The Antioxidant Effect of Beta-Alanine or Carnosine Supplementation on Exercise-Induced Oxidative Stress: A Systematic Review and Meta-Analysis

The objective of this study was to perform a systematic review and meta-analysis of the articles that addressed the effect beta-alanine (BA) or carnosine supplementation on Physical exercise (PE)-induced oxidative stress (OS). We searched throughout PubMed, CAPES Periodic and SPORTDiscus human model peer review, randomized control studies with chronic BA or carnosine supplementation on PE-induced OS. We search papers published before May 2018.  A total of 128 citations were found. Only four articles met criteria for inclusion. All four studies used healthy young (21y) sedentary, recreationally active or athletic participants. After a chorionic BA (~30 days) or carnosine (14 days) supplementation, the studies evaluated PE-induced OS both immediately and several hours after exercise (0.5 to 48 h). In response to PE-induced OS, BA/carnosine supplementation increased total antioxidant capacity (TAC) and glutathione concentrations while decreased pro-oxidant markers and superoxide dismutase (SOD) activity. BA or carnosine supplementation did not prevent the increase in peroxidation markers (e.g., 8-isoprostane, protein carbonyl or malonaldehyde). In humans, following PE-induced OS, initial treatment trials of BA or carnosine supplementation seemed to increase TAC and GSH concentrations, while decreasing SOD activity. Also, albeit mitigating the acute increase in pro-oxidants, treatment did not decrease measured values of peroxidation markers.


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It is well known that carnosine is a potent and safe antioxidant [1]. Recent animal models and 42 humans (with type 2 diabetes) studies has been shown that carnosine supplementation can restore prescribed in disease that presents elevated ROS and RNS (reactive oxygen and nitrogen species, 48 respectively) production, with the intention to improve the antioxidant system and decrease the OS.

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However, both ROS and RNS are necessary to cellular function, although its high production is 50 detrimental, at the same time their low production is also detrimental to cellular function [6].

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Therefore, the prescription of antioxidants cannot be indiscriminate.

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Acute physical exercise (PE) is known to induce high ROS/RNS production and consequently to 53 promote an acute OS milieu [7,8]. Recent evidence has suggested that the acute increase in ROS/RNS 54 production during PE is necessary to promote adaptations (e.g., improve athletic performance and 55 VO2max) and the improvement in the antioxidant system itself [9,10]. It is also suggested that the use 56 of exogenous antioxidants may be counterproductive in individuals who already have a balanced 57 oxidant/antioxidant system [11]. However, beta-alanine (BA; a rate-limiting precursor in the 58 synthesis of carnosine) and carnosine supplementation are popular ergogenic aids and also 59 prescribed indiscriminately as antioxidant for athletic population. Studies with healthy humans 60 [12][13][14] and animal models [15,16] have investigated whether increased carnosine in the skeletal 61 muscle (induced by carnosine or BA supplementation) mitigates the high ROS/RNS production (as 62 well as acute OS milieu condition) during exercise. In animal studies, carnosine and BA 63 supplementation were shown to effectively mitigate the OS produced by exercise [15][16][17]. However, 64 in human studies, the finding were unclear. For instance, both recreationally activity men [13] 65 and women [12] who received BA supplementation had reduced LP after an acute bout of physical 66 exercise (wen compared to pre-supplementation, but not to placebo condition). Although, in other 67 studies with male athletes, carnosine [18] and BA [14] supplementation did not change/mitigate the 68 increase in LP values after an acute bout of PE, despite increasing the GSH (Glutathione) antioxidant 69 potential when compared to pre-treatment condition. Such studies from the same laboratory showed 70 that improvement in antioxidant system seemed to occur only in women when compared to the pre-71 supplementation condition [12,13], instead other laboratories shown improvement in men [14,18].

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Therefore, it is necessary to systematize and meta-analyze studies with humans to evaluate the 73 effectiveness of BA or carnosine supplementation as an antioxidant during PE-induced OS. If

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The search of PubMed, SPORTDiscus and CAPES periodic provided a total of 128 citations (titles 155 and abstracts were accessed). 116 articles were removed (both duplicates and articles that met the 156 exclusion criteria). We examined the full text of the remaining 12 articles and only four articles [12-157 14,18] were included in the review (Fig 1).

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Seven out of eight studies excluded did not meet the criteria of human subjects (animal models 159 were rats and mice). One study involved chronic training [4]  25 heathy recreationally active males (age, 21.9 ± 3.4 y; height, 177.6 ± 5.4 cm; weight, 78.8 ± 9.7 kg) randomly assigned to 28 days of PL or BA (1,6g 3x day, sustained release) supplementation. Blood plasma OS and AO markers were analyzed immediately after, and at 2 and 4 hours after exercise.
40 min on a treadmill at a velocity corresponding to 70%-75% of their measured peak velocity before and after the period of supplementation.
40 min on a treadmill at a velocity corresponding to 70%-75% of their measured peak velocity before and after the period of supplementation 8-ISSO (ELISA)*; SOD, TAC and GSH (colorimetric assay)*

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Comparisons between conditions revealed that immediately after exercise there was a small ES and

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Due to insufficient data, PC and MDA independent analysis was not performed.

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Only the study by Slowinska-Lisowska et al.

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On the other hand, when we compared the conditions involving the later hours after the exercise,

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It was not possible to perform multiple linear regression for ROS/RNS direct markers (H2O2, 3-

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Nitro and NO) due to insufficient data.

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The four studies present less than three reported high or unclear risk domains (Appendix 2).

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Two studies (two high risk) are from the same laboratory and was unable to bling for BA condition 298 (due to paresthesia effect).

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The four studies included in this review observed significant increases in OS after acute physical

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Our ES evaluations (with antioxidant and oxidative stress markers) showed high heterogeneity.

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This meta-analysis pooled together studies with participants from different fitness level, enrolled in

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(immediately after exercise vs. hours after exercise-0.5 to 48 hours) showed that the moment of 375 assessment for both indirect (Fig 3) and direct (Fig 4)