Exercise-Induced Rhabdomyolysis With Supplements (Creatine, β-Alanine, Citrulline Malate, and β-Ecdysterone)

Dietary supplements such as creatine, β-alanine, citrulline malate (CM), phosphatidic acid (PA), and β-ecdysterone are widely used to enhance exercise performance and muscle hypertrophy. Although generally considered safe, their combined use with high-intensity training may increase the risk of exertional rhabdomyolysis and secondary liver or kidney injury. We report the case of a 23-year-old physically active man admitted with severe myalgia, muscle weakness, fever, and dark brown urine following a prolonged (>4 hours) resistance training session. The patient regularly used multiple dietary supplements, including creatine (5 g), β-alanine, CM (10 g), PA (1.5 g), β-ecdysterone, protein, vitamins, and other micronutrients. Laboratory evaluation revealed markedly elevated creatine kinase (>120,000 U/L) and increased aminotransferases (aspartate aminotransferase (AST) 1,275 U/L; alanine aminotransferase (ALT) 337 U/L), with preserved renal function (creatinine 1.0 mg/dL; estimated glomerular filtration rate (eGFR) 108 mL/min/1.73 m²). No electrolyte disturbances or cardiac injury were observed. The patient received intensive intravenous fluid therapy, resulting in gradual clinical and biochemical improvement over 10 days without development of acute kidney injury (AKI). Creatine and β-alanine enhance exercise capacity through complementary mechanisms involving adenosine triphosphate (ATP) resynthesis and intracellular buffering, potentially enabling greater training loads and increasing risk of muscle injury. The ergogenic efficacy of CM remains inconclusive, while PA and β-ecdysterone may stimulate anabolic signaling via mTOR-related and estrogen receptor-mediated pathways, respectively. Although β-ecdysterone has not previously been linked to rhabdomyolysis, its metabolic effects may theoretically exacerbate muscle damage after extreme exertion. Genetic predisposition, including LPIN1 variants, cannot be excluded and represents a limitation of our study, as genetic testing was not performed. This case highlights the potential risk of severe rhabdomyolysis associated with intensive exercise combined with multi-ingredient supplementation. Healthcare professionals should inquire about supplement use in patients presenting with muscle injury. Early recognition and prompt intravenous hydration remain essential to prevent renal complications. Further studies are needed to clarify the safety profile of emerging anabolic supplements, particularly β-ecdysterone.