Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized?

Perim, Pedro; Marticorena, Felipe Miguel; Ribeiro, Felipe; Barreto, Gabriel; Gobbi, Nathan; Kerksick, Chad M.; Dolan, Eimear; Saunders, Bryan

doi:10.3389/fnut.2019.00135

Cited by 45 publications

(33 citation statements)

References 74 publications

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“…Furthermore, we optimised both the dosage and the duration of supplementation in order to increase the muscle carnosine response to BA supplementation. 79 In addition, 3.2 g of BA per day for a duration of 8–10 weeks will result in a cumulative dose of 179–224 g of BA, which will lead to significantly augmented muscle carnosine concentrations (>40%). 80 The protocols also embody other factors that can lead to greater muscle carnosine gains, such as supplement formulation (slow-release formula), ingestion timing in relation to meals (coingestion with breakfast and lunch) and exercise (NLPE or NMES training programme as part of PR).…”

Section: Discussionmentioning

confidence: 99%

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials

et al. 2020

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IntroductionExercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD.Methods and analysisTwo randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured.Ethics and disseminationBoth trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19).Trial registration numberNTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).

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Section: Discussionmentioning

confidence: 99%

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials

et al. 2020

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“…However, we hypothesize that iAUC is presumably the most important measure, as iAUC represents the concentration over time above baseline levels. The current dogma is that the increase of carnosine in muscle depends on the bioavailability of β-alanine in muscle [8]. β-alanine is mainly transported into muscle by the taurine transporter, TauT.…”

Section: Discussionmentioning

confidence: 99%

“…Although higher doses have occasionally been investigated [7], the current dosing recommendation for β-alanine is to supplement a single fixed dosage of about 800-1600 mg, three or four times a day [8]. However, occasionally, weight-relative dosages have also been used [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Fragmented Dosing of β-alanine Induces A Body Weight-Independent Pharmacokinetic Response

Stautemas¹,

Loock²,

Stede³

et al. 2019

Nutrients

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Personalised dosing of performance-enhancing food supplements is a hot topic. β-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48–139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = −0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.

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“…For example, it seems that the largest gains in MCarn are attained in the earlier phases of supplementation (see Figure 4). It would be of interest to identify if strategies such as meal co-ingestion [33], intake in proximity to training [39] or intake in slow-release capsules [35] can influence the early response to supplementation [14] and whether this, in turn, meaningfully impacts exercise performance.…”

Section: Discussionmentioning

confidence: 99%

“…It seems that substantial amounts of BA are required to increase MCarn content, with most studies using doses of approximately 3.2 – 6.4 g·day -1 , for periods ranging from 4 – 24 weeks. But many questions about the nature of the muscle carnosine response to BA supplementation remain open, and substantial research efforts are being made to refine BA dosing strategies in order to optimize its efficacy and applicability [14]. For example, inter-individual variation in response to supplementation is high [12], yet little is known about what factors underpin this [15].…”

Section: Introductionmentioning

confidence: 99%

Human Skeletal Muscle has Large Capacity to Increase Carnosine Content in Response to Beta-Alanine Supplementation. A Systematic Review with Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis

Rezende

Swinton

Oliveira

et al. 2019

Preprint

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34Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn), and is ergogenic in many situations. Currently, many questions on the 35 nature of the Mcarn response to supplementation are open, and the response to these has considerable potential to enhance the efficacy and applications 36 of this supplementation strategy. Objective: To conduct a Bayesian analysis of available data on the Mcarn response to BA supplementation. Methods: A 37 systematic review with meta-analysis of individual and published aggregate data using a dose response (Emax) model was conducted. The protocol was 38 designed according to PRISMA guidelines. A three-step screening strategy was undertaken to identify studies that measured the Mcarn response to BA 39 supplementation. In addition, individual data from 5 separate studies conducted in the authors' laboratory were analysed. Data were extracted from all 40 controlled and uncontrolled supplementation studies conducted on healthy humans. Meta-regression was used to consider the influence of potential 41 moderators (including dose, sex, age, baseline Mcarn and analysis method used) on the primary outcome. Results and Conclusion: The Emax model 42 indicated that human skeletal muscle has large capacity for non-linear Mcarn accumulation, and that commonly used BA supplementation protocols may 43 not come close to saturating muscle carnosine content. Neither baseline values, nor sex, appear to influence subsequent response to supplementation. 44 Analysis of individual data indicated that Mcarn is relatively stable in the absence of intervention, and effectually all participants respond to BA 45 supplementation (99.3% response [95%CrI: 96.2 -100]).46 47

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Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized?

Cited by 45 publications

References 74 publications

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials

Fragmented Dosing of β-alanine Induces A Body Weight-Independent Pharmacokinetic Response

Human Skeletal Muscle has Large Capacity to Increase Carnosine Content in Response to Beta-Alanine Supplementation. A Systematic Review with Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis

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