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Background: Given their antioxidative stress, anti-allergic, anti-inflammatory, and immune-modulating effects, flavonoids are hypothesized to play a role in preventing chronic obstructive pulmonary disease (COPD) and asthma. Objectives: This cohort study aimed to examine associations between flavonoid intake and COPD, asthma, and lung function. Methods: Among 119,466 participants of the UK Biobank, median [interquartile range] age of 60 [53, 65] y, we estimated intakes of flavonoids, flavonoid-rich foods, and a flavodiet score from 24-h diet assessments. Prospective associations with both incident COPD and asthma and cross-sectional associations with measures of lung function [%predicted forced expiratory volume in 1s (FEV1); and FEV1/forced vital capacity (FVC)] were examined using multivariable-adjusted Cox proportional hazards and linear regression models, respectively. We investigated mediation by inflammation––represented by the INFLA score––and stratified analyses by smoking status. Results: Compared with low intakes, moderate intakes of total flavonoids, flavonols, theaflavins + thearubigins, and flavanones, and moderate-to-high intakes of flavanol monomers, proanthocyanidins, anthocyanins, flavones, and the flavodiet score were associated with up to an 18% lower risk of incident COPD {e.g., [hazard ratio (95% confidence interval) for total flavonoids: 0.83 (0.75, 0.92)]} but not incident asthma. Furthermore, compared with low intakes, higher intakes of all flavonoid subclasses (except theaflavins + thearubigins), and the flavodiet score were associated with better percent predicted FEV1 baseline. Associations were most apparent in ever (current or former) smokers. Flavonoid intakes were inversely associated with the INFLA score, which appeared to mediate 11%–14% of the association between intakes of proanthocyanidins and flavones and incident COPD. Conclusions: Moderate-to-high flavonoid intakes were associated with a lower risk of COPD and better lung funct

Importance: A composite score of flavonoid-rich foods (flavodiet) may provide a clear public health message regarding the range of foods with the potential to lower dementia risk. Objective: To examine associations of flavodiet score and intakes of flavonoid subclasses with dementia risk according to genetic risk and presence of depression and hypertension. Design, Setting, and Participants: This prospective, population-based cohort study included dietary data from adults aged 40 to 70 years in the UK Biobank, recruited between 2006 and 2010, with a mean (SD) follow-up of 9.2 (1.5) years. The data analyses were conducted from September 1 to 30, 2023. Exposure: Flavodiet score adherence and intake of flavonoid subclasses derived from 24-hour computerized dietary assessments. Main Outcome and Measures: The main outcome was incident all-cause dementia and interactions with genetic risk, hypertension, and depressive symptoms using multivariable Cox proportional hazards regression models. Results: The sample included 121 986 participants (mean [SD] age, 56.1 [7.8] years; 55.6% female; 882 with incident dementia). Comparing the highest with lowest quintile of flavodiet score, consuming 6 additional servings per day of flavonoid-rich foods was associated with a lower risk of dementia among all participants (adjusted hazard ratio [AHR], 0.72; 95% CI, 0.57-0.89), those at high genetic risk (AHR, 0.57; 95% CI, 0.42-0.78), and those with depressive symptoms (AHR, 0.52; 95% CI, 0.33-0.81) after multivariable adjustment. The greatest risk reduction was observed in participants consuming at least 2 of the following per day: 5 servings of tea, 1 serving of red wine, and 0.5 servings of berries, compared with those who did not achieve any of these intakes (AHR, 0.62; 95% CI, 0.46-0.84). Higher intakes of flavonoid subclasses, including anthocyanins, flavan-3-ols, flavonols, and flavones, of which tea, red wine, and berries are the main contributors, supported these findings, showin

Background: Mechanistic studies and short-term randomized trials suggest higher intakes of dietary flavonoids may protect against nonalcoholic fatty liver disease (NAFLD). Objectives: We aimed to perform the first population-based study with long-term follow-up on flavonoid consumption, incident NAFLD, and validated NAFLD biomarkers. Methods: In a prospective study, we assessed the associations between flavonoid intake based on ≥2 24-h dietary assessments and NAFLD risk among 121,064 adults aged 40–69 y by multivariable Cox regression analyses. We further assessed the associations between flavonoid intake and magnetic resonance imaging-derived liver fat (a subset of n = 11,435) and liver-corrected T1 values (cT1; a subset of n = 9570), a marker of steatosis, more sensitive to inflammatory pathology. Results: Over 10 y of follow-up, 1081 cases of NAFLD were identified. Participants in the highest quartile (Q4) of the flavodiet score reflecting the consumption of foods high in flavonoids, had a 19% lower risk of NAFLD compared to the lowest quartile (Q1) [hazard ratio (HR) (95% confidence interval (CI): 0.81 (0.67, 0.97), P-trend = 0.02)]. Moreover, participants in the Q4 of the flavodiet score had lower liver fat and cT1 values than those in Q1 (liver fat: relative difference Q1 compared with Q4: –5.28%, P-trend = <0.001; cT1: relative difference Q1 compared with Q4: –1.73%, P-trend = <0.001). When compared to low intakes, high intakes of apples and tea were associated with lower NAFLD risk [apples: HR (95% CI): 0.78 (0.67, 0.92), P-trend = <0.01; tea: HR (95% CI): 0.86 (0.72, 1.02), P-trend = 0.03)]. Additionally, when compared to low intakes, high apple, tea, and dark chocolate intakes were significantly associated with lower liver fat values, whereas high tea and red pepper intakes were significantly associated with lower cT1 values. Conclusions: The consumption of flavonoid-rich foods was associated with a reduced risk of NAFLD among middle-aged adults.

Aim: To examine the associations of a diet high in flavonoid-rich foods, as reflected by a “Flavodiet Score” (FDS), the major individual food contributors to flavonoid intake, and flavonoid subclasses with type 2 diabetes (T2D) risk in the UK Biobank cohort. Materials and methods: Flavonoid intakes were estimated from ≥2 dietary assessments among 113,097 study participants [age at enrolment: 56 ± 8 years; 57% female] using the U.S Department of Agriculture (USDA) databases. Multivariable Cox proportional hazards models were used to investigate associations between dietary exposures and T2D. Results: During 12 years of follow-up, 2628 incident cases of T2D were identified. A higher FDS (compared to lower [Q4 vs. Q1]), characterised by an average of 6 servings of flavonoid-rich foods per day, was associated with a 26% lower T2D risk [HR: 0.74 (95% CI: 0.66–0.84), ptrend = <0.001]. Mediation analyses showed that lower body fatness and basal inflammation, as well as better kidney and liver function partially explain this association. In food-based analyses, higher intakes of black or green tea, berries, and apples were significantly associated with 21%, 15%, and 12% lower T2D risk. Among individual flavonoid subclasses, 19–28% lower risks of T2D were observed among those with the highest, compared to lowest intakes. Conclusions: A higher consumption of flavonoid-rich foods was associated with lower T2D risk, potentially mediated by benefits to obesity/sugar metabolism, inflammation, kidney and liver function. Achievable increases in intakes of specific flavonoid-rich foods have the potential to reduce T2D risk.

Background: Adherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. Objectives: To examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. Design: In a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP). Results: Higher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; : −20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively. Conclusion: These novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation.

Background: Plant-based diets are becoming increasingly popular due to favourable environmental footprints and have been associated with lower risk of type 2 diabetes mellitus (T2DM). Here, we investigated the potential mechanisms to explain the lower T2DM risk observed among individuals following plant-based diets. Methods: Prospective data from the UK Biobank, a cohort study of participants aged 40 to 69 years at baseline, was evaluated. Associations between healthful and unhealthful plant-based indices (hPDI and uPDI) and T2DM risk were analysed by multivariable Cox regression models, followed by causal mediation analyses to investigate which cardiometabolic risk factors explained the observed associations. Results: Of 113,097 study participants 2,628 developed T2DM over 12 years of follow-up. Participants with the highest hPDI scores (Quartile 4) had a 24 % lower T2DM risk compared to those with the lowest scores (Quartile 1) [Hazard Ratio (HR): 0.76, 95 % Confidence Interval (CI): 0.68–0.85]. This association was mediated by a lower BMI (proportion mediated: 28 %), lower waist circumference (28 %), and lower concentrations of HBA1c (11 %), triglycerides (9 %), alanine aminotransferase (5 %), gamma glutamyl transferase (4 %), C-reactive protein (4 %), insulin-like growth factor 1 (4 %), cystatin C (4 %) and urate (4 %). Higher uPDI scores were associated with a 37 % higher T2DM risk [HR: 1.37, 95 % CI:1.22- 1.53], with higher waist circumference (proportion mediated: 17 %), BMI (7 %), and higher concentrations of triglycerides (13 %) potentially playing mediating roles. Conclusion: Healthful plant-based diets may protect against T2DM via lower body fatness, but also via normoglycaemia, lower basal inflammation as well as improved kidney and liver function.

Background: Higher baseline intakes of flavonoid-rich foods and beverages are associated with a lower risk of chronic disease and mortality in observational studies. However, associations between changes in intakes and mortality remain unclear. We aimed to evaluate associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a composite measure (termed the ‘flavodiet’) of foods and beverages that are known to be main contributors to flavonoid intake and subsequent total and cause-specific mortality. Methods: We evaluated associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a novel ‘flavodiet’ score and total and cause-specific mortality. We included 55,786 females from the Nurses’ Health Study (NHS) and 29,800 males from the Health Professionals Follow-up Study (HPFS), without chronic disease at baseline in our analyses. Using multivariable-adjusted Cox proportional hazard models, we examined associations of 8-year changes in intakes of (1) flavonoid-rich foods and (2) the flavodiet score with subsequent 2-year lagged 6-year risk of mortality adjusting for baseline intakes. Data were pooled using fixed-effects meta-analyses. Results: We documented 15,293 deaths in the NHS and 8988 deaths in HPFS between 1986 and 2018. For blueberries, red wine and peppers, a 5%, 4% and 9% lower risk of mortality, respectively, was seen for each 3.5 servings/week increase in intakes while for tea, a 3% lower risk was seen for each 7 servings/week increase [Pooled HR (95% CI) for blueberries; 0.95 (0.91, 0.99); red wine: 0.96 (0.93, 0.99); peppers: 0.91 (0.88, 0.95); and tea: 0.97 (0.95, 0.98)]. Conversely, a 3.5 servings/week increase in intakes of onions and grapefruit plus grapefruit juice was associated with a 5% and 6% higher risk of total mortality, respectively. An increase of 3 servings per day in the flavodiet score was associated with an 8% lower risk of total mortality [Pooled HR: 0.92 (0.89, 0.96)]

Background: Plant-based diets have been associated with a lower risk of several chronic diseases, but the relationship with PD is unknown. Objectives: We examined the association of three different plant-based diets with PD incidence in the UK Biobank cohort. Methods: We conducted a prospective study among 126,283 participants from the UK Biobank cohort. Three plant-based diet indices (overall plant-based diet index, PDI; healthful plant-based diet index, hPDI; and unhealthful plant-based diet index, uPDI) were derived from 24-hour dietary recalls based on 17 food groups. Multivariable Cox regression models were used to estimate the risk of PD across quartiles of the PDIs and for each of the food groups that constituted the score. Further analyses were carried out to assess potential heterogeneity in associations between hPDI and PD across strata of some hypothesized effect modifiers. Results: During 11.8 years of follow-up (1,490,139 person-years), 577 cases of PD incidence were reported. After multivariable adjustment, participants in the highest hPDI and overall PDI quartile had lower risk of PD (22% and 18%, respectively), whereas a higher uPDI was associated with a 38% higher PD risk. In food-based analyses, higher intakes of vegetables, nuts, and tea were associated with a lower risk of PD (28%, 31% and 25%, respectively). Stratifying by Polygenic Risk Score (PRS), results were significant only for those with a lower PRS for PD. Conclusions: Following a healthful plant-based diet and in particular the inclusion of readily achievable intakes of vegetables, nuts and tea in the habitual diet are associated with a lower risk of PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background/Objectives: Few studies have investigated the association between dietary flavonoid intake, including all major subclasses, and the long-term risk of ischemic heart disease (IHD). We examined whether dietary flavonoid intake associated with IHD incidence, assessing the possible modifying role of sex and smoking, in participants from the Danish Diet, Cancer, and Health study. Subjects/Methods: In a cohort study design, 54,496 adults (46.8 % male), aged 50 – 64 years, without a history of IHD, were followed for up to 23 years. Habitual dietary flavonoid intake was estimated from food frequency questionnaires using Phenol-Explorer. Incident cases of IHD were identified within Danish nationwide health registries. Restricted cubic splines in Cox proportional hazards models were used to examine associations between flavonoid intake and IHD risk. Results: During follow-up, 5560 IHD events were recorded. No overall association was seen between total flavonoid intake, nor any subclass, and IHD, following adjustment for demographics, lifestyle, and dietary confounders. Stratified by sex and smoking status, higher intakes of specific subclasses associated with lower IHD risk among ever-smokers [Q5 vs. Q1 flavonols HR (95 % CI): 0.90 (0.82, 0.99); flavanol oligo+polymers: 0.88 (0.80, 0.97)], but not among never-smokers, nor either sex specifically. Conclusions: While we did not find clear evidence that higher habitual dietary flavonoid intake was associated with lower IHD risk, these results do not exclude the possibility that certain subclasses may have a protective role in prevention of IHD among population sub-groups; this was evident among smokers, who are at a higher risk of atherosclerosis.

Importance: Plant-based diets have gained popularity for both environmental and health reasons, but a comprehensive assessment of their quality in relation to risk of mortality and major chronic diseases is lacking. Objective: To examine whether healthful vs unhealthful plant-based dietary patterns are associated with mortality and major chronic diseases among UK adults. Design, Setting, and Participants: This prospective cohort study used data from adults in the UK Biobank, a large-scale population-based study. Participants were recruited between 2006 and 2010 and followed up using record linkage data until 2021; follow-up for different outcomes ranged between 10.6 and 12.2 years. Data analysis was conducted from November 2021 to October 2022. Exposures: Adherence to a healthful vs unhealthful plant-based diet index (hPDI vs uPDI) derived from 24-hour dietary assessments. Main Outcomes and Measures: The main outcomes were hazard ratios (HRs) and 95% CIs of mortality (overall and cause specific), cardiovascular disease (CVD [total, myocardial infarction, ischemic stroke, and hemorrhagic stroke]), cancer (total, breast, prostate, and colorectal), and fracture (total, vertebrae, and hip) across quartiles of hPDI and uPDI adherence. Results: This study included 126 394 UK Biobank participants. They had a mean (SD) age of 56.1 (7.8) years; 70 618 (55.9%) were women. The majority of participants (115 371 [91.3%]) were White. Greater adherence to the hPDI was associated with lower risks of total mortality, cancer, and CVD, with HRs (95% CIs) of 0.84 (0.78-0.91), 0.93 (0.88-0.99), and 0.92 (0.86-0.99), respectively, for participants in the highest hPDI quartile compared with the lowest. The hPDI was also associated with lower risks of myocardial infarction and ischemic stroke, with HRs (95% CIs) of 0.86 (0.78-0.95) and 0.84 (0.71-0.99), respectively. By contrast, higher uPDI scores were associated with higher risks of mortality, CVD, and cancer. The associations observed d