The mechanisms of action of flavonoids in the brain: Direct versus indirect effects

Rendeiro, Catarina; Rhodes, Justin S.; Spencer, Jeremy P. E.

doi:10.1016/j.neuint.2015.08.002

Cited by 157 publications

(115 citation statements)

References 217 publications

(203 reference statements)

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“…Our study therefore provides novel data that support a beneficial association between a higher habitual intake of flavanones and lower risk of ischemic stroke and higher anthocyanin intake and lower risk of nonfatal MI in men. The reasons for these differential associations with CVD risk are unclear, but of all of the flavonoid subclasses, flavanones are one of the best absorbed and most effective at crossing the blood-brain barrier (42, 43), inhibiting platelet function, and decreasing plaque progression (3, 14). In addition, one flavanone, naringenin, has been shown to localize in the brain after oral ingestion (44).…”

Section: Discussionmentioning

confidence: 99%

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men,

Cassidy

Bertoia

Chiuve

et al. 2016

The American Journal of Clinical Nutrition

193

133

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Background: Although increased fruit intake reduces cardiovascular disease (CVD) risk, which fruits are most beneficial and what key constituents are responsible are unclear. Habitual intakes of flavonoids, specifically anthocyanins and flavanones, in which >90% of habitual intake is derived from fruit, are associated with decreased CVD risk in women, but associations in men are largely unknown.Objective: We examined the relation between habitual anthocyanin and flavanone intake and coronary artery disease and stroke in the Health Professionals Follow-Up Study.Design: We followed 43,880 healthy men who had no prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of validated food-frequency questionnaires.Results: During 24 y of follow-up, 4046 myocardial infarction (MI) and 1572 stroke cases were confirmed by medical records. Although higher anthocyanin intake was not associated with total or fatal MI risk, after multivariate adjustment an inverse association with nonfatal MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69, 0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke risk. Although flavanone intake was not associated with MI or total stroke risk, higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95% CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in participants aged ≥65 y (P-interaction = 0.04).Conclusions: Higher intakes of fruit-based flavonoids were associated with a lower risk of nonfatal MI and ischemic stroke in men. Mechanistic studies and clinical trials are needed to unravel the differential benefits of anthocyanin- and flavanone-rich foods on cardiovascular health.

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Section: Discussionmentioning

confidence: 99%

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men,

Cassidy

Bertoia

Chiuve

et al. 2016

The American Journal of Clinical Nutrition

193

133

View full text Add to dashboard Cite

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“…Although the specific links between flavonoids and depression are unclear, growing evidence supports a beneficial role for flavonoids on mood and brain health (41, 42), and direct and indirect mechanisms have been suggested (43). Direct mechanisms may include modulating signaling pathways responsible for maintaining neuron survival and inducing synaptic plasticity (7, 42, 44).…”

Section: Discussionmentioning

confidence: 99%

Dietary flavonoid intake and risk of incident depression in midlife and older women

Chang¹,

Cassidy

Willett

et al. 2016

The American Journal of Clinical Nutrition

130

101

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Background: The impact of dietary flavonoid intakes on risk of depression is unclear.Objective: We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk.Design: We followed 82,643 women without a previous history of depression at baseline from the Nurses’ Health Study [(NHS) aged 53–80 y] and the Nurses’ Health Study II [(NHSII) aged 36–55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2–4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations.Results: A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable-adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004–0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed ≥2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significantly (9–12%) lower depression risks. In analyses among late-life NHS participants (aged ≥65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90).Conclusions: Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations.

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“…The mechanisms most likely to be responsible for these effects include interaction with signalling cascades responsible for neurogenesis, synaptic plasticity, and neuronal repair. In addition, polyphenol supplementation may increase antioxidant capacity and hence improve redox balance and vascular function as well as reduce neuroinflammation (for review see Rendeiro et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation

Bowtell

Bakkar

Conway

et al. 2017

Appl. Physiol. Nutr. Metab.

148

158

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Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m −2 ) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m −2 ). Pre-and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/ 21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.Key words: polyphenols, cognitive function, cerebral perfusion, fMRI, blueberry, aging.Résumé : Les bleuets contiennent beaucoup de flavonoïdes lesquels possèdent des propriétés antioxydantes et anti-inflammatoires. Un apport élevé en flavonoïdes atténue le déclin cognitif associé à l'âge, mais il y a peu d'études menées chez des humains. Nous analysons si 12 semaines de supplémentation d'un concentré de bleuets améliorent la perfusion cérébrale, l'activation cérébrale associée à une tâche et la fonction cognitive chez des personnes âgées en bonne santé. On répartit aléatoirement les participants en deux groupes, l'un (5 femmes, 7 hommes; âge 67,5 ± 3,0 ans; l'indice de masse corporelle 25,9 ± 3,3 kg·m −2 ) consommant 30 mL de concentré de bleuets procurant 387 mg d'anthocyanidines et l'autre (8 femmes, 6 hommes; âge 69,0 ± 3,3 ans; l'indice de masse corporelle 27,1 ± 4,0 kg·m −2 ), un placebo isoénergétique. Avant et après la supplémentation, les participants se soumettent à une batterie de tests de la fonction cognitive et au test numérique de Stroop dans un appareil de magnétique fonctionnelle 1.5T pour l'obtention en continu de clichés au moyen de la technique d'imagerie par résonance magnétique fonctionnelle. On détermine le volume de pe...

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The mechanisms of action of flavonoids in the brain: Direct versus indirect effects

Cited by 157 publications

References 217 publications

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men,

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men,

Dietary flavonoid intake and risk of incident depression in midlife and older women

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation

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