Cocoa flavanols, cerebral blood flow, cognition, and health: going forward.

The articles in the issue provide important evidence for the acute effects of cocoa flavanols on the peripheral vascular response in humans. As Hollenberg and Luscher point out, ‘‘not only does flavanol-rich cocoa-induced nitric oxide production show a dramatic influence on blood vessels in healthy individuals, preliminary information available indicates that the influence on nitric oxide synthesis is evident in patients with advanced atherosclerosis, hypertension, or diabetes mellitus.’’ Blood flow, of course, also has a fundamental role in brain function. Neuroimaging techniques designed to measure aspects of cerebral blood flow (CBF)—such as functional magnetic resonance imaging (fMRI), which is based on the increase in blood flow accompanying neural activity in the brain—have amply demonstrated the critical relationships of cerebrovascular responses and cerebrovascular health to human cognitive and emotional functions. The article by Francis et al in this issue provides some of the first evidence that flavanol-rich cocoa can affect CBF in humans. Using blood oxygenation level-dependent (BOLD) fMRI they observed an increase in relative blood flow in brain areas subserving a cognitive switching task in 16 healthy young adults. Equally interesting are their findings from a pilot study on 4 healthy young adults in which arterial spin-labeling sequence (ASL) magnetic resonance imaging (MRI) was used to assess the time course of a single serving of flavanol-rich cocoa on brain blood flow. This study showed that flavanol-rich cocoa could acutely increase CBF in gray matter, suggesting it may have potential for the treatment of cerebrovascular deficits. The reason these data are important for documenting the effects of flavanol-rich cocoa on CBF is because unlike BOLD fMRI, arterial spin-labeling perfusion MRI technique provides a direct quantitative measure of CBF using arterial blood water as an endogenous contrast agent. With excellent reproducibility over long-term time periods and minimal sensitivity to magnetic-field inhomogeneity effects, perfusion fMRI is ideal for imaging the time course of flavanol-rich cocoa effects, and permitting comparisons of CBF before and after consumption of flavanol-rich cocoa. Perfusion fMRI also has reduced scanner noise level and reduced sensitivity to subject motion. Figure 3 in Francis et al illustrates the usefulness of arterial spin labeling MRI for tracking the temporal effects on CBF of an acute dose of high flavanols cocoa drink relative to the effects of a low flavanols cocoa drink. These data leave little doubt that quantitative neuroimaging methods (eg, arterial spin-labeling perfusion fMRI, positron-emission tomography, transcranial Doppler ultrasound) should be the techniques of choice for future studies of flavanol-rich cocoa effects on CBF. Evidence that flavanols increase CBF is a key step in demonstrating their action in the cerebrovasculature, but ideally 1 would also hope to see changes in the functional status of brain, especially because increases in blood flow to neuronal vasculature accompany increases in neural activity in the brain. This is the reason that functional MRI is such a popular and useful tool in the burgeoning area of cognitive neuroscience. Why then, were Francis et al able to measure greater changes from the high flavanols cocoa drink (relative to the low flavanols cocoa