Moderate endurance exercise leads to an improvement in cardiovascular performance, stress resilience, and blood function. However, the influence of chronic endurance exercise over several hours or days is still largely unclear. We examined the influence of a non-stop 160.9/230 km ultramarathon on body composition, stress/cardiac response, and nutrition parameters. Blood samples were drawn before (pre) and after the race (post) and analyzed for ghrelin, insulin, irisin, glucagon, cortisol, kynurenine, neopterin, and total antioxidant capacity. Additional measurements included heart function by echocardiography, nutrition questionnaires, and body impedance analyses. Of the 28 included ultra-runners (7f/21m), 16 participants dropped out during the race. The remaining 12 finishers (2f/10m) showed depletion of antioxidative capacities and increased inflammation/stress (neopterin/cortisol), while energy metabolism (insulin/glucagon/ghrelin) remained unchanged despite a high negative energy balance. Free fat mass, protein, and mineral content decreased and echocardiography revealed a lower stroke volume, left end diastolic volume, and ejection fraction post race. Optimizing nutrition (high-density protein-rich diet) during the race may attenuate the observed catabolic and inflammatory effects induced by ultramarathon running. As a rapidly growing discipline, new strategies for health prevention and extensive monitoring are needed to optimize the athletes’ performance.

Background: Ultramarathon running represents an extreme physiological and metabolic challenge. Despite its growing popularity among recreational and competitive runners, evidence-based guidance for nutrition, energy balance, and recovery remains limited. Understanding metabolic response and hormonal regulation during such events is crucial for improving athletes’ health and performance. Methods: This prospective observational study examined participants of the 2024 TorTour de Ruhr^® (100 km, 160.9 km, and 230 km). Pre- and post-race assessments included body composition, energy intake and expenditure, metabolic and hormonal biomarkers (leptin, ghrelin, insulin, glucagon, irisin, creatine kinase muscle type (CKM), lactate dehydrogenase (LDH)), and continuous glucose monitoring (CGM). Blood and saliva samples, bioimpedance analysis, and validated symptom questionnaires (General Assessment of Side Effects (GASE)) were used. Results: Of the 43 ultra runners (16 women, 27 men), 39 finished the race: 19 participants of the 100 km group, 8 of the 160.9 km group, and 16 of the 230 km group. Mean energy deficit was 6797 kcal (range: 417–18,364 kcal) with carbohydrate-dominant fueling (79%). Significant reductions in leptin and insulin and increases in ghrelin, glucagon, CKM, and LDH were observed, indicating disrupted energy homeostasis and muscle damage. The 230 km subgroup showed the greatest changes. Gastrointestinal and musculoskeletal symptoms increased post-race, aligning with biomarker patterns. Conclusions: Ultramarathon participation induces profound disturbances in metabolic and structural integrity, regardless of race distance. These findings underline the importance of developing individualized nutritional and recovery strategies and highlight the need for future research to investigate how energy deficit and macronutrient composition interact to influence metabolic strain and post-race recovery.