Increasing mixed-berry flavonoid intake may reduce depressive symptoms in older adults: Framingham Heart Study

Depression affects more than 250 million people worldwide. Although epidemiological studies have linked higher dietary flavonoids with depression prevention in older women, it is unknown if increasing dietary flavonoids could effectively reduce depression. Mixed berries (blueberry, blackberry, and raspberry) are a rich source of flavonoids, particularly anthocyanin, flavanol, and flavan-3-ol subclasses. Our aim was to determine the association of mixed-berry flavonoid intake with change in depressive symptoms over ~8 years in older adults from the Framingham Heart Study. This community-based prospective longitudinal study included 1,278 adults with assessments on diet (food frequency questionnaire) and depressive symptoms (Center for Epidemiologic Studies Depression, CES-D) at baseline (1998-2001) and follow-up (2005-2008). Absolute change in mixed-berry flavonoid intake (defined as sum of anthocyanin, flavanol, and flavon-3-ols, mg/day) and change in CES-D scores were calculated. Linear regression estimated beta and standard error (SE) for change in CES-D scores per 250 mg/day increase in mixed-berry flavonoids (obtained from ~3/4 cup of mixed berries), adjusting for baseline age, sex, energy-intake, current smoking, body mass index, physical activity, cardiovascular disease, and non-melanoma cancer. Mean age was 59±9 years (range: 33-81), 57% female and mean change in mixed-berry flavonoid intake was 15.0±72.8 mg/day over ~8 years. In adjusted models, each 250 mg/day increase in mixed-berry flavonoid intake was associated with a 1-point reduction in depressive symptoms (beta: -1.06, SE: 0.61, p=0.08) over ~8 years, although this was not statistically significant. These data highlight the need for randomized clinical trials of flavonoid-rich berries to target depressive symptoms in older adults.

Intake of Flavonoids and Odds of Frailty Onset in Adults in the Framingham Offspring Cohort

Polyphenols (antioxidants derived from plant-foods) could play a role in inhibition of oxidative stress and frailty reduction, yet data on the polyphenol subclass of dietary flavonoids is limited. This study sought to determine the association between dietary flavonoids and frailty onset in middle-aged and older adults. This prospective cohort study included non-frail individuals from the Framingham Offspring Cohort (FOC) with total flavonoid intake (mg/day; defined as sum flavonols, flavan-3-ols, flavonones, flavones, and anthocyanins via Harvard Food Frequency Questionnaire), frailty (via Fried phenotype), and covariate information measured at baseline (1998-2001). Follow-up frailty was evaluated in 2011-2014. Logistic regression estimated odds ratio (OR) and 95% confidence intervals (95% CI) adjusting for relevant confounders. Participants (n=1,701; 55.5% female) had a mean age of 58.4 years (SD ± 8.3). Mean flavonoid intake was 309 mg/d (SD ± 266). After 12.4 years (SD ± 0.8), 224 (13.2%) individuals exhibited frailty. In age and sex adjusted models, every 50 mg/day of higher total flavonoid intake was associated with 3% reduced odds of frailty [OR (95%CI): 0.97 (0.94-1.00), p-value: 0.05). Further adjustment for smoking, energy and protein intake, and disease indicators did not appreciably change the association, and associations became non-significant (p-value=0.12). Thus, there was no association between flavonoid intake and odds of frailty onset in adults in the FOC. This could be due to participants' higher intake of flavonoids compared to average intake of ~200 mg/d in Americans.

Exploring the Impact of Flavonoids on Symptoms of Depression: A Systematic Review and Meta-Analysis

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = −1.65; 95% C.I., −2.54, −0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption.

Microbial Flavonoid Metabolism: A Cardiometabolic Disease Perspective

Cardiometabolic disease (CMD) is a leading cause of death worldwide and encompasses the inflammatory metabolic disorders of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. Flavonoids are polyphenolic plant metabolites that are abundantly present in fruits and vegetables and have biologically relevant protective effects in a number of cardiometabolic disorders. Several epidemiological studies underscored a negative association between dietary flavonoid consumption and the propensity to develop CMD. Recent studies elucidated the contribution of the gut microbiota in metabolizing dietary intake as it relates to CMD. Importantly, the biological efficacy of flavonoids in humans and animal models alike is linked to the gut microbial community. Herein, we discuss the opportunities and challenges of leveraging flavonoid intake as a potential strategy to prevent and treat CMD in a gut microbe–dependent manner, with special emphasis on flavonoid-derived microbial metabolites.

326Flavonoid intake and ischemic stroke incidence in the Danish Diet, Cancer, and Health Cohort

Background Flavonoid-rich foods may contribute to a lower risk of ischemic stroke through their anti-inflammatory, anti-atherogenic, and anti-thrombotic properties. We aimed to examine the relationship between flavonoid intake and ischemic stroke incidence in participants from the Danish Diet, Cancer, and Health study. Methods In this prospective cohort study, 55,169 Danish citizens without a prior ischemic stroke (median [IQR] age at enrolment of 56 [52 – 60] years), were followed for 21 [20 – 22] years. Baseline flavonoid intake was estimated from food frequency questionnaires using the Phenol-Explorer database. Incident cases of stroke were identified from Danish nation-wide public health registries. Associations between quintiles of flavonoid intake and incident ischemic stroke were assessed using Cox proportional hazard models adjusting for age, sex, BMI, smoking status, physical activity, alcohol intake, education, and income. Results During follow-up, 4,317 individuals experienced an ischemic stroke. Compared to participants in quintile one and after multivariable adjustments, those in quintile five for intake of total flavonoids, flavonols and oligo+polymers had a 12% [HR (95% CI): 0.88 (0.81, 0.96)], 10% [0.90 (0.82, 0.98)], and 18% [0.82 (0.75, 0.89)], lower risk of ischemic stroke incidence, respectively. Intake of flavan-3-ol monomers, anthocyanins, flavanones and flavones were not associated with incident ischemic stroke. Conclusions A moderate habitual intake of flavonoids, in particular the flavonol and flavan-3-ol oligo+polymer subclasses, is associated with a lower risk of ischemic stroke. Key messages Flavonoid rich foods appear protective against ischemic stroke.

Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central hemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean ± SD age, 66.0 ± 4.1 years; BMI, 26.4 ± 4.41 kg/m2; 41% male) recruited as part of the Australian Research Council Longevity Intervention (ARCLI) study. Flavonoid intake [i.e., flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption] was estimated from food-frequency questionnaires using the US Department of Agriculture food composition databases. Measures of central hemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP), and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each standard deviation (SD)/day higher intake of anthocyanins (SD=44.3 mg/day) was associated with significantly lower cDBP (−1.56 mmHg, 95% CI: −2.65, −0.48) and cMAP (−1.62 mmHg, 95% CI: −2.82, −0.41). Similarly, each SD/day higher intake of flavanones (SD=19.5 mg/day) was associated with ˜1% lower cAIx (−0.93%, 95% CI: −1.77, −0.09). These associations remained significant after additional adjustment for 1) a dietary quality score and 2) other major nutrients that may affect blood pressure or arterial stiffness (i.e., sodium, potassium, calcium, magnesium, omega-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central hemodynamics and arterial stiffness; these findings require corroboration in further research.