A Walnut-Enriched Diet for 2 Years Changes the Serum Oxylipin Profile in Healthy Older Persons

Background: Oxylipins are products derived from polyunsaturated fatty acids (PUFAs) that play a role in cardiovascular disease and aging. Fish oil -derived n-3 PUFAs promote the formation of anti-inflammatory and vasodilatory oxylipins; however, there are little data on oxylipins derived from alpha-linolenic acid (C18:3n-3), the primary plant -derived n-3 PUFA. Walnuts are a source of C18:3n-3. Objectives: To investigate the effect on serum oxylipins of a diet enriched with walnuts at 15% energy (30-60 g/d; 2.6-5.2 g C18:3n-3/d) for 2 y compared to a control diet (abstention from walnuts) in healthy older males and females (63-79 y). Methods: The red blood cell proportion of alpha-linolenic acid was determined by gas chromatography as a measure of compliance. Ultraperformance liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 53 oxylipins in participants randomly assigned to receive the walnut diet (n = 64) or the control diet (n = 51). Two-year concentration changes (final minus baseline) were log -transformed (base log -10) and standardized (mean -centered and divided by the standard deviation of each variable). Volcano plots were then generated (fold change >= 1.5; false discovery rate <0.1). For each oxylipin delta surviving multiple testing, we further assessed betweenintervention group differences by analysis of covariance adjusting for age, sex, BMI, and the baseline concentration of the oxylipin. Results: The 2-y change in red blood cell C18:3n-3 in the walnut group was significantly higher than that in the control group (P < 0.001). Compared to the control diet, the walnut diet resulted in statistically significantly greater increases in 3 C18:3n-3-derived oxylipins (9HOTrE, 13-HOTrE, and 12,13-EpODE) and in the C20:5n-3 derived 14,15-diHETE, and greater reductions of the C20:4n-6-derived 5-HETE, 19-HETE, and 5,6-diHETrE. Conclusions: Long-term walnut consumption changes the serum oxylipin profile in healthy older persons. Our results add novel mechanistic evidence on the cardioprotective effects of walnuts.