The Optimal Type and Dose of Exercise Interventions on VEGF Levels in Healthy Individuals, as Well as Obesity and Chronic Disease Populations: A Network Meta-Analysis.

Background/

Objectives

Impaired angiogenesis and vascular dysfunction are central features of chronic diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome. Vascular endothelial growth factor (VEGF) plays a pivotal role in vascular repair and metabolic regulation, yet its responses to exercise remain inconsistently reported. This study aimed to systematically compare the effects of different exercise modalities and doses on VEGF levels across diverse populations.

Methods

This review was registered in PROSPERO (CRD42025643709) and followed PRISMA guidelines. PubMed, Web of Science, Embase, and Cochrane Library were searched until 16 January 2025. Eligible studies were randomized or quasi-experimental trials reporting exercise-induced changes in serum/plasma VEGF. Data were extracted and assessed independently using JBI tools. Exercise types were categorized and doses standardized as metabolic equivalents (METs). Network meta-analysis was performed in Stata17.0 (SMD as effect size), with SUCRA used for ranking. Dose-response relationships were examined by meta-regression (remr package), and publication bias was assessed via funnel plots.

Results

Twenty-eight studies (N = 1138) were included. In healthy adults, lower-limb resistance training produced the greatest VEGF increase, with benefits observed above ~600 METs-min/week and peaking near 1950 METs-min/week. Among obese individuals, combined aerobic and resistance training under hypoxic conditions showed the highest VEGF response, though dose-specific effects were not significant. In patients with chronic conditions, upper-limb resistance training within 756-950 METs-min/week was most effective, displaying a U-shaped dose-response relationship. No substantial publication bias was detected.

Conclusions

The VEGF response to exercise appears to be influenced by both population characteristics and training dosage. High-intensity lower-limb resistance training may provide greater benefits for healthy adults, while obese individuals might experience enhanced responses with combined training under hypoxic conditions. For clinical populations, moderate-dose upper-limb resistance training may be particularly beneficial. Large-scale, long-term trials are needed to further clarify and refine exercise prescriptions targeting VEGF-mediated vascular adaptations.