Chronic liver disease (CLD), also known as cirrhosis, is a serious condition that is linked to drastic weight loss and the degradation of lean muscle due to decreased protein production and increased breakdown of muscle protein . Reduced liver function also negatively alters nutrient absorption and this typically leads to malnutrition that is associated with life-threatening complications and an increased risk of death . Indeed, the prevalence of malnutrition in individuals with CLD is about 60-90% for this particular population .
One of the main causes of CLD-induced malnutrition is an imbalance of nitrogen . As nitrogen levels decrease, the body tries to meet its demands for this substance by breaking down more muscle protein and this typically causes protein to be degraded faster than it can be replaced through a regular diet. The body also needs more energy in the form of increased calories to compensate for the body’s attempt to heal the liver damage, but if caloric intake is not significantly increased, the body will also use muscle protein as a source of energy . This process leads to protein-energy malnutrition as well as hepatic cachexia, which is characterized as the progressive loss of muscle due to excessive muscle protein degradation, improper responses to insulin release, and heightened blood sugar levels; all of which contribute to the wasting of muscle . The net effect of this increased protein and calorie (energy) requirement is macronutrient deficiencies that must be addressed through supplementation.
Role of Oral Nutritional Supplements
According to the American Association for the Study of Liver Diseases (AASLD), oral branched-chain amino acids (BCAAs) are a useful alternative or a beneficial addition to the conventional treatment for people with CLD or liver-damage induced brain dysfunction (hepatic encephalopathy), especially for those who have not responded to previous treatments . One of the reasons that BCAA supplementation is beneficial is due to its ability to promote heightened levels of nitrogen, a substance that promotes protein synthesis for muscle growth. BCAAs also target blood sugar-related muscle loss by improving blood sugar regulation . By supporting healthy blood sugar levels, BCAAs help prevent further skeletal muscle loss.
One clinical study involving BCAAs evaluated the introduction of a controlled diet of 45 to 65 grams (g) of protein for 15 days to individuals with CLD, followed by the administration of 0.24 g per kilogram of BCAAs on day 16 in combination with their diet. After three months, the status of the liver significantly improved. This was attributed to enhanced nitrogen balance that remained heightened in response to BCAA supplementation . These types of clinical findings have been repeatedly demonstrated with regard to BCAA supplement for improved liver health [9-12].
BCAA supplementation also targets hepatic encephalopathy, which refers to brain dysfunction that is the result of liver damage [13, 14]. In addition, BCAA supplementation for prolonged periods of time (e.g., 2 years) has been shown to improve event-free survival for people with CLD . Therefore, nutrient supplementation is vital toward the management of CLD.
- Marchesini G, Bianchi G, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792-801.
- Lautz HU, Selberg O, Ko¨rber J, Bu¨rger M, Mu¨ller MJ. Forms of malnutrition in patients with liver cirrhosis. Clin Invest 1992;70:178-186.
- Parkash O, Jafri W, et al. Assessment of malnutrition in patients with liver cirrhosis using protein calorie malnutrition (PCM) score verses bio-electrical impedance analysis (BIA). BMC Res Notes. 2018;11(1):545.
- Nielsen K, Kondrup J, Martinsen C, Shilling B, Wikman B. Nutritional assessment and adequacy of dietary intake in hospitalized patients with alcoholic cirrhosis. Br J Nutr 1993;69:665-679.
- Kalafateli M, Konstantakis C, et al. Impact of muscle wasting on survival in patients with liver cirrhosis. World J Gastroenterol. 2015;21(24):7357-61.
- American Association for the Study of Liver Diseases (AASLD). Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by AASLD and EASL. https://www.aasld.org/sites/default/files/guideline_documents/hepaticencephenhanced.pdf
- Nishitani S, Takehana K. Pharmacological activities of branched-chain amino acids: augmentation of albumin synthesis in liver and improvement of glucose metabolism in skeletal muscle. Hepatol Res. 2004;30S:19-24.
- Marchesini G, Dioguardi FS, et al. Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group. J Hepatol. 1990;11(1):92-101.
- Gluud LL, Dam G, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence? Metab Brain Dis. 2013;28(2):221-5.
- Gluud LL, Dam G, et al. Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. J Nutr. 2013;143(8):1263-8.
- Nakaya Y1, Okita K, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007;23(2):113-20.
- The San-in Group of Liver Surgery. Long-term oral administration of branched chain amino acids after curative resection of hepatocellular carcinoma: a prospective randomized trial. Br J Surg. 1997;84(11):1525-31.
- Gluud LL, Dam G, Les I, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017;5:CD001939.
- Romeiro FG, Ietsugu MDV, et al. Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial. Neuroimage Clin. 2018;19:302-310.
- Muto Y, Sato S, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3(7):705-13.