The Effects of Melatonin and Branched-chain Amino Acids Supplementation, Separately and Together on Inflammatory Factors, Muscle Wasting, Nutritional Status and Quality of Life in Cachectic Heart Failure Patients

Abstract

Background: Cardiac Cachexia (CC), characterized by significant weight loss and muscle wasting, occurs frequently in advanced stage of heart failure. The pathophysiology of CC is multifactorial. Therefore, focusing on an individual therapeutic procedure including drug therapy or diet therapy will not succeed in controlling or improving the symptom of patients. Melatonin exerts antioxidant effects and preliminary studies have shown the effects of melatonin in CC. Branched chain amino acids (BCAAs) are among the essential amino acids and there are promising evidence for their favorable effects in catabolic status. Considering that CC is a complicated and dangerous clinical condition, and due to lack of any clinical trial in CC patients, this study aimed to evaluate effects of melatonin and BCAAs separately and together on inflammatory factors, muscle wasting, nutritional status and quality of life in heart failure patients with cachexia. Materials and Methods: This study was a double-blind four-arm parallel randomized controlled trial which was conducted for eight weeks. Eligible patients were selected based on the inclusion and exclusion criteria referred to the Shahid Madani Medical Research Training Center in Tabriz, Iran. The consent form that was approved by Tabriz University of Medical Sciences completed by eligible participants. The participants were randomly allocated to four groups: 1. melatonin 20 mg/day 2. BCAAs 10 g/day 3. melatonin 20 mg/day and BCAAs 10 g/day together 4. Placebo. Pre and post intervention, inflammatory and muscle markers and lipid profile were measured. Also, body composition, resting metabolic rate (RMR), appetite, fatigue, muscle strength, quality of life, and nutritional risk index (NRI) were assessed. Results: Mean (SD) of the participants age was 50.77 (12.49) years with no statistically significant difference between the groups (p= 0.159). Eight weeks supplementation with melatonin and BCAAs both separately and concomitantly resulted in significant elevation in weight (p= 0.003), BMI (p=0.002), fat free mass (p=0.035) and quality of life (p<0.001) in BCAAs+melatonin group compared to placebo group after adjusting for confounders. However, between groups differences were not statistically significant with respect to fat mass (p=0.065). Moreover, a statistically significant increase was observed in mean appetite score in BCAAs (p<0.001) and BCAAs+melatonin (p<0.001) groups in comparison with placebo group at the end of the intervention. Between group alterations were not statistically significant regarding serum albumin (p= 0.642), RMR (p= 0.928) and NRI (p=0.804). Also, handgrip strength was greater in BCAA and BCAAs+melatonin groups compared to melatonin (p=0.039 and p=0.017, respectively) and placebo groups (p=0.030 and p=0.017, respectively) and a significant reduction was observed in fatigue in melatonin (p= 0.002), BCAAs (p<0.001) and BCAAs+melatonin (p<0.001) groups compared to the placebo group. Considering biochemical variables, a significant reduction was observed in TNF-α levels in melatonin (p=0.034) and melatonin+BCAAs groups (p=0.020) and also hs-CRP and CPK levels in BCAAs+melatonin group (p=0.009 and p=0.008, respectively) compared to placebo group. However, between group differences in IL-6, myoestatin and LDH levels were not statistically significant (p>0.05). With regard to lipid profile, only a statistically significant reduction in total cholesterol and LDL-c levels were observed in melatonin (p=0.010 and p=0.015) and BCAAs+melatonin groups (p=0.019 and p=0.034). However, no significant changes were observed for other components of the lipid profile. Conclusion: Melatonin and BCAAs supplementation could improve CC characteristics including weight, body composition, quality of life, fatigue, appetite and inflammatory and muscle markers and along with that could attenuate clinical symptoms in cachectic HF patients. Further studies are required to establish the findings of this study and to discover the long term and dose-dependent effects of these supplements.