Metabolic syndrome (MetS) represents one of the major public health challenges of our time [1]. The coexistence of central obesity, insulin resistance, hypertension, dyslipidemia, and chronic low-grade inflammation markedly increases the risk of cardiovascular disease, type 2 diabetes, functional decline, and premature mortality [2]. As life expectancy continues to increase, the metabolic changes are becoming increasingly intertwined with biological processes associated with aging, such as mitochondrial dysfunction and the reprogramming of cell metabolism, highlighting the importance of effective preventive and therapeutic strategies that simultaneously address metabolic dysfunction and age-related vulnerability [3].
Nutrition has emerged as a central component of this effort. Beyond its traditional role in maintaining energy balance, nutrition influences multiple biological systems involved in metabolic health, including the gut microbiota, immune function, oxidative stress, vascular homeostasis, and cellular metabolism [4,5]. Advances in nutritional science have also strengthened interest in functional foods, bioactive compounds, probiotics, and lifestyle interventions as complementary approaches for promoting healthy aging and reducing cardiometabolic risk [6].
This Special Issue, “Nutritional Modulation in Aging and Metabolic Syndrome: Combating Obesity, Vascular Disease and Frailty”, brings together six original contributions that collectively illustrate the breadth of the current research in this field. Although each study addresses a distinct aspect of metabolic health, they converge on a common objective: identifying nutritional and lifestyle strategies that modify the biological pathways associated with obesity, vascular dysfunction, frailty, and aging.
In a pilot clinical trial, Ermolenko et al. (contribution 1) explored the therapeutic potential of autoprobiotic supplementation in individuals with MetS. Using indigenous Enterococcus strains demonstrated favorable effects on anthropometric parameters, glycemic control, lipid metabolism, and gut microbiome composition. These findings contribute to the growing body of evidence suggesting that microbiota-directed interventions represent promising strategies for improving metabolic homeostasis [7,8,9].
Vascular aging, a hallmark of cardiometabolic disease, was the focus of two complementary longitudinal studies by Alonso-Diaz et al. (contributions 2 and 3). In the first, higher dietary fiber intake was associated with slower progression of arterial stiffness, whereas increased alcohol and iron consumption correlated with less favorable vascular outcomes over five years. The second study extends these observations by demonstrating inverse associations between the dietary intake of folate (vitamin B9) and vitamin C and the progression of central and peripheral arterial stiffness. Together, these investigations reinforce the concept that specific dietary components contribute to preserving vascular function throughout aging.
The clinical management of obesity was addressed in a randomized, double-blind, placebo-controlled trial conducted by Barbosa et al. (contribution 4). They evaluated the effects of gallic acid supplementation combined with structured physical exercise, which produced improvements in abdominal adiposity, body composition, and selected biochemical markers. The results highlight the potential benefits of integrating naturally occurring polyphenols with exercise-based interventions to optimize metabolic health.
The importance of biological timing in metabolic regulation was examined by Wang et al. (contribution 5). They investigated the interaction between exercise and circadian rhythms in an experimental model of obesity. Their findings reveal distinct tissue-specific adaptations according to the timing of physical activity, suggesting that the metabolic response to exercise is influenced by not only its intensity and duration but also the circadian phase during which the activity is performed. These observations provide new perspectives for the development of chronobiology-informed therapeutic strategies.
This Special Issue concludes with a population-based investigation by Kunutsor et al. (contribution 6), who evaluated composite biomarkers that integrate metabolic malnutrition and systemic inflammation. The authors found that these multimarker indices independently predict all-cause mortality across multimorbidity levels, emphasizing the clinical value of comprehensive metabolic risk assessment in aging populations and supporting the development of more personalized preventive approaches.
Together, the studies presented in this collection underscore the multidimensional nature of metabolic syndrome and healthy aging. They illustrate how nutrition intersects with vascular biology, the gut microbiota, exercise physiology, circadian regulation, and systemic inflammation, reinforcing the need for integrated and interdisciplinary approaches to prevent chronic disease and preserve functional capacity throughout life. By combining mechanistic insights with clinical and epidemiological evidence, these contributions advance our understanding of nutritional modulation as a key component of precision health and healthy aging.
As Guest Editors, we sincerely thank all authors for their valuable contributions and the reviewers for their thoughtful evaluations and commitment to scientific excellence. We are equally grateful to the editorial team of Nutrients for their continuous support throughout the preparation of this Special Issue. We hope that the studies presented here will stimulate further research and foster new collaborative efforts aimed at translating nutritional science into effective strategies for improving metabolic health and promoting healthy aging.
Conflicts of Interest
The authors declare no conflicts of interest.
List of Contributions
- Ermolenko, E.; Sitkin, S.; Alferova, L.; Novikova, N.; Gladyshev, N.; Orlova, V.; Zalicheva, A.; Demchenko, E.; Ergashev, O.; Suvorov, A. Autoprobiotic Supplements Attenuate Obesity and Improve Gut Microbiota, Carbohydrate, and Lipid Metabolism in Patients with Metabolic Syndrome: A Pilot Trial. Nutrients 2026, 18, 2324. https://doi.org/10.3390/nu18142324.
- Alonso-Diaz, J.; Gómez-Sánchez, M.; Sánchez-Moreno, A.; Lugones-Sánchez, C.; Rodriguez-Sanchez, E.; Garcia-Ortiz, L.; Gómez-Sánchez, L.; Gómez-Marcos, M.A.; on behalf of EVA Investigators Group. Association Between Increased Central and Peripheral Arterial Stiffness and Vitamin Intake in Healthy Adults: EVA Follow-Up 3 Study. Nutrients 2026, 18, 745. https://doi.org/10.3390/nu18050745.
- Alonso-Diaz, J.; Gómez-Sánchez, M.; Arjol, D.; Gonzalez-Sánchez, S.; Rodríguez-Sánchez, E.; García-Ortiz, L.; Gómez-Sánchez, L.; Gómez-Marcos, M.A.; EVA Investigators Group. Dietary Fiber Is Inversely Associated with Central Arterial Stiffness Progression, While Alcohol and Iron Intake Are Positively Associated with CAVI: A 5-Year Longitudinal Study. Nutrients 2026, 18, 1314. https://doi.org/10.3390/nu18091314.
- Barbosa, B.K.; Silva, D.V.A.; Batista-Jorge, G.C.; Souza, B.V.O.; Barcala-Jorge, A.S.; Guimarães, A.L.S.; de Paula, A.M.B.; Andrade, J.M.O.; Santos, S.H.S. Combined Effects of Gallic Acid Supplementation and Physical Training on Body Composition and Biochemical Parameters in Obese Patients: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Nutrients 2026, 18, 311. https://doi.org/10.3390/nu18020311.
- Wang, S.; Zhang, Z.; Huang, J.; Tong, Y.; Wu, C.; Kobori, H.; Ma, S.; Suzuki, K. Circadian Phase Determines Tissue-Specific Adaptations to Long-Term Exercise in Obese Mice. Nutrients 2025, 17, 3281. https://doi.org/10.3390/nu17203281.
- Kunutsor, S.K.; Rikhtehgaran, R.; Connelly, M.A.; Shalaurova, I.; Bakker, S.J.L.; Dullaart, R.P.F. Associations of Multimarkers of Metabolic Malnutrition and Inflammation with All-Cause Mortality by Multimorbidity Status. Nutrients 2025, 17, 1747. https://doi.org/10.3390/nu17111747
References
- Dhondge, R.H.; Agrawal, S.; Patil, R.; Kadu, A.; Kothari, M. A Comprehensive Review of Metabolic Syndrome and Its Role in Cardiovascular Disease and Type 2 Diabetes Mellitus: Mechanisms, Risk Factors, and Management. Cureus 2024, 16, e67428. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Gusev, E.; Sarapultsev, A.; Zhuravleva, Y. Insulin Resistance and Inflammation. Int. J. Mol. Sci. 2026, 27, 1237. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Wei, P.; Zhang, X.; Yan, C.; Sun, S.; Chen, Z.; Lin, F. Mitochondrial Dysfunction and Aging: Multidimensional Mechanisms and Therapeutic Strategies. Biogerontology 2025, 26, 142. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Guimarães, V.H.D.; Marinho, B.M.; Motta-Santos, D.; Mendes, G.R.L.; Santos, S.H.S. Nutritional Implications in the Mechanistic Link between the Intestinal Microbiome, Renin-Angiotensin System, and the Development of Obesity and Metabolic Syndrome. J. Nutr. Biochem. 2023, 113, 109252. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Aslam, H.; Trakman, G.; Dissanayake, T.; Todd, E.; Harrison, P.; Alby, C.; Jabeen, T.; Gamage, E.; Travica, N.; Marshall, S.; et al. Dietary Interventions and the Gut Microbiota: A Systematic Literature Review of 80 Controlled Clinical Trials. J. Transl. Med. 2026, 24, 39. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Beaver, L.M.; Jamieson, P.E.; Wong, C.P.; Hosseinikia, M.; Stevens, J.F.; Ho, E. Promotion of Healthy Aging Through the Nexus of Gut Microbiota and Dietary Phytochemicals. Adv. Nutr. 2025, 16, 100376. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Mederle, A.L.; Dima, M.; Stoicescu, E.R.; Căpăstraru, B.F.; Levai, C.M.; Hațegan, O.A.; Maghiari, A.L. Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis. Life 2024, 14, 1485. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Chen, K.; Wang, X.; Cao, Y.; Sun, Y.; Li, X.; Liu, Y.; Zhang, Z.; Wang, Q. Targeting Gut Microbiota as a Therapeutic Target in T2DM: A Review of Multi-Target Interactions of Probiotics, Prebiotics, Postbiotics, and Synbiotics with the Intestinal Barrier. Pharmacol. Res. 2024, 209, 107483. [Google Scholar] [CrossRef] [Scilit] [PubMed]
- Zhang, Z.; Mocanu, V.; Deehan, E.C.; Hotte, N.; Zhu, Y.; Wei, S.; Kao, D.H.; Karmali, S.; Birch, D.W.; Walter, J.; et al. Recipient Microbiome-Related Features Predicting Metabolic Improvement Following Fecal Microbiota Transplantation in Adults with Severe Obesity and Metabolic Syndrome: A Secondary Analysis of a Phase 2 Clinical Trial. Gut Microbes 2024, 16, 2345134. [Google Scholar] [CrossRef] [Scilit] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 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.