IMPACT OF COMBINED SUPPLEMENTATION IN EXERCISE ON CARDIOVASCULAR AND METABOLIC HEALTH: AN INTEGRATIVE APPROACH THROUGH SYSTEMATIC REVIEWS AND META-ANALYSES OF PLACEBO-CONTROLLED RANDOMIZED CLINICAL TRIALS

• Grant number: 25/06769-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Vitor Engrácia Valenti
• Grantee: Vitor Engrácia Valenti
• Host Institution: Faculdade de Filosofia e Ciências (FFC). Universidade Estadual Paulista (UNESP). Campus de Marília. Marília , SP, Brazil

Abstract

Introduction: Cardiovascular and metabolic health is essential for individuals' quality of life and longevity. Conditions such as hypertension, type 2 diabetes, obesity, and dyslipidemia are growing public health concerns and major risk factors for cardiovascular diseases. Regular physical exercise is widely recognized as an effective intervention for preventing and managing these conditions by improving endothelial function, reducing systemic inflammation, and promoting positive adaptations in lipid profile and glycemic control. However, the beneficial effects of exercise can be enhanced by additional strategies, such as nutritional supplementation. Supplements like beetroot, rich in nitrates, have been shown to improve cardiovascular health by promoting nitric oxide production, resulting in vasodilation, blood pressure reduction, and improved endothelial function. This effect is particularly relevant for hypertensive individuals and postmenopausal women. Similarly, creatine is widely used to enhance physical performance by increasing muscle phosphocreatine stores, but it has also been investigated for its antioxidant properties that help modulate oxidative stress, an important factor for post-exercise recovery. Furthermore, protein consumption, especially whey protein, is an effective strategy to promote muscle recovery, improve lipid profiles, and increase insulin sensitivity, particularly in obese and diabetic individuals. Objective: To analyze the effects of combined supplementation with exercise on cardiovascular and metabolic health through systematic reviews and meta-analyses. Methods:This project aims to conduct a systematic review and meta-analysis of randomized, placebo-controlled clinical trials to assess the effects of supplementation (beetroot, creatine, and whey protein) combined with physical exercise on cardiovascular and metabolic health. The research will be conducted following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), with a comprehensive search in major databases, including PubMed, Scopus, Web of Science, and Cochrane Library. Randomized clinical trials investigating the effects of supplements such as beetroot, creatine, and whey protein combined with exercise on variables such as blood pressure, lipid profile, glycemic control, inflammation, and oxidative stress will be included. Data extraction will be performed independently by two reviewers following a pre-defined protocol, with disagreements resolved by a third reviewer. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias tool, and the certainty of evidence will be evaluated using the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). Meta-analyses will be conducted using fixed-effect or random-effect models, depending on the heterogeneity of the included studies. (AU)