Introduction

Sports-based activities depend on both physiological and psychological (i.e., emotional and cognitive) requirements. Physical performance has a dynamic relationship with psychological state (Beal et al. 2005). However, athletes face difficult moments (e.g., precompetitive negative emotions, professional constraints) and may experience disturbances in their psychological states during training and/or competition (Merino Fernández et al. 2019). These disturbances can lead to performance decrements (Carrier and Debois 2003; Gaudreau et al. 2010). Women generally tend to report a higher disruption of temporary emotional state than men (Domes et al. 2010; Damien and Mendrek 2017). Additionally, it is recognized that psychological disturbances can influence the perception and tolerance of pain in both women and men (Jones et al. 2003; Tang and Gibson 2005).

Different strategies must be evaluated to effectively reduce underlying mood disturbances, cognitive performance, and pain perception. For example, previous studies report that acetaminophen (ACTP, paracetamol) has the potential to be a pharmacological strategy for pain relief (Mauger et al. 2010), improving physical (Grgic 2022) and cognitive performance (Pickering et al. 2016), as well as emotional state (DeWall et al. 2010; Manna and Umathe 2015). ACTP is an over-the-counter pain reliever and one of the most widely used medications for pain and fever reduction (Sood et al. 2013). Additionally, ACTP has multiple effects on the central nervous system (Umathe et al. 2009; Manna and Umathe 2015). Although a century has passed since its discovery, the full mechanism of action of ACTP remains unknown (Tanner et al. 2010). However, the main mechanism of action to reduce pain is the inhibition of cyclooxygenase (i.e., the enzyme responsible for the production of prostaglandins from arachidonic acid) (Anderson 2008), modulating afferent and efferent pain pathways (Andersson et al. 2011). ACTP is similar to nonsteroidal anti-inflammatory drugs (NSAIDs), but due to its limited anti-inflammatory action, it is not classified as an NSAID (Graham et al. 2013). Furthermore, ACTP does not directly affect cyclooxygenase (COX) 1 and 2 enzymes; however, it can exert its effects on an enzyme known as COX-3, which is generated through the splicing process of COX-1 (Chandrasekharan et al. 2002; Przybyła et al. 2021). This mechanism leads to the absence of gastrointestinal lesions, adverse cardiorenal effects, and antiplatelet effects (Bertolini et al. 2006). ACTP has a central mechanism of action that involves several neurotransmitters and serotonergic, cannabinoid, opioid, and vanilloid receptors (Sandrini et al. 2007; Ohashi and Kohno 2020). Additionally, ACTP acts on cannabinoid type 1 (CB1) receptors and calcium channels, such as Ca(v), and regulates descending serotonergic pathways and a number of other factors, including A1 receptor potential members of the transient receptor cation channel (Ohashi and Kohno 2020; Przybyła et al. 2021).

The cognitive and emotional variations with ACTP have been examined in animals, and reports suggest that there is an anxiolytic effect (Umathe et al. 2009), which is associated with improved cognitive function (Ishida et al. 2007). The utilization of the cannabinoid mechanism and the augmentation of the antidepressant effect are two key factors through which a small amount of ACTP can facilitate effective management of depression (Manna and Umathe 2015). Preclinical investigations conducted on animal models have demonstrated that administering therapeutic doses of ACTP may enhance cognitive abilities, potentially attributed to its impact on the central serotonergic system. This leads to an augmented release of serotonin and norepinephrine within the brain, thereby potentially improving cognitive performance (Maharaj et al. 2004; Blecharz-Klin et al. 2013). Overall, ACTP seems to enhance cognitive performance, especially attention, and has been shown to do so during the decision-making test and spatial memory, with an acute dose of 2 g in healthy men (Pickering et al. 2016). In addition, using functional magnetic resonance imaging to measure brain activity in healthy participants, it was found that administration of 1 g of ACTP reduced negative emotions in certain brain regions (anterior insula, dorsal anterior cingulate cortex) (DeWall et al. 2010). Furthermore, it has been shown that this ACTP is the most widely used by athletes (Lundberg and Howatson 2018). Traditionally, ACTP has been used in athletes to alleviate the pain of physical exercise (Esh et al. 2017). However, it is also considered an ergogenic aid, which can be misused to enhance sports performance. While the benefits of this drug appeared when administered at therapeutic doses (Prior et al. 2012), ACTP exhibits minimal anti-inflammatory activity, functioning merely as a modest inhibitor of prostaglandin production (Botting 2000), and its analgesic properties are not altered during exercise (Sawrymowicz 1997).

Most studies have focused on the influence of the ACTP on endurance performance (Grgic and Mikulic 2021), and numerous studies have examined the effects of the ACTP on the performance of short-term repeated sprints interspersed with 2–4 min of recovery (Foster et al. 2014, Delextrat et al. 2015). The ability to repeat high-intensity efforts is essential for performance in many sporting specialties (Fernandez-Fernandez et al. 2012; Eryılmaz et al. 2019). Additionally, one of the most important factors in the success of high-intensity exercise is the ability of the athlete to tolerate pain (O’connor 1992).

Indeed, the acute ingestion of 1.5 g ACTP has been shown to improve repeated sprint performance in the Wingate test (8 × 30 s interspersed with 2 min rest) (Foster et al. 2014, Delextrat et al. 2015).

Most studies performing short-term repeated sprint tests after ACTP ingestion were performed on a bicycle ergometer or isokinetic dynamometer for a single member (Foster et al. 2014, Delextrat et al. 2015, Morgan et al. 2018); only one study used a running-based protocol on a treadmill (Park et al. 2016). Therefore, to better understand the influence of ACTP on maximum short-term performance, a field test, such as the 5 m shuttle run test (5mSRT), which involves more muscle activation compared to efforts on a treadmill (Baur et al. 2007; Sedıghı et al. 2019) or bicycle ergometers, is warranted.

The 5mSRT, adopted by the Welsh Rugby Union and modified by the Sports Science Institute of South Africa (Boddington et al. 2001), is one of the most widely used short-duration, high-intensity repeated sprint tests to determine an athlete’s fitness (Pendleton 1997; Boddington et al. 2004). The test consists of maximal shuttle sprints of 6 × 30 s with 35 s recovery in between. In this test, athletes run the greatest possible distance for 30 s, going back and forth over 5 m, then 10 m, then 15 m, then 20 m and so on. In addition, during the 5mSRT, both aerobic and anaerobic metabolisms could be solicited since its total duration is around 6 min (i.e. 6 sprints of 30 s with 35 s rest between sprints) generating high levels of fatigue, biomarkers of muscle damage and inflammation, as well as perceived exertion (RPE), delayed onset muscle soreness (DOMS) and reduced perception of recovery (PRS) (Boukhris et al. 2020).

It is well documented that women are more sensitive to pain than men (Naugle et al. 2014; Templeton 2020) and may also react differently to ACTP (Bartley and Fillingim 2013). Traditionally, there is a lack of participation of women in sports medicine research (Costello et al. 2014), and only one study has examined the effects of ACTP on physical performance in trained females (Delextrat et al. 2015).

To the author’s knowledge, no study has examined the effects of acute ingestion of ACTP on attention and mood states in well-trained female athletes. Thus, this study investigated the influence of an acute ACTP on physical performance during the 5mSRT, rating of RPE, pain perception (PP), DOMS, PRS, attention, and mood states in well-trained female athletes. We hypothesized that ACTP ingestion would have a positive performance effect during the 5mSRT, attention, mood state and PRS as well as reduce PP, DOMS and RPE in female athletes.

Materials and methods

Participants

The minimum needed sample size was calculated using G*power software (version 3.1.9.6; Kiel University, Kiel, Germany) (Faul et al. 2007). We set the values of α and power (1−β) at 0.05 and 0.95, respectively. Based on Delextrat et al. (2015)’s physical performance results and discussions between the authors, the effect size was estimated to be d = 1.1; the needed sample size was thirteen. Fifteen well-trained female athletes (age = 21 ± 2 years, height = 165 ± 6 cm, weight = 62 ± 5 kg) voluntarily participated in the study. The participants practiced combat sports (English boxing) in local clubs and regularly trained 5 days a week for an average of 2 h of session; each had at least 4 years of sporting experience and participated in at least 4 regional/national competitions per year. Prior to starting the study, volunteers were asked to provide written informed consent and complete a Physical Activity Readiness Questionnaire and an ACTP risk assessment questionnaire (Mauger 2009). This study was carried out in accordance with the Declaration of Helsinki, and the protocol has been fully validated by the Ethical Committee for the Protection of Southern Persons (CPP SUD No. 0418/2022). Participants were in good health, did not have kidney or liver disease, did not use anti-inflammatory and analgesic substances (by prescription and over the counter), and did not consume alcohol or smoke cigarettes. They were also needed to not take birth control pills, as taking combined oral contraceptive pills can help stabilize hormonal fluctuations (Vincent and Tracey 2008) and may decrease the perception of experimental pain in women (Dao 2012).

Experimental design

This study utilized a randomized, placebo-controlled, double-blind, crossover design. The 5mSRT was carried out on a tarmac running track. During the experimental period, temperature, humidity and wind ranged from 20 to 22 °C, from 52 to 60% and from 2.5 to 4.16 m. s−1, respectively.

Prior to each visit, participants were asked to abstain from any strenuous exercise for 24 h and caffeine for 12 h before the experiment. They were also asked to refrain from taking analgesics or any form of anti-inflammatory medication during the experiment. After a familiarization session with the experimental procedure (i.e. with the 5mSRT and the questionnaires), participants were asked to maintain their diet and arrive in a state of perfect rest and hydration to perform two separate sessions for a minimum of 72 h where this was verbally confirmed before the start of the trial.

Participants were assigned to a placebo (PLA; Maltodextrin) or a 1.5 g of ACTP, with the supplements enclosed in three small gelatin-coated capsules (3 × 500 mg). The study used a crossover design, where participants switched to the alternate supplementation condition after the initial phase.

For the first group of seven participants:

  • Four participants receive PLA first, followed by ACTP.

  • Three participants receive ACTP first, followed by PLA.

For the second group of eight participants:

  1. o

    Four participants receive ACTP first, followed by PLA.

  2. o

    Four participants receive PLA first, followed by ACTP.

The Profile of Mood Profile (POMS) questionnaire and the digit cancellation test were assessed at 45 min post ingestion. Likewise, the 5mSRT was performed at 60 min post ingestion. This period was chosen because maximum plasma concentrations of ACTP are observed at 30–60 min post ingestion (Anderson 2008). Acute administration of 1.5 g ACTP had a longer plasma half-life and showed no signs of impaired glutathione conjugation or hepatotoxicity in healthy individuals or those with chronic liver disease (Forrest et al. 1979; Alchin et al. 2022). Furthermore, the ergogenic effect of ACTP is most frequently observed when 1.5 g is ingested 30–60 min before physical exercise (Grgic 2022).

To mitigate the effects of diurnal variations, the tests were executed at the same time of day (Hayes et al. 2010), at 17 h 00, for all participants.

During the execution of the 5mSRT test, participants responded to RPE and PP scales immediately after each sprint during recovery periods (i.e. between repetitions). Additionally, participants responded to the PRS scale 5 min post-5mSRT. The DOMS scale was determined 24 h after the end of the 5mSRT. Standardized verbal explanations of the appropriate uses of all questionnaires were provided prior to testing.

Profile of mood states (POMS)

Subjective mood status was assessed using the French version of the POMS questionnaire (Cayrou et al. 2003). Responses to each element range from 0 to 4, with the highest scores indicating a more negative mood (0 indicates “Not at all” and 4 indicates “Extremely”). The POMS assesses mood status (McNair et al. 1971); it contains 65 adjectives and assesses six mood factors: depression, fatigue, tension, anger, vigor, and confusion. Total mood disturbance (TMD) can be calculated by adding the scores for tension, depression, anger, fatigue and confusion and then subtracting the score for vigor.

The digit-cancellation test (DCT)

As described by Hatta et al. (2012), the DCT consists of deleting target numbers (i.e., numbers composed of three grouped digits) and circulating them as much as possible in a limited time (1 min), working line by line, from left to right, leaving aside all the other numbers that were not composed of three digits. The test paper contained 600 signs divided into 36 lines. The sum of correct responses was recorded for analysis.

5-m shuttle run test (5mSRT)

This test consisted of performing 6 repetitions of 30-s shuttle sprints interspersed with a 35-s recovery period. Participants sprinted a maximum distance, back and forth 5 m, then 10 m, then 15 m, then 20 m, etc., for 30 s. After each 30-s repetition, a 35-s recovery was allowed. During the recovery phase, participants returned to the starting position for the next repetition (Boddington et al. 2001).

Depending on the distance covered during each repetition, the following parameters were calculated as used by Boukhris et al. (2022):

  • Greatest distance (GD) (m) = the greatest distance traveled during a 30 s sprint.

  • Total distance (TD) (m) = the total distance traveled during the six 30 s shuttles.

  • The fatigue index (FI) was calculated as follows:

    $$\text{FI} (\text{\%})=\begin{array}{c} \\ \frac{\left[\frac{\left(\text{shuttle }1+\text{ shuttle }2\right) }{2}-\frac{(\text{shuttle }5+\text{ shuttle }6 )}{2}\right]}{\frac{\left(\text{shuttle }1+\text{ shuttle }2\right)}{2}}\end{array} \times 100$$

Pain perception (PP)

After each 30-s repetition, participants selected a score on a 10-point scale accompanied by verbal descriptions to assess perceived pain between conditions. The high intraclass correlations (r = 0.88–0.98) indicate that this scale is a reliable measure of pain during effort (Cook et al. 1997).

Rating of perceived exertion (RPE)

After each 5mSRT repetition, participants completed their subjective RPE score from 0 (very, very light) to 10 (very, very hard). The higher the RPE score is, the greater the degree of effort. This scale is a good indicator of physical exertion, strongly correlated with several physiological measures of exertion, and has good psychometric properties (Haddad et al. 2013, Boukhris et al. 2020). The following formula was applied to obtain the average RPE score in the 5mSRT test:

$$\text{RPE }\left(\text{AU}\right)= \frac{\text{Sum of RPE scores for all repetitions}}{\text{Number of repetitions}}$$

Delayed onset muscle soreness (DOMS)

Delayed onset of muscle soreness (DOMS) was assessed at 24 h after the 5mSRT using a numerical scale ranging from 0 to 10 (Hawker et al. 2011). The values on the scale ranged from 0 “no pain” to 10 “very, very painful”.

Perceived recovery status (PRS)

PRS was assessed 5 min after the 5mSRT using an 11-point scale ranging from “0” to “10;” 0–2 represents “recovery is very low and performance is expected to decrease,” 4–6 means “recovery is low to moderate and performance is expected to be similarly good,” and 8–10 means “perceived high recovery and performance is expected to improve” (Laurent et al. 2011).

Statistical analysis

Values are expressed as the mean ± standard deviation (SD). Statistical analyses were performed using STATISTICA (StatSoft, France, version 10). The normality of the distributions was confirmed by the Shapiro‒Wilk test. The dependent t test was performed for tension, depression, POMS total score, GD, FI, PP and RPE. However, normality was not confirmed for attention, vigor, anger, DOMS, PRS, and TD; therefore, the Wilcoxon test was used. Standardized effect size (Cohen’s d) analysis was used to interpret the magnitude of differences between variables. Significance was accepted for all analyses at the level of p < 0.05. When the STATISTICA output demonstrated significance levels of p = 0.0000, these were corrected to p < 0.0001 (Fig. 1).

Fig. 1
figure 1

Schematic representation of the experimental protocol. ACTP Acetaminophen, RPE Rating of perceived exertion, PP Pain perception, DCT Digit cancelation test, POMS Profile of mood states, PRS Perceived recovery status, DOMS Delayed onset of muscle soreness, r Recovery

Full size image

To determine the percentage of gain or decrease with ACTP compared to PLA for all parameter, Δ was calculated as follows:

$$\Delta \text{\%}=\left[\frac{\left(\text{Higher value}-\text{ lower value }\right)}{\text{Higher value}}\right] \times 100$$

Results

5-m shuttle run test

The TD, GD, and FI during the 5mSRT are presented in Fig. 2. Statistical analysis revealed that TD (+ 11.33%) and GD (+ 10.83%) were significantly higher in the ACTP condition than in the PLA condition (Z = 3.41, p = 0.0007, d = 1.38 and t = 8.29, p < 0.0001, d = 1.1, respectively). Additionally, FI was significantly lower by 21.44% in the ACTP condition than in the PLA condition (t = 4.77, p = 0.0003, d = 0.91).

Fig. 2
figure 2

The total distance (A), greatest distance (B), and fatigue index (C) recorded after ingestion of placebo (PLA) and acetaminophen (ACTP). *(p < 0.001): significant difference compared to PLA

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The digit-cancellation test (DCT)

Statistical analysis showed that DCT scores were higher after ACTP ingestion than after PLA ingestion (Z = 3.4, p = 0.0006, d = 1.09) (Table 1).

Table 1 Values are expressed as the mean ± SD
Full size table

Rating of perceived exertion scale (RPE)

Statistical analysis showed that RPE values were lower after ACTP ingestion than after PLA ingestion (t = 10.56, p =  < 0.0001, d = 3.54) (Table 1).

Rating of perceived pain (PP)

Statistical analysis showed that PP values were lower after ACTP ingestion than after PLA ingestion (t = 12.66, p =  < 0.0001, d = 4.14) (Table 1).

Perceived recovery status (PRS)

Statistical analysis showed that PRS values were higher after ACTP than after PLA (Z = 3.41, p = 0.0006, d = 3.40) (Table 1).

Delayed onset muscle soreness (DOMS)

Statistical analysis showed that DOMS values were lower after ACTP than after PLA (Z = 3.29, p = 0.001, d = 2.3) (Table 1).

Profile of mood states (POMS)

Analyses revealed a significant effect of ACTP ingestion compared to PLA for anxiety, anger, depression, fatigue, vigor, confusion, and TMD score. Anxiety (t = 13.31, p =  < 0.0001, d = 2.29), depression (t = 20.14, p =  < 0.0001, d = 0.86), anger (Z = 3.41, p = 0.0007, d = 0.97), fatigue (Z = 3.41, p = 0.0007, d = 0.95), confusion (Z = 3.3, p = 0.001, d = 0.77) and TMD (t = 19.63, p =  < 0.0001, d = 1.83) were reduced with the ACTP compared to the PLA. However, vigor (Z = 3.41, p = 0.0007, d = 1.16) was increased with ACTP compared to PLA (Table 2).

Table 2 Values of the profile of mood states scores recorded after ingestion of the ACTP and the PLA
Full size table

Discussion

The present study investigated the influence of acute ACTP ingestion on 5mSRT performance, RPE, PP, DOMS, PRS, attention, and mood states in well-trained female athletes. Although some previous studies have investigated physical performance, to the authors’ knowledge, this is the first study examining the effect of ACTP ingestion on cognitive performance and mood states in trained females. Our findings show that acute ACTP ingestion effectively enhanced physical performance during the 5mSRT, attention and mood states.

For cognitive performance and emotional state, our results are consistent with previous reports showing that a nontoxic dose can improve cognitive performance (Blecharz-Klin et al. 2013; Pickering et al. 2016) and emotional state (DeWall et al. 2010; Manna and Umathe 2015). Moreover, preclinical studies report improvements in cognitive performance after a low dose of ACTP (Ishida et al. 2007; Blecharz-Klin et al. 2013). A clinical study indicated that acute ingestion of a nontoxic dose of ACTP improves attention, with better memory acquisition and a tendency to improve problem solving during cognitive tests (Pickering et al. 2016). ACTP may have a pharmacological mechanism that reacts with a variety of physiological pathways, such as the serotonin (5-HT) and endocannabinoid systems (Pickering et al. 2006; Sandrini et al. 2007). Interestingly, the ACTP metabolite N-arachidonoyl-phenolamine induces CB1 receptor activation and acts as a full agonist of the transient receptor potential vanilloid type 1 (TRPV1) receptor (Rawls et al. 2006). Activation of the TRPV1 receptor has been shown to produce antidepressant and anxiolytic efficacy by modulating serotonergic transmission (Manna and Umathe 2015). Moreover, the endocannabinoid system acts on cognitive function, as it improves attention and mood states via CB1 receptors localized to noradrenergic axon terminals, with norepinephrine release and stimulation of the α2 adrenergic receptor (Mendiguren and Pineda 2004; Cathel et al. 2014). Additionally, it has been reported that ACTP increases 5-HT and noradrenaline levels in the brains of rats (Maharaj et al. 2004; Blecharz-Klin et al. 2013).

Regarding emotional state, the ACTP may regulate emotions by decreasing daily feelings of psychological suffering (DeWall et al. 2010). In the present study, mood states estimated by the POMS (i.e., anxiety, depression, anger, vigor, fatigue, confusion, and TMD) were improved by the ACTP. The anxiolytic-type effect of ACTP could be a main feature to improve mood states (Umathe et al. 2009; Viberg et al. 2014). Additionally, a single dose of ACTP (which does not reach the threshold of fluoxetine, a selective serotonin reuptake inhibitor), increases the antidepressant-type effect and may provide better management of depression (Manna and Umathe 2015). Furthermore, 5-HT is a key neurotransmitter involved in mood state regulation (Redelinghuys 2020) and modulates emotion (Meltzer 1990). A significant observation arises from the gender context, where women tend to face a heightened susceptibility to mood and mental disorders (Organization 2022), attributed in part to a 50% reduction in 5-HT synthesis within the central nervous system compared to men (Oh et al. 2023), coupled with an elevated abundance of serotonin transporters (Gressier et al. 2016). Therefore, a therapeutic dose of ACTP can modulate the release/recapture processes of 5-HT (Blecharz-Klin et al. 2013); the antidepressant effect of ACTP may also rebalance serotonin levels (Manna and Umathe 2015). This may explain the improvements in cognitive performance and mood states in our study.

In contrast, our results revealed a significant improvement in physical performance during the 5mSRT (i.e., + 11.33% for TD, + 10.83% for GD and 21.44% for FI). Our result was consistent with studies investigating the effect of ACTP ingestion on performance in repeated sprints (Foster et al. 2014, Delextrat et al. 2015, Morgan et al. 2018).

Foster et al. (2014) used eight bouts of the Wingate test (30 s of all-out cycling) interspersed with 2 min of rest, reporting that ACTP ingestion increased by 5% during the Wingate’s 8 bouts and by 10–11% only during the last 3 bouts (Six to eight bouts) in physically active male participants. Delextrat et al. (2015) used the same Wingate exercise protocol (i.e. 8 × 30 s interspersed with 2 min recovery) and the same ACTP intake used by Foster et al. (2014), but included physically active women, they found an increase in mean power (6%) and more specifically, higher mean power values were observed during the second, third and fifth bouts (11–13%). Previous studies (Foster et al. 2014; Delextrat et al. 2015; Park et al. 2016), reported that the ACTP during the first sprint was not ergogenic. Therefore, it seems that acute ingestion of 1.5 g ACTP is effective in attenuating power loss during repeated sprints.

Indeed, ACTP could improve the reactivity and excitability of the corticospinal tract (Mauger and Hopker 2013). Furthermore, an acute ACTP ingestion can improve muscle activation during maximal intermittent exercise (Morgan et al. 2018). Given that intense repeated sprint exercise has been associated with a decrease in cortical excitability (Pearcey et al. 2016), and that the 5mSRT being a maximal exercise with a short recovery between repetitions (i.e. 35 s), resulting in significant decreases in distance from the first sprint (Boukhris et al. 2020), it is possible that a potential ergogenic mechanism of ACTP may prevent such reductions.

The present study demonstrated the benefits of ACTP ingestion on PP after 5msRT. However, Foster et al. (2014) reported that the ingestion of 1.5 g of ACTP had no beneficial effects on PP following repeated sprint cycling performance in physically active men.

Several mechanisms could be related to these results. Females have a greater sensitivity to pain and a lower pain threshold than males (Templeton 2020). Some gender differences in pain perception are exhibited in the descending pain modulator system, the brain-derived neurotrophic factor, the corticospinal motor pathway (Gasparin et al. 2020), and the impact of sex hormones on these pathways (Templeton 2020). 5-HT is a crucial neurotransmitter involved in the central mechanism of action of ACTP, which reduces the perception of pain (Pickering et al. 2006; Sandrini et al. 2007). Moreover, the influence of estrogen on 5-HT synthesis and reuptake increases the effectiveness of top-down pain inhibition (Paredes et al. 2019), and with the association of the central analgesic mechanism of action on the endocannabinoid system and stimulation of serotonergic pain inhibitory descending pathways (Przybyła et al. 2021), ACTP could lead to a better reduction in pain perception in females.

Overall, studies examining the effects of acute ACTP ingestion on repeated sprint performance included physically active participants (Foster et al. 2014, Delextrat et al. 2015, Park et al. 2016, Morgan et al. 2018), whereas the present study included well-trained participants, and athletes have a higher pain tolerance than non-athletes (Pettersen et al. 2020). Therefore, ACTP may be more likely to be ergogenic in this study.

This study indicated that ACTP ingestion improved FI (21.44%) and RPE compared with PLA. However, Morgan et al. (2019) showed that acute ingestion of ACTP was not effective in reducing RPE, increasing muscle activation or improving intramuscular disruption during fatiguing exercise in men. Several factors may explain the sex differences in RPE and fatigue for responses to ACTP during intermittent fatiguing exercise. It is well known that women are more resistant to fatigue than men, as they feel less peripheral fatigue (Wüst et al. 2008, Gentil et al. 2017). These sex differences are related to the difference in fiber type and composition (Toft et al. 2003), the oxidative system (Russ and Kent-Braun 2003), the level of glycolytic metabolism (Russ et al. 2005), sex hormones (New et al. 2000), the metabolic vasodilators of the muscle (Clifford and Hellsten 2004), and the level of sympathetic activation (Ettinger et al. 1996). Consequently, in this study, it is conceivable that ACTP, serving as a potential central regulator and decreasing strictness (Foster et al. 2014), may account for the observed enhancements in FI and RPE during the 5mSRT.

Considering that 5mSRT induces muscle damage, it leads to an increase in DOMS and a decrease in PRS in males (Boukhris et al. 2020). However, females might encounter lower levels of exercise-induced muscle damage than males, as estrogen plays a protective role in preserving muscle function (Minahan et al. 2015; Morawetz et al. 2020). The ACTP in this study reduced DOMS and increased PRS, which may be attributed to paracetamol’s mild anti-inflammatory properties (Koelsch et al. 2010; Graham et al. 2013). Thus, it could mitigate acute muscle damage, alleviate DOMS, and expedite muscle function recovery after 5mSRT.

Participants in our study were in different phases of the menstrual cycle (eight in the luteal phase and six in the follicular phase). This hormonal fluctuation can amplify the variability of the threshold and the perception of pain (Hellström and Anderberg 2003; da Silva et al. 2021). A previous study found that women’s strength levels differ depending on the phase of the menstrual cycle, which reaches its maximum in the middle of the cycle when estrogen levels are high (Sarwar 1996). Additionally, one study reported faster recovery of exercise-induced muscle lesions in the follicular phase (high estrogen concentration) of the menstrual cycle compared to women in the luteal phase (low estrogen concentration) (Markofski and Braun 2014). Exercise-induced muscle damage for DOMS and strength decline are influenced by hormonal fluctuations throughout the phases of the menstrual cycle, such as estrogen concentrations (Romero-Parra et al. 2021). Furthermore, the sensitivity of experimental pain varies during the menstrual cycle (Kowalczyk et al. 2010); however, fatigability and strength do not demonstrate such variability (Hunter 2014). Furthermore, the results show that the pharmacokinetics of ACTP differ between men and women. The maximum plasma concentration is higher and the half-life of ACTP is longer in women in both phases (follicular and luteal phase) than in men (Wójcicki et al. 1979).

Our study has some limitations: first, we did not take into account the effect of the individual phases of the menstrual cycle in the part of the results. Second, we did not evaluate muscle damage biomarkers such as creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT), nor inflammation biomarkers (such as C-reactive protein CRP).

Future studies may consider additional measurements of biological markers of muscle damage after exercise and for 48 h after exercise, as pain and muscle damage have been reported hours and days after fatiguing exercise (Place et al. 2015).

Acute ingestion of ACTP at therapeutic doses is not associated with a health risk. However, chronic or toxic doses of ACTP significantly increase the risk of hepatic, renal, and gastrointestinal damage (Makin and Williams 1997).

Although hepatotoxicity generally occurs with doses of 10 g or more—well above the doses required to achieve an ergogenic effect (Wong and Graudins 2017), acute ingestion of 1.5 g of ACTP has shown no signs of hepatotoxicity, nor of drug accumulation, in healthy individuals or even in patients with severe liver disease (Forrest et al. 1979; Alchin et al. 2022). Furthermore, the pharmacokinetics of ACTP are not affected by exercise (Sawrymowicz 1997). When administered at recommended doses, ACTP is generally considered the safest and most effective analgesic available globally (Organization 2019). Currently, the use of ACTP is authorized by the World Anti-Doping Agency and is not listed among prohibited substances, although some have suggested that it should be included in the category of substances with therapeutic use exemptions (Lippi and Sanchis-Gomar 2014). The ethical aspects of using over-the-counter analgesics in athletes also need to be considered, as athletes who take such drugs, including NSAIDs, to reduce pain perception and enhance sports performance may in fact use them inappropriately (Alaranta et al. 2006). It is, therefore, crucial to make athletes aware of the potential risks associated with over-the-counter analgesics and to guide them towards using the safest option—namely, paracetamol—administered in the correct dosage and manner (specifically, an acute dose not exceeding 1.5 g and not for chronic use). A careful analysis of these aspects is essential before endorsing ACTP as an ergogenic aid.

Conclusions

The present study showed the benefits of acute ingestion of ACTP on repeated high intensity short-term maximal performance and cognitive and mood status in well-trained women, with decreased pain perception, reduced perceived exertion, reduced delayed muscle pain, and improved perceived recovery. From a practical standpoint, administering acute, nontoxic doses to athletes prior to competition can improve physical and cognitive performances and the sensation of recovery and mood as well as reduce the perception of fatigue, muscle damage and pain.