Fish Oil Omega-3s EPA and Dha Work Differently on Chronic Inflammation

Summary: DHA may be more effective at reducing chronic inflammation than EPA.

Source: Tufts University

The omega-3 fatty acids EPA and DHA work differently against chronic inflammation, according to the results of a small randomized study, suggesting each has its own important role to play in regulating the immune system.

The 34-week trial, led by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (HNRCA), compared the effects of the two omega-3s in a small group of older adults with obesity and chronic low-grade inflammation. The participants were randomly assigned to receive either EPA or DHA supplements twice a day. The results are published today in Atherosclerosis.

EPA and DHA, plentiful in fish and shellfish, have, in some studies, been linked to lower risk of heart disease and are believed to work by reducing inflammation. The results showed that DHA had a stronger anti-inflammatory effect than EPA:

  • DHA lowered the genetic expression of four types of pro-inflammatory proteins, whereas EPA lowered only one type.
  • DHA lowered white blood cell secretion of three types of pro-inflammatory proteins, whereas EPA lowered only one type.
  • DHA also reduced levels of an anti-inflammatory protein, whereas EPA did not.

However, EPA improved the balance between pro- and anti-inflammatory proteins:

  • After being metabolized, EPA produced by-products that were associated with immune function regulation and worked differently from those derived from DHA.

“The jury has been out, so to speak, on how the two major components of fish oil work – and whether one might be better than the other. These results suggest that DHA is the more powerful of the two on markers of inflammation in the body, but that’s not the end of the story,” said Stefania Lamon-Fava, a scientist on the Cardiovascular Nutrition Team at the HNRCA.

Lamon-Fava is also chair of the Division of Biochemical & Molecular Nutrition and an associate professor at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts.

“In our bodies, there is always this balance between pro-inflammatory and anti-inflammatory proteins, and we found EPA was better than DHA at enhancing that balance. For the prevention of cardiovascular disease, previous research tells us that balance is very important,” explained first author Jisun So, who did this work as part of her dissertation at the Friedman School, working on the Cardiovascular Nutrition Team at the HNRCA.

This shows salmon filets
After being metabolized, EPA produced by-products that were associated with immune function regulation and worked differently from those derived from DHA. Image is credited to Tufts

According to the 2015-2020 Dietary Guidelines for Americans, adults should consume at least two servings of seafood (4 ounces per serving) weekly. Salmon, cod, sardines, trout and light, canned tuna are good sources of EPA and DHA.

“Our study gives us a snapshot of how EPA and DHA may work to reduce chronic inflammation, and how each has distinct effects. Our results provide insight for future research to explore why that is the case and who would benefit from one or both of these healthy fats,” Lamon-Fava said.

Methodology

The study was a double-blind trial, meaning neither the participants nor the laboratory workers or scientists knew which supplement each individual received. The 21 participants received EPA or DHA supplements in a sequence that included supplement-free periods to create a blank slate from which to measure the impact of each supplement. During a lead-in phase, participants took supplements containing only high-oleic sunflower oil (similar to olive oil and not containing omega-3 fatty acids), to create a basis for comparison.

Authors and funding

Additional authors on the study are Dayong Wu, Alice H. Lichtenstein, and Nirupa R. Matthan at the HNRCA; Albert K. Tai at Tufts University School of Medicine; and Krishna Rao Maddipati at Wayne State University. 

Funding: This work was supported by the U.S. Department of Agriculture’s National Institute of Food and Agriculture through an Agriculture and Food Research Initiative grant and by The Drs. Joan and Peter Cohn Research Fund. Any opinions expressed in this paper are those of the authors and not the funders. None of the authors disclosed conflicts of interest.

About this inflammation research news

Source: Tufts University
Contact: Audrey Laganas Jenkins – Tufts University
Image: The image is credited to Tufts University

Original Research: Open access.
EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study” by So, J., Wu, D., Lichtenstein, A.H., Tai, A.K., Matthan, N.R., Maddipati, K.R., and Lamon-Fava, S. Atherosclerosis


Abstract

EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study

Highlights

  • eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently modulate the ex vivo inflammatory response of human monocytes.
  • DHA affects a wider range of plasma polyunsaturated fatty acids (PUFA) pro-resolving lipid mediators (SPM) lipidome than EPA.
  • Different subgroups of PUFA derivatives mediate anti-inflammatory effects of EPA and DHA.

Abstract

Background and aims

The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome.

Methods

After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50–75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout.

Results

Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA ( p < 0.001) whereas DHA reduced TNFA ( p < 0.001), IL6 ( p < 0.02), MCP1 ( p < 0.03), and IL10 ( p < 0.01). DHA lowered IL10 expression relative to EPA ( p = 0.03). Relative to baseline, EPA, but not DHA, decreased the ratios of TNFA/IL10 and MCP1/IL10 (bothp < 0.01). EPA and DHA also significantly changed plasma PUFA SPM lipidome by replacing n-6 AA derivatives with their respective derivatives including 18-hydroxy-EPA (+5 fold by EPA) and 17- and 14-hydroxy-DHA (+3 folds by DHA). However, DHA showed a wider effect than EPA by also significantly increasing EPA derivatives and DPA-derived SPM at a greater expense of AA derivatives. Different groups of PUFA derivatives mediated the differential effects of EPA and DHA on monocyte cytokine expression.

Conclusions

EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.

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