Functional foods and effects on cognitive function

The consumption of functional foods is suggested to enhance cognitive performance, potentially through improvements to cerebral blood flow, generally attributed to the polyphenol content. The potential of polyphenols to regulate nitric-oxide (NO) dependent cerebrovascular functions at the cerebral endothelium level, stimulates peripheral and then cerebral blood flow (Spencer, 2008), indirectly enhancing cognitive function (Figure 4). Direct effects relate to the ability of flavonoids to cross the BBB. Some flavonoid metabolites may inhibit cell degeneration and inflammation and interact with cell signalling to enhance neuronal communication, encouraging synaptic plasticity by: expressing signalling kinases (ERK1/2, Akt), neuronal receptors (NMDA (important for memory

and learning), TrkB, and neurotrophins (brain-derived neurotrophic factor, BDNF) (Giacalone et al., 2011; Spencer, 2010a; Vauzour et al., 2008). However, identifying how specific flavonoids

contribute to individual mechanisms requires further research (Shukitt-Hale et al., 2015).

Figure 4. Mechanisms underpinning the effects of dietary flavonoids on memory and learning. Consuming flavonoids might indirectly impact cognitive performance by modulating endothelial NO synthase (eNOS) and Nitric-Oxide (NO) dependent cerebrovascular function at the cerebrovascular level. Flavonoids may cross the BBB to act directly on neuronal receptors (TrkB, NMDA), signalling kinases (Akt, PKA, ERK1/2) and neurotrophins (BDNF) via cellular transcription factors (CREB) and associated proteins (BDNF/ARC) which can lead to changes in synaptic function. Reproduced with copyright permission (Rendeiro, Rhodes, & Spencer, 2015)

Studies suggest that the regular consumption of flavonoid-rich foods is associated with the preservation of cognitive function, but this is mostly based on studies in older adults (Devore, Kang, Breteler, & Grodstein, 2012; Letenneur, Proust-Lima, Le Gouge, Dartigues, & Barberger-

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Gateau, 2007). In a large prospective study (n=16,010; 74 years), a reduced risk of cognitive decline by up to 2.5 years was reported in women with the highest berry intakes; however, only flavonoids were estimated while other polyphenol groups, such as phenolic acids, were not included (Devore, Jae Hee, Breteler, & Grodstein, 2012). Furthermore, intakes were associated with higher PA levels and higher SES, which suggests that improvements may have been due to an overall healthier lifestyle, although the analysis did make adjustments for these factors.

Not all studies report cognitive benefits of flavonoids in healthy populations. Conversely, higher habitual flavonoid intakes were associated with a greater decline in cognitive flexibility in adults (43-70 years); however, greater intakes of lignans, phenolic compounds found in plant foods including seeds, nuts, fruits and tea, were strongly associated with less cognitive decline,

particularly in the memory domain (Nooyens et al., 2015). If lignans were driving cognitive benefits this suggests that they should also be measured in berry studies; however, they are present in very low concentrations in most foods so they may simply represent a marker to an overall healthy lifestyle. In a systematic review of 21 observational and prospective studies, findings were inconclusive due to methodological discrepancies in regards to measures of cognition, dietary assessment methods and reporting of confounding factors (Crichton, Bryan, & Murphy, 2013). Authors concluded that more intervention studies were needed before habitual intakes of antioxidant-rich foods could be attributed to protecting against cognitive decline in adults.

Intervention studies appear more consistent in their findings and a review including thirteen RCTs (Macready et al., 2009) reported a general trend for positive associations between flavonoid intake and cognitive function; however, like the epidemiological data, most studies are based on older adults (>50years). Only two studies included young (<30 years), healthy populations, both reporting improvements in cognitive performance following consumption of soya (File et al., 2001) or cocoa (Francis, Head, Morris, & Macdonald, 2006). Specific to anthocyanins, Hendrickson and Mattes

(2008) investigated whether an acute dose of grape juice would mitigate the deficits in cognition and mood that commonly occur after eating a large meal (Hendrickson & Mattes, 2008).

Approximately 580mg of anthocyanins were served with a standardised lunch to young adult

smokers (n=35, 26 years). There were no significant effects of grape juice on cognitive performance 1h post-prandially when compared to an energy matched placebo control. Positive mood states declined under both conditions, and negative mood states increased, but this did not correlate with cognitive task performance which did not change over time in either condition. Only one cognitive domain (implicit memory) was selected to be measured; however, there were no previous studies cited to support this selection. Caldwell and colleagues also used grape juice to deliver 55mg of anthocyanins in a pilot study in healthy adults (n=6, 18-35 years) (Caldwell, Charlton, Roodenrys, & Jenner, 2016), but saw no significant improvements at 6h on executive function or memory, although the small sample size and a lack of a considered control suggests the study was likely to be underpowered. A summary of acute studies in young people and children also supports the role of flavonoids to benefit attention, working memory, and psychomotor processing speed in healthy populations (Bell et al., 2015). In young adults (n=36; 18-35 years), the consumption of

anthocyanin-rich blackcurrants in a juice or a powder were reported to improve attention and executive function compared to a matched control (Watson et al., 2015). Blood measures were also collected suggesting a potential mechanism for the cognitive improvements observed from the juice, although there were no effects on mood or mental fatigue.

Consuming high-fibre foods that promote a prolonged GR may sustain glucose availability to the brain and improve cognitive performance (Messier, 2004). In healthy adults the consumption of fibre-enriched bread was associated with improvements in cognitive performance compared to low- fibre bread (Nilsson, Radeborg, & Bjorck, 2012). In children, a high-fibre (3g) breakfast did not improve cognitive performance compared to a low-fibre (1g) breakfast, although breakfasts were

there were no significant differences between conditions.

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not matched on all macronutrients (Mahoney et al., 2005). Adolescent studies comparing high- and low- fibre foods and their effects on cognitive performance do so relative to the GI/GL of the meal (chapter 1.9.2).