By George Munoz, MD

The Oasis Institute, Aventura, FL

Dr. Munoz reports he is a consultant for UCB, and is on the speakers bureau for Primus and UCB.

SYNOPSIS: An acute administration of a chocolate rich in flavanols (a subclass of flavonoids) was found to mitigate the cardiovascular and cognitive effects of sleep deprivation in a group of young and healthy individuals.

SOURCE: Grassi D, Socci V, Tempesta D, et al. Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals. J Hypertens 2016;34:1298-1308.

Sleep deprivation has become a major health issue in the United States, with more than 50-70 million adults suffering from sleep disorders. It has been found that sleep deprivation can be detrimental for cardiovascular health and cognitive function. Sleep alters the autonomic nervous system; therefore, disorders interrupt the normal regulation of blood pressure (increasing BP) and can lead to increased inflammation, endothelial dysfunction, and increase oxidative stress. Taking it one step further, high BP has been linked to Alzheimer’s disease, cognitive impairment, and vascular dementia.

There has been great interest in finding a product that can ameliorate the side effects of sleep deprivation. One food that has caught many people’s attention because of its high flavonoid content and potential cardiovascular benefits is cocoa, the (usually) powdered product of chocolate “beans.” Flavanols (a subclass of flavonoids, which include catechins, epicatechins, proanthocyanidins, theaflavins, and thearubigins) have been found to improve endothelial function by increasing nitrous oxide availability (aiding in BP regulation). Hence, they might help increase cerebral blood flow and cognitive impairment. To date, many studies have shown an improvement of hippocampal functioning and cognition in general with a flavanol-rich diet, but none have studied whether flavanols in cocoa can diminish the impairments caused by restricting sleep. In a double-blind, randomized, controlled trial, Grassi et al studied whether cocoa could acutely improve cardiovascular and cognitive function after a night of sleep deprivation.

The study recruited 32 healthy participants (16 men and 16 women) with no history of medical, neurological, or psychiatric disorders. Participants all had a blood pressure of less than 140/90 mmHg and a body mass index (BMI) between 19-30 kg/m2. The researchers excluded smokers, habitual cocoa consumers, and subjects with sleeping disorders, metabolic diseases, or any major cardiovascular risk factor.

Each participant attended four testing sessions: two control sessions in which they were evaluated after undisturbed sleep and two experimental sessions in which they were evaluated after total sleep deprivation. Testing sessions were separated by one week and participants were asked to fast for 12 hours prior to the session. They were given one bar of either a flavanol-rich chocolate (520 mg of flavanols) or a flavanol-poor chocolate (88.5 mg of flavanols). Each chocolate bar weighed 100 g; the flavanol-rich chocolate was 80% cocoa, while the flavanol-poor chocolate was 50% cocoa. Ninety minutes after the chocolate consumption, participants submitted to several cognitive tests and were given a Karolinska sleepiness scale (KSS) to assess their sleepiness. The tests included a psychomotor vigilance task to evaluate response speed and behavioral alertness) and the two-back task (to measure working memory).

Two hours after chocolate consumption, participants were taken into a quiet room where several medical assessments were performed to measure endothelial function, blood pressure, and arterial stiffness. Endothelial function was assessed via the flow mediated dilation (FMD), which tested the brachial artery with the use of ultrasonography. Later, the central and peripheral arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV), using a probe to record the waveforms and the ECG to calculate wave transit time. Finally, repeated measure analyses of variance (ANOVA) were performed on condition and treatment with different dependent variables. Also, correlations were calculated between the two-back test and changes in FMD and PWV after flavanol-rich chocolate consumption. The level of significance was set at P < 0.05.

Results showed that the KSS score (sleepiness) was higher in the sleep deprivation group than the undisturbed sleep group. On the other hand, behavioral measures showed that the average reaction time was slower in the sleep deprivation group (P = 0.00001). In other words, sleep deprivation adversely affected alertness and cognitive functions. Also, it showed that the female group’s accuracy when sleep-deprived was higher when they consumed the flavanol-rich chocolate vs. the flavanol-poor chocolate (P = 0.04). This is significant, since it means that in women, but not men, cocoa was able to improve working memory and cognitive performance altered by lack of sleep.

The cardiovascular measures demonstrated that sleep deprivation does have an effect on cardiovascular health, since it raised the SBP (P = 0.001). Also, the effect of treatment (flavanol-rich vs. flavanol-poor) on pulse pressure was significant (P = 0.004). The pulse pressure was lower in the flavanol-rich group (mean = 46.44) compared to the flavanol-poor group (mean = 48.47).

When analyzing the FMD, the effect of treatment (P = 0.00001) and condition (P = 0.02) were significant. Participants showed a higher FMD after consuming the flavanol-rich chocolate (mean = 7.04%) compared to the flavanol-poor chocolate (mean = 5.00%). This supports previous findings stating that administration of flavanol-rich chocolate can increase and improve endothelial function acutely.

The statistical analysis on the PWV showed a non-significant effect of treatment and a significant effect of condition. The interaction of condition and treatment with the PWV was significant (P = 0.03), while the PWV was higher on deprivation state when compared to the undisturbed sleep, but only after consuming the flavanol-poor chocolate. This means that the flavanol-rich chocolate was able to maintain the arterial stiffness after a night with no sleep, while the flavanol-poor chocolate increased the arterial stiffness or lack of vascular compliance, which is a predecessor to hypertension and left ventricular dysfunction.

On the other hand, when calculating the ANOVA on the aortic systolic pressure, the gender (P = 0.001) and condition (P = 0.006) were found to be significant, but the treatment (P = 0.91) was found to be non-significant. The same effect was seen on the aortic pulse pressure.

Pearson’s r coefficient was used to calculate the relationship between working memory, FMD, and PWV. Researchers found a significant coefficient between FMD and the two-back tests — the higher the FMD, the better the participant performed in the two-back tests (r = 0.41; P = 0.01). There was no correlation between PWV and the two-back test.

COMMENTARY

The Grassi et al study ties into other research, supporting those results and advancing our understanding of the mechanisms behind the effect of cocoa. One of the possible mechanisms that explains the effect of flavanols on BP and arterial function is the ability of flavanols to induce the synthesis and secretion of cortisol, epinephrine, and norepinephrine. Wirtz et al performed a placebo-controlled trial with 64 men to measure cortisol, epinephrine, adrenocorticotropic hormone, and norepinephrine on blood and saliva when subjected to a social stress test after consuming a dark chocolate with flavonoid and another without flavonoids.¹ The study showed that the flavonoids in the dark chocolate buffered the stress reaction at the peripheral level, specifically the adrenal glands (reducing cortisol and epinephrine), when compared to the flavonoid-poor group. Also, they showed that the high epicatechin level (class of flavan-3-ol, flavanol) in the blood reduced the endocrine stress in the flavonoid group, regardless of the age, BMI, and BP of the participants.

Regarding the effect seen on working memory and cognition, specifically on women, the study suggests that there might be hormonal involvement, as per the mechanism below. Stranges et al found a greater risk of hypertension in women after sleep deprivation and the effect was even greater in premenopausal women.² Therefore, it is hypothesized that the greater effect seen in the premenopausal women with the flavanol-rich chocolate may be related to this. More research is needed to determine the mechanism behind the cognitive effects of cocoa flavonoids.

The consumption of one bar of a high-quality dark chocolate (80% cocoa), in contradistinction to milk chocolate containing less cocoa and more sugar, can mitigate the effects of one night of sleep deprivation, especially its cardiovascular repercussions. Hence, it makes sense clinically to encourage patients to consume this type of high-quality chocolate in moderation. Based on these results and previous work, cocoa flavonoids could be a used as a supplement or aid in sleeping disorders. Overall, this study should promote more research on larger and more diverse populations to determine the minimum amount of high-quality chocolate needed to create a positive physiologic effect and at what frequency. Specifically, more research is needed on elderly populations, patients with sleep disorders, and patients with hypertension to investigate if cocoa flavonoids can ameliorate their consequences.

Acknowledgment: Special thanks to Isabela Leoni Garcia, MS Nutrition and Human Performance, Nutrition Intern at The Oasis Institute, for her help and research assistance in this review.

REFERENCES

1. Wirtz PH, Von Känel R, Meister RE, et al. Dark chocolate intake buffers stress reactivity in humans. J Am Coll Cardiol 2014;63:2297-2299.
2. Stranges S, Dorn JM, Cappuccio FP, et al. A population-based study of reduced sleep duration and hypertension: The strongest association may be in premenopausal women. J Hypertens 2010;28:896-902.