John C. Fuller

β-Hydroxy-β-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men.

The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of b-hydroxyb-methylbutyrate (HMB-FA) on indices of muscle damage, protein breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P¼0·004, d ¼ 1·6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9·1 (SEM 0·4) to 4·6 (SEM 0·5)) than in the HMB-FA group (9·1 (SEM 0·3) to 6·3 (SEM 0·3)) (P¼0·005, d ¼ 20·48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P¼0·08, d ¼ 0·12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session.

Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt.

The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

Enhancement of Cellular and Humoral Immunity in Young Broilers by the Dietary Supplementation of β-Hydroxy-β-Methylbutyrate

As a dietary supplement, beta-Hydroxy-beta-Methylbutyrate (HMB), a catabolite of leucine, has been shown to reduce broiler mortality. In a series of experiments, male broilers (Experiments 1 and 2, n = 576) were grown for 21 days on diets that contained HMB at 0, 0.01. 0.05, and 0.10% of diet. In Experiment 3 (n = 240), chicks were fed diets containing 0, 0.05, 0.075, and 0.10% HMB. HMB dietary supplementation did not significantly affect broiler weight gain in any experiment. However, a trend toward increased mean broiler weight gain per bird was observed in Experiments 1 and 3 when HMB was consumed at 0.10% of the diet. Mean feed to gain ratio was not affected by the inclusion of HMB in broiler diets. In Experiment 3, HMB supplemented diets did not affect bursa of Fabricius, thymus, and spleen weights at 21 days of age. Cutaneous basophilic hypersensitivity response against pokeweek mitogen was higher (P < or = 0.05) at 48 and 72 hours post-injection in chicks on 0.05% dietary HMB (Experiment 1). In Experiment 2, this increase occurred 24 hours post-injection in chicks fed HMB at 0.01% of the diet. On the contrary, the T-cell mediated response against PHA-P mitogen was comparable between all dietary treatments in multiple experiments. Macrophage function profiles were determined at 21 days of age. All chicks in experiments 1 and 2 on HMB supplemented diets showed an increase in the recruitment of Sephadex-G50-elicited abdominal exudate cells (AEC). A 2-fold increase in AEC numbers occurred at the 0.10% HMB level (Experiment 1, P < or = 0.05). Although HMB supplementation did not significantly affect the phagocytic potential of the abdominal macrophages, nitrite levels in the macrophage culture supernatants were higher in 0.01% and 0.05% treatment groups as compared to the controls (Experiment 2, P < or = 0.04; Experiment 3, P < or = 0.05). HMB supplementation did not alter the birds ability to clear Escherichiacoli or Salmonella arizona from the bloodstream. Beginning 7 days post-hatch, chicks were injected i.v. with a 7% sheep red blood cells suspension. Serum samples were collected to determine the primary and secondary antibody response. Chicks receiving the 0.1% HMB diet in Experiments 1 and 2 exhibited increased IgG and total anti-sheep red blood cell (SRBC) antibody levels during the primary response. During the secondary response, birds consuming the 0.10% HMB diet had elevated IgM levels as well as increased total anti-SRBC levels over the controls in Experiments 1 and 3. These studies show that HMB supplementation improves several immunological functions in young broilers, and such improvement may result in decreased mortality.

Effects of oral adenosine-5'-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men

BackgroundCurrently, there is a lack of studies examining the effects of adenosine-5′-triphosphate (ATP) supplementation utilizing a long-term, periodized resistance-training program (RT) in resistance-trained populations. Therefore, we investigated the effects of 12 weeks of 400 mg per day of oral ATP on muscular adaptations in trained individuals. We also sought to determine the effects of ATP on muscle protein breakdown, cortisol, and performance during an overreaching cycle.MethodsThe study was a 3-phase randomized, double-blind, and placebo- and diet-controlled intervention. Phase 1 was a periodized resistance-training program. Phase 2 consisted of a two week overreaching cycle in which volume and frequency were increased followed by a 2-week taper (Phase 3). Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of ATP; assessment performance variables also occurred at the end of weeks 9 and 10, corresponding to the mid and endpoints of the overreaching cycle.ResultsThere were time (p < 0.001), and group x time effects for increased total body strength (+55.3 ± 6.0 kg ATP vs. + 22.4 ± 7.1 kg placebo, p < 0.001); increased vertical jump power (+ 796 ± 75 ATP vs. 614 ± 52 watts placebo, p < 0.001); and greater ultrasound determined muscle thickness (+4.9 ± 1.0 ATP vs. (2.5 ± 0.6 mm placebo, p < 0.02) with ATP supplementation. During the overreaching cycle, there were group x time effects for strength and power, which decreased to a greater extent in the placebo group. Protein breakdown was also lower in the ATP group.ConclusionsOur results suggest oral ATP supplementation may enhance muscular adaptations following 12-weeks of resistance training, and prevent decrements in performance following overreaching. No statistically or clinically significant changes in blood chemistry or hematology were observed.Trial registrationClinicalTrials.gov NCT01508338

Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals.

Abstract Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843–1854, 2016—Adenosine-5′-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of &bgr;-hydroxy-&bgr;-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3–5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms.

β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) μmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.

Adenosine-5′-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets.

BackgroundIntracellular concentrations of adenosine-5’-triphosphate (ATP) are many times greater than extracellular concentrations (1–10 mM versus 10–100 nM, respectively) and cellular release of ATP is tightly controlled. Transient rises in extracellular ATP and its metabolite adenosine have important signaling roles; and acting through purinergic receptors, can increase blood flow and oxygenation of tissues; and act as neurotransmitters. Increased blood flow not only increases substrate availability but may also aid in recovery through removal of metabolic waste products allowing muscles to accomplish more work with less fatigue. The objective of the present study was to determine if supplemental ATP would improve muscle torque, power, work, or fatigue during repeated bouts of high intensity resistance exercise.MethodsSixteen participants (8 male and 8 female; ages: 21–34 years) were enrolled in a double-blinded, placebo-controlled study using a crossover design. The participants received either supplemental ATP (400 mg/d divided into 2 daily doses) or placebo for 15 d. After an overnight fast, participants underwent strength and fatigue testing, consisting of 3 sets of 50 maximal knee extensions performed on a Biodex® leg dynamometer.ResultsNo differences were detected in high peak torque, power, or total work with ATP supplementation; however, low peak torque in set 2 was significantly improved (p < 0.01). Additionally, in set 3, a trend was detected for less torque fatigue with ATP supplementation (p < 0.10).ConclusionsSupplementation with 400 mg ATP/d for 15 days tended to reduce muscle fatigue and improved a participant’s ability to maintain a higher force output at the end of an exhaustive exercise bout.

Subchronic (90-day) repeated dose toxicity study of 2-hydroxybenzylamine acetate in rats

ABSTRACT 2‐Hydroxybenzylamine (2‐HOBA), a naturally occurring compound found in buckwheat, can protect cells and tissues from oxidative stress. In this study, 2‐HOBA acetate was orally administered to male and female rats for 90 consecutive days at doses of 100, 500, and 1000 mg·kg BW−1·d−1 (n = 20 per sex/group). Subchronic administration of 2‐HOBA was well tolerated at all dose levels. 2‐HOBA‐treated male rats were slightly heavier in the last weeks of the study, but this difference was very small (<5%), did not show a dose–response relationship, and was not observed in female rats. Similarly, some statistically significant changes in serum biochemistry and hematology parameters were noted, but these were not considered to be of biological or toxicological significance. Sporadic differences in organ weights were observed between groups, but all were small (<10%) and unlikely to indicate toxicity. The incidence of histopathological lesions was similar between treated and control groups across all organs. Based upon these findings, the no‐observed‐adverse‐effect level was determined to be ≥ 1000 mg·kg BW−1·d−1, which was the highest dose tested. These results further support no toxicity associated with oral consumption of 2‐HOBA acetate in rats and the continued development of 2‐HOBA as a dietary supplement or functional food. HighlightsNinety days of daily oral administration of 2‐hydroxybenzylamine (2‐HOBA) acetate was tested in rats.2‐HOBA doses up to 1000 mg·kg BW−1·d−1 did not induce toxicological effects.These results provide additional support for the safety of 2‐HOBA as a functional food agent or dietary supplement.

Oral ATP administration improves blood flow response to exercise in an animal model and in resistance trained athletes

Extracellular adenosine triphosphate (ATP) is hypothesized to stimulate vasodilation by binding to endothelial ATP/UTP-selective P2Y2 receptors; a phenomenon which is posited to be accelerated during exercise. Nonetheless, no studies to our knowledge have delineated if supplemental ATP enhances the blood flow response to exercise. Herein, we used a rat model to examine how different dosages of acute oral ATP administration affected the femoral blood flow response prior to, during, and after an exercise bout. In addition, we performed a single dose chronic administration study in resistance trained athletes.

Effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid, adenosine triphosphate, or a combination on muscle mass, strength, and power in resistance trained individuals

Adenosine-Triphosphate (ATP) supplementation maintains performance and increases volume under high fatiguing contractions. However, greater fatigue increases recovery demands between training sessions. Studies utilizing HMB free acid (HMB-FA) supplementation suggest that the supplement speeds regenerative capacity. However, we are unaware of studies investigating whether synergism exists between the two. Therefore, we investigated the effects of 12 weeks of HMB-FA, ATP, or a combination of the two on lean mass (LBM), strength, and power in trained individuals. We also determined these supplements effects on performance during an overreaching cycle.