In this study, we examined the acute effects of CAF+ and caffeine on different cognitive functions. This was done in a double-blind placebo-controlled randomized cross-over design. We found that caffeine improved working memory performance in the n-back task at the most difficult level and outperformed CAF+ treatment on the delayed verbal memory task. Further, caffeine increased the speed of responding in the incompatible reaction time task. On a physiological level, caffeine increased the diastolic blood pressure whereas CAF+ did not have an effect on blood pressure. Interestingly, CAF+ increased subjective alertness. Based on these data, it is concluded that caffeine improved cognitive performance and that CAF+ did not.

It is well known that caffeine has various effects on cognitive functions. This was replicated in the current study and further supports this well-documented effect. The hypothesis of the current study was that CAF+ would have stronger effects than caffeine alone. This hypothesis could not be confirmed; CAF+ did not have an effect on the cognitive performance. In the verbal memory task, we found that the performance after CAF+ treatment was worse compared to the caffeine treatment. Also, in the reaction time task, CAF+ treatment was associated with slower response times as compared to caffeine. These data indicate clearly that CAF+ does not improve cognitive functions in young healthy volunteers at the dose used. However, it could be speculated that chronic treatment with CAF+ may have positive effects.

The dose used for the caffeine capsule (100 mg) is in the range of the reported cognition-enhancing effects (McLellan et al. 2016). The same dose was used for the CAF+ formulation. CAF+ also contains other ingredients that may boost the brain systems that increase the improved cognitive performance in young subjects. It could be argued that the combination of the extra ingredients in addition to the caffeine may constitute a dose that is too high to have beneficial effects on cognition and would have placed participants non-optimally on the inverted-U curve of stress/arousal, leading to less than optimal performance on the tasks. However, CAF+ includes ingredients that both promote and reduce arousing drive, as discussed in the introduction. It is not likely, for this reason, that the addition of the ingredients in CAF+ necessarily causes a shift to the right on the on the inverted-U curve. Similarly, it has been shown in young and healthy students that the effects of caffeine only benefited memory during participant’s non-optimal phase (Sherman et al. 2016). In the current study, it may have been the case that the possible de-arousing effects of l-theanine and l-tyrosine in CAF+ did not sufficiently place participants in their non-optimal phase in order for the arousal-promoting ingredients to benefit task performance. Additionally, the inverted-U may be shifted for different tasks (Salehi et al. 2010). The tasks in this study were performed sitting quietly, with no accessory motions. It should be considered whether the CAF+ dose can be optimally developed for such tasks, which have limited to no stress component. Finally, ingredients may have a different pharmacological profile when added together than when administered alone. For example, it has repeatedly been shown that caffeine and l-theanine added together have different effects on cognition and mood, leading to cognitive benefits not seen when administered alone (Camfield et al. 2014; Einother et al. 2010; Haskell et al. 2008). More research is needed to look into the mechanisms underlying such effects.

Since our participants were young and healthy, it may have been the case that they performed at their maximum level already, leaving little room for improvement. On the other hand, it may reasonably be expected that a cognition enhancer would also be able to improve cognition in such a population. This was demonstrated in two studies examining the effects of the cognitive enhancer methylphenidate in healthy young volunteers: methylphenidate was found to decrease response times and improve episodic memory in one study (Linssen et al. 2014) and to improve declarative memory, attention, and response inhibition in another study (Linssen et al. 2012). We did find some effects of caffeine, although it must be mentioned that absolute differences were relatively small. Further studies could explore the effects of CAF+ in older participants (> 40 years old), who generally perform less well in the current tasks when compared to their younger counterparts.

It is interesting to note that CAF+ had effects on a subjective measure of alertness. Participants reported to be more alert with CAF+ as compared to the placebo treatment, but only 30 min after intake of the capsule. A comparable study by Giesbrecht et al. (2010) looked at the combination of caffeine and l-theanine on cognition and subjective alertness in young adults. They found that attention switching improved but performance on the other cognitive tasks did not, while subjective alertness was increased overall. Similar to our results, no differences in heart rate were found, ruling out the influence of this factor on the feelings of alertness. It could be argued that the combination of caffeine and l-theanine helps focus attention, but not enough to show improved performance in a majority of cognitive tasks.

Additionally, our findings suggest that the (subjective) effects of CAF+ appear quite quickly and disappear after 90 min, which was not the case in the aforementioned study. As the dose of caffeine and l-theanine in CAF+ is higher than the dose of these ingredients in the study by Giesbrecht et al. (40 mg vs 100 mg caffeine; 97 mg vs 200 mg l-theanine), the possibility of an inverted-U dose-response relationship may also exist for subjective alertness. In other studies that use combined ingredients with a higher dose of caffeine, such as Red Bull Energy Drink, results differ. Red Bull contains 80 mg of caffeine, and among other ingredients, vitamin B 6 and B 12 . Wesnes et al. (2017) found that in a similar population of young volunteers, Red Bull improved cognition and subjective alertness. However, alertness was not improved by the sugar-free version of the drink. On the other hand, Kammerer et al. (2014) did not find improvements in cognition, although self-reported alertness was not measured here.

Finally, this study also shows that caffeine intake exerts some effects on physiological measures. An increased (diastolic) blood pressure is a well-known effect of caffeine, which tends to peak in 1–2 h after intake (Mort and Kruse 2008), as the current study’s findings also show. Interestingly, treatment with CAF+ did not result in a blood pressure increase or at least mitigated the blood pressure increase due to caffeine alone. This is in line with previous research (Dodd et al. 2015), and suggests that the additional ingredients of CAF+ may act against the arousing influence of caffeine. Another well-known effect of caffeine is its ability to increase alertness (Mikalsen et al. 2001). While we were not able to find a statistically reliable effect of caffeine on alertness, the mean values on the alertness scale were higher after caffeine treatment (30 and 90 min) than after placebo treatment. Furthermore, alertness was measured subjectively by means of a questionnaire here, forming only an indirect indication of participant’s alertness level.

In conclusion, the current study did not show a positive effect of CAF+ on cognitive functions. Future research should focus on including more complex and/or stressful tasks or investigating stress-induced cognitive deficits. Additionally, the dose of the different ingredients could be adjusted, and inclusion of older participants may be another approach to explore the potential cognition-enhancing effects of CAF+ or other combinations of nootropic ingredients.