Nutrición Hospitalaria ISSN: 0212-1611 info@nutrició Grupo Aula Médica España

Albert, Francisco J.; Morente-Sánchez, Jaime; Ortega, Francisco B.; Castillo, Manuel J.; Gutiérrez, Ángel Usefulness of -hydroxy--methylbutyrate (HMB) supplementation in different sports: an update and practical implications Nutrición Hospitalaria, vol. 32, núm. 1, 2015, pp. 20-33 Grupo Aula Médica Madrid, España

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Revisión Usefulness of β-hydroxy-β-methylbutyrate (HMB) supplementation in different sports: an update and practical implications Francisco J. Albert1, Jaime Morente-Sánchez2, Francisco B. Ortega2, Manuel J. Castillo1 and Ángel Gutiérrez1 1Department of Medical Physiology, Faculty of Medicine, University of Granada. 2Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Spain.

Abstract EFICACIA DE LA SUPLEMENTACIÓN CON β-HYDROXY-β-METHYLBUTYRATE (HMB) β β Introduction: although -hydroxy- -methylbutyrate EN EL DEPORTE: ACTUALIZACIÓN E (HMB) is generally marketed as a supplement for increa- IMPLICACIÓN PRÁCTICA sing muscle mass and strength, it is still not fully unders- tood how and in which particular sports and conditions HMB can be more effective. Resumen Aims: the primary purpose of this review is to update Introducción: aunque el β-hidroxi-β-metilbutirato and summarize the current knowledge about the useful- (HMB) se ha empleado generalmente como suplemento ness of HMB and to organize this information by diffe- para aumentar la masa muscular y la fuerza, es necesario rent sports with specific reference to sports with high un mejor entendimiento de su función y averiguar en qué wear and tear phenomena as soccer, rugby or football. deportes es más efectivo. Methods: a search was performed in PubMed databa- Objetivos: el objetivo principal de esta revisión es ac- se. This review presents the results about HMB use in tualizar y resumir el conocimiento existente en torno a la sport. utilización del HMB para clasificarla en función de cada Results: the articles identified in this review support modalidad deportiva, con especial mención a aquellas the notion that HMB could help to attenuate tissue cata- actividades con un alto grado de destrucción muscular, bolism and initiate muscle particularly in un- como pueden ser el fútbol, el rugby o el fútbol americano. trained individuals exposed to strenuous exercise or when Métodos: se utilizó la de datos PubMed para la trained individual are exposed to periods of high physical búsqueda de artículos. Esta revisión presenta los resul- stress. HMB could therefore be applied in some specific tados sobre la utilización de HMB clasificados por de- periods of athlete’s season where there are high-intensity portes. training periods, high density of competitions and little Resultados: la mayoría de los artículos seleccionados recovery time between them, starting recovery phases sugieren que cuando una persona entrenada o no entre- from an injury period and/or any other different situa- nada se somete a un ejercicio intenso o diferente al ha- tion where performance or recovery could be affected by bitual, el HMB puede atenuar el catabolismo muscular a great catabolic environment. producido e iniciar los procesos anabólicos necesarios Conclusion: this update contributes to clarify and de- para recuperar lo antes posible. De esta forma, el HMB fine possible mechanisms and/or effectiveness of HMB podría aplicarse en algunos momentos concretos de la supplementation related to endurance sports (i.e. cycling temporada deportiva en los que hubiera períodos con and athletics), strength-power sports (i.e. resistance trai- entrenamientos de alta intensidad, o durante un periodo ning, football, rugby, soccer, judo, waterpolo and rowing) con alta densidad competitiva y con poca recuperación and recreational activities. entre competiciones, o bien durante las primeras fases (Nutr Hosp. 2015;32:20-33) de la readaptación física después de una lesión y/o du- rante cualquier otra situación en la que el rendimiento o DOI:10.3305/nh.2015.32.1.9101 la recuperación se pueden ver afectados por un entorno Key words: HMB. Recovery. DOMS. Signalling-molecu- altamente catabólico. le. mTOR. Conclusión: esta revisión pretende aclarar y definir los posibles mecanismos por los que la suplementación con HMB puede ser efectiva en deportes de resistencia (ciclismo y carreras de fondo), en deportes de fuerza-po- tencia (fútbol, yudo, waterpolo, remo, fútbol americano y Correspondence: Francisco J. Albert García. musculación) y en actividades deportivas recreacionales. Department of Physiology. Faculty of Medicine. (Nutr Hosp. 2015;32:20-33) University of Granada. Av. de Madrid s/n. 18012 Granada, Spain. DOI:10.3305/nh.2015.32.1.9101 E-mail: [email protected] Palabras clave: HMB. Recuperación. DOMS. Molécula de Recibido: 10-IV-2015. señalización. mTOR. Aceptado: 24-IV-2015.


005_9101 Eficacia de la suplementacion.indd 20 16/06/15 19:47 Abbreviations and supply of adequate . Essential nutrients are particularly important. The branched chain amino 3-MH: 3-methylhistidine. acids (BCAAs) , and have AMPK: monophosphate . been widely studied in this context1. Leucine has BCAAs: Branched chain amino acids. important roles in protein metabolism2-4, ho- Ca-HMB: β-hydroxy-β-methylbutyrate . meostasis5, insulin action6. Leucine has anti-catabolic CD: Cool Down. properties7 and facilitates recovery from exercise8,9. CK: Kinase. In 1996, it was suggested that a plausible candidate Cr: Creatine. responsible for these effects could be its intracellular CHO: . derived metabolite β-hydroxy-β-methylbutyrate wi- CRP: C-reactive protein. dely known as HMB10, which is endogenously produ- CWI: Cold Immersion. ced in animals and humans11. The first step in HMB DOMS: Delayed onset muscle soreness. production is the reversible of leucine F: Female. to α-ketoisocaproate (KIC) by the branched FM: Mass. chain transferase12. Then, KIC is either FML: Fat Mass Lost. metabolized into isovaleryl-CoA in the mitochondria, FFM: Fat Free Mass. by the enzyme α-ketoacid dehydrogenase, or into GH: . HMB in the cytosol, by the enzyme alpha-ketoisoca- H: Hamstring. proate dioxygenase12. KIC is mainly metabolized into HMB: β-hydroxy-β-methylbutyrate. isovaleryl-CoA, with only some 5% of leucine being HMB-FA: β-hydroxy-β-methylbutyrate-Free Acid. converted into HMB. Isovaleryl-CoA is further me- HMG-CoA: β-hydroxy-methylglutaryl-CoA. tabolized to beta-methyl crotonyl-CoA and then to IGF-1: Insulin-like growth factor. beta-methyl gluconyl-CoA and β-hydroxy-methylglu- KIC: Ketoisocaproic Acid. taryl-CoA (HMG-CoA). Similarly, HMB can also be LBM: Lean Body Mass. converted to beta-hydroxy-methylbutyrate-CoA and LDH: . then to HMG-CoA. HMG-CoA is a precursor in cho- M: Male. lesterol synthesis or alternatively can be degraded to MAPK/ERK: Mitogen activated / ex- Acetoacetyl-CoA, acetyl CoA and acetoacetate, a ke- tracellular signal regulated kinase. tone body. MAS: Running speed during an incremental test at Consequently, as precursor of it may which VO2max. is attained. have structural functions by its incorporation to cell MCV: Maximal Voluntary Contraction. membranes and through acetyl CoA or ketone body N: No. may serve as an energy . NE: No Effect. Empirically, HMB has been classically proposed NR: Not Reported. and is widely used as a nutritional supplement to limit Q: Quadriceps. muscle damage during exercise and to increase mus- OBLA: Onset of Lactate Accumulation. cle gain after strenuous exercise or hard training. The PI3K/Akt: Phosphoinositide 3-kinase / Protein ki- effectiveness of HMB supplementation needs further nase B. clarification into how to optimize its administration PRS: Perceived Recovery Scale. (dosage and timing) and better specify in which parti- RCP: Respiratory Compensation Point. cular conditions its use is recommended and effective. Sirt1: Silent information regulation transcripts. A dose of 3g/day of HMB produces better results on Tac: Tactical exercises. performance markers and has potential health benefits. Tec: Technical exercises. Since HMB is a metabolite of leucine, the question is TNFa: Tumor Necrosis Factor Alpha. why not simply taking , BCAA or leucine ins- TNFR1: Tumor Necrosis Factor 1. tead of its metabolite. To put this into perspective, a V: Velocity. subject would need to consume over 600 g of high qua-

VO2peak: Peak oxygen consumption. lity protein to obtain the amount of leucine (60 grams) VT: Ventilatory Threshold. necessary to produce the typical 3 g daily dosage of WU: Warm-Up. HMB used in human studies13. Since consumption of Y: Yes. this amount of protein is not realistic and perhaps not even healthy either, HMB is typically administered via dietary supplementation14. Introduction In athletic context, a number of studies during the last 15 years have indicated that HMB supplementa- Limiting the wear and tear process while exercising tion may elicit several ergogenic benefits, including and adequate recovery afterwards is fundamental for better recovery15,16, increased strength17-19, increased preserving athletes’ health and their optimal perfor- lean body mass (LBM)20, decreased body fat3, increa- mance. The two key components of recovery are rest sed power21,22 and improvements in aerobic23,24 and

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 21 (HMB) supplementation in different sports: an update and practical implications

005_9101 Eficacia de la suplementacion.indd 21 16/06/15 19:47 anaerobic25 performance. Moreover, HMB supplemen- mage, restoration of muscle functionality, attenuation tation has been used as a potential strategy in the treat- of the loss in lean mass and shrinkage recovery of the ment of patients with muscular atrophy, cachexia26,27 fiber. The third mechanism of action is related to the and sarcopenia28,29. While the above mentioned stu- protective effect of HMB against contractile activi- dies supported the efficacy of HMB, other studies do ty-induced damage that is associated with increased not30,31. Part of these discrepancies can be explained by stability of muscle plasma membrane39. This effect differences in the length of the study, type of training is the result of several biochemical chain reactions and differences in the participants’ previous level of in which β-hydroxy-β-methylglutaryl-CoA (HMG- training13. CoA) is synthased in mitochondria and HMG-CoA In the present review we focus on the usefulness of reductase is inhibited, playing an important role in HMB in athletic population and special care is taken increasing metabolic efficiency, stimulating to assess various influencing variables including exer- in and increasing oxidation cise modality and type of sport, training loads, trai- capacity of skeletal muscle40. The fourth proposed ning experience, age, and several dependent measures mechanism is, on one side, the increased expression such as markers of muscle damage, strength, and de- of insulin-like growth factor 1 (IGF-1) and growth layed onset muscle soreness (DOMS) in an attempt to hormone (GH) that could stimulate the mTOR signa- explain possible reasons for the reported conflicting lling pathway17,41,42. On the other hand, the increased results. proliferation, differentiation and fusion of satellite Taking into account the studies mentioned above, a muscle cells to possibly enhance mitochondrial bio- primary aim of this review is to update and summarize genesis and fat oxidation. This effect could allow to the current knowledge on the use of HMB and to or- increase metabolic efficiency43 through improving ganize this information by different sports. The output kinase as sensor of energy of this review will then have practical implications balance44, Sirt1 (Silent information regulator trans- for sport coaches, nutritionists and/or physicians who cripts) and Sirt3 activity45 in 3T3- adipocytes and want to know the current evidence about the efficacy cells46. Summarizing, all these pro- of HMB in their specific sport discipline. teins could act improving mitochondrial biogenesis, energy and the reactive oxygen defen- se system44,45. Exactly how HMB induces changes Previous reviews on this topic and what this in Sirt proteins, adenosine monophosphate kinase review adds (AMPK), and mitochondria remains unclear. Howe- ver, these results could have implications for obesity, Existing scientific literature explains the sug- insulin resistance, and , as well as for athletic gested mechanisms of action of HMB. Based on performance. the studies that assessed the mechanisms of action When comparing studies, special care should be of HMB32,33,12,34-36, it is postulated that such supple- taken in relation to critical details of each study such as mentation could involve the following mechanisms: training status, exercise variability, dose, duration of 1) increased protein synthesis via mTOR pathway; the intervention, magnitude and nature of the effects, 2) inhibition of protein degradation via and/or training stimulus. This will help to and decreasing cell apoptosis, leading to a prolon- explain possible reasons for conflicting results and de- ged cell survival; 3) enhancement of sarcolemma velop well defined training conditions that would help integrity via higher availability of cytosolic choles- to establish a correct meta-analytical model13,18. terol; 4) increased proliferation, differentiation and The present review has summarized the existing fusion of satellite muscle cells via the mitogen ac- information to this date (April 2015) and classified it tivated protein kinase/extracellular signal regulated into 3 tables (tables I to III), grouping different sport kinase (MAPK/ERK) and phosphoinositide 3-kinase/ disciplines with specific physiological demands. This - protein kinase (PI3K/Akt) pathways approach will contribute to clarify and define possi- and enhanced IGF-1 ; and, 5) modula- ble mechanisms, interactions and/or effectiveness of tion of the autophagic-lysosomal system. The first HMB supplementation (see figure 1 for a summary mechanism underlying the effects of HMB supple- of the proposed mechanisms) in combination with mentation is the stimulation of the mTOR signalling aerobic, anaerobic, strength and power activities that pathway that enhance the biochemical mechanisms characterize each sport in order to provide a more necessary for protein synthesis, leading to increases practical guide for coaches, nutritionists and/or sport in strength and fat free mass37. Synergy generated physicians. by second and fifth mechanisms implies inhibition We hypothesize that HMB could act as signalling of the -proteasome system that is involved molecule indicating the need of ending catabolic reac- in skeletal muscle atrophy12,38 and modulation of the tions and subsequent activation of anabolic reactions. autophagic-lysosomal system36, respectively. These It is known that an increase in some specific catabolic actions could explain the positive effects of HMB conditions16,28,47,48 may promote HMB positive effects sup plementation in the rate of repair of muscle da- on recovery and/or performance22,49.

22 Nutr Hosp. 2015;32(1):20-33 Francisco J. Albert García et al.

005_9101 Eficacia de la suplementacion.indd 22 16/06/15 19:47 Fig. 1.—Hypothesized meta- bolism for β-hydroxy-β-me- thylbutyrate (HMB) with spe- cial focus on sports. “+”: promotion; “-“: inhibi- tion. Modified from Hawley et al.87

Practical implications and use of HMB in specific sports

The scientific literature on the effects of HMB on different physiological components evidences that it is population specific and that it depends on the subjects’ physical training status, age, and health status (see fi- gure 2 for a summary of HMB reviews in athletic con- text). The data show that HMB supplementation could assist in increasing strength and decreasing body fat in untrained healthy individuals50 as well as in elderly individuals24,51,52. Several studies have failed to find statistically sig- nificant changes in strength and body composition among those subjects who were already on a physical training regimen13,19,52. The lack of significant changes in such articles has been related to the lack of adequa- te exercise stimulus14. When high exercise intensity (>80% 1 repetition maximum [1RM]) or progressive loading periodization programs are used in trained in- dividuals, HMB supplementation has shown similar results to untrained or recreational populations14,53. This information is presented in table I. Furthermore, new evidence has shown that HMB supplementation could increase strength, hypertrophy, and power af- ter a 12-week periodized program53. Therefore, HMB seems to be more effective during periods of enhanced proteolysis14. Consequently, HMB, at the recommended dose, appears to interact with the training protocol utilized as well as with the experience of the athlete. It is likely that HMB will work ideally if consumed at a dosage Fig. 2.—Reviews on HMB supplementation in physiology bio- of 3g/day for 2 weeks prior a high intensity bout of markers and sport performance.

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 23 (HMB) supplementation in different sports: an update and practical implications

005_9101 Eficacia de la suplementacion.indd 23 16/06/15 19:47 Y Y Y Y Y Y N Efficacy Test training training training training protocol Protocol Strength Running Training Training Modality resistance Acute 4 days Eccentric (1 day) 14 days Downhill 4 weeks Weight 8 weeks Progressive 8 weeks Resistance Duration NR 8 weeks Resistance 1RM Load running exercise protocol Training Training eccentric Downhill Eccentric Exercises Isokinetic 55 Maximal 11 exercises 11 3 days/week Lower Body 3 times/week Isometric and Exercises and unilateral knee 1h Upper Body testing protocol 3x3-6 reps 90% extension/flexion -methylbutyrate Calcium Salt; NR: Not Reported; OBLA: β ne Kinase; TNFa: Tumor Necrosis Factor Alpha; TNFR1: Tumor Tumor TNFR1: Alpha; Necrosis Factor Tumor TNFa: ne Kinase; Tactical exercises; CD: Cool Down; V: Velocity. V: exercises; CD: Cool Down; Tactical NE 3xMVC H&Q es; N: No; MAS: Running speed during an incremental test at which dose) Sport Sport torque output strength FM: Fat Free Mass; FML: Mass Lost; Cr: Creatine; -hydroxy- Isometric Improved 60deg·s-1 upper body β Function and and isometric Performance strength 1RM (independent of Rapid Recovery Isokinetic torque Greater isokinetic urine DOMS Decreased CK, no effect CK, no effect Decreased CK Greater increase Decreased CK Increased power on profile, in or renal function Decreased blood (before exercise) Table I Fat Body Body Fat % -methylbutyrate-Free Acid; Ca-HMB: β Body Mass Composition Increased LBM Decreased Body No effect on FML on FML No effect Decreased in Body (independent dose) -hydroxy- β Training Training Untrained Untrained NE NE NE bout Single Experience Recreational NR CK Decreased and KIC HMB Untrained NE LDH Decreased HMB Untrained Increased LBM HMB Trained Decreased CaHMB and Trained CaHMB Untrained LBM Greater Ca-HMB HMB-FA HMB-FA HMB and -methylbutyrate; HMB-FA: β Studies examining the effect of HMB on performance in recreational sport practitioners Studies examining the effect of HMB on performance in recreational 3g/day 3g/day KIC or Placebo Placebo Placebo Placebo Placebo Placebo HMB-FA HMB and 3 g/day or Ca-HMB or or 76 mg/kg -hydroxy- β 36F 16F 19-24 40M 3g/day or 30±5,5 14M 3 g/day Iran NR 24M 3g/day or USA NR 37M Placebo, 38 USA 20-40 39M USA 23±2 16M 3 g/day or USA 24,3±2,2 17M Great South Africa Britain 68 71 65 70 max. is attained; MCV: Maximal Voluntary Contraction; H: Hamstring; Q: Quadriceps; WU: Warm-Up; Tec: Technical exercises; Tac: Tac: exercises; Technical Tec: Warm-Up; WU: Contraction; H: Hamstring; Q: Quadriceps; Voluntary Maximal max. is attained; MCV: 2 66 67 69 Reference Country Age N (Sex) Dosage Form Faramarzi et al. Muller Wilson et Wilson al. Onset of Blood Lactate Accumulation; RCP: Respiratory Compensation Point; NE: No Effect; LDH: Lactate Dehydrogenase; CK: Creati Accumulation; RCP: Respiratory Compensation Point; NE: No Effect; Onset of Blood Lactate Threshold; LBM: Lean Body Mass; F Ventilatory VT: Necrosis Factor Receptor 1; CRP: C-reactive protein; 3-MH: 3-methylhistidine; Y Y: Immersion; M: Male; F: Female; Water Acid; CHO: Carbohydrate; CWI: Cold PRS: Perceived Recovery Scale; KIC: Ketoisocaproic VO Abbreviations used in the table. HMB: Gallagher et al. Panton et al. Xing Nunan et al.

24 Nutr Hosp. 2015;32(1):20-33 Francisco J. Albert García et al.

005_9101 Eficacia de la suplementacion.indd 24 16/06/15 19:47 exercise able to induce muscle damage49. Supplements hold measures that reflect the physiological response should be taken at a dose of 1-2 g, 30-60 minutes prior to moderate and/or severe intensity exercise23,24,57. to exercise if consuming HMB-FA and 60-120 minutes The mechanism for these benefits of HMB on ae- prior to exercise if consuming HMB-Ca. Many of the robic performance and fat loss are poorly understood. earlier studies used HMB formulated as a calcium salt However, recent evidence demonstrated that HMB (HMB-Ca); however, a new free acid form of HMB supplementation could improve fatty acid oxidation (HMB-FA) has been shown to yield higher plasma as has been previously described in HMB’s mecha- concentrations in shorter amount of time compared to nisms of action46. the calcium salt form54. These results offer the theore- tical advantages of achieving a greater of HMB and providing potential benefits to improve Effects of HMB on Strength and Power Sports training adaptations54,55. Strength and power are two of the most critical attributes of success in sport58,59. Effects of HMB in Endurance Sports increases muscle fiber size and maximal tension ou- tput. These adaptations are attained by positive muscle Cardiorespiratory endurance refers to the ability of protein balance and satellite cell addition to pre-exis- performing activity for prolonged periods of time56. ting fibers60. Also, the activation of mTOR signalling Previous studies have demonstrated the potential be- pathway appears to be very important for contraction nefits of HMB for aerobic athletes. This information induced increases in muscle protein synthesis14,61. is shown in table II. Vukovich and Dreifort24 investi- Several research groups in this area19,52,62 reported gated the effects of HMB supplementation on peak conflicting results when men and women where su-

oxygen consumption (VO2peak) and the onset of pplemented with HMB during a resistance training blood lactate accumulation (OBLA) in eight endu- programme. Among the outcome variables analyzed rance-trained master-level competitive cyclist with in these studies were 1RM bench press, 1RM dead- an average training volume of 300 miles per week. lifts, 1RM rowing, 1RM shoulder press, 1 RM chin Participants performed a graded cycle ergometer test up, 1RM leg extension, 1RM squats, and 1RM biceps until exhaustion. Results from the graded exercise curl. In addition, other physiological variables, such as test indicated that HMB supplementation increased body composition, power production,

by 8% the time to reach (VO2peak) while leucine and levels, and lactate dehydrogenase, were also evalua- the placebo did not have any effect. The VO2 at 2 mM ted. This information is presented in table III together blood lactate (OBLA) increased with HMB (9.1%) with studies that showed strength and power benefits and leucine (2.1%) supplementation, but did not in sport-specific movements, i.e. squat, bench press change with placebo supplementation. The discre- and vertical jump10,19,21,22. In contrast, researchers have pancy with other endurance training studies23,24 could found small treatment effect when using non-specific, be due to training experience of the participants in the isolated movements19,62. Furthermore, as previously investigation. It has been suggested that active men mentioned, the lack of significant changes in perfor- and women not used to high intensity interval trai- mance could be attributed to the absence of periodized ning may benefit more from HMB-Ca supplementa- and progressive exercise programs. Finally, benefits of tion than trained athletes who are used to high inten- HMB supplementation are more marked when exerci- sity interval training57. Individualized high intensity se involves multi-joint movement that stresses a grea- interval training (HIIT) programs were applied based ter total amount of the skeletal muscle system. on each participant’s baseline fitness level and moni- The results of several studies22,63 suggest that chan- tored throughout the 28 days of training. It should be ges in strength and power following HMB supplemen- take into account that the training stimulus to stimu- tation are optimized within a context of a periodized as late physiological adaptation12,13,16 can be insufficient compared to a non periodized training program19. Fur- in some studies15,24. thermore, those findings suggest that supplementation The results obtained from high intensity interval with β-hydroxy- β-methylbutyrate plus Adenosine training studies23 shows that a four-week HIIT pro- Triphosphate (HMB/ATP) in combination with a high gram in combination with HMB-FA is an effective intensity undulating periodization-training model re- training stimulus for improving aerobic performance. sults in increases in LBM, muscle hypertrophy, stren- In addition, the use of HMB-FA supplementation, in gth and power. Translated into athletes and coaches’ combination with HIIT, resulted in greater changes languages, this means that when facing periods of high

in VO2peak, power output at ventilatory threshold training frequencies (overreaching cycle of training) (PVT) and ventilatory threshold (VT) than HIIT alo- HMB and/or HMB/ATP supplementation may not ne. These results are in accordance with other studies only prevent typical declines in performance (power, that used HMB supplementation with aerobic trai- strength and perceived recovery) that are characteris- ning methods for augmenting the beneficial effects tic of overreaching but might also results in additional on aerobic performance by increasing thres- gains in strength22.

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 25 (HMB) supplementation in different sports: an update and practical implications

005_9101 Eficacia de la suplementacion.indd 25 16/06/15 19:47 Y Y Y Y Y Efficacy training exercise exercise exercise exercise Training Training Modality condition condition condition condition endurance Endurance 1 week Specific 4 weeks HIIT Y Duration NR 2 weeks Specific NR 2 weeks Specific Load 3 times/ Training Training Downhill (1minRec) %VO2max week 5x2min 5x100% MAS 5 weeks Interval running protocol VT NR Prolonged run 1 week Specific RCP Sport Sport soreness time to reach time to reach Performance VO2 peak and VO2 peak and Power VT and Power VT VO2 at OBLA VO2 at OBLA in VO2max and in VO2max and NR Greater increase and CK Biochemistry Table II II Table Body Body or FM Composition Training Training Experience CaHMB Trained NR NR HMB increased CaHMB Trained NR NR HMB increased CaHMB Trained NR NR HMB lowered CaHMB Untrained on LBM effect No CaHMB Trained NR Lowered LDH HMB-FA Trained NE NR Greater increased Studies examining the effect of HMB on performance stratified by endurance sports HMB HMB, HMB, 3 g/day Placebo Placebo Placebo Placebo Leucine or 3g/day 3 g/day or 3 g/day or Placebo or Placebo or Leucine or Creatine or 19F 16M 16M USA NR 8MUSA 3 g/day NR 8M Placebo, USA 20-50 16F USA NR 28MUSA 3 g/day 21±2,4 21M Canada 23±1 16F 72 23 58 24 15 73 Reference Country Age N (Sex) Dosage Form Athletics Knitter et al. Vukovich Vukovich & Drei- fort Lamboley et al. Robinson et al. Cycling Vukovich & Adams Byrd et al.

26 Nutr Hosp. 2015;32(1):20-33 Francisco J. Albert García et al.

005_9101 Eficacia de la suplementacion.indd 26 16/06/15 19:47 Y Y Y Y Y Y N Efficacy training training training training training training Exercise Exercise Intensity Training Training Modality Eccentric Eccentric resistance 7 weeks Weight 3 weeks Weight 2 weeks Weight 4 weeks High 9 weeks Weight 7 Weeks Weight NR 6 days Test 1RM 1RM 1RM session training resistance Monitored progressive 9 exercises/ 3times/week 6 times/week 3 times/week 3x4 reps 90% 3x5 reps 90% High Intensity Training LoadTraining Duration · 45-75% 1RM 3x10 reps 70% during 3 weeks during 3 weeks 30-90s recovery 2-3 set 5-15 reps 1-4 set x 5-8 reps Sport Sport ROM ROM DOMS strength strength (3-15%) Creatine Squat lift extension HMB and weight lift Decreased Bench and Performance body strength additive effect additive effect Lower DOMS biceps curl and biceps curl and Increased Total Increased Total Increased 1RM on weight lifted (Dose dependent) NR Greater upper urine urea and 3-MH Only HMB plasma urea lowered CK, nitrogen, and Table III III Table Cr) FML LBM (additive effect HMB and effect Greater LBM and Body Composition Biochemistry Trained Increased FFM NR Increased 1RM Training Training Untrained Experience and Powder CaHMB Untrained NR NR on effect No CaHMB Untrained NR CK Decreased Greater 1RM CaHMB Untrained LBM Decreased CK Decrease CaHMB CaHMB Untrained on effect Positive CaHMB and Trained CaHMB Trained NR NR leg Greater HMB Studies examining the effect of HMB on performance stratified by strength and power sports Studies examining the effect of HMB on performance stratified by strength 3 g/day 3 g/day 3 g/day 3 g/day 3 g/day Creatine HMB and 3 g HMB, Placebo or Placebo or Creatine or 3 g/day KIC 39M 24±4 34M Placebo or 20-24 8M 3 g/day New USA 19-29 41M 0, 1.5 or USA 19-22 32M 0, 1.5 or USA 20-40 36F USA 19-23 40M Placebo, Great Britain Zealand Australia 21-22 17M 0 or 30 77 76 10 74 66 75 Reference Country Age N (Sex) Dosage Form Resistance Training Nissen et al. Van Someren Van et al. Panton et al. Paddon- Jones et al. Thomson Nissen et al. Jowko et al.

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 27 (HMB) supplementation in different sports: an update and practical implications

005_9101 Eficacia de la suplementacion.indd 27 16/06/15 19:47 Y Y Y Y Y Efficacy training training training training Exercise Training Training Modality 4 days Resistance 4 days Resistance 9 weeks Weight 4 weeks Weight 2 weeks Eccentric session exercise 50%RM 3x12reps resistance Isometric: 3 exercises 3 exercises 3 exercises 3 exercises Single bout 9 exercises/ of eccentric 5days/week 4 sets 10reps 60-100%RM 70-80%1RM 3 times/week 3 times/week 5 times/week reps 80%RM 70-80% 1RM Weightlifting: Weightlifting: : Training LoadTraining Duration 3x3reps or 3x4 30-90s recovery 2-3 set 5-15 reps NR 4 sets 10reps body Sport Sport torque DOMS repetition Maintained ROM, lower Performance Strength lower biceps curl and average power/ NR Improve muscle and TNFR1 (HMB-FA+CWI) content Table III (cont.) III (cont.) Table Decreased water Body Composition Biochemistry Training Training Experience HMB Trained Increased LBM HMB Trained FM Decreased NR Increased CaHMB Untrained NR CK Decreased Greater 1RM HMB-FA Trained NRHMB-FA Trained Attenuated TNFa NR Attenuated CRP KIC CWI CWI 20mg HMB HMB, Studies examining the effect of HMB on performance stratified by strength and power sports Studies examining the effect of HMB on performance stratified by strength 900mg Placebo Placebo Placebo Placebo 3 g/day effect of effect of effect Additive Additive Creatine or HMB-FA or HMB-FA or HMB-FA L-, 23±4 8M 3 g/day 24±4 34M 3g/day or New USA 22,3±2,4 40M 3 g/day USA 23,8±3 40M 3 g/day Great Britain Poland NR 182M 2g/day Zealand 79 78 19 80 63 Reference Country Age N (Sex) Dosage Form Kruszewski Townsend et Townsend al. Van Someren Van et al. Gonzalez et al. Thomson et al.

28 Nutr Hosp. 2015;32(1):20-33 Francisco J. Albert García et al.

005_9101 Eficacia de la suplementacion.indd 28 16/06/15 19:47 Y Y N N Efficacy Weight Weight training training training training training Training Training Modality and Agility 4 weeks Off-Season 12 weeks Resistance 12 weeks Resistance NR 4 weeks Weight 1RM Phase1: Phase2: Phase1: Phase2: Phase 3: Phase 3: 3x3-5RM 1x3-5RM 3x3-5RM 1x3-5RM 5x5maxV 5x5maxV 5x5maxV 5x5maxV 3x8-12RM 3x8-12RM 3x8-12RM 3x8-12RM Undulation Undulation 1-3sets x 2-8 Periodization Periodization 5 hours/week Overreaching Overreaching reps · 60-95% Training LoadTraining Duration Sport Sport strength Wingate) jump and Increased Improved Improved strength or strength and No effect on No effect No effect on No effect performance Performance Increased total power (vertical Recovery (PRS) Recovery (PRS) strength + power Intermittent High Intensity exercise and LDH and Cortisol Attenuated CK No effect markers No effect No effect markers No effect of muscle damage of muscle damage Fat Table III (cont.) III (cont.) Table LBM or FM LBM or FM Decreased Body Body Composition Biochemistry Trained Increased LBM CK Attenuated Training Training Experience and ATP CaHMB Trained on effect No HMB-FA Trained Increased LBM HMB-FA HMB-FA Studies examining the effect of HMB on performance stratified by strength and power sports Studies examining the effect of HMB on performance stratified by strength 6 g/day HMB-FA or Placebo or Placebo 400mg ATP 400mg ATP USA 21,7±0,4 17M 3 g/day USA 21,6±0,5 20M 3 g/day USA 20-22USA 40M 20-22 0, 3 or 18M 0, 3 g/day CaHMB Trained on effect No 22 49 81 82 Reference Country Age N (Sex) Dosage Form Lowery et al. Kreider et al. Wilson et Wilson al. Football Kreider et al.

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 29 (HMB) supplementation in different sports: an update and practical implications

005_9101 Eficacia de la suplementacion.indd 29 16/06/15 19:47 Y Y N N N N N Efficacy camp training training training specific training training Training Training Training Training Weight + Weight Modality Endurance 3 days Specific 6 days Specific 6 weeks Weight 4 weeks Football 4 weeks 1 week + 4 weeks + NR 6 weeks Weight 10’CD) program Training Endurance 4 hours/day Pre-Season Strength: 10 4 days/week reps 70-90% exercises (V) Tec + 30’Tac + 30’Tac Tec Regular Judo + 25’Game Team training Team (10’WU + 15’ (10’WU + 15’ 2-3 days/week Training LoadTraining Duration 8-12 sets x 2-10 1RM Endurance exercises/session specific training 3-5sets x 4-6 reps exercises (tempo): Sport Sport strength strength strength Increased anaerobic mean power No effect on No effect No effect on No effect performance performance Performance weight lifting Increased peak or elbow flexor soreness, ROM, power Increased decreases in power NR Attenuates NR on No effect and CK No effect markers No effect No effect markers No effect of muscle damage of muscle damage or FM Table III (cont.) III (cont.) Table composition LBM or FM Body Composition Biochemistry Increased Fat Loss; Training Training Experience HMB Trained on LBM effect No CaHMB Trained NE NR NE NR 6 weeks Weight CaHMB Trained on effect No CaHMB Trained NR NR on effect No CaHMB Trained NR LDH Decreased CaHMB Trained on body effect No and Studies examining the effect of HMB on performance stratified by strength and power sports Studies examining the effect of HMB on performance stratified by strength 3 g/day 3 g/day Placebo 6g CHO HMB or or HMB Creatine Creatine (HMBCr) HMB and 3g Creatine Iran 20±0,7 24M P 3 g/day, USA 20-22 35M Placebo or USA 20-22 26M 0 or Taiwan 21,8±1,1 8F 3 g/day or Australia 25±1 27M 3 g/day Australia 25±1 30M 3g HMB Australia 24-26 27M 0 or 3 g/day CaHMB Trained on LBM effect No 31 86 85 53 84 83 25 Reference Country Age N (Sex) Dosage Form Judo Hung et al. Waterpolo and Rowing Waterpolo Slater et al. Ransone et al. O’Connor & Crowe Soccer Faramarzi et al. Rugby O’Connor & Crowe Jay Hoffman Jay Hoffman et al.

30 Nutr Hosp. 2015;32(1):20-33 Francisco J. Albert García et al.

005_9101 Eficacia de la suplementacion.indd 30 16/06/15 19:47 When a long-term (12 weeks) periodized training References program is used in trained individuals, HMB has been found to increase strength, power, and muscle mass 1. Harper A, Miller R, Block K. Branched-chain amino acid me- 53 tabolism. Annu Rev Nutr. 1984; 4(1): 409-54. in major upper and lower muscle groups . Moreover, 2. Garlick PJ. The role of leucine in the regulation of protein me- when similar outcome variables were evaluated in tabolism. J Nutr. 2005; 135(6): 1553S-1556S. healthy untrained individuals after a supervised resis- 3. Norton LE, Layman DK. Leucine regulates initia- tion of protein synthesis in skeletal muscle after exercise. J tance-training program 3 times per week for 8 weeks, Nutr. 2006; 136(2): 533S-537S. torque generation, creatine phosphokinase and body 4. Wilson G, Wilson GJ. 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Portal S, Zadik Z, Rabinowitz J, Pilz-Burstein R, Adler-Por- Future research will additionally contribute to eluci- tal D, Meckel Y, et al. The effect of HMB supplementation on date the underlying mechanisms by which HMB acts body composition, fitness, hormonal and inflammatory media- improving high-intensity training adaptations. tors in elite adolescent volleyball players: a prospective ran- domized, double-blind, placebo-controlled study. Eur J Appl Physiol. 2011; 111(9): 2261-9. 18. Rowlands DS, Thomson JS. Effects of β-hydroxy-β-methylbu- Acknowledgements tyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis. J Strength Cond Res. 2009; 23(3): This work was supported by the Andalusian Sports 836-46. Medicine Centre (C.A.M.D.) through project no. EX- 19. Thomson J, Watson PE, Rowlands DS. Effects of nine weeks 2005/07. of β-Hydroxy-β-Methylbutyrate supplementation on strength FBO is granted by the Ministry of Economy and and body composition in resistance trained men. J Strength Cond Res. 2009; 23(3): 827-35. Competitiveness (RYC-2011-09011). 20. Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson The content is solely the responsibility of the au- LS, Kimball SR. Leucine stimulates translation initiation in thors and does not necessarily represent the official skeletal muscle of post-absorptive rats via a rapamycin-sensiti- ve pathway. J Nutr. 2000; 130(10): 2413-9. views of the funding body. The funders had no role in 21. Kraemer WJ, Hatfield DL, Volek JS, Fragala MS, Vingren JL, this study content. Anderson JM, et al. Effects of amino acids supplement on phy-

Usefulness of β-hydroxy-β-methylbutyrate Nutr Hosp. 2015;32(1):20-33 31 (HMB) supplementation in different sports: an update and practical implications

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