Does cocoa increase anxiety?

The caffeine in caffeinated cocoa can enhance attention while the brewed cocoa can attenuate the anxiety provoking effects of caffeine alone.

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Cocoa versus placebo

Cocoa enhanced two aspects of Bakan dual task performance compared to placebo. Cocoa reduced overall false alarm errors progressively across time with 0.92, 1.44 and 2.35 fewer false alarms on average at 22–48, 60–86 and 98–124 min post-consumption. Cocoa also improved processing speed during the secondary task of the Bakan dual task. The improvement in reaction time (11 ms faster) was apparent at 22–48 min post-consumption and there was a slight additional improvement (a total of 17 ms faster) that was maintained throughout the subsequent two testing times. Regression to the mean could not be ruled as an explanation for the significant effects of cocoa on the Bakan test because there were significantly fewer false alarm errors (mean = 4.6) and slower reaction time (mean = 25 ms) at baseline in the placebo condition compared to the cocoa condition. Mood states (i.e., POMS) were not improved after taking cocoa alone compared to placebo which is consistent with studies that found no effect of theobromine on mood [14], but inconsistent with prior work suggesting that higher feelings of energy can increase performance in the high-event rate component of a dual task [39]. It is difficult to compare the Bakan secondary task results directly to other cocoa investigations because dual tasks were not used in the prior related cocoa studies [24, 26]. One prior study did not show fewer false alarms after 520- or 994-mg cocoa [26]. The failure of cocoa to significantly improve reaction time on the primary task of the Bakan test, serial three accuracy, serial seven errors, and feelings of mental fatigue were in contrast to the results of the study by Scholey and colleagues that is most similar in design to the present study [26]. A key difference between the present study and the Scholey study is the absence of dairy and calories in the present study compared to the dairy-based cocoa drink with ~217 kcals used by Scholey and colleagues. The Bakan test used in this study also may have different psychometric properties from the conceptually similar rapid visual information processing test used in the Scholey et al. [26] study which may have contributed to different results. For example, the reliability or the sensitivity for measuring change might differ between the Bakan and the rapid visual information processing test because of procedural differences in the tests. The rapid visual information processing test requires participants to react to both odd and even sequences while the Bakan requires responses to odd sequences as a primary task and a single even number as a secondary task. Also, the Bakan task duration was three times longer and the stimuli in the rapid visual information processing test were presented at a rate of 100 per minute while the Bakan test presented stimuli at a rate of 60 per minute. Another study using a 500-mg cocoa drink showed results that appear to be generally consistent with the present findings, but two of three testing times were confounded by the post-cocoa consumption of a lunch [40], which reduces the ability to make meaningful comparisons to the calorie-free cocoa drink used here.

Cocoa + caffeine versus caffeine-only

Cocoa + caffeine compared to caffeine-only allowed for an assessment of the potential role of cocoa flavanols combined with theobromine, which were both absent in the caffeine-only drink. Anxiety was the only significant interaction observed. Cocoa + caffeine attenuated the increase in anxiety that occurred at the final testing time in the caffeine-only condition. Elevated anxiety is a common side effect of caffeine consumption in low caffeine consumers [41] (such as those in this study) and many participants in past studies using similar protocols have anecdotally reported that repeatedly completing the attention task is stressful [7, 42]. Thus, the anxiety elevation at the final testing time in the placebo condition, while not hypothesized, is not unexpected. Theobromine and flavanols, or their metabolites, could plausibly influence anxiety by binding to adenosine or benzodiazepine receptors [42–44]. One study found that 500 mg cocoa acutely increased calmness; however, increased calmness did not occur after an acute cocoa administration at the start of the investigation but only after an acute administration was preceded by 30-days of daily cocoa supplementation [40], as could plausibly occur because of receptor up-regulation [45].

Cocoa + caffeine compared to cocoa

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Cocoa + Caffeine compared to cocoa allowed for an assessment of the impact of 49 mg of supplemental caffeine on the outcomes. Supplemental caffeine improved accuracy and resulted in fewer omission errors on the primary task of the Bakan test, but otherwise had no statistically significant motivation, mood or cognitive interaction effects. Improved accuracy and fewer omission errors on the primary Bakan task occurred after the caffeine alone condition but the effect was smaller. Caffeine can improve vigilance performance by improving accuracy, reducing errors and reducing reaction time [46, 47] so it is unclear why the effects of supplemental caffeine were limited to the primary task of the Bakan test. One possibility is that the participants in the present study were not especially responsive to the mood, motivation and attention enhancing influence of caffeine. Genetic factors are known to influence caffeine sensitivity and relevant genotypes, such as for adenosine A 2A receptors, were not assessed in this study [42]. Another possibility is that caffeine may only influence the most challenging component of the more difficult dual task. It has been suggested that while high event tasks take more cognitive resources, low event tasks, such as the primary task of the Bakan, require greater vigilance [48].

Caffeine-only versus placebo

Caffeine alone resulted in small changes that were generally in the direction expected based on prior research [49] but were small in magnitude and statistically non-significant. For instance, compared to pre-test, there were small, non-significant increases in motivation, feelings of energy and accuracy in the cognitive tests as well as small decreases in fatigue, errors and reaction times. Mean anger scores did not change in the caffeine condition, as is consistent with prior studies [50]; however, a significant interaction emerged because anger increased in the placebo condition. We speculate that anger scores increased in response to the stress of completing 104 total mins (4 x 26 mins sessions) of sustained vigilance testing across 2.75 h testing sessions and caffeine attenuated the effect.

Possible mechanisms

Caffeine crosses the blood-brain barrier and exerts central nervous system (CNS) effects by antagonizing adenosine receptors [51]. Dietary flavonoids are less well studied but experiments in rodents and pigs show that polyphenols can traverse the blood-brain-barrier and accumulate throughout the brain [52] and act on neural or glial cell-signaling pathways and increase cerebral blood flow [53]. One human study showed increased cerebral blood flow 2–4 h after consuming cocoa flavanols and a subsequent study found a similar increase in elderly persons, except that it was delayed until 8 h after ingestion [4, 54]. Thus, it is possible that the cognitive effects observed in the present study were the result of changes in brain blood flow, although no study has measured such responses < 2 h after cocoa administration. Adequate brain blood flow is known to be required for normal cognitive performance [55] but nutrition-induced increases in blood flow do not always produce improvements in cognitive performance [56]. Adequate blood flow to cognition-related neural circuitry is necessary but cognitive performance also appears to depend on a host of excitatory and inhibitory neurotransmitters (e.g., gamma-aminobutyric acid and glutamate), neuromodulators (e.g., dopamine and norepinephrine) and neuropeptides (e.g., cholecystokinin, corticotropin releasing factor, galanin) [57]. For example, caffeine can reduce overall and regional brain blood flow [58, 59] yet cognitive performance is often improved after caffeine is consumed. Therefore, it is plausible that the effects observed in the present study were not exclusively explained by blood flow changes. Brain neurons use glucose for energy and the treatment effects observed here could stem from actions on glucose or its regulation [6]. Both caffeine and dietary flavonoids can impair glucose regulation [60, 61]; consequently, improvements in blood flow may have been opposed by alterations in glucose regulation. Also, the methylxanine treatments may have stimulated the release of neurotransmitters or neuromodulators. Increased dopamine release in the frontal, prefrontal and medial cortices is hypothesized to deactivate the default mode network and is known to play a role in attentional processing [62, 63]. It is thought that caffeine antagonizes adenosine receptors in the basal ganglia which is known to contribute to the modulation of the default mode network [63, 64]. Increased dopamine in the nucleus accumbens also plays a role in motivation and feelings of energy [65]. One study comparing the mood and cognitive effects of theobromine and caffeine concluded that theobromine might exert anti-anxiety effects by lowering blood pressure rather than directly influencing the CNS. In short, the methylxanthines studied here potentially work via multiple, complex, interacting central and peripheral mechanisms. The present study was not designed to obtain data directly related to any of these potential mechanisms. This study did obtain correlational data that could, indirectly, have relevance for the mechanisms involved in the behavioral effects observed here. In the caffeine only condition, changes in theobromine and paraxanthine were positively related to changes in accuracy and negatively related to changes in omission errors, but only in the more difficult Bakan dual task. These associations were attenuated when caffeine was combined with cocoa or when cocoa was consumed alone. The overall pattern of results suggests changes in cognitive performance and changes in salivary methylxanthine metabolites measured 2-hrs after 66-mg caffeine consumption are only modestly related, task dependent, and attenuated by the co-consumption of cocoa.

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The correlational finding related to mood suggests that participants with higher salivary caffeine 2-hrs post-consumption, and hence with a slower metabolism of caffeine, also showed a greater increase in feelings of physical fatigue 2 h after caffeine had been consumed. It is uncertain why a correlation of a similar magnitude did not emerge for mental fatigue also measured with a visual analog scale (r = 0.12) or fatigue measured with the POMS category scale (r = 0.26). It should be noted that physical activity is not required to induce feelings of physical fatigue. Indeed, recent studies show that sitting and being sedentary for extended periods can contribute to feelings of fatigue [66]. This effect may be exacerbated by cognitive work involving attention.

Limitations

The study reported here had several features that may limit the generalizability of the findings. First, recruitment was limited to those reporting average or lower than average consumption of fruits and vegetables and other foods and beverages containing flavanols. Second, not all participants were medication-free, a relatively small number of participants were tested, and the timing and composition of the meals preceding testing were not controlled. Third, the potential role of sensory aspects of cocoa were not examined; there is evidence that sensory aspects of another drink made from cacao beans (e.g., mouth exposure to chocolate milk) can produce specific brain responses (e.g., increased blood flow in the orbitofrontal region) which may have contributed to changes in attentional task performance that were more rapid than any that stemmed from drink consumption [67, 68]. Fourth, we did not obtain saliva samples between completion of beverage consumption and the second mental energy test battery, so it is unclear if caffeine and metabolites were bioavailable prior to initiating the second mental energy test battery; however, previous evidence suggests the amount of time that orally consumed caffeine takes to reach peak bioavailability was within the time-range of the second mental energy test battery [69]. In addition, the cocoa or caffeine dose was not administered relative to bodyweight, but was absolute (i.e., 70 mg caffeine), which limits direct comparison to studies that did administer caffeine relative to body weight. Finally, the study design was block randomized (not fully randomized) and multiple statistical tests were conducted which increases the risk that one of the statistically significant results occurred by chance.

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