Effects of Long-Term Combined Aerobic and Resistance Training According to MTHFR C677T Genotype in Patients with Chronic Stroke

Elevated plasma homocysteine (tHcy) is a modifiable risk factor for stroke and cardiovascular disease, influenced by genetic and lifestyle factors. Resistance-based training may reduce tHcy, but the impact of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism remains unclear. This study examined the effects of a 26-week combined aerobic and resistance training program on stroke-related risk factors and tHcy levels in patients with chronic ischemic stroke, stratified by MTHFR genotype. Forty-six patients (mean age: 57.7 ± 8.9 years) completed supervised training three times per week. Assessments before and after the intervention included anthropometry, cardiorespiratory fitness, biochemical markers, and tHcy. Dietary intake was monitored and remained stable. Significant improvements were observed in body weight, fat mass, waist-to-hip ratio, VO2max, and 6 min walk distance. tHcy decreased significantly overall (p < 0.01), with reductions confined to the CC genotype group (p < 0.01). BMI declined in CC and CT groups (p < 0.01 and p < 0.05), while fat-free mass, triglycerides, fasting glucose, and blood pressure showed no changes, likely due to pharmacological control. These findings suggest that combined training improves body composition and functional capacity, while genotype-specific reductions in tHcy highlight the potential of personalized rehabilitation strategies integrating genetic and nutritional considerations in stroke care.