Effect of Taurine Supplement on Aerobic and Anaerobic Outcomes: Meta-Analysis of Randomized Controlled Trials

ABSTRACT Taurine is a well-known free amino acid that has gained prominence in recent years despite its little or no role in protein formation. Few studies on the ergogenic effect of taurine exist with inconsistent results. This study aimed to reach a consensus about whether taurine supplementation is effective on aerobic and anaerobic performance outputs. Google Scholar, Pubmed databases, clinical trial websites, and grey literature were reviewed until November 2021. Mean differences were pooled using random or fixed-effects models according to the heterogeneity degree of related outcomes. Although 17 studies were detected for the meta-analysis between 2001-2021, 15 studies were grouped. Only randomized controlled trials were considered. Taurine supplementation had a significant effect on vertical (MD = 3.60; 95% CI [2.32 to 4.89], p < 0.00001) and countermovement (MD = 8.50; 95% CI [4.78 to 12.22], p < 0.00001) jump performance when compared to a placebo group. Taurine supplementation had no significant effect on V̇o2max level and rate of perceived exertion (respectively, MD = –0.54 mL/kg/min; 95% CI [–6.84 to 5.75], p = 0.87; MD = –0.24; 95% CI [–0.74 to 0.27], p = 0.35) when compared to a placebo group. Taurine improves potentially jumping performance and time to exhaustion.


A B S T R A C T
Taurine is a well-known free amino acid that has gained prominence in recent years despite its little or no role in protein formation. Few studies on the ergogenic effect of taurine exist with inconsistent results. This study aimed to reach a consensus about whether taurine supplementation is effective on aerobic and anaerobic performance outputs. Google Scholar, Pubmed databases, clinical trial websites, and grey literature were reviewed until November 2021. Mean differences were pooled using random or fixed-effects models according to the heterogeneity degree of related outcomes. Although 17 studies were detected for the meta-analysis between 2001-2021, 15 studies were grouped.

INTRODUCTION
T aurine is a well-known free amino acid that has expanded in popularity in recent years and plays little or no part in protein biosynthesis. However, interaction with ion channels provides a variety of physiological functions, including membrane stability and cellular osmoregulation (56,59). Taurine has an intracellular concentration range of around 5-20 mmol/g in many tissues, notably excitable tissues including the skeletal muscle, heart, and brain. Meat, shellfish, sea vegetables, and dairy products are the main sources of dietary taurine (17,40).
The availability of its precursor cysteine affects taurine biosynthesis (17,53). Exercise, which oxidizes the precursor cysteine, is a critical component that can affect taurine production. For instance, high-intensity-induced redox alteration of cysteine might result in a variety of post-translational modifications that affect taurine production, resulting in either muscular adaptation or tiredness (63). External taurine sources may be required in this circumstance. Taurine may help to reduce oxidative damage and restore muscle function in people with muscular dystrophy (17,53,63). In addition, taurineregulated calcium homeostasis can lead to an increase in calcium-binding proteins during muscular contraction, resulting in increased muscle strength and endurance (22,62,70).
Taurine is commonly used orally in the form of capsules or taurine-rich drinks (23,68). Taurine plasma concentrations rise about 10 minutes after consumption and generally peak (0.03-0.06 mmoL) 1 hour later. Taurine's impact on performance is influenced by various aspects, including taurine ingestion timing, administration type, and exercise technique. Taurine levels return to baseline within 6.5 hours after this absorption phase (23). In published human trials, taurine dosages ranged from 500 mg/ d to 10 g/d (58). The amount of taurine present in the muscle is influenced by the training status (higher in trained than untrained muscle and fiber type higher in type I than type II) (24,28). Taurine has been reported to improve exercise performance (47,54) and reduce recovery time from damaging and stressful exercise in some but not all studies (5,31). According to ISSN's (2018) report, the categories of nutritional supplements vary according to the quality and quantity of scientific studies on supplementation (38). Taurine is in the "Limited or Mixed Evidence Supporting Efficacy" category according to this ISSN report. It is believed that more scientific studies are needed to prove its efficacy and safety.
The ergogenic effects of taurine supplementation are still controversial, according to previous studies. Waldron, et al. (67) found that single doses of 1-6 g per day for up to 2 weeks significantly improved endurance exercise performance. Two studies found that taurine might have a role in recovery from muscular injuries and improving resistance exercise performance (13,51). Oral intake of 50 mg/kg 14 days before and 7 days after injury boosted strength along with reducing discomfort and muscle damage indicators (51). Finally, taurine has been shown to work as an antioxidant, improving the ability of the cellular environment to endure exercise stress (9,20). While more research on taurine is being published, the results of these studies are still uncertain for taurine's ability to improve physical performance (5,10).
A previous review study with taurine supplementation addressed the doseresponse relationship in aerobic and strength exercises (10). No previous meta-analysis has examined the effects of taurine on aerobic and anaerobic exercise outcomes. Therefore, the purpose of this meta-analysis was twofold, to evaluate the effects of taurine intake on (a) aerobic and (b) anaerobic outputs. The results are believed to benefit athletes and practitioners in a variety of sports where aerobic and anaerobic capacity and/or power performance are important determinants.

SEARCH STRATEGY AND QUALITY ASSESSMENT OF STUDIES
A systematic literature search was conducted using the PubMed and Google Scholar databases, ClinicalTrials.gov website, and gray literature inputs to find studies published from 2001 to November 2021 that looked at the effects of taurine supplementation on aerobic and anaerobic outputs. The keywords used were as follows: "taurine" AND "aerobic performance," "taurine" AND "anaerobic performance". To confirm that all relevant studies were included in the analysis, a thorough search was conducted by the reference lists of identified related documents. Following the eradication of duplicate articles, each study was evaluated in accordance with predetermined inclusion and exclusion criteria, as stated in Figure 1, to determine which articles were eligible. The Cochrane risk-of-bias tool for randomized controlled trials has been used to assess the quality of each article. Random sequence generation, allocation concealment, blinding, as well as the detection of incomplete outcome data, selective outcome reporting, and other possible reasons for bias are all included in the Cochrane risk-of-bias tool scale (29).

STUDY SELECTION CRITERIA
The study inclusion criteria were as follows: (a) healthy individuals and athletes, (b) reporting aerobic or anaerobic performance markers regardless of the nature of the applied exercises, (c) examining the effect of taurine supplementation, (d) all placebo-controlled single and double-blind experimental studies, and (e) studies in English or Turkish. The study excluded criteria were as follows: (a) coingestion with other supplements, (b) individuals with chronic diseases took part, (c) different outcomes from aerobic or anaerobic performance markers, and (d) nonrandomized controlled trials were excluded from the meta-analysis.

DATA EXTRACTION AND OUTCOME MEASURES
Extracted data included (a) information of studies (author's surname, year, and study design), (b) characteristics of the sample (gender, health, training status, age, and weight), (c) duration of supplementation, (d) dosage and form of taurine supplementation, (e) exercise protocols, (f) outcomes of the study, and (g) side effects of taurine supplementation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to retrieve data. WebPlotDigitizer (https://automeris.io/ WebPlotDigitizer/) was used to read data that were only provided graphically. The intercoder reliability for WebPlotDigitizer is strong, given the fact that it relies on hand plotting (Drevon, Fursa & Malcolm, 2017). Previous systematic reviews and meta-analyses, including those on various nutritional supplements, have used WebPlotDigitizer (33,48,67).
In this meta-analysis, aerobic outputs were measured with the following indices: time to exhaustion (TTE) (min), maximal oxygen uptake (VȮ 2 max) (mL/kg/min), and perceived effort; in the case of anaerobic outputs, we retrieved data on peak power (Watts), fatigue index (%), mean power (Watts), blood lactate level (mmol/L), and vertical and countermovement jumping (cm). All data were extracted as mean and SD of taurine and placebo after measurements. Then, it is entered into the excel sheet and transferred into the metaanalysis program.

STATISTICAL ANALYSES
TTE (min), VȮ 2 max (mL/kg/min), and degree of perceived exertion (score) were used to choose results for aerobic performance, whereas peak power (watts), fatigue index (%), mean power (watts), vertical, countermovement jumping (cm), and blood lactate level (mmol/L) were used to select results for anaerobic performance. In the meta-analysis, raw data in the form of a mean, SD, and sample size for taurine and placebo groups were extracted. Unreported values were obtained from WebPlotDigitizer (Version 3.12). The meta-analysis of aerobic and anaerobic performance outputs was conducted using Review Manager 5.4 (Cochrane's Software).
The mean differences (MDs) were used for continuous outcomes to estimate the effects of taurine. The data were analyzed using fixed-effects or random-effects models dependent on the degree of heterogeneity as measured by the I 2 statistic. The MDs between taurine and placebo groups were expressed using Hedges' g and 95 percent confidence intervals (CIs) across trials. MDs of #0.2, 0.2-0.49, 0.5-0.79, and $ 0.8 were considered to represent small, medium, large, and very large effects, respectively (11). To evaluate the tests for the forest plots, subgroup analysis, and quality assessment, Review Manager version 5.4 was used. For all analyses, the statistical significance level was set at p , 0.05.

REGISTER
PROSPERO recording of our work titled "Effect of Taurine Supplement on Aerobic and Anaerobıc Outcomes: Meta-Analysıs of Randomized Controlled Trials" with ID 291146 has been made. However, the protocol of this review was not registered in PROS-PERO because this platform does not accept systematic reviews assessing sports performance as an outcome.

STUDY SELECTION
For this meta-analysis, a total of 17,880 studies were identified. Duplications were eliminated, and the remaining 169 relevant studies were assessed based on their title and abstract. In total, 153 studies were excluded due to the following reasons: coingestion of other supplements (n 5 14), studies related to sports performance measurements not taken (n 5 124), animal studies (n 5 7), participants with chronic health status (n 5 3), not open access study (n 5 1), meta-analysis (n 5 2), and systematic review (n 5 2). Ultimately, the current analysis Taurine Supplementation VOLUME 45 | NUMBER 2 | APRIL 2023 involves 18 studies. Figure 1 depicts the selection procedure.
Although 18 studies were detected for the meta-analysis between 2001 and 2021, 16 studies were grouped. Only randomized controlled trials (single or double-blind) were considered.

ICS OF THE INCLUDED STUDIES
There were 219 participants (145 athletes and 74 healthy individuals) from 18 studies included in the present meta-analysis. The studies' sample sizes ranged from 7 (69) to 21 (64) subjects. The participants' ages ranged from 17 (14) to 34.6 (68) years old on average. Two of the studies (35,65) included women, whereas the others' studies included men. The duration of supplementation varied from acute to 8 weeks. The daily doses of taurine intake were determined as a minimum of 1 g and a maximum of 10 g. One gram of taurine was given as the most common dose. Swimming, running, jumping, cycling performance, and treadmill or cycle ergometer testing were all part of the exercise regimen. Ten of the 18 studies (5,16,21,47,54,(64)(65)(66)68,69) found had aerobic outputs, 8 studies (1,6,14,15,35,39,55) had anaerobic outputs, and in 2 studies (34,69) both aerobic and anaerobic outputs were provided. Characteristics of included studies concerning aerobic and anaerobic performance outputs are presented in Tables  1 and 2.

SUBGROUP ANALYSIS RESULTS OF INDIVIDUAL STUDIES ACCORDING TO THE OUTPUTS
Two distinct subgroup analyses of aerobic and anaerobic performance outputs were performed in this study (Table 3).
In a fixed-effects model, taurine supplementation had no significant effect on the VȮ 2 max level and RPE (respectively, MD

EFFECT OF TAURINE SUPPLEMENTATION ON ANAEROBIC PERFORMANCE OUTPUTS
Two studies (35,69) assessed peak power, fatigue index, and mean power as anaerobic outputs. Three studies (1,34,55) analyzed vertical and countermovement jump as total height (cm). Three studies (6,14,15) assessed the blood lactate level as postmeasure concentration (mmol/L). In total, 8 studies (with 91 participants) were evaluated for anaerobic outputs. In Figure 3, the studies are shown in detail.
In a random-effects model, taurine supplementation had a significant effect on vertical (MD 5 16 and 0% for the blood lactate level, fatigue index, peak and mean power, and total heterogeneity level were calculated as 80%.

RISK OF BIAS
Most of the studies had a low or unclear risk of bias. In one study (68), allocation concealment and blinding and, in 2 studies (16,21), incomplete outcome data, selective reporting, and other biases were unclear. The publication bias analysis is depicted in Figure 4.
The funnel plot of aerobic and anaerobic performance outputs revealed no significant publication bias because of symmetrical distribution except for a few studies.

SIDE EFFECTS
Only 1 study (35) reported anxiety or nervousness and gastrointestinal disturbances as side effects.

DISCUSSION
Although taurine has a variety of functions in muscle, no particular mechanism for increasing muscular capacity or strength or reducing muscle injury has been discovered. Therefore, this study focused on aerobic and anaerobic outputs to evaluate exercise performance. The current meta-analysis study provides up-to-date data for the literature on the effect of taurine intake on aerobic and anaerobic exercise performance. A total of 10 studies were chosen for the evaluation of aerobic capacity, whereas 8 studies were selected for the evaluation of anaerobic ability. Thus, the meta-analysis results indicate that taurine can be an effective ergogenic aid, especially on jumping performance, which is a marker of anaerobic output. Taurine seems to have 3 distinct effects on performance: small, medium, and large. It should be noted that even small improvements in performance in some sports can translate into significant differences in competitive results (43,50 Table 1 Characteristics of included studies related to aerobic outputs (n 5 11) Author  To the best of our knowledge, the effects of taurine on aerobic and anaerobic performance have never been pooled in a meta-analysis before. It shows that taurine can cause practically significant improvements in jumping performance. For this reason, it is believed that taurine supplementation will be important in sports branches where jumping performance is at the forefront. In addition, athletes, trainers, and sports nutritionists should be informed about the ergogenic potential of taurine, and the outputs of this study can be used as a source for future scientific research.

AEROBIC OUTPUTS
TTE, VȮ 2 max, and RPE parameters were used to evaluate aerobic exercise performance. In this study, taurine had no influence on total aerobic performance but had a moderate effect on TTE. According to this metaanalysis, taurine supplementation had no statistically significant effect on VȮ 2 max and RPE. Most studies investigating the effect of taurine intake on aerobic performance have generally used the TTE parameter to assess the aerobic capacity (2,44,71). Results of individual studies evaluating aerobic performance reported a positive effect of taurine administration (44,71). While the effect size of the improvement in taurine status was significant in these studies, it was seen that although there was no significant difference in TTE as a result of the meta-analysis in this study, it had a moderate effect size.
The findings of the present metaanalysis are in line with previous research, as taurine intake has not been shown to affect VȮ 2 max (5,22) and RPE (5,44). By contrast, VȮ 2 max has been shown to increase up to exhaustion after taurine supplementation in individuals in an incremental cycle test (8,71). However, the fact that VȮ 2 max did not differ between conditions despite the significantly shorter completion time in the taurine intake case in the time trial could be interpreted as a positive effect of taurine uptake on central factors or muscle coordination independent of the metabolic effect. It has previously been suggested that the effect of taurine on exercise metabolism during simulated time trial performance would seem to act through interaction with the muscle. Considering that acute taurine use increases not only muscle content but also plasma content, the importance of taurine intake becomes evident (22). Conversely, it is hypothesized that prior taurine intake may reduce taurine losses from muscle during aerobic exercise. However, a 1 g dose of taurine generally used in the studies included in the current meta-analysis would be sufficient to induce a concentration gradient by preventing muscle loss. Although it has been demonstrated that the content of taurine in muscle decreases after aerobic exercise (12,24), more research is needed to fully clarify the problem.
The effect of oral taurine on performance versus time has been inconsistent. For example, Ward, et al. (68) reported no effect of taurine on 4-km cycling time-trial performance, but Balshaw, et al. (5) reported improvement in the 3-km time trial. The energetics of exercise over long distances is largely reliant on capacity in the severeintensity domain, and based on the current findings, we would predict clear effects on closed-loop events of this distance. Indeed, ischemia preconditioning, beet juice, beta-alanine, and caffeine had equal or stronger effects on severe-intensity exercise TTE (7,25,37,41,60). As a result, although the explanation for the differences in research findings is not known clearly, the doses used and supplementation periods can still be associated with the training status of the individuals.
In an experimental investigation conducted by 11 male cyclists on a bicycle ergometer, it was revealed that 1 g of taurine supplement ingested before the 4-km time trial performance did not influence VȮ 2 max (68). In a doubleblind randomized study examining the effects of acute administration of 1 g taurine on the 3-km time trial performance on a treadmill in middle-distance runners, it was stated that taurine supplementation did not influence VȮ 2 max (5). Zhang, et al. (71), in their experimental study conducted with 11 healthy male individuals, exercised on a bicycle ergometer after the participants were given 6 g of taurine daily for 1 week. As a result, it has been reported that daily taurine supplementation of up to 6 g provides a significant improvement in VȮ 2 max. Torun (64), in his study with 21 healthy men, had the Bruce protocol applied, and after the protocol, the participants were included in a 1 week 3 and 6 g taurine loading process. As a result, it was observed that VȮ 2 max increased significantly after 6 g taurine loading. It can be seen that the effects of taurine on the VȮ 2 max parameter provide mixed outcomes. However, studies in the literature suggest that high dosages of $6 g may improve VȮ 2 max.

ANAEROBIC OUTPUTS
Peak power, fatigue index, mean power, jumping performance (vertical and countermovement jumps), and blood lactate levels were used to assess anaerobic exercise performance. Taurine is known to increase Ca 2+ transport to the sarcoplasmic reticulum, which aids skeletal muscle activation and muscle strength development Figure 2. Effect of taurine on aerobic performance outputs. Green circle, low risk of bias; red circle, high risk of bias; blank space, unclear risk of bias. A, random sequence generation; B, allocation concealment bias; C, blinding of participants and personnel; D, blinding of outcome assessment; E, incomplete outcome data; F, selective reporting; G, other bias; CI, confidence interval. (12,49). Jumping is a complex action involving multiple joints that require high power and strength generation.
Vertical jump distance has an important place among measurement methods in many sports branches (4,52). Vertical jump performance is linked to maximal lower-body strength, according to several studies (3,36,45). In addition, the rapid stretch provided by the countermovement jump, which is one of the most frequently used vertical jump tests, could lead to increased muscle activation and force production (61).
In this meta-analysis, it was observed that taurine intake significantly improved jumping performance. Akalp (1), compared the measurements by performing the vertical jump test on 10 healthy men who took 0.1 g/kg taurine 1 hour before and 1, 24, 48, and 72 hours after strength exercise. As a result, the ability of taurine to reveal a statistically significant difference in vertical jump performance was determined. There was no agreement on whether taurine intake affects jumping  performance. Taurine supplementation of 15 mg/kg per day for 10 days did not influence the athletes' countermovement jump performances, according to an experimental investigation involving 10 male taekwondo athletes who were given an exercise program in which the taekwondo race day was mimicked (55). In a placebo-controlled double-blind study conducted with 14 healthy individuals, it was reported that 1 g of taurine consumed before 3 vertical jump trials did not have a statistically significant effect on vertical jump performance compared with placebo (34). Although it was emphasized that taurine did not affect jumping performance due to the individual results of studies with different groups, taurine had a significant effect on jumping performance in this metaanalysis when compared with the placebo group.
The blood lactate-lowering effect of taurine is believed to be most likely because of a potential interaction between taurine and the calcium in mitochondrial buffering (19). Taurine supplementation did not affect blood lactate levels in this research. When the results of this metaanalysis are compared with the literature, it is shown that taurine has no effect on blood lactate levels in certain studies (5,14,15) but does in others (6,39).
There are many mechanisms explaining the role of taurine, but most of the time it is at the forefront with its effect on Ca 2+ storage and intracellular utilization in the sarcoplasmic reticulum through increased Ca 2+ activated AT-Pase pump activity in both skeletal and cardiac myocytes (30,40). In addition, an antioxidative role has been attributed to taurine based on in vitro studies showing the pH buffering capacity of taurine in the mitochondrial matrix. In this case, taurine facilitates the function of rate-limiting oxidative enzymes (i.e., isocitrate dehydrogenase) and reduces the production of reactive oxygen species, thereby stabilizing the mitochondrial matrix and increasing the efficiency of ATP conversion for energy-demanding processes in the cell (27,40). The combination of these mechanisms partially explains the effects of taurine on endurance activities and short-term power production.
In this meta-analysis study, taurine intake seems to be ineffective on peak, mean power performance, and fatigue index. Although ergogenic effects of taurine have been demonstrated, mixed results seem to be evident with anaerobic exercise (40). In a study by Karayigit,et al. (35), 1 g of taurine did not improve anaerobic power during WAnT (Wingate) in fasting female athletes. When evaluated in different studies, anaerobic power output during repeated sprints (6 3 10 seconds sprints) was not increased or even decreased by taurine intake in female lacrosse players (65). By contrast, 3.7 g of taurine improved critical power and tolerance to vigorous-intensity exercise in male participants (66). After strenuous exercise, type II muscle fibers consumed 25% of the taurine concentration (46). Warnock, et al. (69) indicated that approximately 4.3 g of taurine significantly increased the mean and peak power of the 3-rep WAnT. Another study showed that 6 g of taurine significantly increased peak and mean power during WAnT in female athletes (18). Collectively, when these findings are evaluated, studies evaluating the relationship between taurine and WAnT performance do not seem to reach a consensus. This situation is believed to be caused by a different population or a dose-response relationship.
It is more difficult to explain that taurine has no significant effect on peak or mean power. Plasma taurine concentrations range from 29 to 49 mM in humans (12) and ;500-fold higher in skeletal muscle (22). This causes an osmotic change in muscle cells. After anaerobic exercise, muscle osmolality increases as a result of increased intracellular lactate production (42) and Strength and Conditioning Journal | www.nsca-scj.com phosphocreatine breakdown (57). To maintain osmolality, muscle removes inorganic ions or organic molecules, including taurine. We hypothesize that taurine supplementation will reduce this osmotic exchange, thereby preventing the transport of solutes out of the muscle cell. Indeed, taurine supplementation is known to suppress taurine release from skeletal muscle (32,40). As a result, the performance decrease in a sprint or explosive power test can be explained by increased osmotic stress and potential cellular damage in cells. The release of taurine by compressing the muscles into plasma by an osmoregulatory process may not affect anaerobic performance (12). This assumption may be speculative at this time, and in vivo research is needed to confirm it. In addition, studies on taurine will provide more scientific explanations instead of assumptions. Therefore, we emphasize that more studies are needed to address the relationship between taurine and anaerobic performance.

CONCLUSION
Taurine supplementation has a considerable significant effect on jumping performance (p , 0.0001), according to the results of experimental research conducted over the last 20 years. When compared with placebo, it had no ergogenic effect on aerobic outputs (RPE and VȮ 2 max), although it may improve the TTE parameter. More controlled trials with a larger number of people and more diverse groups are needed to develop a consensus on taurine's ergogenic effects on sports performance and to extend these findings. In addition, traditional methods were used to analyze the data for anaerobic measures for which taurine supplementation was determined to be significant, whereas modern methods were used to test anaerobic parameters that were not significant. As a result, contemporary anaerobic tests should be used to illustrate the link between future taurine supplementation and anaerobic performance.
Owing to taurine's ability to modulate lipid metabolism by stimulating genes and proteins responsible for mitochondrial biogenesis and respiratory function, taurine is associated with improvements in aerobic metabolism (8,26,27). Although no significant results have been obtained on aerobic parameters in our current meta-analysis study, we believe that the number of studies addressing the relationship between taurine and aerobic exercise should be increased to clarify this situation. There is minimal information available on how taurine affects anaerobic metabolism; however, previous research has shown that taurine can reduce lactate concentrations (15,39). It seems that the literature on the effect of taurine on both anaerobic and aerobic metabolism is scarce. Considering this situation, we suggest that researchers who evaluate this issue in the future should direct their studies.

LIMITATIONS
The study's limitations include a lack of research, difficulties grouping because of the use of a wide variety of exercises, different doses and intervention periods, and small sample size. The analysis of various athletes' competition levels is also another limitation of this study. Exercise protocols were asked to show concordance when aerobic and anaerobic performances were evaluated.

PRACTICAL APPLICATIONS
This meta-analysis aimed to assess the effects of taurine intake on aerobic and anaerobic outputs.
According to research conducted over the last 20 years, taurine can be an effective ergogenic aid, especially on jumping performance, which is a marker of anaerobic output.
Taurine did not influence overall aerobic performance, although it showed a tendency to increase the TTE.
Only one study reported adverse reactions from taurine ingestion, such as anxiety and gastrointestinal disturbances.
Taurine supplement in sports branches where jumping is at the forefront, especially because of the improvement of jumping performance; it can be recommended to coaches, athletes, and experts interested in the subject.