The main purpose of this study was to examine the ergogenic effect of a 10-day TAU vs. placebo supplementation on inflammation and performance indices in TKD athletes. To the best of authors’ knowledge, this research was unique as the first attempt, rigorously comparing the inflammatory and functional responses of TKD athletes to a SCTD, with an emphasis on TAU supplementation as a nutrient gaining popularity for its protective effect against inflammation-induced exercise training. Exercise performance was also assessed using the SCTD with the same physiological pressure in elite male TKD athletes.
Regarding inflammatory disorders, moderate physical activity seems to benefit health since exercise training is necessary to improve the immune system ; however, strenuous exercise training such as combat competition can attenuate the immune system and may cause inflammation if the innate immune system is not effective [25, 26], thereby compromising athletic performance . Therefore, utilization of immunonutrition aims to prevent the immune system disorders and possibly enhance athletic performance .
Accordingly, TAU supplement has been considered as an immunonutrition compound due to its various beneficial effects on the immune system  such as inflammation associated with oxidative stress, inhibition of cytokine production , and microbicidal activity .
Numerous studies have also confirmed the effectiveness of TAU supplementation on inflammation process [13, 32]. However, the attenuating effects of TAU on inflammatory disorders have been occasionally limited, especially in case of intensive exercise training [13, 33, 34]. Consequently, further effective nutritional strategies need to be discovered.
In the present study, the effects of TAU supplementation on the SCTD-induced inflammation were investigated via a placebo-controlled and double-blinded trial, because TAU was illustrated to improve the immune system following exercise-induced metabolic stress. The study results suggested that supplementation with TAU or a placebo for a10-day period did not improve cytokines of IL-8, -17, hs-CRP, and TNF-α in TAU vs. placebo occasions.
The supplementation with TAU together with the SCTD did not also improve the immune system parameters in comparison with the SCTD alone, but significantly increased IL-15 levels after 24 h. Besides, the study observations did not provide support for the capacity of TAU supplement (a dose of 15 mg/ body weight, approximately three servings per day, one after each main meal) to moderate acute inflammation in TKD. Contrary to the hypotheses raised in this study, non-significant changes in pro-inflammatory cytokines (i.e., IL-8, -17, hs-CRP, and TNF-α) between the two occasions (placebo vs. TAU) might be relevant to the simulated protocol used in present study, which was extremely intense for TKD athletes, leading them to increase the inflammatory factors following this protocol even in TAU occasion. Not only intense training such as this protocol could alter inflammatory responses, but eccentric-type training observed in this protocol also resulted in acute muscle damage and inflammation. The study participants were TKD athletes with an average age lower than that in other studies with TAU treatment, in which improvements had been observed in inflammatory status . In addition, these subjects were healthy and physically fit compared with others with significant improvements following TAU supplementation [35-38].
While no effect with orally administered TAU was detected, it was demonstrated in the present study that TAU supplementation did not exhibit anti-inflammatory effects when the type of administration was ingestion (15 mg/ body weight, approximately three servings per day). This may be due to the rapid clearance of TAU, resulting in low mean blood levels . Moreover, TAU possesses anti-inflammatory effects in-vivo only when administered through intracerebroventricular injection (ICVI) . In addition, it could be concluded that the differences observed on the effects of TAU in this trial with exogenous TAU might be the result of the more rapid tissue distribution or clearance of the natural product and prolonged plasma half-life of the TAU in-vivo.
Thus, it was concluded that TAU ingestion could not alleviate inflammation biomarkers, but may improve anti-inflammatory cytokine IL-15. In this respect, Shirvani et al. had reported that TAU administered in the same way had significantly attenuated the severity of inflammation during pressure-filled week of competition and training in elite soccer players.
In conflict with the study findings, Zhang et al. had found that a 7-day TAU supplementation (6 g/day) had decreased the levels of lipid peroxidation biomarkers. In an animal study, Silva et al. had further evaluated the effects of a 15-day high dose TAU supplementation on oxidative stress biomarkers following a long-term eccentric exercise and had concluded that TAU had mitigated oxidative stress .
As precise mechanisms, underlying TAU inhibition of inflammation, have not been fully understood and demand further studies, the above data did not support the proposal that TAU may be a useful candidate for complementary treatment for elite TKD athletes following a competition day. However, the stability of TAU should be increased in body to improve TAU efficiency. It has been shown that C-methylated derivatives of TAU with better stability  and a synthetic form of TAU (namely, taurolidine: TRD) can be a potential candidate as an immunonutrition .
In contrast to the research hypotheses, this type of supplement could change systemic IL-15 levels compared with the placebo 24 h after the SCTD, suggesting that these elevations might be related to damage to fibers  following such an intense exercise training protocol.
This discrepancy between studies might be due to differences in testing protocols as well as duration and dose of TAU supplementation. These findings based on this higher intensity TKD performance testing suggested that taking TAU in a short term before the SCTD protocol might not prevent severe inflammation. In addition to protocol intensity, the amount of oral TAU intake and administration time can be of important factors for preventing exercise-induced inflammation. According to Ghandforoush-Sattari et al. , TAU dose needed to be adjusted according to body mass and maximum circulating TAU concentrations may be reached 90 min at the post-ingestion stage, because TAU administration is expected to increase the availability and the utilization of TAU after exercise, stimulate glycogen synthesis, and improve protein synthesis.
In support of the given hypotheses, the study findings revealed no effect of oral TAU ingestion (15 mg/ body weight) on performance and blood lactate responses compared with the placebo trial. This study was also unable to assess the circulating TAU levels during this protocol, which may provide a more complete evaluation of the dynamics of TAU metabolism. It seems that any potential ergogenic effect of TAU could only occur through interactions with receptors on the muscle membrane or by affecting other organs such as the liver and the adipose tissues during the exercise training protocol, and not within the muscle itself.
At odds with this study, other investigations had not shown any ergogenic effects of chronic TAU supplementation in blood lactate responses and athletic performance following intense exercise training upon using TAU-containing energy drinks [10, 46-48]. Variables such as time, period, amounts of TAU intake as well as testing protocols may thus contribute to whether or not TAU ingestion enhances performance capacity and to what extent . For example, chronic TAU supplementation improves muscle TAU content and contributes to maintenance of performance improvement . However, the absence of measuring intracellular TAU content after chronic TAU supplementation was a limitation of present study. Further studies should accordingly consider the effects of different TAU supplementation periods in individuals with various physical fitness levels using sophisticated techniques for evaluation of bimolecular mechanisms.
From a practical perspective, the results of the present trial did not support others in terms of demonstrating the ergogenic effect of TAU ingestion (15 mg/ body weight of TAU for a 10-day period) on performance and inflammation status. There have been also no adverse side effects reported across studies using doses of 15 mg/ body weight, inferring the safety and tolerability of this supplement. The effects of TAU on endurance performance are fairly well established among TKD athletes, but, to date, there has been no work carried out on elite TKD athletes, which makes it necessary to develop an understanding of the scope of ergogenic effects induced by TAU.