Cocoa flavonoids protect humans against vascular disease, as evidenced by improvements in peripheral
endothelial function, likely through nitric oxide signaling. Emerging evidence also suggests that
flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized
double-blind within-subject acute study in healthy young adults, we link these two lines of research
by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation
responses to hypercapnia, as well as higher performance only when cognitive demand is high.
Individual difference analyses further show that participants who benefit from flavanols intake during
hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis
that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They
further show the importance of studies combining physiological and graded cognitive challenges in
young adults to investigate the actions of dietary flavonoids on brain function.
Lifespan wear and tear of the vascular system due to poor nutrition and lack of fitness, among other factors, can
accelerate cognitive aging and lead to dementia. There is epidemiological evidence suggesting that flavonoids, a
group of small molecules present in fruits and vegetables, can protect against vascular disease and cardiovascular related mortality.
In particular, cocoa flavanols, a sub-group of flavonoids (also present in berries, grapes,
apples and tea) have been shown to improve endothelial function in humans quite rapidly (within 1–2 h) by
enhancing vasodilatory properties of peripheral arteries. Acute benefits translate effectively into short-term
(2–8 weeks) clinically relevant improvements in blood pressure and endothelial function (as measured by brachial
flow-mediated dilatation, FMD), comparable to those of drugs, such as statins. Mechanistically, the beneficial effects of cocoa flavanols on endothelial function have been linked to increases in bioavailability of nitric
oxide (NO), which is known to be affected in the earliest stages of vascular disease. While the acute effects of
flavanols have been mainly attributed to phase I/II-derived (−)-epicatechin metabolites, the short to long term
benefits may be also driven by gut-derived metabolites, although this remains to be established. Another
emerging line of research further suggests that this class of plant-derived compounds may protect against cognitive decline in aging14–16 and cognitive resilience to neuropsychiatric disorders and stress. Yet, the extent to which increases in circulatory levels of flavanols can translate into benefits in the brain vasculature, and effectively influence cognitive performance in humans, is poorly understood. Cerebral blood flow is controlled by neuronal activity but also by levels of arterial blood gases, in particular carbon dioxide (CO2). Relevant to our hypothesis is the fact that it is known to contribute to CO2-dependent
increases in cerebral blood flow in humans (hypercapnia). Furthermore, cerebrovascular reactivity to CO2
is widely accepted as a key biomarker of cerebrovascular health and has been strongly associated with cognitive function in health and disease states. Hence, hypercapnia represents a robust model to test whether flavanol-mediated increases in endothelial function (as assessed by gold-standard FMD) mediate benefits in
cerebrovascular and cognitive function.
Only a handful of studies have previously reported effects of flavanols on the human cerebral vasculature, both
in a resting state and in response to cognitive challenges, albeit in opposite directions
(increase/decrease in blood flow/velocity). Further, modulation of cerebral physiological outcomes by flavanols in the context of neuronal/cognitive challenges frequently and surprisingly fail to translate into cognitive benefits. A possibility is that the benefits of flavanols may only be visible at high levels of task difficulty. This highlights that, while some of these studies could provide ecological validity (as they target aging adults with cognitive and/or vascular problems), they were not designed in a manner that allows for an evaluation of the underlying physiological effects of these compounds in the human brain. This leaves some uncertainty about whether flavanols’ benefits in peripheral vascular function are reflected by similar effects on cerebrovascular reactivity, and whether the cognitive and vascular benefits are related.
So during this stressful Holiday season you decide, Is a hot cup of cocoa right for you or that chocolate treat?