Citation: Mates , , L.; Popa, D.-S.; Rusu, M.E.; Fizes , an, I.; Leucut , a, D. Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Antioxidants 2022, 11, 1412. https:// doi.org/10.3390/antiox11071412 Academic Editor: Stanley Omaye Received: 10 June 2022 Accepted: 19 July 2022 Published: 21 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 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/). antioxidants Systematic Review Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Letit , ia Mates , 1 , Daniela-Saveta Popa 1, * , Marius Emil Rusu 2, * , Ionel Fizes , an 1 and Daniel Leucut , a 3 1 Department of Toxicology, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes, 400012 Cluj-Napoca, Romania; micu.letitia@umfcluj.ro (L.M.); ionel.fizesan@umfcluj.ro (I.F.) 2 Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes, 400012 Cluj-Napoca, Romania 3 Department of Medical Informatics and Biostatistics, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes, 400012 Cluj-Napoca, Romania; dleucuta@umfcluj.ro (D.L.) * Correspondence: dpopa@umfcluj.ro (D.-S.P.); rusu.marius@umfcluj.ro (M.E.R.); Tel.: +40-264-450-555 (D.-S.P.) Abstract: Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human health. A systematic search in PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov databases was performed to retrieve randomized controlled trials published from the beginning of each database through November 2021, reporting on the outcomes of walnut consumption over 22 metabolic syndrome and inflammatory markers in middle-aged and older adults. The search strategy rendered 17 studies in the final selection, including 11 crossover and 6 parallel trials. The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters. Although further studies and better-designed ones are needed to strengthen these findings, the results emphasize the benefits of including walnuts in the dietary plans of this age group. Keywords: nuts; tree nuts; nut consumption; aging; age-related diseases; cardiometabolic markers; antioxidants; inflammation; lipid profile; diabetes 1. Introduction Metabolic syndrome (MetS) conditions, chronic, low-grade inflammation, and oxida- tive stress are significant risk factors for morbidity and mortality with higher prevalence in the aging population [1]. These pathophysiological components increase the probability of age-associated diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D), cognitive impairment, neurodegenerative disorders, or cancer [2,3]. Compelling evidence demonstrates that inflammatory markers, such as serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are predictors and factors in cellular senescence and chronic inflammatory conditions [4]. Human and animal examinations suggested that plant matrices rich in antioxidant and anti-inflammatory compounds could prove efficient in protecting against oxidative stress and excessive inflammation [5–8]. Extensive research examined the effects of plant-based diets on various health outcomes [9,10]. Tree nuts, important plant nutrient sources, are rich Antioxidants 2022, 11, 1412. https://doi.org/10.3390/antiox11071412 https://www.mdpi.com/journal/antioxidants