To compare the effects of EPA+DHA supplementation versus placebo on inflammatory markers and wound healing in CVLU patients.
- To investigate the relationship between PMN markers and wound area reduction.
Main Methods:
- A randomized controlled study involving CVLU patients receiving standard compression therapy.
- Patients were assigned to either oral EPA+DHA therapy (n=16) or a placebo (n=19).
- Measurements of PMN markers (CD15, CD66b) and proteases (human neutrophil elastase, matrix metalloproteinase-8) were taken from wound fluid at baseline, Day 28, and Day 56.
Main Results:
- The EPA+DHA group showed a significant reduction in activated PMNs (CD66b+ cells) by Day 56 compared to baseline and Day 28.
- Trends towards decreased levels of matrix metalloproteinase-8 and human neutrophil elastase were observed in the EPA+DHA group.
- The EPA+DHA group achieved greater wound area reductions (57% at Day 28, 76% at Day 56) compared to the placebo group (35% and 59%, respectively).
- Reduced PMN counts (CD15+, CD66b+) correlated with significant wound area reduction.
Conclusions:
- Elevated activated PMNs in CVLUs are detrimental to wound healing.
- Oral EPA+DHA therapy demonstrates potential in modulating PMN activity within the CVLU microenvironment.
- EPA+DHA supplementation may serve as an effective adjunct therapy to standard care for promoting CVLU healing.
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