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The Effect of 12 Weeks of ?-Hydroxy-?-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study.

ABSTRACT: Sarcopenia is a frequent complication in liver transplant (LT) recipients. ?-hydroxy-?-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.

SUBMITTER: Lattanzi B

PROVIDER: S-EPMC6769827 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The Effect of 12 Weeks of β-Hydroxy-β-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study.

Lattanzi Barbara B Giusto Michela M Albanese Carlina C Mennini Gianluca G D'Ambrosio Daria D Farcomeni Alessio A Ginanni Corradini Stefano S Rossi Massimo M Merli Manuela M

Nutrients 20190919 9

Sarcopenia is a frequent complication in liver transplant (LT) recipients. β-hydroxy-β-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X- ...[more]

PMID: 31546969

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Project description:Background and aimSarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified.MethodsThis is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2).ResultsAt baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented.ConclusionsOur study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.

Project description:The leucine metabolite, ?-hydroxy-?-methyl butyrate (HMB), is widely used in human nutrition and animal production as a nutritional supplement. Although the HMB usage during late gestation has been demonstrated to have a positive effect on fetal development, knowledge on net absorption and metabolism of HMB and impact of HMB on branched chain amino acids (BCAAs) metabolism is lacking. To address this, we conducted a study using pigs during the perinatal period as a model organism. Eight-second parity sows were fitted with indwelling catheters in the femoral artery and in the portal, hepatic, femoral, and mesenteric veins. Eight hourly sets of blood samples were taken starting 30 min before the morning meal on day -10 and day -3 relative to parturition. Four control (CON) sows were fed a standard lactation diet from day -15 and throughout the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)2/kg body weight mixed in one third of the morning meal from day -10 until parturition. Blood gases, plasma metabolites, milk compositions, and apparent total tract digestibility of nutrients were measured. Arterial plasma concentrations of HMB (p < 0.001), Cys (p < 0.001), and Lys (p < 0.10) were increased in HMB supplemented sows, while arterial plasma triglycerides concentration was decreased (p < 0.05). The net portal recovery of Ala and Asp were increased in HMB sows (p < 0.05). Sows fed HMB had increased hepatic vein flow and net hepatic fluxes of Met, Asn, and Gln (p < 0.05). In contrast, the femoral extraction rates of Ala and Ser were decreased by dietary HMB supplementation (p < 0.05). Dietary HMB treatment and sampling time relative to feeding had an interaction on arterial concentrations, net portal fluxes, and femoral extraction rates of BCAAs. The net portal recovery of HMB was 88%, while 14% of supplemented HMB was excreted through urine and 4% through feces. Moreover, the gastrointestinal tract metabolized 8% while the liver metabolized 12%. Finally, 26% of the daily intake of HMB was secreted via colostrum at the day of farrowing. This study demonstrated that dietary HMB supplementation increased net uptake of amino acids and increased fatty acid oxidation through improving blood flow and insulin sensitivity during the late gestation. Most importantly, oral HMB administration could maintain a stable postprandial absorption and altered metabolism in BCAAs. Net portal flux of HMB at 5.5 to 6.5 h after feeding approached zero, indicating that HMB ideally should be administrated two or three times, daily.

Project description:ObjectivesResistance training (RT) is a promising strategy to slow or prevent fluid cognitive decline during aging. However, the effects of strength-specific RT programs have received little attention. The purpose of this single-group proof of concept clinical trial was to determine whether a 12-week strength training (ST) program could improve fluid cognition in healthy older adults 60 to 80 years of age, and to explore concomitant physiological and psychological changes.MethodsTwenty participants (69.1 ± 5.8 years, 14 women) completed this study with no drop-outs or severe adverse events. Baseline assessments were completed before an initial 12-week control period, then participants were re-tested at pre-intervention and after the 12-week ST intervention. The NIH Toolbox Cognition Battery and standard physical and psychological measures were administered at all three time points. During the 36 sessions of periodized ST (3 sessions per week), participants were supervised by an exercise specialist and challenged via autoregulatory load progression.ResultsTest-retest reliability over the control period was good for fluid cognition and excellent for crystallized cognition. Fluid composite scores significantly increased from pre- to post-intervention (8.2 ± 6.1%, p < 0.01, d = 1.27), while crystallized composite scores did not (-0.5 ± 2.8%, p = 0.46, d = -0.34). Performance on individual fluid instruments, including executive function, attention, working memory, and processing speed, also significantly improved. Surprisingly, changes in fluid composite scores had small negative correlations with changes in muscular strength and sleep quality, but a small positive correlation with changes in muscular power.ConclusionsThus, improvements in fluid cognition can be safely achieved in older adults using a 12-week high-intensity ST program, but further controlled studies are needed to confirm these findings. Furthermore, the relationship with other widespread physiological and psychological benefits remains unclear.

Project description:NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open-label study, we assessed the histological efficacy of NGM282 in patients with biopsy-confirmed nonalcoholic steatohepatitis. Paired liver biopsies from 43 patients who received subcutaneous NGM282 (1 mg, n = 24; 3 mg, n = 19) once daily for 12 weeks were evaluated blinded to time point, subject, and clinical information. At week 12, NGM282 significantly reduced nonalcoholic fatty liver disease activity score (NAS; -1.9; 95% confidence interval, -2.6 to -1.2; P < 0.001 in the 1 mg group; -2.2, -3.1 to -1.3; P < 0.001 in the 3 mg group) and fibrosis (-0.5; -0.9 to 0; P = 0.035 in the 3 mg group) scores. Overall, 50% and 63% of the patients receiving NGM282 1 mg or 3 mg, respectively, improved NAS by 2 or more points without fibrosis worsening. Of the patients receiving NGM282 1 mg or 3 mg, 25% and 42%, respectively, improved liver fibrosis by one stage or more without worsening of steatohepatitis. Treatment with NGM282 led to relative reductions in liver fat content (-58% and -67% in the 1 mg and 3 mg groups, respectively), corrected T1 (cT1; -8% and -9%), alanine aminotransferase (ALT) (-67% and -60%), aspartate aminotransferase (-57% and -52%), and fibrogenesis biomarkers neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3; -22% and -33%) and enhanced liver fibrosis score (ELF; -3% and -6%) at week 12. Greater reductions in Pro-C3, ELF, and cT1, but not in liver fat content, 7alpha-hydroxy-4-cholesten-3-one, or ALT, were observed in histological responders than in nonresponders. Conclusion: In this open-label study, NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and fibrosis scores, accompanied by improvements in noninvasive imaging and serum markers.

Dataset Information

The Effect of 12 Weeks of ?-Hydroxy-?-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study.

Publications

The Effect of 12 Weeks of β-Hydroxy-β-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study.

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