Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function.
Level 4 - case-series / case-control
Uncontrolled prospective before-and-after interventional study in a small healthy cohort
PubMed 2985986 · doi:10.1056/NEJM198505093121903
What was done
Seven normal subjects supplemented their usual diet for six weeks with daily triglycerides containing 3.2 g of eicosapentaenoic acid (EPA) and 2.2 g of docosahexaenoic acid (DHA). Investigators measured neutrophil and monocyte fatty acid composition, 5-lipoxygenase pathway activity (release of [3H]arachidonic acid and leukotriene generation upon activation), neutrophil adherence to bovine endothelial-cell monolayers, and neutrophil chemotaxis to leukotriene B4. Measurements were compared before supplementation, at the end of the six-week diet, and six weeks after discontinuation.
What was found
Dietary supplementation increased EPA content in neutrophils and monocytes more than sevenfold without changing arachidonic acid or DHA quantities. In activated neutrophils, [3H]arachidonic acid and metabolite release decreased by a mean of 37%, and maximum generation of three 5-lipoxygenase products decreased by more than 48%. In activated monocytes, [3H]arachidonic acid release was reduced by a mean of 39%, and leukotriene B4 generation decreased by 58%. Neutrophil adherence to leukotriene B4-pretreated endothelial monolayers was inhibited completely, and average chemotactic response to leukotriene B4 was inhibited by 70% compared with baseline and post-washout values.
Why it matters
This study provides early experimental evidence that high-dose dietary fish oil incorporates into human leukocyte membranes and suppresses 5-lipoxygenase pathway activity and leukotriene B4-mediated neutrophil inflammatory responses.
Limits
The study evaluated only seven healthy participants without a parallel control or placebo group. Outcomes were limited to ex vivo and in vitro leukocyte assays following artificial activation, leaving clinical disease outcomes unmeasured.
Cited by
- supports Three back-to-back papers on omega-3 fatty acids were published in the New England Journal of Medicine on May 9, 1985.