β-Hydroxy-β-methylbutyrate (HMB) is one of the more popular supplements marketed in recent times to resistance training individuals, with claims including increased strength, muscle size, and fat oxidation (14,27,31,32). However, closer examination of the body of published work-largely in healthy adult men-reveals that the effects on strength are variable, with an approximately equal number of groups reporting no clear change or inconclusive outcomes (13,14,23,27,32) or clear substantial increases in strength measures (11,21,25,37). Interestingly, closer examination of the data reveals inconsistent magnitude and (statistical) clarity of strength improvements in upper-body compared with lower-body resistance exercises, with the majority of improvement being in lower-body lifts (8,21,25,37).
The rationale to supplement with HMB to promote strength gains from resistance exercise is based around the promotion of tissue growth via several proposed mechanisms of action extrapolated from research in animal models under severe catabolic stress, proposed HMB biochemistry, and deduction from indirect measures in humans (19,21,31). It has been suggested that HMB may attenuate training-induced proteolysis in the muscle via downregulation of proteolytic pathways (19,21,31,33). In the sarcoplasm, HMB is thought to be metabolized to β-hydroxy-β-methylglutaryl-CoA, providing a readily available carbon source for cholesterol synthesis, which in turn provides material for muscle cell growth (21,31). The HMB may also undergo polymerization and be used as a structural component of the cell membrane, leading to enhanced stability (31). Additionally, HMB has been proposed to increase muscle cell fatty-acid oxidation capacity via unknown mechanisms, leading to decreases in fat mass (31,34). In support of increased tissue growth, 2 groups reported increases in lean body mass in subjects previously untrained in resistance exercise (8,21). However, most have observed no effect on body composition (8,11,14,21,25,32). Training status might affect the interaction of resistance exercise and HMB stimuli on hypertrophy and hypertrophy-induced strength outcomes in the trained skeletal muscle because the physiological mechanisms of action of HMB relate to the promotion of tissue growth, which is limited in the skeletal muscle (1,28). However, the position along the strength-hypertrophy continuum of the subject samples studied to date is from the bottom (untrained) to middle-upper range at best, making the scope for further gains in skeletal muscle strength and hypertrophy in the response to an efficacious intervention in the majority of subjects conceivable.
Further close examination of the literature suggests that strength benefits accruing from HMB are more likely in persons previously untrained in resistance exercise before commencing the intervention. With the exception of the outcome in the trained group in 1 study reporting outcomes from both previously trained and untrained subjects (21), the evidence for statistically clear strength increases with HMB are restricted to previously untrained lifters (8,11,21,25,37). The outcomes from one of these studies may not be attributable to HMB at all because the HMB group was also provided with an isocaloric drink containing greater protein, energy, vitamins, and minerals than the placebo (21). Furthermore, 3 of the 4 studies in adult men reporting strength increases (11,21,25) are generated from the collaboration of common researchers and institutions, leading to concern about clustering effects (7). Finally, in some studies on previously resistance trained subjects, small increases in overall strength gains of between 1.5 and 6.7% have been reported (14,23,27,32), but the level of statistical uncertainty and ill-defined training status of subjects in other studies (8,11) leave the unresolved question of whether there is a worthwhile effect of HMB in previously trained lifters.
The main consumers of HMB supplements are likely to be those who are actively involved in a resistance training program for health and aesthetics or who are training for strength- or power-based sports. The purpose of this study, therefore, was to determine the effect of HMB supplementation during resistance training on strength and body composition in men from these groups experienced in resistance training before the study. Our experiment was designed using best practice in randomized controlled trials in sport science including standardization of diet and training regimen, randomization to treatment conditions, double-blind placebo control, and the use of familiarization trials for performance measures (10). The study duration was the greatest to date, at 12 weeks (9 weeks of HMB supplementation), which we chose as the longest realistic time frame for which adequate control of the primary study parameters and subject retention could be achieved.
Experimental Approach to the Problem
The study was a randomized, double-blind, controlled trial. Subjects in the treatment group received 3 g·d−1 HMB in capsules, whereas the control group received an equal amount of corn starch as placebo via the same method. Data were gathered before and after supplementation in the schema shown in Figure 1. The first day of testing occurred at the beginning of week 1, during which baseline strength was measured. To assess reliability of the performance measure, strength testing was repeated again 1 week later (week 2), and the baseline body composition measures were taken. The following day, the resistance training program and daily HMB supplementation began. At week 11, postintervention strength was measured and supplementation was stopped. Strength was retested and body composition was measured 1 week later to complete the investigation.
Thirty-four men with a minimum of 1 year of resistance training experience were recruited from commercial gyms throughout the Auckland, New Zealand area. Subjects had recreational resistance training backgrounds and were identified with the use of a training history questionnaire and defined as those who had lifted weights regularly for a period of 1 year or more, but without a structured training program designed for the goal of competitive body building, weight lifting, or power lifting. To ensure double-blind study design, subjects were randomly assigned to the HMB or placebo group by an independent third party. Six subjects withdrew from the study for unspecified reasons, 2 moved out of the area, 1 withdrew because of an unrelated illness, 1 withdrew because of time constraints, and the data for 2 subjects were excluded because of failure to comply with study criteria. Twenty-two subjects met all study criteria, leaving a final sample size (data presented) of 9 in the placebo group and 13 in the HMB group.
Subjects were 24 ± 4.0 years old, with an average of 3.9 ± 3.1 years of resistance training experience; they regularly resistance trained 3.3 ± 0.1 times per week for an average of 66 ± 20 minutes per session. Of the muscle groups of interest in this study, previous training consisted of an average of 1.9 ± 1.0 sessions per week for the chest (pectoralis), 1.7 ± 1.0 for the arms (biceps brachii), and 1.2 ± 1.1 sessions for the legs (quadriceps). Baseline subject height, weight, individual skinfolds, sum of 7 skinfolds, body fat, and strength measures are shown in Table 1.
All subjects were provided with an information sheet, the purpose and nature of the study were fully explained, and written informed consent was obtained. Subjects were healthy, with no known medical conditions to contraindicate resistance exercise. The project was approved by the university regional human ethics committee (protocol 02/063).
The effect of HMB supplementation on upper- and lower-body isotonic strength was estimated using the 1-repetition maximum (1RM) method (12). The exercises that were chosen for 1RM testing were the bicep preacher curl and bench press (via Smith machine) for the upper body and the leg extension for the lower body. These lifts were chosen as an ethical requirement to ensure the safety of subjects and to minimize the skill component in the performance outcome. Subjects abstained from exercise for 12 hours before strength testing. During testing, subjects performed a 5-minute warm-up on aerobic equipment and stretched the required muscle groups. The exercise apparatus was adjusted to suit the individual, and adjustments were noted and repeated during later retesting. Position and technique were observed, to ensure that a full range of motion was completed for each attempt. Verbal encouragement was provided in a standardized manner. Analysis of the reliability between consecutive pairs of strength measures was conducted. High reliability was demonstrated, so pairs of pretest and pairs of posttest strength measurements were averaged for calculations of the strength outcomes.
Subjects were instructed to refrain from any physical activity or consumption of alcohol within 12 hours, and not to have eaten within 4 hours before body composition measurements. All subjects were asked to urinate within 30 minutes before body composition measurements, and an attempt was made to measure each subject at the same time of day pre- and postsupplementation. On arrival at the laboratory, height and weight were measured. Skinfolds were taken using a skinfold caliper (Slim Guide, Rosscraft Innovations Incorporated, Surrey, Canada), precision of 1 mm. All skinfold measurements were taken from the right side of the body and were made by the same trained technician (ISAK-accredited level 1) following the procedures outlined by the International Society for the Advancement of Kinanthropometry (22). Skinfold values were the average of 2 test measurements, except where differences greater than 1 mm (10%) existed, when a third measurement would be taken and all 3 measurements averaged and reported. The sum of 7 skinfolds was calculated. The error of measurement in the control group, represented as the coefficient of variation (CV), was in the range of 5.8-17.7% for individual skinfolds and 8.7% for the sum of 7 skinfolds during the 9-week period. To provide a second estimate of dual-compartmental body composition, a single-frequency bioelectrical impedance analyzer (BIA) was used in tetrapolar mode at 50 kHz, 200 μA (model BIM-4, Impedimed Pty Ltd, Queensland, Australia). Subjects were asked to remove jewelry and watches and to lie supine with the arms positioned away from the body and their legs apart; electrodes were placed on the right hand and right foot according to the manufacturer's guidelines. Predictive models for total body water (and, hence, fat mass and fat free mass) were calculated from BIA measurements of resistance and reactance values based on a preprogrammed algorithm, described previously (15). The error of measurement in the control group CV (%) was 1.9, 11.4, and 10.5%, respectively, for fat-free mass, fat mass, and percent body fat during the 9-week period.
The resistance training program consisted of 3 sessions per week with at least 1 day off from resistance exercise between each session. Strength exercises were performed for 9 exercises per session, with 3-4 exercises chosen to isolate the major muscle groups as follows: chest, upper back, shoulders, arms, abdominal, and legs, with 2-3 sets per exercise, 5-15 repetitions per set, and 30-90 seconds of recovery time between sets. Sessions alternated between upper- and lower-body exercises. Subjects were instructed to complete the prescribed number of repetitions or until failure with correct technique; if a greater number of repetitions was achieved, the weight was increased during the following session to permit progressive adaptation. Subjects were asked to maintain participation in other physical activities in conjunction with the study resistance training program. Subjects were provided with training logs and directed to produce these weekly for monitoring of training and physical activity compliance. Reported compliance to the training program was, on average, 84 ± 22%. Subjects were trained and tested on the same type of exercise apparatus and range of motion to optimize the training response specificity for the exercises that were tested (30).
The HMB was sourced from Musashi Ltd (Notting Hill, Victoria, Australia). The placebo was maize starch (National Starch and Chemical NZ Ltd., Auckland, New Zealand). The placebo was chosen to closely resemble the HMB powder, and both it and the HMB were packaged in identical gelatin capsules (Pharmaceutical Compounding, Auckland, New Zealand). Each capsule contained 0.5 g of HMB or placebo. Subjects were required to consume 6 capsules per day divided into 3 doses, which has been shown to maintain high circulating plasma HMB concentrations throughout the day (8,36). Preliminary trials confirmed that the placebo and HMB capsules could not be distinguished.
Dietary intake was standardized: that is, subjects were asked to maintain their normal diets throughout the study. At the beginning and end of the study period, subjects' diets were evaluated, whereby each subject kept a detailed 3-day record of dietary intake for a period of 2 weekdays and 1 weekend day (Figure 1). To reduce the possibility of a synergistic effect with HMB, all subjects were asked to discontinue the use of all sports supplements from 4 weeks before and during the study period.
The effect of HMB on strength and body composition was estimated using a published spreadsheet via the unequal-variances t-statistic (9). The HMB effect was the difference in the post minus pre change score for the HMB and placebo groups. Each change score was expressed as a percentage of baseline score via analysis of log-transformed values to reduce bias from nonuniformity of error. The precision of the estimate was presented as 90% confidence limits, with the associated p value for the effect derived from the t-statistic. In addition, the spreadsheet estimated probabilities that the true population effect was a substantial enhancement, detriment, or trivial/negligible based on the range of the confidence interval relative to the threshold value for the smallest clinical or worthwhile effect (3,9). For strength data, a value for weight lifters of 1.2% was used as the smallest worthwhile effect. This value was derived from the published CV for weight lifting performance of 2.4% (16), where the smallest worthwhile enhancement of athletic performance is likely to be, on average, 0.5 times the CV for the performance measure (10). It is not known how a change in anthropometric variables would affect resistance training performance or aesthetics, so the smallest standardized (Cohen) change in the mean was used as the smallest worthwhile change: 0.2 times the between-subject SD for the baseline average prestudy standard deviation (5). To provide probability-based practical inference, an effect was described as mechanistically unclear if its confidence interval included both substantial positive and negative values (>5% chance that the true value were both substantially positive and negative). Otherwise, chances of positive or negative effect were assessed as the following: <1%, almost certainly not; 1-5%, very unlikely; 5-25%, unlikely; 25-75%, possible; 75-95%, likely; 95-99, very likely; and >99%, almost certain (3). Magnitudes of correlations were interpreted using the Cohen magnitude thresholds: <0.1, trivial; 0.1-0.3, small; 0.3-0.5, moderate; and >0.5, large.
The effect of HMB supplementation on upper- and lower-body strength is shown in Figure 2, and a statistical summary is provided in Table 2. The HMB supplementation substantially increased leg extension 1RM. In contrast, the effect on bench press or bicep preacher curl was unclear, and the effect on overall combined lift strength was trivial.
Reliability for consecutive pairs of pretrial and posttrial strength tests ranged from 2.7 to 6.2% for test typical error as a CV (%) (Table 3).
There was no evidence of an interaction between previous training experience and group, nor was there any interaction between training experience as a confounder in any strength change during this study (data not shown for brevity).
The effect of HMB supplementation on body composition change is shown in Table 4. The increase in body mass and BIA fat-free mass was negligible. There was a likely substantial decrease in the supraspinale skinfold, but the remaining skinfold outcomes, including sum of 7, were possible reductions of trivial to small magnitude.
Over the study duration, average energy intake and fat intake increased in the HMB group. Changes in dietary energy and macronutrient intake over the study duration are shown in Table 5. There was a moderate positive correlation (r = 0.32) in percent change in total energy intake with percent change in leg extension 1RM. Percent change in fat intake had a small positive correlation (r = 0.18) with percent change in leg extension 1RM. When correlations were analyzed by treatment group (HMB or placebo), there was only a small correlation between percent change in fat intake per kilogram of body weight with percent change in leg extension lift in the HMB group (r = 0.12), and there was a moderate negative correlation in the placebo group (r = −0.32). There were no differences evident between groups regarding changes in carbohydrate and protein intake throughout the study duration.
The principle finding of this study was that 9 weeks' HMB supplementation during a resistance training program in previously resistance trained men resulted in a clear-cut, negligible effect on overall combined strength. However, outcomes were different with respect to individual lifts, with our measure of lower-body strength being substantially enhanced by HMB, whereas the effect on upper-body strength was inconclusive. Second, HMB supplementation resulted in likely trivial reducing effects on skinfold and BIA estimates of fat and fat-free mass.
The finding that HMB has negligible effects on overall average strength measures in previously resistance trained men is consistent with the body of published outcomes to date. In fact, the only report citing strength gains with HMB supplementation in previously trained adult male weight lifters (21) also provided greater protein, energy, vitamins, and minerals in the HMB group compared with the placebo (21). In contrast, overall average strength generally seems to be enhanced in previously untrained subjects (8,11,25,37), although attribution of strength gains to HMB in one of the key seminal studies (21) is uncertain, because of the addition of greater protein, energy, vitamins, and minerals in the HMB group compared with the placebo. Our data also concur with another emerging pattern: that of the strength change being of greater magnitude in lower-body exercises compared with exercises in the upper body. Two groups (21,37) also report greater strength increases in lower-body compared with upper-body lifts. However, the results are not entirely consistent with others (21,25,37) showing the opposite pattern-for example, a greater increase in bench press compared with squat (21) and leg extension strength (25). It is possible that the greater reliability of lower-body strength measures contributes to the clarity of the outcome statistic (Table 3), but it is often difficult in strength and conditioning research to determine the likely true magnitude and direction of the population treatment effect by way of qualitative assessment of multiple individual study conclusions based on an assessment of p values, which can be very misleading (28). Consequently, we decided to conduct a meta-analysis of the effect of HMB supplementation during resistance training on strength, markers of muscle damage, and body composition outcomes (29). In this companion paper, the quantitative meta-analytical HMB effect was for a clear, small benefit to lower-body strength; however, only negligible improvement for the upper body and overall strength outcomes were discovered. When the studies were analyzed by training status (previously trained vs. untrained subjects), there was no effect of HMB on any strength outcomes in previously trained subjects, but there were clear, small increases in overall average and lower-body strength in untrained subjects (29).
Together, the findings of the present study with the meta-analysis suggest that HMB is more efficacious to individuals initiating resistance training programs and, possibly, also in less well-trained muscle groups. One prospect for this outcome is that the untrained or relatively less well-trained muscle is both more susceptible to muscle damage and has greater protein turnover in response to a bout of resistance exercise and, therefore, may have greater potential for adaptive facilitative responses linked to an anabolic or anticatabolic substance (1,26,32). Although it is possible that our resistance training program was not intense enough to elicit sufficient muscle damage and protein catabolism to allow for an HMB-induced attenuation of protein breakdown or stimulation of protein synthesis, several previous studies using very intensive training programs have also failed to show ergogenic effects of HMB in trained individuals (13,14,27). The resistance training program used in the current study was consistent with common and recommended practice that included repetitions to failure and progressive adaptation (28). It is also possible that the 9-week study period was not long enough to establish the effect of HMB on gains in strength; however, past research has found strength gains using shorter supplementation and training periods in trained individuals (21), although the results from this study are cofounded by nutritional cointervention.
The findings of a pattern of greater strength gain in lower- compared with upper-body lifts in the current study and the meta-analysis are not entirely consistent with other studies. This discrepancy may be attributable to differential sensitivity to HMB stimulation in muscle with particular physiological characteristics. For instance, rates of protein turnover in response to resistance exercise and nutrient provision have been found to vary to a small degree depending on muscle anatomic location, which can be partly explained by differences in muscle fiber-type composition, distribution of translational initiation factors, and muscle function and contractile activity (4,17). Further, an in vitro study of animal muscle tissue by Ostaszewski et al. (24) points to evidence of a difference in sensitivity to the effect of HMB on protein synthesis and breakdown with muscle type; HMB seemed to suppress proteolysis to a greater extent in muscles with more type II fibers. Collectively, these results suggest that the differences found in upper- and lower-body strength changes in the current study and in some previous studies may be a function of the effect of specific muscle type and anatomic location on the use of HMB in different muscles rather than a generalized upper- or lower-body regional difference. Limitations of the current study in determining differential sensitivity to HMB in various muscle groups are that strength measures of only 3 lifts (leg extension, bench press, and bicep preacher curl) were measured, that no measures of muscle cross-sectional area to determine hypertrophy were taken, and that the effect of HMB on protein turnover was not investigated directly. To our knowledge, no other research has directly examined the effect of HMB on protein turnover in humans, which is probably fortunate because methodological resolution may not warrant the investment.
It is possible that dietary fats and total energy intake may have some association with HMB's mechanism of action. We found evidence from dietary diaries to suggest increased total fat and energy intake in the HMB group over the study duration, relative to the placebo group. The percent increase in energy had a moderate correlation with the percent increase in lower-body strength in the HMB group, whereas in the placebo group there was a moderate, negative correlation between fat intake and lower-body strength. If HMB acts as suggested via accentuating cholesterol synthesis (19,20,31) and is used as a structural component of cell membranes (31), it may support membrane function that is essential for excitation and optimal contractile performance during resistance exercise. Alternatively, HMB may interact with other nutrients that are similarly used in muscle cell-membrane structure and functioning; for instance, the dietary fatty-acid profile is known to modulate skeletal muscle fatty-acid profile and, hence, affect membrane stability and functioning (2). Although an interesting discussion point, data from dietary diaries are prone to error, particularly underestimation of total energy intake because of underreporting of some foods such as mayonnaise and high-fat spreads (6). Additionally, whether a change in dietary composition would be sufficient to induce a synergistic interaction with HMB is not easily reconciled. Consequently, these relationships should be viewed conservatively.
With respect to body composition measures, we observed trivial gains in lean body mass and small or likely trivial reducing effects in fat mass in response to HMB supplementation. There was, however, a likely decrease in the supraspinale skinfold, and although this may indicate a decrease in abdominal subcutaneous fat, which is readily mobilized with physical activity and dietary change (18), this was not supported by like changes in abdominal or iliac crest skinfolds. These findings are consistent with most previous research (13,14,21,23,25,27,32) but differ from the results of others (8,21,35) who have shown significant decreases in fat mass. Discrepancies in results could be related to differing methodologies used to measure body composition and the inherent reliability and validity of these methods. In the present study, the coefficients of variation were greater than the percentages of change for the BIA and supraspinale skinfold measurements, which likely contributes to the lowered statistical confidence in the observed reducing patterns found in these measures.
To conclude, in trained men, supplementation of HMB in conjunction with resistance training may result in meaningful improvements in lower-body strength. Benefits to lean mass are unlikely, but small reductions in fat mass are possible.
The magnitude of the leg strength gain (leg extension) observed in the present study (9%) is substantial relative to the likely smallest worthwhile effect in trained lifers of around 1.2%. If the quadriceps outcome transpires to other key lower-body muscle groups (e.g., hip extensors and flexors), then the lower body (or the lower-body component of competitive compound lift performances) may be substantially enhanced, but further research is required. We found that gains in lean mass with HMB are likely to be trivial, but the finding of a possible small reducing effect of HMB on fat mass may have been clouded by the error associated with body fat assessment. Although small reductions in fat mass are possible with HMB and may be of interest to competitive body builders, for the average recreational resistance exerciser most concerned with fitness and health, the trivial (or, at best, small) possible benefits to body fat reduction, combined with the high cost of the supplement, suggest that HMB is of minor worth.
The authors would like to express their gratitude to Ms. Megan Gibbons for her help with the study and to Ms. Shirley McKain and staff at the YMCA North Shore, Auckland, for use of the gym facilities.
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