Article

Usefulness of Branched-Chain Amino Acid for the Treatment of Muscle Cramp in Liver Cirrhosis.

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Abstract

We examined the effectiveness of a branched-chain amino acid (BCAA) granule preparation in relieving muscle cramp in 29 patients with liver cirrhosis. At baseline, muscle cramp was noted in 66% of the subjects (19 patients), and there was a significant inverse relationship between the frequency of muscle cramp development (times/week) and plasma taurine levels (p < 0.05). At the end of the treatment period, a significant decrease in frequency was observed in these subjects, together with a significant increase in plasma taurine levels (p < 0.01) and a decreasing trend in methionine levels (p < 0.1), suggesting the BCAA-induced activation of taurine synthesis. It can thus be concluded that BCAA granule preparations are effective both in improving nutritional condition and in relieving muscle cramp.

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... Our primary interest was the effect of BCAA treatment, because BCAA supplementation therapy is widely used to improve liver function in patients with chronic hepatic disease in Japan. Indeed, there is a clinical report that chronic BCAA supplementation increased the circulating taurine level in cirrhotic patients (Goto et al. 2001). ...
... Cirrhotic patients are often prescribed supplementation with these amino acids in Japan. Some clinical reports have demonstrated that oral supplementation of BCAA to patients successfully suppressed the occurrence of muscle cramps (Goto et al. 2001;Sako et al. 2003). In one case, BCAA supplementation resulted in an increased circulating taurine level together with decrease in methionine level (Goto et al. 2001). ...
... Some clinical reports have demonstrated that oral supplementation of BCAA to patients successfully suppressed the occurrence of muscle cramps (Goto et al. 2001;Sako et al. 2003). In one case, BCAA supplementation resulted in an increased circulating taurine level together with decrease in methionine level (Goto et al. 2001). From these observations, we assume that the effect of BCAA on ameliorating muscle cramps can be attributed in part to improved taurine biosynthesis in the liver. ...
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Taurine deficiency has been suggested to contribute to the pathogenesis and complications of advanced hepatic diseases. The molecular basis for a low level of taurine associated with hepatic failure is largely unknown. Using carbon tetrachloride (CCl4)-induced cirrhotic rat model, we found that the activity and expression of cysteine dioxygenase (CDO), a rate-limiting enzyme in taurine synthesis, were significantly decreased in the liver of these rats. To investigate the underlying mechanisms for the suppression, we examined the effects of pathological cytokines on CDO expression in human hepatoma HepG2 cells. Among the several cytokines, transforming growth factor-β (TGF-β), one of the key mediators of fibrogenesis, suppressed Cdo1 gene transcription through the MEK/ERK pathway. Finally, we further examined potential effects of branched-chain amino acids (BCAA) on CDO expression, as it has been reported that oral BCAA supplementation increased plasma taurine level in the patients with liver cirrhosis. BCAA, especially leucine, promoted Cdo1 gene transcription, and attenuated TGF-β-mediated suppression of Cdo1 gene expression. These results indicate that the low plasma level of taurine in advanced hepatic disease is due to decreased hepatic CDO expression, which can be partly attributed to suppressive effect of TGF-β on Cdo1 gene transcription. Furthermore, our observation that BCAA promotes Cdo1 expression suggests that BCAA may be therapeutically useful to improve hepatic taurine metabolism and further suppress dysfunctions associated with low level of taurine in hepatic diseases. Electronic supplementary material The online version of this article (doi:10.1007/s00726-014-1693-3) contains supplementary material, which is available to authorized users.
... Also, it has been reported that the causes for cramps are mechanism of peripheral neuropathy or myogenic, and decrease in blood taurine levels, which suppress abnormal excitation at the neuromuscular junction. Goto et al. discussed that BCAA formulations improved the symptom via decreased levels of free L-tryptophan caused by increased serum albumin levels, followed by facilitated ability to synthesize taurine through correction of amino acid imbalance [10]. We sometimes come across cases in which muscle symptoms occur as a result of carnitine deficiency in dialysis patients as well [11]. ...
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The patient was an 81-year-old female who had been receiving hemodialysis (HD) for 21 months. The patient was obese (body mass index [BMI]: 25.1±0.1); malnourished (serum albumin level: 3.3±0.03 g/dL, percentage creatinine generation rate [%CGR]: 56.0±1.8); and exhibited reductions in her muscle strength, walking speed, and ability to perform activities of daily living (which was considered to be due to frailty rather than sarcopenia). As the patient suffered frequent cramps and intradialytic hypotension, she was forced to stop receiving HD. HD removes not only uremic toxins, but also various nutrients, including water-soluble vitamins and amino acids. Therefore, there is a possibility that the amounts of nutrients removed by HD exceed those consumed via dietary intake, even after 4 hours HD (blood flow rate [QB]=200 mL/min, dialysis fluid flow rate [QD]=500 mL/min). Human energy levels are maintained by gluconeogenesis, which involves amino acid catabolism. Most amino acid catabolism involves glutamate as a reaction intermediate. In this study, the patient’s blood glutamate concentration increased after HD; nevertheless, HD removes plenty of glutamate. However, low-efficiency HD (QD: 200 mL/min, QB: 95 mL/min from 0-30 minutes, 170 mL/min from 30 to 90 minutes, 230 mL/min from 90 to 240 minutes) suppressed the increase in the patient’s blood glutamate concentration seen after HD. In other words, it suppressed gluconeogenesis. Eventually, low-efficiency HD significantly improved the patient’s nutritional status (serum albumin level: 3.6±0.1 g/dL, p=0.020; %CGR: 81.7±11.9, p=0.0024), BMI (27.1±0.22), and catabolic status. Furthermore, the number of rounds of treatment required for cramp combined with intradialytic hypotension dramatically decreased after the introduction of low-efficiency HD.
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