Superior bioavailability of the calcium salt form of ß-hydroxy-ß-methylbutyrate compared with the free acid form.

We investigated the bioavailability of the calcium salt (HMB-Ca) and the free acid (HMB-FA) forms of ß-hydroxy-ß-methylbutyrate (HMB). Sixteen young individuals received the following treatments on three different occasions in a counterbalanced crossover fashion: (1) HMB-FA in clear capsules; (2) HMB-Ca in gelatine capsules; (3) HMB-Ca dissolved in water. All treatments provided 1 g of HMB. Blood samples were taken before and on multiple time points following ingestion. The following parameters were calculated: peak plasma (Cmax), time to peak (Tmax), slope of HMB appearance in blood, area under the curve (AUC), half-life time (t1/2) and relative bioavailability (HMB-Ca in water set as reference). All treatments led to rapid and large increases in plasma HMB. HMB-Ca in capsules and in water showed similar plasma HMB values across time (p = 0.438). HMB-FA resulted in lower concentrations vs. the other treatments (both p < 0.001). AUC (HMB-Ca in capsules: 50,078 ± 10,507; HMB-Ca in water: 47,871 ± 10,783; HMB-FA: 29,130 ± 12,946 µmol L-1 × 720 min), Cmax (HMB-Ca in capsules: 229.2 ± 65.9; HMB-Ca in water: 249.7 ± 49.7; HMB-FA: 139.1 ± 67.2 µmol L-1) and relative bioavailability (HMB-Ca in capsules: 104.8 ± 14.9%; HMB-FA: 61.5 ± 17.0%) were lower in HMB-FA vs. HMB-Ca (all p < 0.001). HMB-Ca in water resulted in the fastest Tmax (43 ± 22 min) compared to HMB-Ca in capsules (79 ± 40 min) and HMB-FA (78 ± 21 min) (all p < 0.05), while t1/2 was similar between treatments. To conclude, HMB-Ca exhibited superior bioavailability compared to HMB-FA, with HMB-Ca in water showing faster absorption. Elimination kinetics were similar across all forms, suggesting that the pharmaceutical form of HMB affects the absorption rates, but not its distribution or elimination.

The Muscle Carnosine Response to Beta-Alanine Supplementation: A Systematic Review With Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis.

Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn), and has many proven, and purported, ergogenic, and therapeutic benefits. Currently, many questions on the nature of the MCarn response to supplementation are open, and the response to these has considerable potential to enhance the efficacy and application of this supplementation strategy. To address these questions, we conducted a systematic review with Bayesian-based meta-analysis of all published aggregate data using a dose response (Emax) model. Meta-regression was used to consider the influence of potential moderators (including dose, sex, age, baseline MCarn, and analysis method used) on the primary outcome. The protocol was designed according to PRISMA guidelines and a three-step screening strategy was undertaken to identify studies that measured the MCarn response to BA supplementation. Additionally, we conducted an original analysis of all available individual data on the MCarn response to BA supplementation from studies conducted within our lab (n = 99). The Emax model indicated that human skeletal muscle has large capacity for non-linear MCarn accumulation, and that commonly used BA supplementation protocols may not come close to saturating muscle carnosine content. Neither baseline values, nor sex, appeared to influence subsequent response to supplementation. Analysis of individual data indicated that MCarn is relatively stable in the absence of intervention, and effectually all participants respond to BA supplementation (99.3% response [95%CrI: 96.2-100]).

Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.

Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography - HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error.

24-Week ß-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males.

PURPOSE: To investigate the effects of chronic beta-alanine (BA) supplementation on muscle taurine content, blood clinical markers and sensory side-effects. METHODS: Twenty-five healthy male participants (age 27 ± 4 years, height 1.75 ± 0.09 m, body mass 78.9 ± 11.7 kg) were supplemented with 6.4 g day-1 of sustained-release BA (N = 16; CarnoSyn™, NAI, USA) or placebo (PL; N = 9; maltodextrin) for 24 weeks. Resting muscle biopsies of the m. vastus lateralis were taken at 0, 12 and 24 weeks and analysed for taurine content (BA, N = 12; PL, N = 6) using high-performance liquid chromatography. Resting venous blood samples were taken every 4 weeks and analysed for markers of renal, hepatic and muscle function (BA, N = 15; PL, N = 8; aspartate transaminase; alanine aminotransferase; alkaline phosphatase; lactate dehydrogenase; albumin; globulin; creatinine; estimated glomerular filtration rate and creatine kinase). RESULTS: There was a significant main effect of group (p = 0.04) on muscle taurine, with overall lower values in PL, although there was no main effect of time or interaction effect (both p > 0.05) and no differences between specific timepoints (week 0, BA: 33.67 ± 8.18 mmol kg-1 dm, PL: 27.75 ± 4.86 mmol kg-1 dm; week 12, BA: 35.93 ± 8.79 mmol kg-1 dm, PL: 27.67 ± 4.75 mmol kg-1 dm; week 24, BA: 35.42 ± 6.16 mmol kg-1 dm, PL: 31.99 ± 5.60 mmol kg-1 dm). There was no effect of treatment, time or any interaction effects on any blood marker (all p > 0.05) and no self-reported side-effects in these participants throughout the study. CONCLUSIONS: The current study showed that 24 weeks of BA supplementation at 6.4 g day-1 did not significantly affect muscle taurine content, clinical markers of renal, hepatic and muscle function, nor did it result in chronic sensory side-effects, in healthy individuals. Since athletes are likely to engage in chronic supplementation, these data provide important evidence to suggest that supplementation with BA at these doses for up to 24 weeks is safe for healthy individuals.

Effects of ß-alanine and sodium bicarbonate supplementation on the estimated energy system contribution during high-intensity intermittent exercise.

The effects of ß-alanine (BA) and sodium bicarbonate (SB) on energy metabolism during work-matched high-intensity exercise and cycling time-trial performance were examined in 71 male cyclists. They were randomised to receive BA + placebo (BA, n = 18), placebo + SB (SB, n = 17), BA + SB (BASB, n = 19), or placebo + placebo (PLA, n = 18). BA was supplemented for 28 days (6.4 g day-1) and SB (0.3 g kg-1) ingested 60 min before exercise on the post-supplementation trial. Dextrose and calcium carbonate were placebos for BA and SB, respectively. Before (PRE) and after (POST) supplementation, participants performed a high-intensity intermittent cycling test (HICT-110%) consisting of four 60-s bouts at 110% of their maximal power output (60-s rest between bouts). The estimated contribution of the energy systems was calculated for each bout in 39 of the participants (BA: n = 9; SB: n = 10; BASB: n = 10, PLA: n = 10). Ten minutes after HICT-110%, cycling performance was determined in a 30-kJ time-trial test in all participants. Both groups receiving SB increased estimated glycolytic contribution in the overall HICT-110%, which approached significance (SB: + 23%, p = 0.068 vs. PRE; BASB: + 18%, p = 0.059 vs. PRE). No effects of supplementation were observed for the estimated oxidative and ATP-PCr systems. Time to complete 30 kJ was not significantly changed by any of the treatments, although a trend toward significance was shown in the BASB group (p = 0.06). We conclude that SB, but not BA, increases the estimated glycolytic contribution to high-intensity intermittent exercise when total work done is controlled and that BA and SB, either alone or in combination, do not improve short-duration cycling time-trial performance.

Twenty-four Weeks of ß-Alanine Supplementation on Carnosine Content, Related Genes, and Exercise.

INTRODUCTION: Skeletal muscle carnosine content can be increased through ß-alanine (BA) supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity. PURPOSE: This study aimed to investigate the effects of 24 wk of BA supplementation on muscle carnosine content, gene expression, and high-intensity cycling capacity (CCT110%). METHODS: Twenty-five active males were supplemented with 6.4 g·d of sustained release BA or placebo for a 24 wk period. Every 4 wk participants provided a muscle biopsy and performed the CCT110%. Biopsies were analyzed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2, and PAT1). RESULTS: Carnosine content was increased from baseline at every time point in BA (all P < 0.0001; week 4 = +11.37 ± 7.03 mmol·kg dm, week 8 = +13.88 ± 7.84 mmol·kg dm, week 12 = +16.95 ± 8.54 mmol·kg dm, week 16 = +17.63 ± 8.42 mmol·kg dm, week 20 = +21.20 ± 7.86 mmol·kg dm, and week 24 = +20.15 ± 7.63 mmol·kg dm) but not placebo (all P > 0.05). Maximal increases were +25.66 ± 7.63 mmol·kg dm (range = +17.13 to +41.32 mmol·kg dm), and absolute maximal content was 48.03 ± 8.97 mmol·kg dm (range = 31.79 to 63.92 mmol·kg dm). There was an effect of supplement (P = 0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P = 0.05) with possible to almost certain improvements across all weeks. CONCLUSIONS: Twenty-four weeks of BA supplementation increased muscle carnosine content and improved high-intensity cycling capacity. The downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with BA supplementation, whereas the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of BA may also bear a major influence on muscle carnosine content.

(In)Consistencies in Responses to Sodium Bicarbonate Supplementation: A Randomised, Repeated Measures, Counterbalanced and Double-Blind Study.

OBJECTIVES: Intervention studies do not account for high within-individual variation potentially compromising the magnitude of an effect. Repeat administration of a treatment allows quantification of individual responses and determination of the consistency of responses. We determined the consistency of metabolic and exercise responses following repeated administration of sodium bicarbonate (SB). DESIGN AND METHODS: 15 physically active males (age 25±4 y; body mass 76.0±7.3 kg; height 1.77±0.05 m) completed six cycling capacity tests at 110% of maximum power output (CCT110%) following ingestion of either 0.3 g∙kg-1BM of SB (4 trials) or placebo (PL, 2 trials). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, post-exercise and 5-min post-exercise. Total work done (TWD) was recorded as the exercise outcome. RESULTS: SB supplementation increased blood pH, bicarbonate and base excess prior to every trial (all p ≤ 0.001); absolute changes in pH, bicarbonate and base excess from baseline to pre-exercise were similar in all SB trials (all p > 0.05). Blood lactate was elevated following exercise in all trials (p ≤ 0.001), and was higher in some, but not all, SB trials compared to PL. TWD was not significantly improved with SB vs. PL in any trial (SB1: +3.6%; SB2 +0.3%; SB3: +2.1%; SB4: +6.7%; all p > 0.05), although magnitude-based inferences suggested a 93% likely improvement in SB4. Individual analysis showed ten participants improved in at least one SB trial above the normal variation of the test although five improved in none. CONCLUSIONS: The mechanism for improved exercise with SB was consistently in place prior to exercise, although this only resulted in a likely improvement in one trial. SB does not consistently improve high intensity cycling capacity, with results suggesting that caution should be taken when interpreting the results from single trials as to the efficacy of SB supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02474628.