Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega‐3 fatty acids

Abstract

Scope In contrast to well-characterized polyunsaturated fatty acid (PUFA) levels in serum, little is known regarding their downstream metabolic products. However, many of these compounds are lipid mediators with prominent roles during pro- and anti-inflammatory processes. Methods and Results In this double blind crossover study on asthmatics, shifts in serum levels of ω-3 and ω-6 PUFA-derived oxidized fatty acids (e.g., eicosanoids, oxylipins) were quantified following dietary fish oil supplementation. Serum was obtained from subjects following fasting at 3 occasions; 1) Prior to supplementation, 2) Following a 3-week supplement intake of either placebo or fish oil, and 3) Following a 3-week washout period with a subsequent 3-week period of either fish oil or placebo supplement. A total of 87 oxylipins representing cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary alterations observed were in CYP- and 15-LOX-derived EPA- and CYP-derived DHA oxylipins. Conclusion The results indicate that intake of an ω-3 rich diet altars not only the PUFA ratio, but also the ratio of downstream oxylipins. These data further support that dietary manipulation with ω-3 PUFAs affects not only PUFA levels, but importantly also the downstream metabolic profile.

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

“…These in vivo fi ndings are in line with the results of previous in vitro studies on recombinant enzymes showing that various human AA-metabolizing CYP isoforms accept EPA and DHA as effi cient alternative substrates ( 1,(19)(20)(21)(22). Our results also indicate that CYP-eicosanoid and vicinal diols were reported from studies that treated healthy volunteers for 4 weeks with 4 g of an EPA/DHA supplement ( 46 ) or asthmatic patients for three weeks with 4 g EPA + 2 g DHA per day ( 47 ). Even without dietary intervention, the individual differences in the serum concentrations of EPA-derived epoxy-and dihydroxy-metabolites correlated well with the EPA content in RBCs, as shown in a recent study comparing the metabolite profi les in hyperand normolipidemic men ( 48 ).…”

Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery

“…Similar results have also been demonstrated in patients with chronic stable disease, including asthma and IgA nephropathy ( 14,31 ). Each of these prior studies was quite small (n = 10 to 30) and did not include evaluation of MEFA responses following acute tissue stress/ infl ammation, when their function may be most relevant.…”

Dietary flax oil rich in α-linolenic acid reduces renal disease and oxylipin abnormalities, including formation of docosahexaenoic acid derived oxylipins in the CD1-pcy/pcy mouse model of nephronophthisis

“…Further, flax oil feeding slows disease progression in the pcy mouse [13], as well as other models of renal disease [14][15][16], and since dietary n-3 fatty acids can alter fatty acid and oxylipin compositions [17,18], we examined whether flax oil feeding would increase DHA levels and whether it would affect any of the renal oxylipin alterations in this disease.…”