How much does our diet have an effect on human memory and learning? Jeremy Spencer of the University of Reading, UK, considers the case of the flavonoids 

The notion that diet can influence brain function may appear obvious. Nutrients such as lipids are vital components of both neurons and the glial cells that support them and it has been suggested that their structure (saturated or unsaturated) plays a role in brain function. Also, the brain has a very high energy demand and uses a lot of the dietary energy intake even when at rest. However, the impact on brain function of other dietary-derived components is less obvious. 

The response to this has been a large number of dietary intervention studies in humans and animals. In particular, those using foods and beverages derived from Vitis vinifera (grapes), Camellia sinensis (tea), Theobroma cacao (cocoa) and Vaccinium spp (blueberries) have demonstrated beneficial effects on blood flow to the brain and on improving memory and learning. While such foods and beverages differ greatly in chemical composition, nutrient content and caloric load per serving, they have in common that they are all major dietary sources of a group of plant pigments called the flavonoids.

Flavonoids are found in fruits, vegetables, cereals, tea, wine and fruit juices. Initially their biological actions in the body were believed to derive from antioxidant properties that would allow them to scavenge potentially damaging species such as oxygen and nitrogen radicals. However, they are extensively metabolised in the body which, added to a low brain bioavailability, means that they are unlikely to have a concentration high enough to act in this way. An alternative suggestion is that their neuroprotective effects are due to interactions with signalling pathways in neurons that are pivotal for cell survival, differentiation and memory. 

Flavonoids are thought to interact with cell signalling pathways key to neuron survival and growth

The main flavonoid classes that have possible positive effects on the brain are the isoflavones (found in soy), the flavanols (in tea, cocoa and red wine) and the anthocyanins (in berries and red wine). These classes differ chemically and so their mechanism of action also differs. For example, the isoflavones act by mimicking the actions of oestrogens in the brain, whilst flavanols and anthocyanins interact with neuronal signalling pathways, such as the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase (PI3 kinase)/Akt signalling cascade. 

Both the MAPK and PI3 kinase pathways are known to be critical in controlling the morphological mechanisms behind memory storage in the hippocampus and cortex of the brain. As a result, by activating kinases within these pathways, flavonoids have the potential to enhance memory and learning. One way they act is by regulating proteins such as the cAMP response element-binding protein (CREB), which is involved in the expression of important genes linked to memory. For example, CREB is crucial for the production of neurotrophins - proteins responsible for neuronal survival, differentiation, and function. Recent studies indicate that flavonoid-rich diets can both promote CREB activation and increase levels of the neurotrophin BDNF (brain-derived neurotrophic factor) in the hippocampus. 

Flavonoid-induced changes are likely to lead to memory enhancement in a number of ways and represent a vital stage in converting brief nerve impulses into long-lasting memory. Increased neuronal protein synthesis may result in more synapses and neurotransmitters, reinforcing the strength of communication between neurons and aiding the flow of information. The specific molecular changes evoked by flavonoids may also lead to neurogenesis, the process by which neurons are created from neuronal stem cells. 

The flavonoids' ability to impact on memory seems attributable to their beneficial effects on the brain's cellular architecture. In fact, given that this architecture is known to deteriorate with aging, a flavonoid-rich diet could conceivably reverse the deterioration process. Whether this is the case and which flavonoids are responsible remain subjects for further study. Nevertheless, there is the strong possibility that these widespread dietary agents will provide the first candidates for a new generation of memory-enhancing drugs.

Read more in Jeremy Spencer's critical review 'The impact of flavonoids on memory: physiological and molecular considerations' in Chemical Society Reviews.