BackgroundThe preoperative period is a good time to improve nutrition status, compensate for nutrient deficiencies, and optimize immune function in patients’ underlying surgery. In some medical conditions, supplementation with a combination of l-glutamine (Gln), β-hydroxy-β-methylbutyrate (HMB), and l-arginine (Arg) had promising effects on improving recovery. The present study aimed to evaluate the effect of supplementation with Gln/Arg/HMB in patients undergoing heart surgery.MethodsThis randomized clinical trial was conducted on 70 patients undergoing cardiac surgery. Participants were requested to consume 2 sachets of a combination of 7 g l-arginine, 7 g l-glutamine, and 1.5 g daily HMB or placebo 30 days before operation. At the baseline and end of the study, left ventricular ejection fraction and the serum levels of troponin, creatine phosphokinase (CPK), CPK-MB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were measured. Also, the Sequential Organ Failure Assessment (SOFA) score, time of stay in hospital and intensive care unit (ICU), and postoperative complications were recorded after surgery.ResultsIn total, 60 preoperative patients (30 in each group) with a mean age of 53.13 ± 14.35 years completed the study (attrition rate = 85.7%). Subjects in the Gln/Arg/HMB group had lower serum levels of CPK-MB (median [IQR] = 49 [39.75] vs. 83 [64.55]; P = 0.011), troponin (median [IQR] = 2.13 [1.89] vs. 4.34 [1.99]; P < 0.001), bilirubin (median [IQR] = 0.50 [0.20] vs. 0.40 [0.22]; P < 0.001), and SOFA score (median [IQR] = 2 [2] vs. 5 [2]; P < 0.001) at end of the study compared to the placebo. Also, the time of stay in the hospital (median [IQR] = 5 [1] vs. 6 [3]; P < 0.001) and ICU (median [IQR] = 2.50 [1.00] vs. 3.50 [1.50]; P = 0.002) was lower in the Gln/Arg/HMB group.ConclusionThe present study showed that perioperative supplementation with a combination of Gln, Arg, and HMB enhances the recovery, reduces myocardial injury, and decreases the time of hospital and ICU stay in cardiac surgery patients. These results need to be confirmed in a larger trial.Trial registrationIRCT.ir IRCT20120913010826N31. Registered on 13 October 2020.