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‘Brain food’: The direct versus indirect mechanisms of action of cocoa flavonoids in the human brain

Primary supervisor: Dr Catarina Rendeiro, School of Sport, Exercise and Rehabilitation Sciences

Non-academic partner: Barry Callebaut

Project Title: ‘Brain food’: The direct versus indirect mechanisms of action of cocoa flavonoids in the human brain

Project description:

This project is in collaboration with Dr Sam Lucas, an exercise physiologist from the University of Birmingham and Dr Gemma Bale, an expert in non-invasive optical neuromonitoring techniques, (e.g. NIRS) from the University of Cambridge.

Age-associated cognitive decline is a leading cause of disability in the UK, with incidence predicted to increase three-fold by 2060. Despite the projected global rise in cognitive dysfunction, there are no effective disease-modifying treatments and no established preventive lifestyle guidelines. Yet, modifiable lifestyle factors, such as diet, can account for as much as 35% of the dementia burden later in life. For example, diets rich in flavonoids, a sub-group of plant-derived compounds found in fruits and vegetables (e.g. cocoa, berries) appear to delay cognitive decline in older adults for up to 4 years over a 10-year period (1), yet the mechanisms underpinning the protective effect for the brain remains unclear.

We have shown that one dose of cocoa flavonoids improves brain tissue oxygenation as well as cognitive function in young adults (2), highlighting a potential indirect mechanism-of-action via flavonoid-induced improvements in brain vascular function. On the other hand, animal and cellular models exposed to flavonoids showdirect effects on neurons and muscle (3), including mitochondrial function (4). Neurons are very energy-dependent, so mitochondrial transport/turnover is critical for neuronal function and it declines in ageing/disease. Cytochrome-c-oxidase (COX) is the final enzyme in the Electron-Transport-Chain used for energy synthesis and is a key marker of mitochondrial function. Remarkably, recent developments in the field of optical imaging, mean that broadband near infrared spectroscopy (NIRS) can non-invasively detect with high specificity the oxidative state of COX, providing a unique and novel form of assessing mitochondrial metabolism in the human brain (5).

Intrinsically, flavonoids might be exerting their effects in cognition by indirectly improving blood flow and oxygenation to the brain or may also directly improve neuronal mitochondria metabolism. This project will explore these two mechanistic pathways by which flavonoids exert positive effects on brain health and cognitive function.

The first aim is to establish whether acute (2-8h) and short-term (2-4 weeks) intake of cocoa flavonoids improves cerebral blood flow regulation and tissue oxygenation (Doppler/functional NIRS) and/or mitochondrial metabolism (broadband NIRS) during hypercapnia and hypoxia challenges in young healthy adults (Study 1 and 2).

The second aim is to test the efficacy of cocoa flavonoids at improving cerebral blood flow regulation and tissue oxygenation and mitochondrial metabolism in older adults, and establish whether modulation of these mechanisms translate into improved cognitive function (Study 3).

Muscle oxygenation and mitochondrial metabolism will also be assessed by NIRS, as these have been shown to be modified by flavonoid intake in rodents and cells (4). This will address a third aim, by providing, for the first time, a direct comparison of the mechanisms of action of flavonoids on both the muscle and brain of humans.

Desirable Skills:

A background in medicine/neuroscience with an interest in medical physics/engineering and/or nutrition, or a background in physical science/engineering with an interest in nutrition/neuroscience. Experience with programming (MATLAB, Python, etc.) is advantageous. The candidate must have (or expect to obtain) a 1st or 2:1 degree in a STEM subject.

The successful candidate will have a strong interest in nutrition and neuroscience and experimental work with .human subjects. They should: enjoy working between different disciplines; be keen to take the initiative and exhibit strong motivation towards the project. Examples of any past experience that demonstrates these characteristics should be highlighted in the cover letter that accompanies any application.

Candidates are encouraged to contact Dr Rendeiro to discuss the project before applying if they wish to.


  1. Letenneur et al.(2007).Am. J. Epidemiol.165 (12):1364-1371
  2. Gratton et al.(2020).Scientific Reports.doi:10.1038/s41598-020-76160-9
  3. Rendeiro et al.(2015).Neurochem Int.89:126-39.
  4. Daussin et al.(2020).Nutrition Reviews Vol.79(1):25–41
  5. Bale et al.(2016).J. Biomed. Opt. doi: 10.1117/1.JBO.21.9.091307.

Contact: Dr Catarina Rendeiro, University of Birmingham