Gil-Zamorano, JuditCofán, MontserratLópez de las Hazas, María del CarmenGarcía-Blanco, TatianaGarcía-Ruiz, AlmudenaDoménech, MónicaSerra-Mir, MercèRoth, IreneValls Pedret, CintaRajaram, SujathaSabaté, JoanRos, EmilioDávalos, AlbertoSala Vila, Aleix2022-10-132022-10-132022Gil-Zamorano J, Cofán M, López de Las Hazas MC, García-Blanco T, García-Ruiz A, Doménech M, Serra-Mir M, Roth I, Valls-Pedret C, Rajaram S, Sabaté J, Ros E, Dávalos A, Sala-Vila A. Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders. Nutrients. 2022 Apr 1;14(7):1473. DOI: 10.3390/nu140714732072-6643http://hdl.handle.net/10230/54362The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63-79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL; p = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.application/pdfeng© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/nu14071473Alpha-linolenic acidBiomarkersCholesterolLipid metabolismNutsinfo:eu-repo/semantics/openAccess