The Cocoa Clarity Study: Shedding light on the direct vs indirect mechanisms of action of dietary flavonoids in the human brain

"Age-related cognitive decline is a major cause of disability in the UK, with incidence expected to triple by 2060. Modifiable lifestyle factors, such as diet, account for up to 35% of dementia risk. Diets rich in flavonoids-plant compounds found in foods like cocoa and berries-may delay cognitive decline by up to four years over a decade (1), but the underlying mechanisms remain unclear.
This lab previously showed that a single dose of cocoa flavonoids improves brain oxygenation and cognitive function in young adults (2), suggesting an indirect mechanism via enhanced brain vascular function. Conversely, animal and cellular studies suggest direct effects of flavonoids on neurons, specifically mitochondria function (3,4).
Novel optical imaging systems, broadband near-infrared spectroscopy (bNIRS), allow non-invasive assessment of mitochondrial metabolism alongside brain haemodynamic (5).
Flavonoids may enhance cognition by indirectly improving cerebral blood flow and oxygenation and/or by directly supporting neuronal mitochondrial metabolism. This project will explore both pathways by investigating:
1. Acute effects (2 hours) of cocoa flavonoids on cognitive function, cerebral blood flow regulation (Doppler), tissue oxygenation (bNIRS), and mitochondrial metabolism (bNIRS) during hypoxia in young (18-40 y/o) and older (65+ y/o) healthy adults.
2. Chronic effects (8 weeks) of cocoa flavonoids on the same outcomes.
3. During the acute and chronic studies, muscle oxygenation and mitochondrial metabolism will also be assessed (bNIRS), therefore, a direct comparison of the mechanisms of action of flavonoids on both the muscle and brain of humans will also be provided.

References:
1. Letenneur et al. (2007) Am. J. Epidemiol. 165(12):1364-1371
2. Gratton et al. (2020) Sci. Rep. 24;10(1):19409
3. Rendeiro et al. (2015) Neurochem Int. 89:126-39
4. Daussin et al. (2020) Nutr. Rev. 79(1):25-41
5. Bale et al. (2016) J. Biomed. Opt. 21(9):091307"