Multiple nutritional strategies could be used to improve performance of competitive athletes. Long-term (chronic) diets may be beneficial for multiple physiological adaptations such as gains of muscle mass using proteins (1). Acute supplementations may also enhance numerous aspects of performance (2). Supplementation may act at different physiological levels, including the central nervous system. For instance, supplementation could reduce serotonin synthesis or increase the concentration of neurotransmitters and therefore lower mental fatigue or increase the cognitive function (i.e., attention or vigilance) (2, 3). Confirming this assumption, the authors have observed that the negative effects of fatigue during a long duration offshore sailing race (feeling of fatigue and decrease in memory) were lowered with protein feeding (4). Nutrition supplementation could therefore be beneficial during numerous sporting situations for physical performance (i.e., improve performance and delay fatigue) and/or for neural and cognitive performance (e.g., improve attention and vigilance for fast decision makings or short reaction times).

Numerous nutrients have been proposed to act at these different levels. Among the wide possibilities, Salvia species are promising candidates according to their various active constituents such as caffeic acid, salvianolic acid, sagecoumarin, and sagerinic acid (5). Among the possible effects (5) of Salvia have been demonstrated effective for acetylcholinesterase inhibition (6) that would likely originate from the monoterpenoid constituents (7). Concomitant improved mood and cognitive performance were observed (6, 7). Terpenoids (e.g., eucalyptol, camphor, α-, β-pinene, and others), particularly present in Salvia essential oil, have also been shown to include antioxidant effects by inhibiting reactive oxygen species production and increasing endogenous antioxidant compounds (8). Anti-inflammatory effects are also observed as a result of phenolic diterpenes present in some species of Salvia (e.g., Salvia officinalis) that reduce, for instance, cytokines or interleukins (5). Different trials have shown positive effects for attention, memory, speed of memory, alertness, or calmness after single intake in healthy individuals (9–11). Salvia also includes numerous polyphenols (e.g., rosmarinic acid, apigenin glucosides, luteolin glucosides, and others) components with a well-known antioxidant effect (5, 12). Polyphenols are of particular interest for endurance-type performance. Indeed, in a preceding study, we have observed the positive effects of acute apple and grape polyphenols intake to increase cycling time to exhaustion and delay the maximal perceived exertion (13).

Salvia plants include numerous species with considerable constituent variations and resultant potential effects (5). To date, most clinical studies have confirmed the acute and chronic effects of a given particular species. In contrast, a recent study demonstrated that a combination of Salvia was more efficient than a single constituent (14). This study observed larger improvements in memory and learning (Y-maze and Morris water maze tests) on in vivo rodents using a combination of S. officinalis (leaf extract mostly characterized for polyphenol content) and Salvia lavandulaefolia (encapsuled essential oil with predominant terpenoids) (14). This specific combination of Salvia has also been demonstrated efficient for working memory in healthy humans using various tasks (9). However, to date and to the best of our knowledge, no study has explored the effects of Salvia, in sports or physical activity settings. The aim of this study was to explore the acute effects of a supplementation of S. officinalis and S. lavandulaefolia on cognitive function in athletes performing a fatiguing cycling task. According to the positive effects of Salvia on cognitive function, we hypothesized that Salvia will improve cognition during exercise and that these positive effects were exacerbated in a fatigue state.

Seventeen volunteers were considered for analyses (Table 1). Nine volunteers were lost due to the COVID-19 sanitary crisis (Figure 3). The mean power output during the two experimental procedures (power at 80% MAP) was similar between the two sessions (178.3 ± 50.6 W vs. 179.7 ± 48.8 W during SAGE and PLACEBO, respectively, P = 0.196). Results from the two-way ANOVA during the two experimental sessions are presented in Table 2. Briefly, a significant supplementation effect was observed for RPE, reaction time, and responses of the memory test. A significant time effect was obtained for heart rate, RPE, reaction time, and Stroop reaction time. Significant interactions were obtained for RPE and the accuracy of the Stroop test.

Post hoc analyses revealed that heart rate was significantly greater during T2 and T3 (during the fatiguing exercise) as compared to T1 and T4 (warm-up and recovery, respectively) (Figure 4, P < 0.001). No difference was observed between T2 and T3 (mean difference ± SD (95%CI): 4.9 ± 11.7 bpm (−2.9; 12.7), d = 0.419, small, P = 0.545). Heart rate remained significantly greater at T4 than at T1 (mean difference ± SD (95%CI): 11.5 ± 11.7 bpm (3.7; 19.4), d = 0.985, medium, P = 0.001). The post hoc analysis conducted on the interaction for RPE revealed various effects. With SAGE and PLACEBO, RPE was significantly lower at T1 as compared to T2, T3, and T4 (Figure 4, P < 0.001). For both SAGE and PLACEBO, RPE was significantly greater at T2 and T3 than at T4 (P < 0.001). However, RPE was significantly greater with PLACEBO as compared to SAGE at T3 [mean difference ± SD (95%CI): 0.6 ± 0.7 (0.1; 1.2), d = 0.901, medium, P = 0.005] and T4 [mean difference ± SD (95%CI): 0.7 ± 0.7 (0.1; 1.3), d = 0.705, medium, P = 0.002]. The main supplementation effect revealed lower RPE, all time points merged, with SAGE as compared to PLACEBO [mean difference ± SD (95%CI): 0.3 ± 0.3 (0.1; 0.5), d = 0.868, medium, P = 0.002].

Reaction time was not altered during the exercise. However, reaction time (Figure 4) was significantly longer with PLACEBO as compared to SAGE [mean difference ± SD (95%CI): 33.7 ± 55.4 ms (5.2; 62.2), d = 0.608, medium, P = 0.023]. During the Stroop task, reaction time (Figure 5) was significantly longer at T1 as compared to T4 [mean difference ± SD (95%CI): −86.4 ± 92.4 ms (−24.7;148.1), d = 0.935, medium, P = 0.02]. The post hoc analysis did not reveal any differences for Stroop accuracy. During the digit span memory test, the results revealed a significant supplementation effect (Figure 5). A significant greater span score was measured with SAGE as compared to PLACEBO [mean difference ± SD (95%CI): 6.0% ± 11.4 (0.2; 11.9), d = 0.53, medium, P = 0.044].

This study aimed to explore the acute effects of a supplementation of S. officinalis and S. lavandulaefolia on cognitive functions in athletes performing a fatiguing cycling task. The main findings are as follows: (1) The combination of Salvia improved the cognitive function (as witnessed by perceived exertion, working memory, and reaction time) throughout the experimental procedure and (2) the positive effects were maintained with fatigue. The present findings partly confirmed our initial hypothesis. We can conclude that an acute supplementation with a combination of S. officinalis and S. lavandulaefolia is beneficial on some cognitive function outcomes in the context of an endurance cycling exercise.

The results of this study confirmed previously published observations that revealed beneficial effects of Salvia on the cognitive function (9–11). These positive results were previously obtained with chronic supplementation in humans suffering from different diseases such as Alzheimer's disease or in patients with chronic fatigue syndrome (23, 24). Acute Salvia supplementation was also beneficial in healthy individuals for mood, memory, or attention (7, 9–11, 25). More specifically, in healthy individuals, the two species of Salvia under investigation in the present study (S. officinalis and S. lavandulaefolia) have, separately, demonstrated improvements for immediate or delayed word recall, speed of memory, and Stroop test (7, 10, 26). These positive effects have been observed within the first 4 h post-ingestion (6, 26). The combination of these two species has been explored more recently (9). Similar positive effects, for instance in working memory, have been obtained in healthy individuals just 2 h after supplementation but also after a chronic administration (9, 14).

The nootropics properties of Salvia are partly described and begin to be explained (5). Inhibition of the acetylcholinesterase is often proposed as a mechanism for memory retention (27, 28). Interestingly, acetylcholinesterase inhibition is demonstrated for the two species of Salvia tested here whether it is an aqueous extract from leaves or essential oil. In addition, terpenes particularly identified in S. lavandulaefolia essential oil are able to attenuate oxidative stress by inhibiting reactive oxygen species production (8). Other effects originating from the phenolic constituents of Salvia include antioxidant, anti-inflammatory activities in neurons as well as increases in brain-derived neurotrophic factor (5). A preclinical trial also demonstrated that chronic ingestion of S. officinalis combined with S. lavandulaefolia increased the expression of calcium/calmodulin-dependent protein kinase II (14). This enzyme has large impact for improving working memory and cognitive processes since it acts in numerous neuronal functions, including neurotransmitter metabolism, neuronal signal transduction, or synaptic plasticity [see (29, 30)]. However, further studies are clearly needed to verify these hypotheses after a single intake and elucidate the Salvia-induced mechanisms.

To date and to the best of our knowledge, no study has explored the acute effects of Salvia in the context of sport, physical activity, or exercise-induced fatigue. In humans, fatigue has previously been considered in those complaining of chronic fatigue (23) with chronic supplementation of Salvia miltiorrhiza combined with Astragali. In healthy individuals, fatigue from exercise was explored with chronic supplementation in a single study performing a downhill running with S. miltiorrhiza combined with panax ginseng (31). A faster recovery of the joint range of motion and a lower increase in creatine kinase were obtained with supplementation after this eccentric-type exercise (31). Moreover, interleukin-6 increased with the placebo group, while it remained unchanged in the supplementation condition (31). Two other studies used animals performing a forced swimming test with chronic supplementation of Tanshinone IIA, a constituent from S. miltiorrhiza (32), or S. miltiorrhiza combined with Astragali (33). These two studies revealed an anti-fatigue effect of Salvia with reductions in serum glucose and lactate levels and by attenuating oxidative and inflammatory response (32, 33). Taken together, these studies with chronic supplementation confirmed that Salvia could be beneficial during exercise.

This study was the first to explore the acute effects of Salvia supplementation during exercise. Despite positive findings in some outcomes, our results are partly in contradiction with our initial hypothesis. Indeed, we hypothesized that the positive effects of the supplementation would be exacerbated with fatigue. Considering cognitive tests, no additional supplementation effect was obtained with fatigue. It signified that the positive effects of the supplementation were obtained in fresh conditions and were maintained during the exercise. In contrast, RPE was significantly altered during the intensive cycling exercise and during recovery (lower values with SAGE as compared to PLACEBO). At first sight, this outcome could appear trivial in sporting situations, but it is of paramount importance. Indeed, the central nervous system is well-known to play a very important role in the fatigue process (34, 35). For instance, numerous studies have demonstrated the negative impact of mental fatigue in sport-specific situations such as decision making in team sports or reaction time (35–38). After a demanding cognitive task, RPE was one of the most altered outcomes (36, 38, 39). The authors concluded that mental fatigue would limit exercise tolerance through higher perception of effort (39) and often consider RPE as a limiting factor for endurance performance instead of a simple marker of exercise intensity (40). Considering this psychobiological approach, the lower RPE observed with Salvia clearly suggested that supplementation could positively impact performance during fatiguing exercises. Such hypothesis should be further investigated since the present procedure was not conducted until complete exhaustion.

The lower RPE obtained with Salvia supplementation is not surprising. Salvia is a well-described supplement with numerous active constituents, including polyphenols with antioxidant effects (5, 12). Phenolic constituents are rosmarinic acid, caffeic acid, salvianolic acid, sagecoumarin, and sagerinic acid (5, 9). Polyphenols have been demonstrated to positively impact endurance performance in recreational and elite athletes (13, 41) concomitantly with a delay in maximal perceived exertion. Interestingly, one species of Salvia considered here (S. officinalis) has the highest antioxidant effects (42). Furthermore, the monoterpenes of the co-administered S. lavandulaefolia have been demonstrated to inhibit reactive oxygen species production (8). One should acknowledge that other studies failed to identify positive effects of polyphenols on endurance performance (43, 44). These conflicting findings could be related to the training status. Elite athletes (43) or well-training cyclists (44) were included, while physically active individuals were tested here.

Taken together, our results demonstrated the positive effects of Salvia during fatiguing exercises with lower RPE and maintained cognitive performance. Such finding has large impact for performance but also for injury prevention. Indeed, a recent study pointed out altered kinematics of landing that could increase injury risks in people conducting a perceptual-cognitive task combined with fatigue (45) such as those regularly occurring in numerous sports. Increasing awareness with, for example, cognitive training has been suggested to be efficient as prevention programs for a better neuromuscular control (46). Combining these preventive programs with supplementation could be hypothesized to emphasize prevention. Therefore, investigating the effects of supplementation in specific technical tasks would be of interest to confirm a potential positive effect for injury prevention.

Several limitations could be acknowledged. First, like in other studies, although the present study was double-blind, some volunteers were able to identify the product ingested. It is attributed to the herbal taste during some reflux at the end of the fatiguing exercise. Nevertheless, statistical analyses were similar when including or excluding these volunteers (n = 2). In addition, we decided to evaluate the cognitive function while cycling. This double task, often observed during sporting events, could be a limitation. Nevertheless, care was taken to familiarize individuals during two separate sessions. The fatiguing exercise consisted in two 10-min high-intensity cycling (with RPE > 8). This exercise was designed to be achievable by physically active individuals; it could be interesting to repeat such experimental design with a greater exercise difficulty, for instance, as often performed, until exhaustion (13). Finally, cognitive function was investigated using some specific tasks. It should be acknowledged that the Stroop task was not sensitive to fatigue with values very close to the maximal performance (100% of accuracy). Additional measurements for the Stroop test could be suggested to increase its sensitivity to fatigue or to the supplementation. Additional cognitive tasks could be applied in order to have a more exhaustive view of Salvia acute effects. Moreover, additional cognitive tasks, specific to some real-world sporting situations (for example, reaction time while playing tennis), should be tested in order to conclude that the observed effects could be translated to sporting events. In line with this perspective, the exercise under investigation should also be more specific (for example, while modeling a sporting event).

In conclusion, this study is consistent with previous experiments conducted in healthy individuals after acute Salvia supplementation. As compared to placebo, it revealed improved cognitive function (perceived exertion, reaction time, and working memory) after an acute Salvia intake (2 h after ingestion). Most effects were observed independently of the time point (before, during, or after a fatiguing cycling exercise). It is therefore suggested that Salvia effects are not negatively or positively affected by the exercise performed. Salvia demonstrated universal effects in fresh or fatigued conditions. It has a potential impact in the context of sport performance and more generally in the context of physical activity but requires more real-world exercises and cognitive tasks.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by University of Burgundy Institutional Ethics Committee. The patients/participants provided their written informed consent to participate in this study.

NB conceived and designed the experiment, analyzed the data, performed statistical analysis, and wrote the first draft of the paper. AN, NA, and CC performed the experiments. AN and CC performed data collection. NB and DG interpreted the data. All authors reviewed the manuscript and approved the final version of the paper.

This study was supported by the Centre d'Expertise de la Performance from the Université of Bourgogne. The product under investigation was provided by Nexira. The authors declare that this study received funding from Nexira to cover the costs of publication. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

DG was employed by Nexira. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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