RESUMO
The leucine metabolite, 3-hydroxy-3-methylbutyrate (HMB), primarily utilized as the calcium salt (CaHMB) has become one of the most widely used supplements and food ingredients to promote muscle health. While both CaHMB and HMB free acid have published sub-chronic toxicity studies, and CaHMB has published studies on genotoxicity, data are lacking on the acute dosing of HMB which is important for regulatory and transportation classification as well as in cases of accidental overconsumption. Therefore, an acute oral toxicity study was conducted with CaHMB following OECD 420 guidelines. One rat was used in the dosage sighting study and four rats were used in the main study. In both studies, rats were given a single oral dose of 2000 mg/kg body weight by gavage and monitored for 14 days following the dosage for changes in body weight, clinical signs as noted in OECD 420, and at the end of the study a necropsy was conducted to determine any gross tissue abnormalities. The dosage of CaHMB administered resulted in no deaths, no significant adverse clinical signs, and no findings of lesions or abnormal tissues. Under the Global Harmonized System of classification, CaHMB was found to be in the least toxic Category 5 or non-toxic.
Assuntos
Compostos de Cálcio/toxicidade , Suplementos Nutricionais/toxicidade , Administração Oral , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Feminino , Ratos , Ratos Sprague-Dawley , Solubilidade , Testes de ToxicidadeRESUMO
OBJECTIVE: To determine the effects of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits. METHODS: A total of 21, female rabbits were divided into 3 groups (n=7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs. RESULTS: Injected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p<0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p<0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively. CONCLUSION: While HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.
Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Força Muscular/efeitos dos fármacos , Debilidade Muscular/prevenção & controle , Músculo Esquelético/efeitos dos fármacos , Valeratos/uso terapêutico , Animais , Suplementos Nutricionais , Feminino , Humanos , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Músculo Quadríceps/efeitos dos fármacos , Músculo Quadríceps/patologia , Coelhos , Valeratos/administração & dosagemRESUMO
The primary aim of this study was to determine whether supplementation with calcium ß-hydroxy-ß-methylbutyrate (HMB) and vitamin D3 (D) would enhance muscle function and strength in older adults. Older adults over 60 years of age with insufficient circulating 25-hydroxy-vitamin D (25OH-D) levels were enrolled in a double-blinded controlled 12-month study. Study participants were randomly assigned to treatments consisting of: (a) Control + no exercise, (b) HMB+D + no exercise, (c) Control + exercise, and (d) HMB+D + exercise. The study evaluated 117 participants via multiple measurements over the 12 months that included body composition, strength, functionality, and questionnaires. HMB+D had a significant benefit on lean body mass within the nonexercise group at 6 months (0.44 ± 0.27 kg, HMB+D vs -0.33 ± 0.28 kg, control, p < .05). In nonexercisers, improvement in knee extension peak torque (60°/s) was significantly greater in HMB+D-supplemented participants than in the nonsupplemented group (p = .04) at 3 months, 10.9 ± 5.7 Nm and -5.2 ± 5.9 Nm, respectively. A composite functional index, integrating changes in handgrip, Get Up, and Get Up and Go measurements, was developed. HMB+D + no exercise resulted in significant increases in the functional index compared with those observed in the control + no exercise group at 3 (p = .03), 6 (p = .04), and 12 months (p = .04). Supplementation with HMB+D did not further improve the functional index within the exercising group. This study demonstrated the potential of HMB and vitamin D3 supplementation to enhance muscle strength and physical functionality in older adults, even in individuals not engaged in an exercise training program.
Assuntos
Cálcio/administração & dosagem , Força Muscular/efeitos dos fármacos , Treinamento Resistido , Valeratos/administração & dosagem , Vitamina D/administração & dosagem , Idoso , Composição Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Adenosine-5'-triphosphate (ATP) is the primary source of energy for cells and oral supplementation with ATP offers numerous different health benefits, including the regulation of blood flow and muscle contraction. In this study, ATP, disodium salt, was administered by gavage to rats for 90 consecutive days at doses of 0 (control), 500, 1000, and 2000 mg kg BW-1·d-1 (n = 10 per sex/group). Subchronic administration of ATP was well tolerated at all dose levels. Body weights and feed consumption body weight gains were similar between ATP-treated and control rats. Minor differences were seen in hematology and blood chemistry; however, these changes were not dose related and therefore not of biological or toxicological significance. Only one difference was observed in absolute organ weights, females of the high dose had increased kidney and increased relative kidney and liver weights; however, these differences were not seen in males nor appeared to be dose related. No biological or toxicological significant differences were observed in thyroid function or urine analysis. The incidence of histopathological lesions was low and similar between treated and control groups. Based upon these findings, the no-observed-adverse-effect level (NOAEL) was determined to be ≥ 2000 mg kg BW-1·d-1, which was the highest dose tested.
Assuntos
Trifosfato de Adenosina/toxicidade , Administração Oral , Animais , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , Testes de Toxicidade SubcrônicaRESUMO
BACKGROUND: 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease. METHODS: This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated. RESULTS: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10-3.27 h, and an accumulation ratio of 1.38-1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing. CONCLUSIONS: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement. TRIAL REGISTRATION: Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).
Assuntos
Benzilaminas/farmacocinética , Suplementos Nutricionais , Administração Oral , Adulto , Benzilaminas/efeitos adversos , Benzilaminas/sangue , Benzilaminas/líquido cefalorraquidiano , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: 2-Hydroxybenzylamine (2-HOBA) is a selective scavenger of dicarbonyl electrophiles that protects proteins and lipids from being modified by these electrophiles. It is currently being developed for use as a nutritional supplement to help maintain good health and protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline associated with Mild Cognitive Impairment and Alzheimer's disease. METHODS: In this first-in-human study, the safety, tolerability, and pharmacokinetics of six ascending single oral doses of 2-HOBA acetate were tested in eighteen healthy human volunteers. RESULTS: Reported adverse events were mild and considered unlikely to be related to 2-HOBA. There were no clinically significant changes in vital signs, ECG recordings, or clinical laboratory parameters. 2-HOBA was fairly rapidly absorbed, with a tmax of 1-2 h, and eliminated, with a t1/2 of approximately 2 h. Both tmax and t1/2 were independent of dose level, while Cmax and AUC increased proportionally with dose level. CONCLUSIONS: 2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate for continued development as a nutritional supplement. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03176940).
Assuntos
Acetatos/farmacocinética , Benzilaminas/farmacocinética , Suplementos Nutricionais , Fármacos Neuroprotetores/farmacocinética , Acetatos/sangue , Administração Oral , Adulto , Área Sob a Curva , Benzilaminas/sangue , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Fármacos Neuroprotetores/sangue , Adulto JovemRESUMO
2-hydroxybenzylamine (2-HOBA), a naturally occurring compound found in buckwheat, has potential for use as a nutrition supplement due to its ability to protect against the damaging effects of oxidative stress. In a series of rodent toxicity studies, 2-HOBA acetate was well-tolerated and did not produce any toxic effects over 28 or 90 days of repeated oral administration. However, it remained necessary to test the potential toxicity of 2-HOBA acetate in a non-rodent species. In this investigation, 2-HOBA acetate was orally administered to male and female New Zealand White Rabbits for 90 days at doses of 100, 500, and 1000â¯mg·kg BW-1·day-1 (nâ¯=â¯5 per sex/group). As previously observed in rodents, 2-HOBA acetate administration was well tolerated. No toxic effects of 2-HOBA acetate were detected in body weight, feed consumption, hematology, blood chemistry, urine chemistry, organ weights, gross pathology or histopathology. Based on these findings, the no-observed-adverse-effect-level of 2-HOBA acetate in rabbits was determined to be 1000â¯mg·kg BW-1·day-1, which was the highest dose tested. These results provide further support for the safety of 2-HOBA acetate administration.
Assuntos
Benzilaminas/toxicidade , Administração Oral , Animais , Suplementos Nutricionais , Feminino , Alimento Funcional , Masculino , Nível de Efeito Adverso não Observado , Coelhos , Testes de Toxicidade SubcrônicaRESUMO
2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA.
Assuntos
Benzilaminas/farmacologia , Adulto , Proteínas Sanguíneas , Sistema Enzimático do Citocromo P-450/metabolismo , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Eritrócitos/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of ß-hydroxy-ß-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.
Assuntos
Trifosfato de Adenosina/farmacologia , Composição Corporal/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Valeratos/farmacologia , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Interações Medicamentosas , Teste de Esforço , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Treinamento Resistido , Ultrassonografia , Adulto JovemRESUMO
ß-Hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) µmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.
Assuntos
Cálcio/sangue , Cálcio/farmacocinética , Valeratos/sangue , Valeratos/farmacocinética , Adulto , Disponibilidade Biológica , Cálcio/administração & dosagem , Estudos Cross-Over , Suplementos Nutricionais , Exercício Físico , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Valeratos/administração & dosagem , Adulto JovemRESUMO
Calcium ß-hydroxy-ß-methylbutyrate-monohydrate (CaHMB) is a dietary supplement used as an ergogenic aid and in functional and medical foods. A new delivery form has been developed, ß-hydroxy-ß-methylbutyric free acid (HMBFA), which has improved bioavailability. While the safety of CaHMB is well documented, there are few published studies demonstrating the safety of HMBFA. Because HMBFA results in greater serum levels of ß-hydroxy-ß-methylbutyrate (HMB) and greater clearance rates, a 91-day subchronic toxicity study was conducted in male and female Sprague-Dawley Crl:CD rats assigned to HMBFA treatments at either 0%, 0.8%, 1.6%, or 4% of the diet by weight. No deaths or untoward clinical observations, and no negative clinical chemistry or hematology were attributed to the administration of HMBFA. Gross pathology and histopathology results showed no tissue abnormalities due to HMBFA and all measures were within a normal physiological range for the animals or were expected in the population studied. In conclusion, the no-observed-adverse-event-level (NOAEL) for HMBFA was the highest level administered, 4% of the diet, which corresponded to an intake of 2.48 and 2.83 g/kg BW d(-1) in the males and females, respectively. The equivalent human dosage using body surface area conversion would be 402 and 459 mg/kg BW d(-1) for men and women, respectively.
Assuntos
Valeratos/toxicidade , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade SubcrônicaRESUMO
INTRODUCTION: Studies utilizing beta-hydroxy-beta-methylbutyrate (HMB) supplementation in trained populations are limited. No long-term studies utilizing HMB free acid (HMB-FA) have been conducted. Therefore, we investigated the effects of 12 weeks of HMB-FA supplementation on skeletal muscle hypertrophy, body composition, strength, and power in trained individuals. We also determined the effects of HMB-FA on muscle damage and performance during an overreaching cycle. METHODS: A three-phase double-blind, placebo- and diet-controlled randomized intervention study was conducted. Phase 1 was an 8-week-periodized resistance-training program; Phase 2 was a 2-week overreaching cycle; and Phase 3 was a 2-week taper. Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of HMB-FA; and assessment of these, as well as cortisol, testosterone, and creatine kinase (CK) was performed at weeks 9 and 10 of the overreaching cycle. RESULTS: HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1 ± 18.4 vs. 25.3 ± 22.0 kg, p < 0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W, p < 0.001); and increased lean body mass gain (7.4 ± 4.2 vs. 2.1 ± 6.1 kg, p < 0.001) in HMB-FA- and placebo-supplemented groups, respectively. During the overreaching cycle, HMB-FA attenuated increases in CK (-6 ± 91 vs. 277 ± 229 IU/l, p < 0.001) and cortisol (-0.2 ± 2.9 vs. 4.5 ± 1.7 µg/dl, p < 0.003) in the HMB-FA- and placebo-supplemented groups, respectively. CONCLUSIONS: These results suggest that HMB-FA enhances hypertrophy, strength, and power following chronic resistance training, and prevents decrements in performance following the overreaching.
Assuntos
Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Treinamento Resistido , Valeratos/farmacologia , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiologia , Valeratos/administração & dosagem , Adulto JovemRESUMO
The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of b-hydroxyb-methylbutyrate (HMB-FA) on indices of muscle damage, protein breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P»0·004, d » 1·6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9·1 (SEM 0·4) to 4·6 (SEM 0·5)) than in the HMB-FA group (9·1 (SEM 0·3) to 6·3 (SEM 0·3)) (P»0·005, d » 20·48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P»0·08, d » 0·12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session.
Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Proteínas Musculares/urina , Doenças Musculares/tratamento farmacológico , Treinamento Resistido , Valeratos/uso terapêutico , Levantamento de Peso/fisiologia , Adulto , Biomarcadores/metabolismo , Creatina Quinase/sangue , Humanos , Masculino , Doenças Musculares/etiologia , Doenças Musculares/metabolismo , Percepção , Descanso , Valeratos/farmacologia , Adulto JovemRESUMO
BACKGROUND: Older adults supplemented for 1 year with ß-hydroxy-ß-methylbutyrate, arginine, and lysine (HMB/ARG/LYS) were previously shown to have significant gains in fat-free mass (FFM) but not muscular strength. OBJECTIVE: Recently, increasing levels of serum vitamin D have been associated with an increase in muscle function, particularly in the elderly. To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS, the authors performed post hoc analysis of strength based on the participants' vitamin D status. METHODS: Elderly (age 76.0 ± 1.6 years) adults were recruited for a double-blinded, controlled study and were randomly assigned to either an isonitrogenous control (n = 37) or HMB/ARG/LYS (n = 40) for the yearlong study. Participants were further segregated based on their vitamin D status of either <30 or ≥30 ng 25OH-vitD(3)/mL serum, and an analysis was performed on the 4 cohorts. RESULTS: Regardless of vitamin D status, HMB/ARG/LYS resulted in significantly increased FFM (P < .02), but only in those with vitamin D status ≥30 ng 25OH-vitD(3)/mL was there a significant increase in strength with HMB/ARG/LYS (P < .01). Control-supplemented participants, regardless of vitamin D status, and the HMB/ARG/LYS-supplemented participants with vitamin D status <30 ng 25OH-vitD(3) failed to show improvements in strength. CONCLUSIONS: The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status, but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and vitamin D.
Assuntos
Aminoácidos/farmacologia , Butiratos/farmacologia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Aptidão Física/fisiologia , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Idoso , Arginina/farmacologia , Compartimentos de Líquidos Corporais/efeitos dos fármacos , Estudos de Coortes , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lisina/farmacologia , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
The leucine metabolite, ß-hydroxy-ß-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) µmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.