The main finding of the study was that there was no placebo effect of caffeine in women habituated to caffeine when misled to believe that they had ingested 6 mg/kg of caffeine. The lack of placebo effect of caffeine was evident in both the 1RM test as well as on all measured variables during the strength-endurance test performed at 50% 1RM. Therefore, the use of a deceptive protocol to induce the placebo effect of caffeine is likely an ineffective measure to enhance muscle performance in women athletes who are habituated to caffeine. To this respect, the actual ingestion of caffeine may be recommended  although doses higher than the daily level of its consumption may be necessary to obtain the potential ergogenic effect of caffeine in athletes habituated to this substance [23, 24].
To the best of our knowledge, this is the first study analyzing the placebo effect of caffeine on exercise performance in women habituated to this stimulant. In contrast to the outcomes of this study, previous research on male athletes showed a placebo effect of caffeine on resistance exercise performance [10, 13, 16]. Pollo et al.  showed that placebo intake increased exercise performance during a strength-endurance test in a group of men who believed they had ingested high doses of caffeine. Similarly, a placebo effect of caffeine was obtained by Duncan et al. , who additionally strengthened their deceptive experimental design by providing the participants with scientific data confirming the effectiveness of acute caffeine intake on resistance exercise. Lastly, Costa et al.  observed that placebo intake, when the athletes were informed they were taking caffeine, was effective to enhance bench press throw performance in Paralympic weightlifters. The main difference between these three investigations and the current protocol, beyond the sex of the participants, is the habituation to caffeine. In the current investigation, participants were habituated to caffeine because they ingested on average 4.1 ± 1.6 mg of caffeine per kg of body mass per day. Due to high daily caffeine intake, beliefs of acute caffeine intake in habitual users of caffeine may differ in comparison to naive or low users. It has been found that chronic caffeine ingestion results in more newly created adenosine receptors that partially reduce the blocking-action of caffeine on the central nervous system  and may modify the physiological and cognitive responses to acute caffeine intake, which could negatively impact its ergogenic effect [33, 34]. If such suppressed reactions represent beliefs of habitual caffeine users, it could explain no improvement in performance in this group. These results suggest that resistance-trained athletes familiarized with the use of caffeine-containing products do not obtain the placebo effect of caffeine. Those athletes not familiarized with caffeine may be effectively mislead about caffeine intake to obtain a potential performance improvement, but this remains to be studied in women.
The lack of placebo effect of caffeine in individuals habituated to caffeine may be reinforced by outcomes of previous investigations. While the placebo effect of caffeine has been confirmed by using several depictive protocols [9, 10, 12–18], the two investigations carried out with participants habituated to caffeine showed that the deception was not successful. Foad et al.  found that, in participants ingesting at least 300 mg/day of caffeine, informing that they had received caffeine, when they had ingested placebo, was not effective at increasing performance during a 40-km cycling time trial. In fact, the actual intake of 5 mg/kg of caffeine was effective to increase cycling performance, irrespective of whether they were informed that they received caffeine or placebo. Similarly, Tallis et al.  observed that the placebo effect of caffeine was not present in individuals habituated to caffeine (92 mg/day) during a test of maximal voluntary concentric force of the knee flexors and extensors. Again, the actual ingestion of 5 mg/kg of caffeine was necessary to obtain muscle performance benefits in comparison to a control situation. All this information, together, point towards the lack of placebo effect of caffeine in endurance and resistance-based exercise in individuals who are habituated to caffeine. Thus, the acute ingestion of caffeine seems necessary to obtain the potential effect of this substance in the population samples.
Despite the uniqueness of the presented results, there were several limitations in the experimental design employed which should be addressed to understand the significance of the outcomes. First, this study did not contain a double-dissociation design. This is because we did not aim to study the additive effect of being informed of receiving caffeine plus actually receiving caffeine, as previous investigations have done . Instead, the purpose of the current investigation was to determine in isolation the placebo effect of caffeine in women athletes habituated to this substance. For this reason, we used a deceptive experimental design that included two identical trials that differed only in the participant’s believe of having received caffeine. Second, the study did not include any measurement to assess how effective was our deceptive protocol in terms of participants’ actual belief on receiving caffeine. Thus, the current investigation is unable to determine the effect of participants’ expectations on the placebo effect of caffeine in our study sample. Lastly, as our participants were moderate caffeine users, it would also be interesting to assess withdrawal symptoms in the two trials to determine whether our participants perceived the lack of feelings habitually associated to caffeine. Despite these limitations, we believe the current manuscript is sound to determine the lack of the placebo effect of caffeine on women athletes habituated to caffeine. The manuscript adds valuable information for resistance-trained women seeking to obtain benefits related to caffeine supplementation.