Fatigue resistance in repeated high-intensity bouts of exercise is a much sought after attribute in athletics. During fatiguing contractions, acute adaptations in blood flow occur to stave off declines in force generating capacity (1,6). There is a tight coupling between oxygen demand in skeletal muscle and increases in blood flow (6). A great deal of research suggests that it is red blood cells that regulate this response by acting as “oxygen sensors” through secreting adenosine-5′-triphosphate (ATP) into the plasma under conditions of low O2 availability (6). Extracellular ATP directly promotes the increased synthesis and release of nitric oxide and prostacyclin (PGl2) within skeletal muscle and therefore directly affects tissue vasodilation and blood flow (20). This is supported by research suggesting increased vasodilation and blood flow in response to intra-arterial infusion of ATP (8).
The physiological effects of ATP have led researchers to investigate the efficacy of oral supplementation of ATP (14). However, Coolen et al. (2) questioned the bioavailability of oral ATP supplementation, but if sampled in venous portal blood, oral ATP is indeed bioavailable (15). Measuring the bioavailability of oral ATP in the systemic blood may be difficult as ATP in blood is primarily found in erythrocytes (9). Any increases in ATP or metabolites of ATP, adenosine in particular, are likely to affect systemic purinergic signaling (11). Support for ATP's effects was first demonstrated by Jordan et al. (13) who found that 225 mg per day of enteric-coated ATP supplementation for 15 days resulted in increased total bench press lifting volume (i.e., sets × repetitions × load) and within-group set-1 repetitions to failure. More recently, Rathmacher et al. (22) found that 15 days of 400 mg per day of ATP supplementation increased minimum peak torque in set 2 of a knee extensor bout. Collectively, the results discussed indicate that ATP supplementation maintains performance and increases training volume under high fatiguing conditions. However, greater fatigue increases recovery demands between training sessions. One possible nutrient that may, therefore, augment ATP's effectiveness is the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) (21,27).
Current evidence suggests that HMB acts by speeding regenerative capacity from muscle damaging exercise (19,30,34). Moreover, we have shown that 12 weeks of β-hydroxy-β-methylbutyrate free acid (HMB-FA) supplementation increases skeletal muscle hypertrophy, strength, and power in trained athletes (33). Finally, acute ingestion of 2.4 g of HMB-FA has been demonstrated to increase skeletal muscle protein synthesis and decrease protein breakdown by 70 and 57%, respectively (29).
Given the volume modulating effects of ATP, and the ability of HMB to augment recovery after high volume training, it is possible that supplementing the combination may have synergistic effects on long-term training adaptations. Therefore, the primary purpose of this study was to test the hypothesis that supplementation with HMB-FA/ATP would result in advantageous effects on measures of muscle mass, strength, and power during a 12-week resistance training protocol. The secondary purpose of our investigation was to determine if HMB-FA/ATP supplementation was able to prevent the typical decay seen in performance after an overreaching cycle performed in the ninth and 10th weeks of the study.
Experimental Approach to the Problem
This study was a randomized, double-blind, placebo-, and diet-controlled experiment consisting of 12 weeks of periodized resistance training designed to test the effects of HMB-FA combined with ATP supplementation on muscle mass, strength, and power. The training protocol was divided into 3 phases (Tables 1, 2, and 3). Phase 1 consisted of a nonlinear periodized resistance training program (3 times per week) modified from Kraemer et al. (16,17) (Table 1). Phase 2 (Table 2) consisted of a 2-week overreaching cycle. Finally, phase 3 consisted of a tapering of the training volume for weeks 11 and 12 (Table 3). Muscle mass and body composition were measured at baseline (week 0) and at the end of weeks 4, 8, and 12. Muscle strength and power were measured at baseline (week 0) and at the ends of weeks 4, 8, 9, 10, and 12. Finally, perceived recovery status (PRS), resting plasma testosterone, cortisol, C-reactive protein (CRP), and creatine kinase (CK) were measured at baseline (week 0) and after weeks 1, 4, 8, 9, 10, and 12. Urinary 3-methylhistidine to creatinine ratio (3MH:Cr) was measured at baseline (week 0) and after weeks 1, 8, 9, and 10 to assess protein degradation after changes in training intensity. An overview of the study design is summarized in Figure 1.
Seventeen resistance-trained males aged 21.7 ± 0.4 years (20-28 years of age) with an average squat, bench press, and deadlift of 1.7 ± 0.07, 1.3 ± 0.05, and 2.0 ± 0.06 times their body weight were recruited for the study. Participants could not participate if they were currently taking anti-inflammatory agents, any other performance-enhancing supplement, or if they smoked. There were no differences between the participants for age (placebo = 22.0 ± 0.8, HMB-FA/ATP = 21.4 ± 0.3 years); height (placebo = 180.9 ± 2.5, HMB-FA/ATP = 177.2 ± 1.3 cm); body mass (placebo = 87.1 ± 4.8, HMB-FA/ATP = 81.9 ± 2.1 kg); or body mass index (placebo = 26.4 ± 0.7, HMB-FA/ATP = 26.1 ± 0.6) at the start of the study. Each participant signed an informed consent approved by the University of Tampa Institutional Review Board before participating in the study. The study was conducted as per good clinical practices guidelines and as per the Helsinki Declaration. The study was listed at ClinicalTrials.gov with the identifier NCT01508338.
Muscle Strength, Power, Body Composition, and Skeletal Muscle Hypertrophy Testing
After familiarization with the testing procedures, muscle strength was assessed through 1 repetition maximum (1RM) testing of the back squat, bench press, and deadlift. Each lift was performed as described by the International Powerlifting Federation rules as described in Gilbert and Lees (5). Body composition (lean body mass [LBM], fat mass, and total mass) was determined by dual x-ray absorptiometry (DXA; Lunar Prodigy enCORE 2008, Madison, WI, USA). Skeletal muscle hypertrophy was determined through the combined changes in ultrasonography-determined muscle thickness (MT) of the vastus lateralis and vastus intermedius muscles. Measurements of MT were taken at 50% of the distance between the head of the greater trochanter to the lateral epicondyle. The probe was placed longitudinally in the sagittal plane parallel to the muscle tissue. The intraclass correlation coefficient (ICC) for the test-retest as determined on separate days of MT measurements was r = 0.97.
Muscle power was assessed during maximal cycling (Wingate test) and jumping movements. During the cycling test, volunteers were instructed to cycle against a predetermined resistance (7.5% of body weight) as fast as possible for 10 seconds (26). The saddle height was adjusted to the individual's height to produce a 5–10° knee flexion while the foot was in the low position of the central void. A standardized verbal stimulus was provided to each participant. Power output was recorded in real time during the 10-second sprint test, by a computer connected to the standard cycle ergometer (Monark model 894e; Monark, Vansbro, Sweden). Peak power (PP) was recorded using Monark Anaerobic Wingate Software, Version 1.0 (Monark). The ICC of muscle PP was r = 0.96.
Measurements of PP were also taken during a vertical jump test performed on a multicomponent AMTI force platform (Advanced Mechanical Technology, Inc., Watertown, MA, USA) interfaced with a personal computer at a sampling rate of 1,000 Hz (18). Data acquisition software (LabVIEW, version 7.1; National Instruments Corporation, Austin, TX, USA) was used to calculate PP. The best attempt out of 3 attempts was used for analysis. Peak power was calculated as the peak combination of ground reaction force and peak velocity during the accelerated launch on the platform. The ICC of the vertical jump PP test was r = 0.97.
Supplementation, Diet Control, and Exercise Protocol
Before the study, participants were randomly assigned to receive either 3 g per day of HMB-FA (Metabolic Technologies, Inc., Ames, IA, USA) plus 400 mg per day of Disodium ATP (PEAK ATP; TSI, Inc., Missoula, MT, USA), or a placebo. The HMB-FA was provided as gel packs containing 1 g of HMB-FA, polydextrose, water, corn syrup, stevia, and orange flavoring; and the ATP was provided in 2-piece hard gel capsules. Placebos were provided as matching gel packs and 2-piece hard gel capsules containing maize starch. The HMB-FA administration was spread out in 3 servings per day, whereas the ATP was given as 1 serving. Subjects were instructed to consume a gel pack and capsule 30 minutes before exercise as well as 1 gel pack before lunch and 1 before dinner. On the nontraining days, participants were instructed to consume 1 gel pack and the hard gel capsule 30 minutes before breakfast and 1 additional gel pack with lunch and dinner. The supplementation was continued daily throughout the training and testing protocols.
The participants must not have taken any nutritional supplements for at least 3 months before the start of data collection. Two weeks before and throughout the study, participants were placed on a diet consisting of 25% protein, 50% carbohydrates, and 25% fat by a registered dietician who specialized in sports nutrition. The participants met as a group with the dietitian, and they were given individual meal plans at the beginning of the study. Diet counseling was continued weekly on an individual basis throughout the study.
All participants performed a high volume resistance training protocol during the 12-week study. The phases of the study and measurements taken are shown in Figure 1, and the exercise protocols for each phase of the study are shown in Tables 1, 2, and 3. The training was divided into 3 phases, with phase 1 consisting of daily undulating periodization (weeks 1–8), phase 2 consisting of the overreaching cycle (weeks 9 and 10), and phase 3 consisting of the taper cycle (weeks 11 and 12).
The purity of both the HMB-FA and ATP was determined by the manufacturer (TSI, Inc.) using high-pressure liquid chromatography. Both products were near 100% pure and met all certificate of analysis (C of A) specifications. The primary impurities in the HMB-FA were acetate and water. Metabolic Technologies, Inc., independently assayed both the HMB-FA and ATP for purity and confirmed the C of A results. In addition, MTI assayed the HMB-FA for dehydroepiandrosterone (DHEA), a contaminant which has been found in nutritional supplements, using gas chromatography-mass spectrometry. No DHEA was detected in the HMB-FA. Additionally, a sample of the HMB-FA was sent to an independent laboratory (MVTL Laboratories, Inc., New Ulm, MN, USA) for microbial and heavy metals testing. The HMB-FA tested negative for E. coli, Listeria, and Salmonella. Copper, zinc, calcium, mercury, cadmium, and lead were less than the detection limits, and arsenic was detected at 37 ppb, which is low, and well below supplement and food standards.
Resting Blood Draws
All blood draws throughout the study were obtained by means of venipuncture after a 12-hour fast by a trained phlebotomist. Whole blood was collected and transferred into appropriate tubes for obtaining serum and plasma and centrifuged at 1,500g for 15 minutes at 4° C. Resulting serum and plasma were then aliquoted and stored at −80° C until subsequent analyses.
Samples were thawed 1 time and analyzed in duplicate for each analyte. All blood draws were scheduled at the same time of the day to negate confounding influences of diurnal hormonal variations. Serum total and free testosterone, cortisol, and CRP were assayed using ELISA kits obtained from Diagnostic Systems Laboratories (Webster, TX, USA). All hormones were measured in the same assay on the same day to avoid inter-assay variance. Intra-assay variance was <3% for all analytes. Serum CK, an indirect marker of muscle damage, was measured using colorimetric procedures at 340 nm (Diagnostics Chemicals, Oxford, CT, USA). Twenty-four hour urine collections were performed and 3-methylhistine (3MH) was determined by previously described methods (23,34). Urinary creatinine (Cr) was measured using a colorimetric Jaffe's reaction (Caymen Chemical, Ann Arbor, MI, USA). The 3MH:Cr ratio over the 24-hour period was then calculated.
Perceived Recovery Status Scale
Perceived Recovery Status (PRS) scale was measured at weeks 0, 1, 4, 8, 9, 10, and 12 to assess subjective recovery during the training phases. The PRS scale consists of values between 0 and 10, with 0–2 being very poorly recovered and with anticipated declines in performance, 4–6 being low to moderately recovered and expected similar performance, and 8–10 representing high perceived recovery with expected increases in performance (25,34).
Baseline characteristics were analyzed by a 1-way analysis of variance (ANOVA) model using the Proc GLM procedure in SAS (version 9.1; SAS Institute, Cary, NC, USA). The main effect of treatment (Trt) was included in the model. To test the hypothesis that supplementation with HMB-FA/ATP would result in advantageous effects on measures of muscle mass, strength, power, muscle damage, hormonal status, and PRS during a 12-week RT protocol, a repeated-measures ANOVA using the Proc Mixed procedure in SAS was used. The initial value, week 0, was used as a covariate with the main effects of HMB-FA/ATP and time in the model. The actual values were used for the statistical analysis. To determine if HMB-FA/ATP supplementation was able to prevent the typical decay seen in performance after an overreaching cycle, a repeated-measures ANOVA with the Proc Mixed procedure in SAS was used; however, the value measured at the week 8 time point was used as a covariate with the main effects of HMB-FA/ATP and time. The least squares means procedure was then used to compare Trt means at each time point (post hoc t-test). The number of subjects (n) was based on LBM changes as found in the study by Kraemer et al. (16). Statistical significance was determined at p ≤ 0.05.
Muscle Strength and Power
As a result of the periodized resistance training, both muscle strength and power increased over the 12-week study (time, p < 0.001; Figures 2–4). Percent change in total strength, sum of 1RM of squat, bench press, and deadlift, over the 12-week study is shown in Figure 2. Supplementation with HMB-FA/ATP significantly increased total strength gains during the study (Trt × time, p < 0.001) and the 12-week total strength increase was 96.0 ± 8.2 kg in the HMB-FA/ATP-supplemented participants and 25.3 ± 7.3 kg in the placebo-supplemented participants (t-test, p ≤ 0.05; Figure 2). During the overreaching cycle in weeks 9 and 10, total strength declined in the placebo-supplemented participants by 20.2 ± 5.1 kg from weeks 8–10, whereas total strength increased 6.0 ± 3.6 kg in the HMB-FA/ATP-supplemented participants (t-test, p ≤ 0.05). Figures 3A, B, and C show the percentage gains for bench press, squat, and deadlift, respectively. In each exercise, HMB-FA/ATP supplementation prevented the decrease in both upper- and lower-body strength during the overreaching phase of the training.
Muscular power was assessed using both the vertical jump and Wingate PP tests and the results are shown in Figures 4A, B, respectively. Both of these measures of power were significantly increased during the study with HMB-FA/ATP supplementation (Trt × time, p < 0.001). Compared with placebo-supplemented participants, vertical jump power was significantly increased at all measurement times with the 12-week total increase in the HMB-FA/ATP-supplemented participants of 1,076 ± 40 W compared with 630 ± 56 W in the placebo-supplemented participants (t-test, p ≤ 0.05; Figure 4A). Similarly, HMB-FA/ATP supplementation resulted in a greater increase in Wingate PP over the 12-week training period. The HMB-FA/ATP-supplemented participants gained 210 ± 20 W compared with the placebo-supplemented participants gain of 103 ± 21 W (t-test, p ≤ 0.05; Figure 4B). Over the study, HMB-FA/ATP supplementation resulted in increased Wingate PP at 4, 8, 9, 10, and 12 weeks (t-test, p ≤ 0.05).
As expected, vertical jump power during the overreaching cycle decreased in the placebo-supplemented group by 293 ± 28 W compared with a much smaller decrease in the HMB-FA/ATP-supplemented group of only 128 ± 29 W (t-test, p ≤ 0.05; Figure 4A). Similarly, during the 2-week overreaching cycle Wingate PP decreased by 44 ± 18 W in the placebo group and only 21 ± 11 W in the HMB-FA/ATP group (t-test, p ≤ 0.05; Figure 4B).
Body Composition and Muscle Hypertrophy
Resistance training resulted in increased LBM and quadriceps thickness (time, p < 0.001), whereas fat percentage was decreased with the training at weeks 0, 4, 8, and 12 (time, p < 0.001). Lean body mass increased 2.1 ± 0.5 kg in placebo-supplemented participants, whereas HMB-FA/ATP-supplemented participants gained 8.5 ± 0.8 kg of LBM over the 12-week study (t-test, p ≤ 0.05; Figure 5). Similarly, fat percentage decreased by 2.4 ± 1.1% and 8.5 ± 0.9% in the placebo- and HMB-FA/ATP-supplemented participants over the 12-week study, respectively (t-test, p ≤ 0.05). Training resulted in increased quadriceps thickness over the 12-week study (time, p < 0.001; Figure 6). Supplementation with HMB-FA/ATP resulted in a 7.8 ± 0.4 mm increase in quadriceps thickness, whereas the placebo-supplemented participants gained only 2.4 ± 0.7 mm in thickness over the 12 weeks (Trt × time, p < 0.001).
Muscle Damage, Hormonal Status, and Performance Recovery Scale
Muscle damage was assessed by blood CK, which was increased by training, particularly after the changes in training volume at the initiation of the study and at weeks 9 and 10 during the overreaching cycle (time, p < 0.001). The initial training resulted in a 361 ± 69% increase and the 2-week overreaching cycle resulted in a 153 ± 62% increase in CK levels in the placebo-supplemented group. Supplementation with HMB-FA/ATP significantly attenuated the increase in CK at both the initiation of training (weeks 0–1, 104 ± 25% increase, t-test, p ≤ 0.05) and during the overreaching cycle (weeks 9 and 10, 35 ± 17% increase, t-test, p ≤ 0.05). In addition, the CK level in the HMB-FA/ATP-supplemented participants was also lower than in placebo-supplemented participants at week 4 of the 12-week study (t-test, p ≤ 0.05).
The rate of muscle protein degradation was evaluated by measuring urinary 3MH:Cr ratio. Supplementation with HMB-FA/ATP resulted in a significant increase in 3MH:Cr when compared with the placebo group at the initiation of training during week 1 (t-test, p ≤ 0.05); however, no significant difference was observed between the HMB-FA/ATP- and placebo-supplemented groups during the overreaching cycle. C-reactive protein levels were not significantly affected by HMB-FA/ATP supplementation during the study. Supplementation with HMB-FA/ATP did result in decreased cortisol levels compared with placebo supplementation after both the initiation of training, week 1, and the overreaching and taper cycles, weeks 9, 10, and 12 (t-test, p ≤ 0.05). There were no effects seen with HMB-FA/ATP supplementation on either free or total testosterone levels during training.
Muscle recovery and readiness to train in the next training session was measured by perceived recovery status score (PRS; Figure 7). Supplementation with HMB-FA/ATP resulted in the participants maintaining an improved PRS over the 12-week study (Trt × time, p < 0.001). At weeks 1, 4, 9, 10, and 12, the HMB/ATP-supplemented group showed significantly improved PRS compared with the placebo-supplemented group (t-test, p ≤ 0.05). During initiation of training, week 1, PRS decreased from 9.1 ± 0.4 to 4.6 ± 0.5 after 1 week of training, whereas with HMB-FA/ATP supplementation PRS decreased from 9.6 ± 0.2 to 6.6 ± 0.3 (t-test, p ≤ 0.05). The decrease in PRS seen during the overreaching phase of training was also similarly blunted with HMB-FA/ATP supplementation. The PRS with HMB-FA/ATP decreased from 8.5 ± 0.3 to 7.4 ± 0.2 over the 2-week overreaching compared with the placebo-supplemented group that had a much larger decrease from 7.7 ± 0.2 to 4.4 ± 0.3 over this intense training period (Trt × time, p < 0.001).
The primary purpose of this study was to test the hypothesis whether supplementation with HMB-FA/ATP would result an increase in measures of muscle mass, strength, and power during a 12-week periodized resistance training protocol. Our primary findings were that the combination of HMB-FA and ATP enhanced LBM, muscle hypertrophy, strength, and power. Additionally, HMB-FA/ATP prevented declines in strength and power during the overreaching phase, and the supplementation blunted the increase in muscle damage and cortisol during this period of time.
The Effects of HMB/ATP on Skeletal Muscle Strength and Power Development
Strength and power are 2 of the most critical attributes underlying success in sport (24,31). These variables are intimately related and allow athletes to be successful in their respective sport (3,4). The collective results of this study, as well as those from Kraemer et al. (16), suggest that changes in strength and power after HMB supplementation are optimized within the context of a periodized as compared with a nonperiodized training program (25). Moreover, Rathmacher et al. (22) found that 400 mg of supplemental ATP per day for 15 days was effective in improving set-2 leg muscle minimum peak torque and tended to decrease set-3 leg muscle fatigue during 3 successive sets of knee extension exercises. Our group had previously reported the effect of HMB-FA (33) and ATP (32) on LBM when supplemented alone using the identical chronic RT program. In a retrospective evaluation of these studies, supplementation with HMB-FA, ATP, and the HMB-FA/ATP additively increased total strength gains by 77.1 ± 5.6, 55.3 ± 6.0, and 96.0 ± 8.2 kg, respectively, compared with the placebo-supplemented participants who gained 22.4 ± 7.1 kg over the 12-week study. Intriguingly, the percentage increases in vertical jump power were synergistic with HMB and ATP supplemented in combination. Over the 12-week training, vertical jump power increased 614 ± 52, 991 ± 51, 796 ± 75, and 1,076 ± 40 W in placebo, HMB-FA-, ATP-, and HMB-FA/ATP-supplemented groups, respectively. The results of this study suggest that HMB-FA/ATP supplementation may result in increased strength and power adaptations compared with just HMB-FA or ATP supplementation alone. Moreover, the synergistic effects seen in power suggest that for athletic performance the combination of the 2 may be optimal.
The Effects of HMB/ATP on Skeletal Muscle Hypertrophy and Changes in Lean Body Mass
The effects of HMB on indices of muscle mass have been studied for nearly 2 decades (19,30). Recently, Kraemer et al. (16) demonstrated an approximately 3-fold increase in LBM as compared with placebo after 12 weeks of resistance training in men supplemented with HMB. These results demonstrated that HMB can drastically alter skeletal muscle adaptations under periodized training conditions where muscle damage is high (16). However, this study represents the first formal investigation of the effects of HMB plus oral ATP supplementation on LBM and MT after a chronic RT program. These results both agreed with Kraemer et al. (16) and add additional information to the current body of knowledge. In a retrospective evaluation, our previous work with HMB and ATP studies (32,33) LBM was increased in an additive manner by 2.1 ± 0.5, 7.4 ± 0.4, 4.0 ± 0.4, and 8.5 ± 0.8 kg in placebo-, HMB-FA-, ATP-, and HMB-FA/ATP-supplemented participants, respectively. Furthermore, additive increases in quadriceps thicknesses were seen of 2.5 ± 0.6, 7.1 ± 1.2, 4.9 ± 1.0, and 7.8 ± 0.4 mm in the placebo-, HMB-FA-, ATP-, and HMB-FA/ATP-supplemented groups, respectively.
There are a number of possible reasons for the ergogenic effects of HMB-FA/ATP on muscle mass that we have observed. In addition to ATP's capacity to buffer fatigue (22) during repeated high volume sets and increased total training volume, the supplement may increase skeletal muscle blood flow (7), thereby enhancing nutrient and oxygen uptake to the muscle. Additionally, HMB seems to work ideally when training with higher volume. The resulting outcome would then be an improved recovery response and ultimately lead to greater adaptations in skeletal muscle size.
The Effects of HMB/ATP on Muscle Damage and Perceived Recovery
The effects of overtraining and overreaching are complicated and generally lead to negative effects on training outcomes (10,17). The primary cause of overreaching seems to be an imbalance between the training stimulus and recovery (10,17). If the stimulus exceeds the athlete's adaptive capacity, decrements in performance will result, which may ultimately take weeks (overreaching) to months (overtraining) to recover from. For ethical reasons, a great deal of research in strength and conditioning has centered on overreaching protocols rather than overtraining protocols (10).
This study attempted to overreach participants through increased training frequency and volume. Our results indicated that the overreaching cycle was able to decrease power, strength, and perceived recovery in the placebo, but not HMB-FA/ATP combination group. Moreover, the HMB-FA/ATP containing supplement was able to blunt the characteristic rise in CK, an indicator of skeletal muscle damage, and an elevation in the serum stress hormone cortisol after the overreaching cycle. Finally, after a 2-week taper in which the training volume was lowered, the placebo group regained their baseline performance, whereas the HMB-FA/ATP combination group experienced robust increases in both strength and power. These results indicate that a typical overreaching stimulus stagnates recovery capabilities in a nonsupplemented state. However, HMB-FA/ATP provides a novel solution to the problems typically encountered during an overreaching cycle. Although our design was certainly innovative, the outcomes found agree with previously published studies. For example, HMB has been demonstrated to attenuate decreases in power and LBM in calorically restricted judo athletes subjected to high-intensity training loads (12). Additionally, HMB supplementation has also been found to acutely blunt rises in cortisol after resistance training (16,33), as well as decrease or prevent the rise in serum indices of muscle damage (19,28), along with subjective measures of recovery after rigorous acute training regimens (33,34). Moreover, ATP has been found to increase training volume under high-intensity and high fatiguing situations (22).
This is the first study to show that there are both additive and synergistic effects when combining HMB and ATP supplementation. The collective findings of this study suggest that supplementation with HMB/ATP in combination with a high intensity, frequently undulating, periodization training model results in increases in LBM, muscle hypertrophy, strength, and power. Moreover, when faced with greater training frequencies, as demonstrated with the overreaching cycle of training, HMB/ATP may not only prevent typical declines in performance that are characteristic of overreaching but may also result in additional gains in strength. Elite athletes and military personnel who have to train at consistently high levels may benefit from HMB/ATP supplementation. Future research should seek to elucidate the underlying synergistic mechanisms that may exist between HMB/ATP.
This research was funded in part through a grant from by TSI, Inc., Missoula, MT, USA, and in part by a grant from Metabolic Technologies, Inc., Ames, IA, USA. TSI, Inc., also provided the Peak ATP and placebo supplements used in the study. R. P. Lowery, J. M. Joy, M. C. Shelley, R. Jäeger, M. Purpura, S. M. C. Wilson, and J. M. Wilson declare no competing interests. J. Rathmacher, J. Fuller, and S. Baier are employed by Metabolic Technologies, Inc., which engages in business trade with TSI, Inc. The publication of the results of this study does not constitute an endorsement of any products used in the study by the National Strength and Conditioning Association.
1. Barnes JN, Trombold JR, Dhindsa M, Lin HF, Tanaka H. Arterial stiffening following eccentric exercise-induced muscle damage. J Appl Physiol (1985) 109: 1102–1108, 2010.
2. Coolen EJ, Arts IC, Bekers O, Vervaet C, Bast A, Dagnelie PC. Oral bioavailability of ATP after prolonged administration. Br J Nutr 105: 357–366, 2011.
3. Cormie P, McGuigan MR, Newton RU. Developing maximal neuromuscular power: Part 1–biological basis of maximal power production. Sports Med 41: 17–38, 2011.
4. Cormie P, McGuigan MR, Newton RU. Developing maximal neuromuscular power: Part 2-training
considerations for improving maximal power production. Sports Med 41: 125–146, 2011.
5. Gilbert G, Lees A. Changes in the force development characteristics of muscle following repeated maximum force and power exercise. Ergonomics 48: 1576–1584, 2005.
6. Gonzalez-Alonso J. ATP as a mediator of erythrocyte-dependent regulation of skeletal muscle blood flow and oxygen delivery in humans. J Physiol 590: 5001–5013, 2012.
7. Gonzalez-Alonso J, Mortensen SP, Dawson EA, Secher NH, Damsgaard R. Erythrocytes and the regulation of human skeletal muscle blood flow and oxygen delivery: Role of erythrocyte count and oxygenation state of haemoglobin. J Physiol 572: 295–305, 2006.
8. Gonzalez-Alonso J, Mortensen SP, Jeppesen TD, Ali L, Barker H, Damsgaard R, Secher NH, Dawson EA, Dufour SP. Haemodynamic responses to exercise, ATP infusion and thigh compression in humans: Insight into the role of muscle mechanisms on cardiovascular function. J Physiol 586: 2405–2417, 2008.
9. Gorman MW, Feigl EO, Buffington CW. Human plasma ATP concentration. Clin Chem 53: 318–325, 2007.
10. Halson SL, Jeukendrup AE. Does overtraining exist? An analysis of overreaching and overtraining research. Sports Med 34: 967–981, 2004.
11. Heinonen I, Kemppainen J, Kaskinoro K, Peltonen JE, Sipila HT, Nuutila P, Knuuti J, Boushel R, Kalliokoski KK. Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 302: R385–R390, 2012.
12. Hunga W, Liub T-H, Chenc C-Y, Chang C-K. Effect of [beta]-hydroxy-[beta]-methylbutyrate supplementation during energy restriction in female judo athletes. J Exerc Sci Fit 8: 50–53, 2010.
13. Jordan AN, Jurca R, Abraham EH, Salikhova A, Mann JK, Morss GM, Church TS, Lucia A, Earnest CP. Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc 36: 983–990, 2004.
14. Khakh BS, Henderson G. ATP receptor-mediated enhancement of fast excitatory neurotransmitter release in the brain. Mol Pharmacol 54: 372–378, 1998.
15. Kichenin K, Seman M. Chronic oral administration of ATP modulates nucleoside transport and purine metabolism in rats. J Pharmacol Exp Ther 294: 126–133, 2000.
16. Kraemer WJ, Hatfield DL, Volek JS, Fragala MS, Vingren JL, Anderson JM, Spiering BA, Thomas GA, Ho JY, Quann EE, Izquierdo M, Hakkinen K, Maresh CM. Effects of amino acids supplement on physiological adaptations to resistance training
. Med Sci Sports Exerc 41: 1111–1121, 2009.
17. Kraemer WJ, Ratamess NA. Fundamentals of resistance training
: progression and exercise prescription. Med Sci Sports Exerc 36: 674–688, 2004.
18. Lowery RP, Duncan NM, Loenneke JP, Sikorski EM, Naimo MA, Brown LE, Wilson FG, Wilson JM. The effects of potentiating stimuli intensity under varying rest periods on vertical jump performance and power. J Strength Cond Res 26: 3320–3325, 2012.
19. Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC Jr, Connelly AS, Abumrad N. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training
. J Appl Physiol (1985) 81: 2095–2104, 1996.
20. Nyberg M, Mortensen SP, Thaning P, Saltin B, Hellsten Y. Interstitial and plasma adenosine stimulate nitric oxide and prostacyclin formation in human skeletal muscle. Hypertension 56: 1102–1108, 2010.
21. Panton LB, Rathmacher JA, Baier S, Nissen S. Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) during resistance training
. Nutrition 16: 734–739, 2000.
22. Rathmacher JA, Fuller JC Jr, Baier SM, Abumrad NN, Angus HF, Sharp RL. Adenosine-5′-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. J Int Soc Sports Nutr 9: 48, 2012.
23. Rathmacher JA, Link GA, Flakoll PJ, Nissen SL. Gas chromatographic/mass spectrometric analysis of stable isotopes of 3-methylhistidine in biological fluids: Application to plasma kinetics in vivo. Biol Mass Spectrom 21: 560–566, 1992.
24. Robbins DW, Docherty D. Effect of loading on enhancement of power performance over three consecutive trials. J Strength Cond Res 19: 898–902, 2005.
25. Sikorski EM, Wilson JM, Lowery RP, Joy JM, Laurent CM, Wilson SM, Hesson D, Naimo MA, Averbuch B, Gilchrist P. Changes in perceived recovery status scale following high-volume muscle damaging resistance exercise. J Strength Cond Res 27: 2079–2085, 2013.
26. Smith JC, Fry AC, Weiss LW, Li Y, Kinzey SJ. The effects of high-intensity exercise on a 10-second sprint cycle test. J Strength Cond Res 15: 344–348, 2001.
27. 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.
28. van Someren KA, Edwards AJ, Howatson G. Supplementation with beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC) reduces signs and symptoms of exercise-induced muscle damage in man. Int J Sport Nutr Exerc Metab 15: 413–424, 2005.
29. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate (HMB) on human skeletal muscle protein metabolism. J Physiol 591: 2911–2923, 2013.
30. 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 (Lond) 5: 1, 2008.
31. Wilson JM, Duncan NM, Marin PJ, Brown LE, Loenneke JP, Wilson SM, Jo E, Lowery RP, Ugrinowitsch C. Meta-analysis of post activation potentiation and power: Effects of conditioning activity, volume, gender, rest periods, and training
status. J Strength Cond Res 27: 854–859, 2013.
32. Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier S, Wilson SMC, Rathmacher JA. Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy, and recovery in resistance-trained men. Nutr Metab (Lond) 10: 57, 2013.
33. Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM, Stout JR, Duncan N, Fuller JC, Baier SM, Naimo MA, Raathmacher J. The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: A randomized, double-blind, placebo-controlled study. Eur J Appl Physiol 114: 1217–1227, 2014.
34. Wilson JM, Lowery RP, Joy JM, Walters JA, Baier SM, Fuller JC Jr, Stout JR, Norton LE, Sikorski EM, Wilson SM, Duncan NM, Zanchi NE, Rathmacher J. beta-Hydroxy-beta-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men. Br J Nutr 110: 538–544, 2013.