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β-Hydroxy-β-Methylbutyrate (HMB) Supplementation Does Not Affect Changes in Strength or Body Composition during Resistance Training in Trained Men

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This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on training responses in resistance-trained male athletes who were randomly administered HMB in standard encapsulation (SH), HMB in time release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects ingested 3 g x day(-1) of HMB or placebo for 6 weeks. Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation. The testing battery assessed body mass, body composition (using dual energy x-ray absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical parameters, including markers of muscle damage and muscle protein turnover. While the training and dietary intervention of the investigation resulted in significant strength gains (p < .001) and an increase in total lean mass (p = .01), HMB administration had no influence on these variables. Likewise, biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation. The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes.
... The quality of the studies is presented in Table 2. Briefly, random sequencing generation was unclear in 3 studies (Crowe et al., 2003;Hoffman et al., 2004). Participants and outcome blinding and incomplete outcome data were high and unclear risk of bias in only two studies, respectively (Crowe et al., 2003;Slater et al., 2001). ...
... And then ranked as low risk of bias for 5 studies (Asadi et al., 2017;Durkalec-Michalski & Jeszka, 2015;Durkalec-Michalski et al., 2017;Hoffman et al., 2004;Portal et al., 2011), medium risk of bias for 1 study (Slater et al., 2001), and high risk of bias for 1 study (Crowe et al., 2003). Most of studies had a low risk of bias for selective reporting and other sources of bias except for one study (Crowe et al., 2003). ...
... Two studies were conducted in Poland (Durkalec-Michalski & Jeszka, 2015; Durkalec-Michalski et al., 2017), 1 in the United States (Hoffman et al., 2004), 1 in Iran (Asadi et al., 2017), 2 in Australia (Crowe et al., 2003; Slater et al., 2001), and 1 in Israel (Portal et al., 2011). The effect of exercise on testosterone and cortisol concentration was examined in 7 studies (Asadi et al., 2017; Crowe et al., 2003; Durkalec-Michalski & Jeszka, 2015; Durkalec-Michalski et al., 2017; HoffmanPortal et al., 2011;Slater et al., 2001); and 8 effect sizes were extracted from these studies for testosterone and cortisol concentration. The total number of subjects who completed the studies with inclusion criteria was 121 in the intervention and 107 in the placebo groups. ...
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Background: β-hydroxy β-methylbutryate (HMB) is a metabolite of leucine amino acid and it has several ergogenic benefits. Previous studies also showed that it may affect beneficially the testosterone and cortisol concentration in athletes. Due to the contradiction results between studies, we aimed to conduct this meta-analysis to assess the HMB supplementation effect on testosterone and cortisol in trained athletes. Methods: Scopus, Medline, and Google scholar were systematically searched up to August 2021. The Cochrane Collaboration tool for evaluating the risk of bias was applied for assessing the studies' quality. Random-effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used for estimating the overall effect. Between-study heterogeneity was evaluated applying the chi-squared and I2 statistic. Results: Seven articles were included in the meta-analysis. Although the meta-analysis generally showed that HMB consumption did not have any effect on the cortisol and testosterone concentration (p > .05), subgroup analysis based on the exercise type showed a significant decrease in the cortisol concentration in resistance training exercises (WMD = -3.30; 95% CI: -5.50, -1.10; p = .003) and a significant increase in the testosterone concentration in aerobic and anaerobic combined sports (WMD = 1.56; 95% CI: 0.07, 3.05; p = .040). Conclusion: The results indicate that HMB supplementation in athletes can reduce the concentration of cortisol in resistance exercises and increase the concentration of testosterone in aerobic and anaerobic combined exercises. Nevertheless, more studies are required to confirm these results.
... Two studies were conducted in Poland (19,29), 1 in the United States (30), 1 in Iran (31), 2 in Australia (20, 32) and 1 in Israel (7). The effect of exercise on testosterone and cortisol concentration was examined in 7 studies (7,19,20,(29)(30)(31)(32); and 8 effect sizes were extracted from these studies for testosterone and cortisol concentration. The total number of subjects who completed the studies in inclusion criteria was 121 subjects in the intervention and 107 in the placebo groups. ...
... Briefly, random sequencing generation was unclear in 3 studies (20,30). Participants and outcome blinding and incomplete outcome data were high and unclear risk of bias in only two studies, respectively (20,32). And then ranked as low risk of bias for 5 studies (7,19,(29)(30)(31), medium risk of bias for 1 study (32), and high risk of bias for 1 study (20). ...
... Participants and outcome blinding and incomplete outcome data were high and unclear risk of bias in only two studies, respectively (20,32). And then ranked as low risk of bias for 5 studies (7,19,(29)(30)(31), medium risk of bias for 1 study (32), and high risk of bias for 1 study (20). Most of studies had a low risk of bias for selective reporting and other sources of bias except for one study (20) Table 3 and the forest plot is shown inFigure 2 . ...
... β-hydroxy-β-methylbutyrate (HMB) is a metabolite derived from the essential amino acid leucine [1]. Some research suggests that HMB is an anabolic compound that increases resistance exercise training-(RET)-induced gains in fat-free mass (FFM) [2][3][4][5][6][7][8][9]. Also, many studies have been conducted to examine the impact of HMB on body fat loss and muscle strength and performance-related outcomes [7,[10][11][12]. ...
... Two additional studies were excluded (Table S2) after visual funnel plots symmetry analysis ( Figure S1A) [35,36]. No asymmetry was detected when considering the remaining studies [2,[4][5][6][8][9][10]12,[37][38][39] (Figure S1B). One study received high risk of bias classification in three domains (selection bias, performance bias and other bias) [2]. ...
... One study received high risk of bias classification in three domains (selection bias, performance bias and other bias) [2]. Seven studies received an unclear risk classification for detection bias (blinding of the outcome assessment), due to lack of detailed description in the respective papers ( Figure S2A and S2B) [2,[4][5][6]10]. ...
... 17,27 Participants and outcome blinding and incomplete outcome data were high and unclear risk of bias in only two studies, respectively. 17,29 And then ranked as low risk of bias for 5 studies, 7, 25-28 medium risk of bias for 1 study, 29 and high risk of bias for 1 study. 17 Most of studies had a low risk of bias for selective reporting and other sources of bias except for one study. ...
... 17,27 Participants and outcome blinding and incomplete outcome data were high and unclear risk of bias in only two studies, respectively. 17,29 And then ranked as low risk of bias for 5 studies, 7, 25-28 medium risk of bias for 1 study, 29 and high risk of bias for 1 study. 17 Most of studies had a low risk of bias for selective reporting and other sources of bias except for one study. ...
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Introduction The β-hydroxy β-methyl butyrate (HMB) is an amino acid leucine metabolite with several ergogenic benefits. It is known that it can benefit testosterone and cortisol concentration in athletes. However, no systematic review and meta-analysis has focused on the effects of HMB supplementation on testosterone and cortisol in trained athletes. Objectives The meta-analysis evaluates the effect of HMB supplementation on testosterone and cortisol in trained athletes and verifies conflicting results between studies. Methods A systemic review was performed in Scopus, Medline, and Google scholar databases of articles published until August 2021. The Cochrane Collaboration tool was used to assess the risk of bias and assess the quality of the studies. Random effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used to estimate the overall effect. Results Although the meta-analysis showed that HMB consumption does not alter cortisol and testosterone concentration, subgroup analysis based on exercise type exhibited a significant decrease in cortisol concentration in resistance training exercises (P<0.05) and a significant increase in testosterone concentration in combined aerobic and anaerobic sports (P<0.05). Conclusion The results indicate that HMB supplementation in athletes can reduce cortisol concentration in endurance exercise and increase testosterone concentration in combined aerobic and anaerobic exercise. Evidence Level II; Therapeutic Studies – Investigating the results. Keywords: Hypertrophy; Dietary supplements; Testosterone; Hydrocortisone; Meta-Analysis
... Thus, practitioners, coaches, and trainers commonly recommend concurrent training for individuals aiming to gain muscle and lose fat (24). Most importantly, despite the zeitgeist that well-trained individuals cannot gain muscle mass and lose fat simultaneously, there have been many chronic randomized controlled trials conducted in resistance-trained individuals that have demonstrated body recomposition (3,13,16,21,36,52,62,72). ...
... Several studies among trained individuals have reported body recomposition where nutritional intake was not reported or was similar between the interventions (1,36,52,62,72,75). For example, Alcaraz et al. (1) recruited participants who were able to produce a force equal to twice their body mass during an isometric squat at the beginning of the intervention. ...
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Despite the lack of standardized terminology, building muscle and losing fat concomitantly has been referred to as body recomposition by practitioners. Although many suggest that this only occurs in untrained/novice and overweight/obese populations, there is a substantial amount of literature demonstrating this body recomposition phenomenon in resistance-trained individuals. Moreover, 2 key factors influencing these adaptations are progressive resistance training coupled with evidence-based nutritional strategies. This review examines some of the current literature demonstrating body recomposition in various trained populations, the aforementioned key factors, nontraining/nutrition variables (i.e., sleep, hormones), and potential limitations due to body composition assessments. In addition, this review points out the areas where more research is warranted.
... There is considerable evidence to indicate that HMB stimulates non-speci c immune mechanisms, including phagocytosis, in many animal species: pigs [35], chicken [31,36], geese [32] and sh [34,37,38] however, these effects have been rarely investigated in calves [28]. HMB is a strong anticatabolic agent and a regulator of protein metabolism, and it is widely used in sports and bodybuilding to increase strength, muscle mass and exercise performance [39,40,41,42,43]. Immune health is also highly correlated with protein synthesis because mounting immune responses require the generation of new cells and the synthesis of antigen-presenting machinery, immunoglobulins, cytokines, cytokine receptors and acute phase proteins. ...
... Similar results were reported by Siwicki et al. [38], where a spectrophotometric analysis in the respiratory burst activity test revealed that the production of highly reactive oxygen species by head kidney phagocytes doubled in rainbow trout whose diets were supplemented with HMB for 8 weeks. In a study of rainbow trout (Oncorhynchus mykiss) and carp (Cyprinus carpio) [40], the addition of > 50 mg/ml HMB to the culture medium increased respiratory burst activity by up to 84% (p < 0.01) in pronephric phagocytes grown in a culture medium (RPMI-1640) containing 0, 0.1, 1, 5, 10, 25, 50 or 100 mg HMB/mL relative to the cells cultured without HMB. In an in vitro study, Peterson et al. [36] evaluated macrophages that were isolated from a chicken macrophage cell line (MQ-NCSU) and cultured in the presence of 20, 40 and 80 μg of HMB. ...
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Background A healthy immune system plays a particularly important role in newborns, including in calves that are far more susceptible to infections (viral, bacterial and other) than adult individuals. Therefore, the present study aimed to evaluate the influence of HMB on the chemotactic activity (MIGRATEST® kit), phagocytic activity (PHAGOTEST® kit) and oxidative burst (BURSTTEST® kit) of monocytes and granulocytes in the peripheral blood of calves by flow cytometry. Results An analysis of granulocyte and monocyte chemotactic activity and phagocytic activity revealed significantly higher levels of phagocytic activity in calves administered HMB than in the control group, expressed in terms of the percentage of phagocytising cells and mean fluorescence intensity (MFI). HMB also had a positive effect on the oxidative metabolism of monocytes and granulocytes stimulated with PMA (4-phorbol-12-β-myristate-13-acetate) and Escherichia coli bacteria, expressed as MFI values and the percentage of oxidative metabolism. Conclusion HMB stimulates non-specific cell-mediated immunity, which is a very important consideration in newborn calves that are exposed to adverse environmental factors in the first weeks of their life. The supplementation of animal diets with HMB for both preventive and therapeutic purposes can also reduce the use of antibiotics in animal production.
... Introduction athletes, do not support these results and may reflect differences in dose and duration of HMB supplementation or total protein intake [49][50][51]. ...
... . However, the effects of HMB supplementation in athletes are less clear. Most studies conducted on trained subjects have reported non-significant gains in muscle mass possibly due to a greater variability in response of HMB supplementation among athletes[77][78][79] . Consequently, there is fairly good evidence showing that HMB may enhance training adaptations in individuals initiating training. ...
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β-Hydroxy β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, is one of the latest dietary supplements promoted to enhance gains in strength and lean body mass associated with resistance training. Unlike anabolic hormones that induce muscle hypertrophy by increasing muscle protein synthesis, HMB is claimed to influence strength and lean body mass by acting as an anticatabolic agent, minimising protein breakdown and damage to cells that may occur with intense exercise. Research on HMB has recently tested this hypothesis, under the assumption that it may be the active compound associated with the anticatabolic effects of leucine and its metabolites. While much of the available literature is preliminary in nature and not without methodological concern, there is support for the claims made regarding HMB supplementation, at least in young, previously untrained individuals. A mechanism by which this may occur is unknown, but research undertaken to date suggests there may be a reduction in skeletal muscle damage, although this has not been assessed directly. The response of resistance trained and older individuals to HMB administration is less clear. While the results of research conducted to date appear encouraging, caution must be taken when interpreting outcomes as most manuscripts are presented in abstract form only, not having to withstand the rigors of peer review. Of the literature reviewed relating to HMB administration during resistance training, only 2 papers are full manuscripts appearing in peer reviewed journals. The remaining 8 papers are published as abstracts only, making it difficult to critically review the research. There is clearly a need for more tightly controlled, longer duration studies to verify if HMB enhances strength and muscular hypertrophy development associated with resistance training across a range of groups, including resistance trained individuals.
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This review develops the hypothesis that a metabolite of leucine termed β-hydroxy β-methylbutyrate (HMB) plays a key role in animal metabolism and that in certain circumstances insufficient amounts of HMB are either consumed in the diet or produced endogenously to supply tissue needs. The origin and metabolism of HMB is reviewed including the role of HMB in cholesterol biosynthesis. HMB feeding studies in animals are reviewed, which indicate that dietary supplementation of HMB can improve immune function and health and can increase the fat content of milk in lactating animals. Seven human studies are reviewed where HMB was fed. The results of both animal and human studies indicate that dietary supplementation of HMB is safe, as evidenced by lack of physical adverse effects and a lack of effect on blood hematology and chemistry. The only consistent change in blood chemistry was a decrease in LDL cholesterol, which changed 7% (P < .01). In humans undergoing resistance training, HMB supplementation increased lean mass gains from 50 to 200%, with similar percentage increases in strength when compared with unsupplemented subjects. The effects of HMB on muscle size and function seems to result from a diminution of exercise-related muscle damage and muscle protein breakdown. A general hypothesis is proposed that HMB is metabolized to HMG-CoA in tissues such as muscle, mammary tissue, and certain immune cells and is used for de novo cholesterol synthesis. In times of stimulated growth and/or differentiation. HMG-CoA may be rate-limiting for cholesterol synthesis, which could limit cell growth or function. It is proposed that feeding HMB can provide a saturating source of cytosolic HMG-CoA for cholesterol synthesis and in turn allow for maximal cell growth and function.
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The effects of supplementation of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) were examined in a resistance training study. Thirty-nine men and 36 women between the ages of 20–40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174.4 ± 26.8 to 173.5 ± 17.0 U/L; P:155.0 ± 20.8 to 195.2 ± 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 ± 0.6 kg; P:5.2 ± 0.6 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 ± 0.2 kg and decreased percent fat by 1.1% ± 0.2% while the placebo groups increased fat-free weight by 0.9 ± 0.2 kg and decreased percent fat by 0.5% ± 0.2% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program.
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A simple and rapid method for measuring 3-methylhistidine (3MH) in plasma and urine is described. Internal standard, 1-methylhistidine (1MH), was added to plasma, acidified and absorbed onto cation-exchange columns. It was then eluted from columns, dried, and derivatized for gas chromatography/mass spectrometry. A major fragment of 3MH was monitored at 238 u and 3-methyl-(methyl-2H3)histidine (d3-3MH) (used for in vivo kinetics) at 241 u, whereas 1MH was monitored at 340 u and eluted 0.5 min later than 3MH. Standard curves for plasma analysis were linear and nanamole amounts of 3MH in plasma were determined with a precision of 3.5%. 3MH was also quantitated in urine; however, because of substantial amounts of 1MH, (18O2)1MH was used as the internal standard. Nanamole amounts of 3MH were determined in urine with a precision of 2.7%. Application of the 3MH analytical method was used to develop a kinetic compartmental model by using the stable isotope of 3MH, d3-3MH. Cattle, like humans, quantitatively excrete 3MH in the urine. A young bovine was injected with d3-3MH and the enrichment curve in plasma was evaluated in order to obtain a steady-state production rate of 3MH. The decay curve was modeled through the use of NIH-SAAM modeling program. The kinetics of d3-3MH from plasma were adequately described by a three-pool compartmental model. The de novo production rate of 3MH estimated in the calf was 665 mumol per day. This corresponded to an estimated fractional turnover rate of 1.56% per day, which was similar to estimates obtained from urine collections.(ABSTRACT TRUNCATED AT 250 WORDS)
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A method for measuring the branched chain hydroxy acid beta-hydroxy-beta-methyl butyrate (HMB, a product of leucine catabolism) has been described. A [2H6]HMB internal standard was added to plasma and standards, and samples were extracted with diethyl ether, backextracted into neutral phosphate, dried, and derivatized for gas chromatography and mass spectrometry. The natural HMB was monitored at 175 amu and the deuterated HMB was monitored at 181 amu. Standard curves were linear to at least 25 microns and were quantitatively recovered from plasma. Basal concentrations of plasma HMB were from 1 to 2 microM in sheep and increased three- to fourfold when leucine's alpha-ketoacid (alpha-ketoisocaproate, KIC) was fed to lambs. This method can also be adapted to quantitate KIC and other branched chain ketoacids in plasma during the same run.
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