With the increase in individuals with chronic diseases or temporary health conditions, strength and conditioning specialists need to acquire or expand their knowledge, skills, and abilities to effectively manage the health of these individuals with unique health-related needs. Novel alternatives in the management of special populations geared toward increased accomplishment on health-related goals consider a more holistic approach that may include the utilization of nutritional supplements. The purpose of this article is to review some of the scientific evidence related to the use of β-hydroxy-β-methylbutyrate (HMB) in various special populations.
HMB is a naturally occurring metabolite derived from the amino acid leucine (1,16,23,25). This metabolite is also found naturally in foods, such as avocado, citrus fruits, cauliflower, and catfish (1). HMB is marketed as a nutritional supplement to prevent protein breakdown, enhance protein synthesis, and increase muscle strength (1,16,23,25). However, HMB utilization-related effects reported in the literature are population specific and may not be generalized to other populations.
Most of the effectiveness of HMB has been found in individuals not involved in training programs, individuals trained at high intensities, and those with illnesses that impair muscle anabolism. Impaired muscle anabolism is highly related to a decrease in fat-free mass (FFM), a major cause of sarcopenia, which leads to decrease in muscle strength (5,7,22). Loss of muscle strength is directly associated with impairments in walking, increased risk of falling, and loss of independence in activities of daily living (5,7). Therefore, if HMB can enhance muscular protein synthesis while preventing muscle protein breakdown, it may be an ideal nutritional supplement to consider in the health-related care of special needs populations, such as the elderly and those suffering from chronic debilitating diseases (1,23).
BIOCHEMISTRY OF β-HYDROXY-β-METHYLBUTYRATE
HMB is a metabolite derived from the essential branched chain amino acid leucine. This amino acid helps regulate protein synthesis within human muscles (1,16,23,25). When leucine-rich food products are consumed, leucine is metabolized and transaminated to α-ketoisocaproate (KIC) within the muscle (Figure 1). KIC is then transported from the muscle to the liver, where 90–95% is oxidized to isovaleryl coenzyme A (CoA) in the mitochondria. Finally, it is metabolized to acetyl-CoA and used within the citric acid cycle. The remaining 5–10% of KIC is converted to HMB and released to the circulation (1,16,23,25). HMB is converted into β-hydroxy-β-methylglutaryl-CoA, which finally transforms into cholesterol.
Even though mechanisms are not well understood, it has been hypothesized that the effects HMB has on muscle protein degradation and muscle protein synthesis are accomplished through several pathways, such as stabilization of muscle cell membrane, modulation of protein degradation, and upregulation of protein synthesis (1,23,25). Stabilization of the muscle cell membrane is accomplished given that HMB is a precursor of cholesterol, which, in turn, is a structural component of cell membranes (1,13,19,25). Additionally, the modulation of protein degradation and upregulation of protein synthesis are accomplished through inhibition of nuclear factor kappa β and activation of the mammalian target of rapamycin protein, respectively (Figure 2) (1,23,25). As a result, HMB is hypothesized to enhance the biochemical mechanisms necessary for protein synthesis, leading to increase in strength and FFM.
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. Research has shown that supplementation with HMB assists in increasing strength, function, and lean mass and decreases body fat in untrained healthy individuals (8), elderly individuals (6,20), or patients suffering from chronic conditions, such as human immunodeficiency virus (HIV) (2) or cancer (12). However, most of the literature has failed to find clinically significant changes in strength and body composition among those subjects who already perform a physical training regimen (14,17,18,23). The lack of significant changes in such articles has been related to the lack of adequate exercise stimulus (24). When high exercise intensity (≥80% 1 repetition maximum [1RM]) or progressive loading periodization programs are used in trained individuals, HMB supplementation has shown similar results to untrained populations (3,24). New evidences in abstract form have found that HMB supplementation increases strength, hypertrophy, and power after a 12-week periodized program (3). Therefore, HMB seems to be most effective during periods of proteolysis (24).
EFFECTS OF HMB IN CARDIORESPIRATORY ENDURANCE
Cardiorespiratory endurance refers to the ability of performing activity for prolonged periods of time (22). Literature on the effectiveness of HMB in relation to improvements in aerobic capacity has shown a trend toward improving cardiorespiratory endurance (V[Combining Dot Above]O2peak and onset of lactate accumulation at V[Combining Dot Above]O2peak) in elite cyclists (20). This particular study conducted a repeated measures double-blinded placebo trial in which cyclists were randomly assigned to receive HMB, leucine, or placebo. Each cyclist completed three 4-week cycles of intervention. Each cycle consisted of a 2-week treatment period and a 2-week washout period. Maximal exercise testing in a cycle ergometer was conducted at the end of each treatment period. Their results showed an improvement of 8% in time to reach V[Combining Dot Above]O2peak and a 9.1% change in onset of blood lactate. Likewise, a study conducted in adolescent volleyball players during the first 7 weeks of training also found a trend toward improvement in strength, body composition, and anaerobic power (15). Therefore, results suggest that HMB may enhance energy metabolism by several pathways that remain to be explained.
EFFECTS OF β-HYDROXY-β-METHYLBUTYRATE ON STRENGTH AND POWER
Several research groups (14,17,18) reported debatable results regarding HMB supplementation in men and women who regularly participate in resistance training. Among the outcome variables analyzed in these 3 studies were a 1RM bench press, 1RM deadlifts, 1RM rowing, 1RM shoulder press, 1RM chin-up, 1RM leg extension, 1RM squats, and 1RM bicep curl. In addition, other physiological outcome variables, such as body composition (skinfold thickness and bioimpedance analysis), power production, creatine kinase levels, and lactate dehydrogenase, were also evaluated. All subjects had no less than 1-year experience with resistance training and were supplemented with HMB for 6 (14) weeks, 9 (18) weeks, or immediately after workout (17). One of the studies (18) found an increase (9%) in 1RM leg strength (leg extension). This 9% increase in leg strength might be of importance to an athlete who competes in a sport or event in which leg strength is a strong predictor of performance. As previously mentioned, the lack of significant changes in performance could be attributed to the absence of periodized and progressed exercise programs. Conversely, when a long-term (12 weeks) periodized training program has been used in trained individuals, HMB has been found to increase strength, power, and muscle mass in major upper and lower muscle groups (3). However, this newer evidence has been only presented in abstract form. When similar outcome variables were evaluated in healthy untrained individuals after a supervised resistance-training program 3 times per week for 8 weeks, torque generation, creatine phosphokinase and body composition significantly improved among those supplemented with HMB, as compared with those not supplemented (8). Once more, evidence points toward positive outcomes of HMB supplementation in periods of proteolysis and high intensity. Therefore, it seems appropriate to hypothesize that HMB supplementation would help in increasing cardiorespiratory fitness, strength, power, and physical function in those experiencing the effects of negative protein turnover.
EFFECTS OF β-HYDROXY-β-METHYLBUTYRATE SUPPLEMENTATION IN THE ELDERLY AND AMONG INDIVIDUALS WITH CHRONIC DISEASES
Elderly individuals and those with chronic diseases primarily suffer from a reduction and impairment of physiological function, respectively (5,7). Within these specific special needs populations, HMB supplementation has been reported to be effective. Investigators have reported that HMB supplementation in the elderly (>65 years old) improved body composition by increasing FFM, decreasing body fat percentage (6,21), and increasing leg and arm strength and function (6). Vukovich et al. (21) conducted a double-blinded randomized trial in which 31 subjects were randomly allocated to either a placebo (n = 17) or a 3 g/d HMB supplementation (n = 14), respectively. Outcomes were determined by body composition measured by skin folds, bone mineral density measured by dual-energy X-ray absorptiometry, and computerized tomography scans. Each subject participated in supervised strength training at a designated facility for a period of 8 weeks. At the end of the study period, those receiving HMB supplementation showed a significant decrease in percentage of body fat and a significant increase in FFM. A different double-blinded randomized trial (6) conducted exclusively in women (mean age 76.7) assigned 23 and 27 subjects to the placebo and 2-g HMB supplementation groups, respectively. These women were evaluated at baseline and 12 weeks after initiation of the trial. Measures of body composition were assessed through bioelectrical impedance (BI), physical function with a “timed-get-up-go-task” (TUG), and strength by an isokinetic device. In addition, protein turnover was estimated by using 3.75 mg/kg of 15N-glycine isotopes and measuring 15N-urea and 15N-ammonia 24 hours after consumption of the isotope. After 12 weeks, women in the HMB supplementation group showed significant improvements in body composition, physical function, and strength. Results showed an increase in FFM by 0.7 ± 0.3 kg, a decrease in body fat by −0.5 ± 0.6%, an increase in their function by walking 17% faster in the 3-m TUG, and increases in quadricep torque generation by 3.0 ± 1.5 kg, hamstrings torque generation by 0.8 ± 0.7 kg, and grip strength by 0.6 ± 0.6 kg. Elderly women receiving placebo did not show significant improvements in any of the body composition, physical function, and strength outcome variables. The rate of whole protein turnover was 20% greater in the HMB group than in the placebo group. Therefore, it was concluded that elderly women taking 2 g of HMB for 12 weeks could improve body composition, physical function, strength, and protein turnover even without performing strength training. Hence, it could be hypothesized that elderly women supplemented with HMB and who also participate in strength training might be able to improve even further their body composition, function, and strength.
The groups of individuals who seem to benefit greatly from HMB supplementation are those suffering from chronic diseases, such as cancer and HIV/acquired immune deficiency syndrome (AIDS). These 2 conditions are characterized by generalized impaired function because of physiological impairments, such as low protein turnover, extreme fatigue, muscle wasting, and decreased strength, among others (4,5). May et al. (12) evaluated 32 men and women diagnosed with stage IV cancer during their course of treatment. By using a double-blinded randomized design, the patients were divided into placebo (n = 14) and experimental (n = 18) groups. The experimental group received 3 g/d of HMB/arginine/lysine supplementation. Outcome variables evaluated were body composition and health-related quality of life (HRQoL). Body composition was measured by bioimpedance analyzer from which FFM and percentage of body fat were estimated. HRQoL was assessed with a self-reported questionnaire (SF-36). Outcome variables were assessed at 4- and 12-week follow-ups on both groups. At the 4-week follow-up, the patients in the experimental group increased their body weight by 0.95 ± 0.66 kg, whereas the control group lost −0.26 ± 0.78 kg. When FFM was estimated, the experimental group increased 1.12 ± 0.68 kg in comparison with the control group who lost −1.34 ± 0.78 kg. At the 12-week follow-up, these measures continued to improve within the experimental group (2.27 ± 1.17 kg). Although HMB supplementation improved body composition, no differences were found for HRQoL measures. A similar study assessed the effectiveness of HMB in combination with glutamine and arginine in body composition, lymphocytes, and viral load in a sample of 43 patients diagnosed with HIV (2). They conducted a randomized double-blinded trial where the placebo group consisted of 21 subjects (18 men and 3 women) and the experimental group consisted of 22 individuals (20 men and 2 women). Body composition was considered and evaluated as body weight, FFM, and body fat by using an air plethysmography and a thigh CT scan. These measures were assessed at baseline and 8-week follow-up. The patients in the experimental group were given 3 g of HMB combined with 14 g of glutamine and 14 g of arginine. At follow-up, the experimental group increased their body mass by 3.0 ± 0.5 kg with a related FFM weight increase of 2.55 ± 0.75 kg. The placebo group only gained 0.37 ± 0.84 kg with a net loss of −70 ± 0.69 kg in FFM. Assessment of lymphocytes showed an increase in the experimental group (0.29 ± 0.14 × 103 cells/mm3), whereas the placebo group exhibited a decrease in these cells (−0.31 ± 0.15 × 103 cells/mm3). Viral load count in the HMB group decreased significantly, whereas the placebo group showed a statistically significant increase. The investigators concluded that supplementation with HMB, arginine, and glutamine are as effective as hormonal treatment to increase body composition in patients with HIV/AIDS.
EFFECTS OF β-HYDROXY-β-METHYLBUTYRATE SUPPLEMENTATION IN OTHER CRITICALLY ILL POPULATIONS
The effectiveness of HMB supplementation has also been assessed in more critically ill individuals, such as hospitalized trauma patients in intensive care unit (11) and hospitalized patients with chronic obstructive pulmonary disease (COPD) (10). Kuhls et al. (11) assessed nitrogen balance in critically ill trauma patients hospitalized in an intensive care unit. Negative nitrogen balance is one of the main precursors of muscle wasting, morbidity, and mortality within these patients. Using a double-blinded design study, they randomized 100 individuals equally either receiving HMB supplementation or isonitrogenous solutions via feeding tubes for 14 days. At the end of the 14 days, patients receiving HMB supplementation exhibited greater nitrogen balance than those in the isonitrogenous group. Therefore, improvement in nitrogen balance suggests an increased protein synthesis in those patients recovering from trauma (11). In a similar study, Hsieh et al. (10) evaluated 34 hospitalized patients with COPD who received HMB or placebo via nasogastric tubes. The authors evaluated inflammatory markers (C-reactive protein), pulmonary function, creatinine, and cholesterol upon admission and 7 days later. At reevaluation, those patients receiving HMB supplementation exhibited lower values of CRP, greater pulmonary function, lower levels of creatinine, and higher levels of cholesterol. All these improvements suggest that HMB reduces catabolic processes during hospitalization from COPD and improves pulmonary function faster than patients receiving standard nasogastric supplementation (10). In summary, HMB supplementation can reduce catabolic processes of those critically ill patients, suggesting faster recovery and return to function.
SAFETY OF β-HYDROXY-β-METHYLBUTYRATE SUPPLEMENTATION
An important factor for the consideration and utilization of any nutritional supplement is its safety. A dose of ≤76 mg/kg/d of HMB supplementation had no effect on hepatic enzymes, lipid profile, renal function, or immune system response in men who are 18–29 years old (9). Two other recent literature reviews (1,23) on the topic of HMB supplementation reported that HMB utilization has been proven safe in several populations, such as the young healthy, elderly, HIV/AIDS positive, and cancer patients, in dosages that ranged from 3 to 8 g daily. Therefore, dosages of HMB within this frame seem to be safe and nontoxic.
Although HMB is marketed for all those interested in increasing muscle mass and strength, the evidence shows that benefits are population and training specific. HMB has proven to be effective in individuals without a history of strength training, trained individuals after high-intensity periodized programs, the elderly, and those with chronic diseases, such as cancer and HIV/AIDS. HMB is proven safe and nontoxic when consumed in the recommended dosages making it an appropriate supplement for those with health impairments. Therefore, the evidence suggests that HMB supplementation may improve muscle strength/power and body composition.
1. Abbott Laboratories. HMB (β-hydroxy-β-methylbutyrate): A Scientific Review. Abbott Park, IL: Abbott Laboratories, 2010.
2. Clark RH, Feleke G, Din M, Yasmin T, Singh G, Khan FA, Rathmacher JA. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: A randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr 24: 133–139, 2000.
3. Dunsmore K, Lowery R, Duncan N, Davis G, Rathmacher JA, Baier S, Sikorski E, Morrison T, Naimo M, Walters J, Wilson S, Wilson JM. Effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid gel supplementation on muscle mass, strength
, and power in resistance trained individuals. In: Proceedings of the Ninth International Society of Sports Nutrition (ISSN) Conference, Clearwater, FL, 2012.
4. Durstine JL and American College of Sports Medicine. ACSM's Exercise Management for Persons With Chronic Diseases and Disabilities. Champaign, IL: Human Kinetics, 2009. pp. 211–225.
5. Ehrman JK. Clinical Exercise Physiology. Champaign, IL: Human Kinetics, 2009. pp. 135–148.
6. Flakoll P, Sharp R, Baier S, Levenhagen D, Carr C, Nissen S. Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength
, functionality, body composition, and protein metabolism in elderly women. Nutrition 20: 445–451, 2004.
7. Frontera WR, Slovik DM, Dawson DM. Exercise in Rehabilitation Medicine. Champaign, IL: Human Kinetics, 2006. pp. 311–331.
8. Gallagher PM, Carrithers JA, Godard MP, Schulze KE, Trappe SW. Beta-hydroxy-beta-methylbutyrate ingestion, part I: Effects on strength
and fat free mass. Med Sci Sports Exerc 32: 2109–2115, 2000.
9. Gallagher PM, Carrithers JA, Godard MP, Schulze KE, Trappe SW. Beta-hydroxy-beta-methylbutyrate ingestion, part II: Effects on hematology, hepatic and renal function. Med Sci Sports Exerc 32: 2116–2119, 2000.
10. Hsieh LC, Chien SL, Huang MS, Tseng HF, Chang CK. Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr 15: 544–550, 2006.
11. Kuhls DA, Rathmacher JA, Musngi MD, Frisch DA, Nielson J, Barber A, MacIntyre AD, Coates JE, Fildes JJ. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients. J Trauma 62: 125–131, 2007; discussion, 131–122.
12. May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg 183: 471–479, 2002.
13. Mougios V. Exercise Biochemistry
. Champaign, IL: Human Kinetics, 2006. pp. 67–80.
14. O'Connor DM, Crowe MJ. Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on strength
, power, and anthropometry of highly trained athletes. J Strength
Cond Res 21: 419–423, 2007.
15. Portal S, Zadik Z, Rabinowitz J, Pilz-Burstein R, Adler-Portal D, Meckel Y, Cooper DM, Eliakim A, Nemet D. The effect of HMB supplementation on body composition, fitness
, hormonal and inflammatory mediators in elite adolescent volleyball players: A prospective randomized, double-blind, placebo-controlled study. Eur J Appl Physiol 111: 2261–2269, 2011.
16. Slater GJ, Jenkins D. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength
. Sports Med 30: 105–116, 2000.
17. Stock MS, Young JC, Golding LA, Kruskall LJ, Tandy RD, Conway-Klaassen JM, Beck TW. The effects of adding leucine to pre and postexercise carbohydrate beverages on acute muscle recovery from resistance training. J Strength
Cond Res 24: 2211–2219, 2010.
18. Thomson JS, Watson PE, Rowlands DS. Effects of nine weeks of beta-hydroxy-beta-methylbutyrate supplementation on strength
and body composition in resistance trained men. J Strength
Cond Res 23: 827–835, 2009.
19. Tiidus PM, Tupling AR, Houston ME, Houston ME. Biochemistry
Primer for Exercise Science. Champaign, IL: Human Kinetics, 2012. pp. 205–245.
20. Vukovich MD, Dreifort GD. Effect of beta-hydroxy beta-methylbutyrate on the onset of blood lactate accumulation and V(O)(2) peak in endurance
-trained cyclists. J Strength
Cond Res 15: 491–497, 2001.
21. Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr 131: 2049–2052, 2001.
22. Wilmore JH, Costill DL, Kenney WL. Physiology of Sport and Exercise. Champaign, IL: Human Kinetics, 2008. pp. 122–141–421, 402–421.
23. Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review. Nutr Metab 5: 1, 2008.
24. Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J. International Society of Sports Nutrition Position Stand: Beta-hydroxy-beta-methylbutyrate (HMB). J Int Soc Sports Nutr 10: 6, 2013.
25. Zanchi NE, Gerlinger-Romero F, Guimaraes-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH Jr. HMB supplementation: Clinical and athletic performance-related effects and mechanisms of action. Amino Acids 40: 1015–1025, 2011.