Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients (BCAA-CLD)

Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients

Effect of Branched Chain Amino Acids Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in Patients With Chronic Liver Disease - A Randomized Controlled Trial.

Loss of muscle mass (sarcopenia) is a major complication in a patient with cirrhosis, impacting the disease outcome, quality of life and survival. Cirrhotics lose muscle mass (MM) while waiting for liver transplant (LT) and even after LT, impacting the outcome of LT. Moreover, LT is elusive for majority of patients in India. The pathophysiology of muscle loss is complicated, multifactorial, interlinked and primarily nutrition driven, which gives clues for targeted therapeutic modalities other than feeding alone. Experimental studies have instilled faith in BCAA in successfully counteracting the pathogenesis of muscle loss. But there is lack of convincing data from clinical studies with direct evidence on muscle growth per se.

Reduction in muscle mass (sarcopenia) is well documented in patients with chronic liver disease (CLD)leading to increased morbidity, mortality and poor quality of life. An equilibrium is maintained between the synthesis and degradation of muscles to maintain the muscle mass. However, an imbalance between the synthesis and degradation leads to loss of muscle mass. Various factors like alteration in dietary intake, hyper-metabolism, changes in amino acid profile, decreased physical activity, endotoxemia, hyperammonemia, increased myostatin levels have been postulated in the pathogenesis of muscle loss in liver disease. Reduced dietary intake, altered amino acid profile, decreased physical activity down regulate the anabolic pathway while the others increase the catabolic pathway. Increased level of myostatin inhibits the mTOR signaling and increases catabolism. Various therapeutic strategies such as increased calorie and protein intake, branched chain amino acid (BCAA) supplementation, late evening snack (LES), increased physical activity are the well accepted therapies. Hormone therapy (testosterone/growth hormone) also has been tried to improve muscle mass and function, reduce muscle catabolism in patients with CLD, however these newer treatment modalities i.e. hormone replacement, immune-nutrition and anti-myostatin antibodies are not free from adverse side-effects. Branched chain amino acids, a group of three essential amino acids (leucine, isoleucine, valine) have been tried since years in the setting of chronic liver disease patients for the treatment of hepatic encephalopathy and improvement in nutritional status. However, the studies assessing the impact of nutrition and BCAA in CLD have not assessed the direct impact on the muscle per se. The nutritional status has been assessed using different subjective methods like mid arm muscle circumference, triceps skin fold, nitrogen balance. Nutritional management is the cornerstone of the overall management of patients with cirrhosis, wherein BCAA constitutes an important therapeutic modality in the realm of nutrition in liver disease. In the present study all the eligible cirrhotic patients will be randomized to a control group (receiving the nutritional therapy as per the standard nutritional practices and guidelines) or the intervention group (receiving BCAA supplementation over and above the standard nutrition therapy as per the standard nutritional practices and guidelines). Branched chain amino acids (BCAA) have the potential to up-regulate the anabolic pathway of muscle synthesis leading to improvement in muscle mass. Muscle mass as assessed by DEXA, along with changes in muscle histology, markers of the pathways that regulate muscle growth, functional capacity, and quality of life will be assessed after 3 months of BCAA intervention.

As it is a nutritional intervention study masking either the participant or the investigator is not possible.

The patients would receive customized diet charts providing 30-35Kcal/ideal body wt/day and 1.5 gm protein/ideal body wt/day) describing the food items along with the quantity and approximate household measurements. Diet would be so planned for each patient keeping in mind the individual food habits and choices. This group would not receive any supplement other than the prescribed diet. Whey protein will be included in this group.

The patients would receive customized diet charts providing 30-35Kcal/ideal body wt/day and 1.5 gm protein/ideal body wt/day) describing the food items along with the quantity and approximate household measurements. Diet would be so planned for each patient keeping in mind the individual food habits and choices. In addition to the normal diet this group would receive 16gm of branched chain amino acid (BCAA) supplement (Commercial oral BCAA granules) daily in 4 divided doses, keeping the protein levels within the same range of 1.5 gm/Kg/day.

Whey protein will be given to the standard treatment arm including in the same amount of 1.5gm/kg/IBW.

Change in nitrogen balance will be assessed using formula : Nitrogen Balance = Protein intake (gm) / 6.25 - (UUN + 4 gm)

The Functional capacity of the patients would be assessed by Hand Grip Strength using the Handgrip Dynamometer .

The Health Related Quality of Life (HRQoL) of the patients would be assessed using the Chronic liver disease questionnaire(CLDQ)

Inclusion Criteria: Patients with decompensated cirrhosis (CTP 7-9) Adult patients Age 18-60 years Patients with corrected BMI in the range <22.9 Those who give consent for muscle biopsy INR <1.5 or 1.5-2.5 after correction with Vitamin K Platelets > 80000 All etiologies Exclusion Criteria: Presence of overt hepatic encephalopathy Patients with co-morbidities e.g. acquired immunodeficiency syndrome, HCC, Other cancer, Diabetes Mellitus, chronic kidney disease, congestive heart disease , chronic respiratory disease Patients with alcohol intake in past 3 months Patients with TIPS Patients on steroids INR >2.5 Refusal to participate in the trial