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The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study.
Lattanzi, B, Bruni, A, Di Cola, S, Molfino, A, De Santis, A, Muscaritoli, M, Merli, M
Nutrients. 2021;(7)
Abstract
BACKGROUND AND AIM Sarcopenia 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. METHODS This 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). RESULTS At 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. CONCLUSIONS Our 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.
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A randomized controlled trial to determine whether beta-hydroxy-beta-methylbutyrate and/or eicosapentaenoic acid improves diaphragm and quadriceps strength in critically Ill mechanically ventilated patients.
Supinski, GS, Netzel, PF, Westgate, PM, Schroder, EA, Wang, L, Callahan, LA
Critical care (London, England). 2021;(1):308
Abstract
BACKGROUND Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. METHODS Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. RESULTS Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. CONCLUSIONS These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. TRIAL REGISTRATION ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .
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Urinary Titin N-Fragment Evaluation in a Randomized Controlled Trial of Beta-Hydroxy-Beta-Methylbutyrate for Acute Mild Trauma in Older Adults.
Nakano, H, Hashimoto, H, Mochizuki, M, Naraba, H, Takahashi, Y, Sonoo, T, Matsuishi, Y, Ogawa, Y, Shimojo, N, Inoue, Y, et al
Nutrients. 2021;(3)
Abstract
The effects of beta-hydroxy-beta-methylbutyrate (HMB) complex administration and the significance of titin, a biomarker of muscle injury, in elderly minor trauma patients in acute phase has not been established. In this single-center, randomized controlled study, trauma patients aged ≥ 70 years with an injury severity score < 16 were included. Titin values on days 1 and 3 were measured and the intervention group received HMB complex (2.4 g of HMB + 14 g of glutamine + 14 g of arginine) and the control group received glutamine complex (7.2 g of protein including 6 g of glutamine). The cross-sectional area of the rectus femoris (RFCSA) on ultrasound, grip strength, and the Barthel Index were assessed on the first day of rehabilitation and after 2 weeks. We analyzed 24 HMB and 25 control participants. Titin values on day 3 correlated with grip strength (r = -0.34, p = 0.03) and the Barthel Index (r = -0.39, p = 0.01) at follow-up. HMB complex supplementation had no effect on the RFCSA (2.41 vs. 2.45 cm2, p = 0.887), grip strength (13.3 vs. 13.1 kg, p = 0.946), or the Barthel Index (20.0 vs. 50.0, p = 0.404) at follow-up. Titin values might associate with subsequent physical function. Short-term HMB complex supplementation from acute phase did not ameliorate muscle injury.
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Impact of β-hydroxy-β-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT.
Viana, MV, Becce, F, Pantet, O, Schmidt, S, Bagnoud, G, Thaden, JJ, Ten Have, GAM, Engelen, MPKJ, Voidey, A, Deutz, NEP, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(8):4878-4887
Abstract
PURPOSE Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process. METHODS Prospective randomized, placebo-controlled double blind trial. INCLUSION CRITERIA ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days. PRIMARY OUTCOME magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15. SECONDARY OUTCOMES body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI. RESULTS Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04). CONCLUSION HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS. GOV IDENTIFIER NCT03628365.
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Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials.
Costa Riela, NA, Alvim Guimarães, MM, Oliveira de Almeida, D, Araujo, EMQ
Annals of nutrition & metabolism. 2021;(1):16-22
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Abstract
BACKGROUND The aging process has great impact on body composition, such as the increase of adipose tissue in abdominal region, and the decrease of lean body mass, due to skeletal muscle loss. A reduction in muscle mass is associated to high risk of fractures and falls, loss of mobility, and increased number of hospitalizations. Beta-hydroxy-beta-methylbutyrate (HMB) is a biological substance derived from leucine metabolism, with anabolic and anticatabolic properties. Some HMB effects are tissue repair stimulation and protein anabolism. AIMS We aimed to evaluate the effects of HMB supplementation on body composition and muscle strength in elderly, as well as to identify the efficient dosages to reach these effects. METHODS This review included studies that evaluated muscle mass and muscle strength, associated or not with physical exercise and diet in elderly people. Only studies published from 2008 to 2019 were selected for analysis. RESULTS Six articles were included in the review. The used doses varied from 1.5 to 3 g. In 5 studies, HMB supplementation was associated with calcium; only 1 study did not use the oral administration route. Two studies used 4 g of maltodextrin as a vehicle; 1 used HMB with a hypercaloric and hyperproteic supplement; 1 associated HMB with lysine and arginine; and 1 with arginine and glutamine. Supplementation of 3 g of HMB has shown to be most beneficial in improving strength and body composition in people over 65 years, especially in bed rest and untrained conditions. CONCLUSION Our findings suggest that HMB has a positive effect on body composition and strength, especially in bedridden or sedentary elderly, due to its anticatabolic properties.
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Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3.
D'Onofrio, N, Martino, E, Mele, L, Colloca, A, Maione, M, Cautela, D, Castaldo, D, Balestrieri, ML
International journal of molecular sciences. 2021;(15)
Abstract
Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.
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Elastic-band resistance exercise or vibration treatment in combination with hydroxymethylbutyrate (HMB) supplement for management of sarcopenia in older people: a study protocol for a single-blinded randomised controlled trial in Hong Kong.
Chow, SK, Chim, YN, Cheng, KY, Ho, CY, Ho, WT, Cheng, KC, Wong, RM, Cheung, WH
BMJ open. 2020;(6):e034921
Abstract
INTRODUCTION Sarcopenia is a geriatric syndrome characterised by progressive loss of skeletal muscle mass and function with risks of adverse outcomes and becomes more prevalent due to ageing population. Elastic-band exercise, vibration treatment and hydroxymethylbutyrate (HMB) supplementation were previously proven to have positive effects on the control of sarcopenia. The purpose of this study is to evaluate the effectiveness of elastic-band exercise or vibration treatment with HMB supplementation in managing sarcopenia. Our findings will provide a safe and efficient strategy to mitigate the progression of sarcopenia in older people and contribute to higher quality of life as well as improved long-term health outcomes of elderly people. METHODS AND ANALYSIS In this single-blinded, randomised controlled trial (RCT), subjects will be screened for sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) definition and 144 sarcopenic subjects aged 65 or above will be recruited. This RCT will have three groups evaluated at two time points to measure changes over 3 months-the control and the groups with combined HMB supplement and elastic-band resistance exercise or vibration treatment. Changes in muscle strength in lower extremity will be the primary outcome. Muscle strength in the upper extremity, gait speed, muscle mass (based on AWGS definition), functional performance in terms of balancing ability and time-up-and-go test and quality of life will be taken as secondary outcomes. In addition, each participant's daily activity will be monitored by a wrist-worn activity tracker. Repeated-measures analysis of variance will be performed to compare within-subject changes between control and treatment groups at two time points of pretreatments and post-treatments. ETHICS AND DISSEMINATION The procedures have been approved by the Joint CUHK-NTEC Clinical Research Management Office (Ref. CREC 2018.602) and conformed to the Declaration of Helsinki. Results will be disseminated through peer-reviewed publications, conferences and workshops. TRIAL REGISTRATION NUMBER NCT04028206.
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The addition of β-Hydroxy β-Methylbutyrate (HMB) to creatine monohydrate supplementation does not improve anthropometric and performance maintenance across a collegiate rugby season.
Mangine, GT, VanDusseldorp, TA, Hester, GM, Julian, JM, Feito, Y
Journal of the International Society of Sports Nutrition. 2020;(1):28
Abstract
BACKGROUND Muscular damage sustained while playing rugby may hinder performance across a season. β-Hydroxy β-Methylbutyrate (HMB) may help attenuate muscle damage and maintain lean mass and performance. This study sought to determine the effect of combining HMB with creatine monohydrate supplementation on measures of stress and muscle damage, body composition, strength and sprinting kinetics throughout a rugby season. METHODS This double-blind, cross-over investigation recruited 16 male collegiate rugby players to provide resting blood samples and complete assessments of body composition, strength and sprinting performance prior to their fall season (PREFALL). After testing, the athletes were matched for fat-free mass and assigned to consume one of two supplementation regimens for 6 weeks: 5 g HMB + 5 g creatine per day (HMB-Cr: 20.9 ± 1.1 years; 177 ± 2 cm; 88.4 ± 4.9 kg) or 5 g creatine + 5 g placebo per day (Cr: 21.4 ± 2.1 years; 179 ± 2 cm; 88.3 ± 4.9 kg). After 6 weeks (POSTFALL), PREFALL testing was repeated in 13 of the original 16 athletes before a 10-wk wash-out period. Athletes who returned for the spring season (n = 8) repeated all fall-season procedures and testing prior to (PRESPRING) and following (POSTSPRING) their 6-wk spring season, except they were assigned to the opposite supplementation regimen. RESULTS Linear mixed models with repeated measures revealed group x time interactions (p < 0.05) for observed for several measures but did not consistently and positively favor one group. During the fall season, knee extensor peak torque was reduced by 40.7 ± 28.1 Nm (p = 0.035) for HMB-Cr but remained consistent for Cr, and no group differences or changes were noted in the spring. In the spring, greater knee flexor rate of torque development (~ 149 Nm·sec- 1, p = 0.003) and impulse (~ 4.5 Nm·sec, p = 0.022) were observed in Cr at PRESPRING but not at POSTSPRING. Although significant interactions were found for cortisol concentrations, vastus lateralis pennation angle, and sprinting force, post-hoc analysis only revealed differences between fall and spring seasons. No other differences were observed. CONCLUSIONS The combination of HMB and creatine monohydrate supplementation does not provide a greater ergogenic benefit compared to creatine monohydrate supplementation alone. Body composition, strength, and sprinting ability did not change across the season with creatine monohydrate supplementation.
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Combined protein and calcium β-hydroxy-β-methylbutyrate induced gains in leg fat free mass: a double-blinded, placebo-controlled study.
Stahn, AC, Maggioni, MA, Gunga, HC, Terblanche, E
Journal of the International Society of Sports Nutrition. 2020;(1):16
Abstract
BACKGROUND The leucine metabolite β-hydroxy-β-methylbutyrate (HMB) is widely used as an ergogenic supplement to increase resistance-training induced gains in fat free mass (FFM) and strength in healthy adults. Recent studies have questioned the effectiveness of HMB, particularly when a high protein diet is habitually consumed. To investigate the additive resistance-training induced effects of HMB and protein in untrained individuals, we conducted a randomized double-blind, placebo-controlled study that compared the effects of combined protein and HMB supplementation to protein supplementation alone on FFM and muscle strength after 12-week resistance training. METHODS Sixteen healthy men (22 ± 2 yrs) performed a periodized resistance-training program for twelve weeks (four sessions per week). The program comprised two mesocycles, characterized by a linear periodization and non-linear periodization, respectively, and separated by a 1-week tapering period. All participants received 60 g of whey protein on training days and 30 g of whey protein (WP) on non-training days. Participants were randomly assigned to additionally receive 3 g of calcium HMB (WP + HMB) or a placebo (WP + PLA). Body composition and physical fitness were tested before and after the 12-week training program. Whole-body and arm and leg fat free mass (FFM) were assessed by bioimpedance spectroscopy; upper arm and leg fat free cross sectional areas were also quantified using magnetic resonance imaging (MRI); upper and lower body strength were measured by One-repetition maximum (1-RM) bench press and leg press. RESULTS Whole-body and segmental FFM increased in both groups (P < 0.001). However, gains in leg FFM were higher in WP + HMB vs. WP + PLA (arm FFM: + 6.1% vs. + 9.2%, P = 0.2; leg FFM: + 14.2% vs. + 7.0%, P < 0.01). No change in fat mass was observed (P = 0.59). 1-RM increased in both groups (P < 0.001). CONCLUSIONS Combined protein and HMB supplementation resulted in segmental, but not whole-body increases in FFM compared to protein supplementation alone. These findings could explain some of the controversial effects of HMB reported in previous studies and have practical implications for maximizing training-induced gains in FFM and clinical conditions associated with skeletal muscle deconditioning such as aging, sedentary lifestyles, bed rest and spaceflight.
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Leucine Metabolites Do Not Enhance Training-induced Performance or Muscle Thickness.
Teixeira, FJ, Matias, CN, Monteiro, CP, Valamatos, MJ, Reis, JF, Tavares, F, Batista, A, Domingos, C, Alves, F, Sardinha, LB, et al
Medicine and science in sports and exercise. 2019;(1):56-64
Abstract
UNLABELLED Leucine metabolites, α-hydroxyisocaproic acid (α-HICA) and β-hydroxy-β-methylbutyrate (calcium, HMB-Ca and free acid, HMB-FA), have been proposed to augment resistance training-induced changes in body composition and performance. PURPOSE We aimed to conduct a double-blind randomized controlled pragmatic trial to evaluate the effects of off-the-shelf leucine metabolite supplements of α-HICA, HMB-FA, and HMB-Ca on resistance training-induced changes in muscle thickness and performance. METHODS Forty men were randomly assigned to receive α-HICA (n = 10, fat-free mass [FFM] = 62.0 ± 7.1 kg), HMB-FA (n = 11, FFM = 62.7 ± 10.5 kg), HMB-Ca (n = 9, FFM = 65.6 ± 10.1 kg), or placebo (PLA; n = 10, FFM = 64.2 ± 5.7 kg). The training program consisted of whole body thrice weekly resistance training for 8 wk (seven exercises per session, three to four sets per session, at 70%-80% one repetition maximum). Skeletal muscle thickness by ultrasound, performance measures, and blood measures (creatine kinase, insulin-like growth factor 1, growth hormone, cortisol, and total testosterone) were evaluated at baseline and at the end of weeks 4 and 8. RESULTS Time-dependent changes were observed for muscle thickness (P < 0.001), one repetition maximum bench press and squat (P < 0.001), Wingate peak power (P = 0.02), countermovement jump height (P = 0.03), power (P = 0.006), creatine kinase, insulin-like growth factor-1, growth hormone, and cortisol (all P < 0.001). No significant between-group or time-group interactions were observed. CONCLUSIONS No leucine metabolite resulted in any ergogenic effects on any outcome variable. Supplementation with leucine metabolites-α-HICA, HMB-FA, or HMB-Ca-is not a supplementation strategy that improves muscle growth and strength development in young adult men.