Heating Improves Poor Compliance with Branched Chain Amino Acid-Rich Supplementation in Patients with Liver Cirrhosis: a Before-After Pilot Study

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Heating Improves Poor Compliance with Branched Chain Amino Acid-Rich Supplementation in Patients with Liver Cirrhosis: a Before-After Pilot Study MOLECULAR MEDICINE REPORTS 2: 983-987, 2009 Heating improves poor compliance with branched chain amino acid-rich supplementation in patients with liver cirrhosis: A before-after pilot study MINORU ITOU1, TAKUMI KAWAGUCHI1,2, EITARO TANIGUCHI1, SATOMI SHIRAISHI3, RYOKO IBI3, MICHIKO MUTOU3, TERUYO OKADA3, YUKI UCHIDA4, MOMOKA OTSUKA4, TETSUHARU ORIISHI1, SUIKO TANAKA4, MACHIKO TAKAKURA3, KEIICHI MITSUYAMA1, OSAMU TSURUTA1 and MICHIO SATA1,2 1Division of Gastroenterology, Department of Medicine, 2Department of Digestive Disease Information and Research, Kurume University School of Medicine; Departments of 3Nursing, and 4Nutrition, Kurume University Hospital, Kurume 830-0011, Japan Received November 11, 2008; Accepted April 16, 2009 DOI: 10.3892/mmr_00000202 Abstract. Although branched chain amino acid (BCAA) levels following the heating of the BCAAs to 80˚C. The supplementation improves malnutrition in cirrhotic patients, caloric intake of the BCAA-rich supplement was significantly patient compliance with the administration of BCAA-rich higher with administration after heating to 60˚C, compared to supplements is poor due to their bitter taste. Since tempera- caloric intake with administration at 25˚C. In addition, ture is an important factor affecting taste, we examined the heating of the BCAA-rich supplement significantly increased effect of heating on the stability of BCAAs and on the blood lymphocyte counts. In conclusion, heating did not affect compliance of patients with liver cirrhosis with BCAA-rich the stability of the BCAAs, and may improve compliance supplement administration. A thermal denaturation test was with BCAA-rich supplement administration. As a result, the first conducted, in which the BCAA-rich supplement nutritional status of cirrhotic patients may be improved. Aminoleban® EN was heated to 37, 60, or 80˚C for 30 or 60 min. The concentration of three amino acids, L-valine, Introduction L-leucine and L-isoleucine, was subsequently measured. The nutritional status of the cirrhotic patients was also evaluted. Branched chain amino acid (BCAA) supplementation improves Patients presenting liver failure with a Child-Pugh class of not only hepatic encephalopathy, but also protein-energy A (n=2), B (n=2) or C (n=2) were hospitalized at Kurume malnutrition and quality of life (QOL) in patients with liver University Hospital. Six patients with liver cirrhosis (HCV, cirrhosis (1). However, the long-term compliance of cirrhotic n=3; HBV, n=1; alcohol, n=2) were enrolled. Venous blood patients with BCAA-rich supplement administration is often samples were drawn in the morning after a 12-h overnight poor, as BCAAs have a bitter unpalatable flavor (2,3), and fast. The BCAA-rich supplement was administered to patients as foods with a predominantly bitter taste have been shown at room temperature (25˚C) or heat loaded at 60˚C for to be specifically less preferred by patients with liver disease 10 min, with the temperature maintained above 45˚C. Each compared to healthy controls (4). Although an increase in patient was interviewed by a nationally registered dietitian the particle size of BCAA crystals lowers their bitterness regarding food consumption and intake of the BCAA-rich intensity score as evaluated by human gustatory tests and an supplement immediately after each meal. Nutritional status artificial taste sensor (5), additional measures are required to was evaluated according to serum albumin levels, blood improve the compliance of cirrhotic patients with BCAA-rich hemoglobin, prothrombin time and total lymphocyte count. No supplement administration. significant decrease was noted in valine, leucine or isoleucine The sensory properties of food can regulate appetite (6). Changes in taste, smell, texture and the temperature of foods _________________________________________ influence food intake. Food temperature, in particular, has a strong influence on taste. Warm food changes the taste threshold on the tongue (7). Moreover, warming foods has Correspondence to: Dr Minoru Itou, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, recently been reported to activate thermosensitive molecules 67 Asahi-machi, Kurume 830-0011, Japan in the taste transduction pathway, leading to changes in taste (8). E-mail: [email protected] Nevertheless, the effects of warming BCAA-rich supplements have never been tested. In this study, we examined the effect Key words: heating, branched chain amino acids, liver cirrhosis of heating on the stability of BCAAs and on compliance with the administration of BCAA-rich supplements, and evaluated the resulting nutritional status of cirrhotic patients. 984 ITOU et al: HEATING OF BCAA-RICH SUPPLEMENTATION IMPROVES ITS COMPLIANCE Materials and methods Table I. Composition of Aminoleban EN (per 50 g in 200 ml of water). Materials. All reagents were purchased from Wako Pure ––––––––––––––––––––––––––––––––––––––––––––––––– Chemical Industries (Osaka, Japan) unless otherwise indicated. Total energy 210 kcal Protein 13.5 g Thermal denaturation test for BCAAs. A coffee-flavored Amino acids (Fischer's ratio = 38) ® BCAA-rich supplement (Aminoleban EN, Otsuka L-valine 1.60 g Pharmaceutical Co., Ltd., Tokyo, Japan) was selected, and L-leucine 2.04 g 50 g of the supplement were sonicated in 200 ml of water for L-isoleucine 1.92 g 45 min at 25˚C in a beaker (solution A) (Table I). Solium L-thereonine 0.13 g citrate (39 g) and 32 ml of perchloric acid were diluted in L-tryptophan 0.07 g 2000 ml of water (solution B). A mixture of 1.5 ml of solu- L-arginine hydrochloride 0.30 g tion A and 98.5 ml of solution B was heated in flasks to 37, L-histidine hydrochloride 0.19 g 60 or 80˚C for 30 or 60 min in a thermostatic bath. For the L-lysine hydrochloride 0.24 g stability testing of the BCAAs, 10 µl of each mixture were used. Fat (rice oil) 3.50 g Carbohydrates (dextrin) 31.05 g Measurement of BCAAs. Using high-performance liquid Vitaminsa chromatography, the concentration of three amino acids, Mineralsb L-valine (Val), L-leucine (Leu) and L-isoleucine (Ile), was compared in each of the heated samples with the manufacturer's Deionized water 180 ml specifications for Aminoleban EN. pH 5.5-7.0 ––––––––––––––––––––––––––––––––––––––––––––––––– Patients. Patients presenting liver failure with a Child-Pugh aVitamins include retinol palmitate, ergocalciferol, bisbentiamine, class of A (n=2), B (n=2) or C (n=2) were hospitalized at riboflavin, pyridoxine HCl, cyanocobalamin, folic acid, sodium l-ascorbate, tocopherol acetate, phytonadione, calcium pantothenate, Kurume University Hospital. Six patients with liver cir- b rhosis (HCV, n=3; HBV, n=1; alcohol, n=2) were enrolled. nicotinamide and biotin. Minerals include trace amounts of mag- nesium sulphate, calcium glycerophosphate, potassium iodide, Patient demographic data were collected on the same day potassium chloride, sodium dihydrogen phosphate dihydrate, as blood collection. Venous blood samples were collected sodium ferrous citrate, cupric sulphate, zinc sulphate and manganese in the morning after a 12-h overnight fast. The BMI of sulphate. patients was calculated as the body weight in kilograms ––––––––––––––––––––––––––––––––––––––––––––––––– divided by the square of the height in meters (kg/m2). The BCAA-rich supplement was administered to patients at room temperature (25˚C) or heat loaded at 60˚C for 10 min with the temperature maintained above 45˚C. None of the subjects Results were institutionalized. Informed consent for participation was obtained from each patient. The study protocol was approved Degradation of L-valine, L-leucine and L-isoleucine by by the Ethics Committee of the Kurume University School heating. No significant decrease in the concentration of Val, of Medicine. All experiments were carried out in accordance Leu or Ile was observed in the BCAA supplement under with the Declaration of Helsinki. any of the test conditions (Table II). Compared to baseline concentrations, there was no significant change in Val Food and BCAA-rich supplement intake. Each patient was concentrations following heating of the supplement to 37 or interviewed by a nationally registered dietitian regarding 60˚C for 30 or 60 min, while heating the BCAA supplement food consumption and intake of the BCAA supplement to 80˚C for 30 or 60 min resulted in a significant increase Aminoleban EN immediately after each meal. in Val concentrations compared to the baseline. Leu and Ile concentrations were significantly increased by heating of the Evaluation of nutritional status. Nutritional status was evaluated supplement to 37, 60 or 80˚C for 30 or 60 min, compared to according to serum albumin levels, blood hemoglobin, pro- baseline values (Table III). thrombin time and total lymphocyte count. These nutritional parameters were determined using standard clinical methods Caloric intake of BCAA-rich supplement and compliance (Department of Clinical Laboratory, Kurume University with its administration. Heating the BCAA-rich supplement Hospital). to 60˚C resulted in a longer period of compliance (17.5±10.1 days) compared to the period of compliance Statistical analysis. Data were expressed as the mean ± observed when the supplement was administered at 25˚C SD. Statistical comparisons among multiple groups were (1.8±0.8 days) (Fig. 1A). Caloric intake of the BCAA-rich performed by the Friedman test. Statistical comparisons supplement was significantly higher following heating to between two groups were performed by analysis of variance
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