Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating proinflammatory cytokines in aging adults: A randomized, controlled study

Prostaglandins Leukot Essent Fatty Acids. 2018 May;132:23-29. doi: 10.1016/j.plefa.2018.03.010. Epub 2018 Apr 3.


Background: High levels of circulating proinflammatory cytokines are characteristic of inflammaging, a term coined to describe age-related chronic systemic inflammation involved in the etiology of many age-related disorders including nonhealing wounds. Some studies have shown that supplementing diets with n-3 polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) lowers systemic levels of key proinflammatory cytokines associated with inflammaging. However, findings from the few studies that have focused exclusively on older adults are inconclusive. As such, the objective of this randomized controlled study was to test the effects of EPA+DHA therapy on circulating levels of proinflammatory cytokines in adults in middle to late adulthood.

Methods: Plasma levels of fatty acids and interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were measured in 35 participants with chronic venous leg ulcers (mean age: 60.6 years) randomnly assigned to 8 weeks of EPA+DHA therapy (2.5 g/d) or placebo therapy.

Results: EPA+DHA therapy had a significant lowering effect on levels of IL-6, IL-1β and TNF-α after 4 weeks of therapy and an even greater lowering effect after 8 weeks of therapy. Further, after adjusting for baseline difference, the treatment group had significantly lower levels of IL-6 (p = 0.008), IL-1β (p < 0.001), and TNF-α (p < 0.001) at Week 4 and at Week 8 [IL-6 (p = 0.007), IL-1β (p < 0.001), and TNF-α (p < 0.001)] compared to the control group.

Conclusion: Adults in middle to late adulthood receiving EPA+DHA therapy demonstrated significantly greater reductions in circulating levels of proinflammatory cytokines compared with those receiving placebo therapy. EPA+DHA therapy may be an effective low-risk dietary intervention for assuaging the harmful effects of inflammaging.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / immunology
  • Aging / pathology
  • Chronic Disease
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / blood
  • Double-Blind Method
  • Drug Administration Schedule
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / blood
  • Female
  • Humans
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / blood
  • Interleukin-1beta / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology
  • Varicose Ulcer / blood
  • Varicose Ulcer / diet therapy*
  • Varicose Ulcer / immunology
  • Varicose Ulcer / pathology


  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid