Branched-chain Amino Acids (BCAAs) In Liver Diseases

Giraffe

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Abstract

"Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects."

From that article:

CLINICAL APPLICATION OF BCAAS IN LIVER DISEASES (shortened)

BCAAs for liver cirrhosis

The liver is a central organ for nutrient metabolism, and patients with chronic liver diseases may develop various metabolic and nutrition disorders[41]. Patients with cirrhosis frequently show protein and energy deficiency. Protein deficiency leads to hypoalbuminemia, inducing ascites and edema, whereas energy deficiency decreases fat and muscle mass and causes muscle weakness, decreasing the quality of life of patients with cirrhosis[42]. Several clinical trials have suggested that BCAA supplementation improves the prognosis of cirrhotic patients[43,44]. [...] Furthermore, BCAA supplementation in patients with advanced cirrhosis may improve abnormal glucose tolerance in addition to improving serum albumin concentration[45], and a randomized study showed that oral BCAA was effective in patients with both compensated and decompensated cirrhosis, maintaining or increasing serum albumin concentrations[46]. Oral BCAA treatment has also been reported to improve protein malnutrition in patients, especially during the early stages of liver cirrhosis, increasing serum albumin level to 3.5-3.9 g/dL and increasing total hepatic parenchymal cell mass[47-49]. BCAA treatment also improved nutritional status and reduced the frequency of albumin infusion in children with end-stage liver disease[50]. Taken together, these findings indicate that BCAA supplementation is effective in improving nutritional status in cirrhotic patients, regardless of patient age or disease stage.

Furthermore, BCAA supplementation was reported to improve the quality of life in cirrhotic patients. Two randomized trials showed that BCAA supplementation improved the Short Form-36 scores of general health perception compared with control groups[43,44]. Another randomized study showed that BCAA-enriched supplements improved weakness and fatigue compared with ordinary foods[51]. BCAA-enriched supplementation has also been reported to improve sleep disturbance[52].

Accelerated fat oxidation and a catabolic state after fasting, represented as a decreased respiratory quotient (RQ), are frequently observed in patients with cirrhosis[53]. Late evening snack supplementation with a BCAA mixture was found to improve RQ, nutritional state and glucose intolerance[53,54]. The energy efficiency of BCAAs is higher than that of glucose or fatty acids, suggesting that BCAAs may be the preferred energy substrate for patients with cirrhosis[55]. Others also reported that late evening snacks with BCAAs were useful in improving protein metabolism and lipolysis in cirrhotic patients[56]. [...]

BCAAs for hepatic encephalopathy

[...] A systematic review reported that BCAAs appeared to have a modest effect in improving encephalopathy without adverse events, although convincing evidence was not supplied[62]. [...]

BCAAs for hepatocellular carcinoma

Clinical studies have suggested that BCAA supplementation can help in the management of HCC. Prolonged surgical stress and advanced malignancy can result in systemic catabolism and muscle wasting, with BCAA supplementation having the potential to improve these conditions[67]. [...]

Thus, BCAA supplementation for patients with HCC is of clinical importance in the preservation of liver function and quality of life during treatment, although it is unclear whether BCCAs directly prevent HCC.

Acute liver injury

Although BCAAs have no proven benefit in patients with acute liver injury, enteric nutritional support is essential[85]. Several animal studies have shown that BCAAs may prevent acute liver injury[86-88], although its effects in humans are as yet undetermined. [...]

HCV infection

Insulin resistance occurs frequently in patients infected with HCV and is associated with various complications, such as steatosis, disturbances in glucose metabolism, and carcinogenesis[92]. BCAAs, especially leucine or isoleucine, have been shown to have beneficial effects on glucose metabolism[93]. A randomized study showed that BCAA treatment of patients with chronic hepatitis C and insulin resistance improved HbA1c concentrations in patients with marked peripheral insulin resistance, although BCAA did not significantly affect parameters of glucose metabolism or lipid profiles[94]. A multicenter randomized control trial showed that BCAAs prevented the development of HCC in obese, HCV-infected patients[68]. Furthermore, BCAA treatment can restore impaired interferon signaling caused by malnutrition through the mTOR and FoxO pathways in patients with chronic hepatitis C[95]. Interestingly, valine was reported to reduce HCV viral load, possibly by enhancing DC function or interferon signaling[96]. Thus, BCAA supplementation may be useful for adherence to interferon therapy in patients with chronic hepatitis C and may enhance the effects of interferon in these patients[97].

Liver transplantation

Protein-energy malnutrition is commonly found in patients with end-stage liver disease requiring liver transplantation and is a risk factor for posttransplant morbidity. A report of 50 recipients undergoing living donor liver transplantation (LDLT) showed that absence of preoperative BCAA treatment was an independent risk factor for postoperative severe infection and in-hospital death[98]. Kawamura et al[99] reported that early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in patients with cirrhosis. A retrospective analysis also showed that BCAA treatment before LDLT may reduce the incidence of posttransplant bacteremia[100].

Other clinical problems related to management of liver diseases

Insulin resistance: Increased insulin resistance is found in patients with chronic liver diseases and is a therapeutic target associated with malnutrition and hepatocarcinogenesis. BCAAs are thought to act on insulin target organs, such as skeletal muscles, adipose tissue, and the liver[101]. BCAA infusion was reported to decrease plasma glucose concentrations in patients with advanced liver cirrhosis[102], and oral BCAA administration was recently shown to reduce both blood glucose concentrations[103,104] and insulin resistance in patients with chronic liver diseases, especially in men[19,105]. More recently, long-term BCAA supplementation was shown to improve glucose tolerance in patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis, and may be an alternative treatment for NASH[106].
 
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Giraffe

Giraffe

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According to the article above BCAA supplementation can improve glucose tolerance in patients with liver disease. This study was referenced.

Effects of BCAA Supplementation on Plasma Concentrations of FFAs, Insulin, and Energy Substrates in Young Men

Abstract
The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen."

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Interesting are the tables. FFA were lowered quite a bit after ingestion of 1 or 5 g BCAAs, and then slowly raised again. It took almost three hours until they reached the baseline levels. Keep in mind that these men had fasted before ingesting the BCAAs. The other table show the concentrations of plasma free amino acids, except the BCAAs.
 

goodandevil

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So the mechanism is by reducing serotonin? Besides being a protein source for increased albumin ?
 

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