Higher habitual intakes of flavonoids and flavonoid-rich foods are associated with a lower incidence of type 2 diabetes in the UK Biobank cohort.

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.

Adding salt to food at table as an indicator of gastric cancer risk among adults: a prospective study.

BACKGROUND: While dietary salt intake has been linked with gastric cancer risk in Asian studies, findings from Western populations are sparse and limited to case-control studies. Our aim was to evaluate the frequency of adding salt to food at table in relation to gastric cancer risk among UK adults. METHODS: We evaluated associations between the frequency of adding salt to food and the risk of gastric cancer in the UK Biobank (N = 471,144) using multivariable Cox regression. Frequency of adding salt to food was obtained from a touchscreen questionnaire completed at baseline (2006-2010). 24-h urinary sodium excretion was estimated using INTERSALT formulae. Cancer incidence was obtained by linkage to national cancer registries. RESULTS: During a median follow-up period of 10.9 years, 640 gastric cancer cases were recorded. In multivariable models, the gastric cancer risk among participants reporting adding salt to food at table "always" compared to those who responded "never/rarely" was HR = 1.41 (95% CI: 1.04, 1.90). There was a positive linear association between estimated 24-h urinary sodium levels and the frequency of adding salt to food (p-trend <0 .001). However, no significant association between estimated 24-h urinary sodium with gastric cancer was observed (HR = 1.19 (95% CI: 0.87, 1.61)). CONCLUSIONS: "Always adding salt to food" at table was associated with a higher gastric cancer risk in a large sample of UK adults. High frequency of adding salt to food at table can potentially serve as a useful indicator of salt intake for surveillance purposes and a basis for devising easy-to-understand public health messages.

Chronic and postprandial effect of blueberries on cognitive function, alertness, and mood in participants with metabolic syndrome - results from a six-month, double-blind, randomized controlled trial.

BACKGROUND: Anthocyanin and blueberry intakes positively associated with cognitive function in population-based studies and cognitive benefits in randomized controlled trials of adults with self-perceived or clinical cognitive dysfunction. To date, adults with metabolic syndrome (MetS) but without cognitive dysfunction are understudied. OBJECTIVES: Cognitive function, mood, alertness, and sleep quality were assessed as secondary end points in MetS participants, postprandially (>24 h) and following 6-mo blueberry intake. METHODS: A double-blind, randomized controlled trial was conducted, assessing the primary effect of consuming freeze-dried blueberry powder, compared against an isocaloric placebo, on cardiometabolic health >6 mo and a 24 h postprandial period (at baseline). In this secondary analysis of the main study, data from those completing mood, alertness, cognition, and sleep assessments are presented (i.e., n = 115 in the 6 mo study, n = 33 in the postprandial study), using the following: 1) Bond-Lader self-rated scores, 2) electronic cognitive battery (i.e., testing attention, working memory, episodic memory, speed of memory retrieval, executive function, and picture recognition), and 3) the Leeds Sleep Evaluation Questionnaire. Urinary and serum anthocyanin metabolites were quantified, and apolipoprotein E genotype status was determined. RESULTS: Postprandial self-rated calmness significantly improved after 1 cup of blueberries (P = 0.01; q = 0.04; with an 11.6% improvement compared with baseline between 0 and 24 h for the 1 cup group), but all other mood, sleep, and cognitive function parameters were unaffected after postprandial and 6-mo blueberries. Across the ½ and 1 cup groups, microbial metabolites of anthocyanins and chlorogenic acid (i.e., hydroxycinnamic acids, benzoic acids, phenylalanine derivatives, and hippuric acids) and catechin were associated with favorable chronic and postprandial memory, attention, executive function, and calmness. CONCLUSIONS: Although self-rated calmness improved postprandially, and significant cognition-metabolite associations were identified, our data did not support strong cognitive, mood, alertness, or sleep quality improvements in MetS participants after blueberry intervention. This trial was registered at clinicaltrials.gov as NCT02035592.

Diet patterns and cognitive performance in a UK Female Twin Registry (TwinsUK).

BACKGROUND: Plant-based diets may provide protection against cognitive decline and Alzheimer's disease, but observational data have not been consistent. Previous studies include early life confounding from socioeconomic conditions and genetics that are known to influence both cognitive performance and diet behaviour. This study investigated associations between Mediterranean (MED) diet and MIND diets and cognitive performance accounting for shared genotype and early-life environmental exposures in female twins. METHODS: Diet scores were examined in 509 female twins enrolled in TwinsUK study. The Cambridge Neuropsychological Test Automated Battery was used to assess cognition at baseline and 10 years later (in n = 275). A co-twin case-control study for discordant monozygotic (MZ) twins examined effects of diet on cognitive performance independent of genetic factors. Differences in relative abundance of taxa at 10-year follow-up were explored in subsamples. RESULTS: Each 1-point increase in MIND or MED diet score was associated with 1.75 (95% CI: - 2.96, - 0.54, p = 0.005 and q = 0.11) and 1.67 (95% CI: - 2.71, - 0.65, p = 0.002 and q = 0.02) fewer respective errors in paired-associates learning. Within each MZ pair, the twin with the high diet score had better preservation in spatial span especially for MED diet (p = 0.02). There were no differences between diet scores and 10-year change in the other cognitive tests. MIND diet adherence was associated with higher relative abundance of Ruminococcaceae UCG-010 (0.30% (95% CI 0.17, 0.62), q = 0.05) which was also associated with less decline in global cognition over 10 years (0.22 (95% CI 0.06, 0.39), p = 0.01). CONCLUSIONS: MIND or MED diets could help to preserve some cognitive abilities in midlife, particularly episodic and visuospatial working memory. Effects may be mediated by high dietary fibre content and increased abundance of short-chain fatty acid producing gut bacteria. Longer follow-up with repeated measures of cognition will determine whether diet can influence changes in cognition occurring in older age.

The gut microbiome modulates associations between adherence to a Mediterranean-style diet, abdominal adiposity, and C-reactive protein in population-level analysis.

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; ß: -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.

A healthful plant-based diet is associated with lower type 2 diabetes risk via improved metabolic state and organ function: A prospective cohort study.

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.

Adherence to the EAT-Lancet reference diet is associated with a reduced risk of incident cancer and all-cause mortality in UK adults.

Food systems have been identified as significant contributors to the global environmental emergency. However, there is no universally agreed-upon definition of what constitutes a planetary healthy, sustainable diet. In our study, we investigated the association between the EAT-Lancet reference diet, a diet within the planetary boundaries, and incident cancer, incident major cardiovascular events, and all-cause mortality. Higher adherence to the EAT-Lancet reference diet was associated with lower incident cancer risk (hazard ratio [HR]continuous: 0.99; 95% confidence interval [CI]: 0.98-0.99]) and lower all-cause mortality (HR continuous: 0.98; 95% CI: 0.98-0.99), while mostly null associations were detected for major cardiovascular event risk (HR continuous: 1.00; 95% CI: 0.98-1.01). Stratified analyses using potentially modifiable risk factors led to similar results. Our findings, in conjunction with the existing literature, support that adoption of the EAT-Lancet reference diet could have a benefit for the prevention of non-communicable diseases.

Higher Habitual Dietary Intakes of Flavanols and Anthocyanins Differentially Associate with Lower Incidence of Ischemic Stroke Subtypes-A Follow-Up Analysis.

BACKGROUND: We previously reported that habitual consumption of dietary flavanol oligomers + polymers and anthocyanins is associated with a lower risk of ischemic stroke. However, no studies have investigated their relationship with ischemic stroke subtypes. OBJECTIVES: In this follow-up analysis, we aimed to examine the association of flavanol oligomers + polymers and anthocyanin intake with ischemic stroke subtypes, including the following: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) other determined etiology, and 5) undetermined etiology. METHODS: Participants (n = 55,094) from the Danish Diet, Cancer, and Health Study were followed up for <16 y for first-time ischemic stroke events, which were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Intakes of flavanol oligomers + polymers and anthocyanins were calculated from food frequency questionnaires using the Phenol-Explorer database, and their relationships with ischemic stroke subtypes were investigated using restricted cubic splines within Cox proportional hazards models. After multivariable adjustment, higher habitual intakes (quintile 5 compared with quintile 1) of flavanol oligomers + polymers and anthocyanins were associated with a lower risk of specific ischemic stroke subtypes, including large-artery atherosclerosis [flavanol oligomers + polymers, hazard ratio {HR} (95% confidence interval {CI}): 0.64 (0.47, 0.87)], cardioembolism [anthocyanins, HR (95% CI): 0.45 (0.25, 0.82)], and small-vessel occlusion [flavanol oligomers + polymers, HR (95% CI): 0.65 (0.54, 0.80); anthocyanins, HR (95% CI): 0.79 (0.64, 0.97)], but not stroke of other determined or undetermined etiology. CONCLUSIONS: Higher habitual intakes of flavanols and anthocyanins are differentially associated with a lower risk of ischemic stroke from atherosclerosis and/or cardioembolism but not with other subtypes.

Plant-Based Dietary Patterns and Parkinson's Disease: A Prospective Analysis of the UK Biobank.

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.

Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols.

Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as a cellular defense mechanism from acquiring potentially harmful genetic faults. However, recent studies highlight that senescent cells might also alter the local tissue environment and concur to chronic inflammation and cancer risk by secreting inflammatory and matrix remodeling factors, acquiring a senescence-associated secretory phenotype (SASP). Indeed, during aging and age-related diseases, senescent cells amass in mammalian tissues, likely contributing to the inevitable loss of tissue function as we age. Cellular senescence has thus become one potential target to tackle age-associated diseases as well as cancer development. One important aspect characterizing senescent cells is their telomere length. Telomeres shorten as a consequence of multiple cellular replications, gradually leading to permanent cell cycle arrest, known as replicative senescence. Interestingly, in the large majority of cancer cells, a senescence escape strategy is used and telomere length is maintained by telomerase, thus favoring cancer initiation and tumor survival. There is growing evidence showing how (poly)phenols can impact telomere maintenance through different molecular mechanisms depending on dose and cell phenotypes. Although normally, (poly)phenols maintain telomere length and support telomerase activity, in cancer cells this activity is negatively modulated, thus accelerating telomere attrition and promoting cancer cell death. Some (poly)phenols have also been shown to exert senolytic activity, thus suggesting both antiaging (directly eliminating senescent cells) and anticancer (indirectly, via SASP inhibition) potentials. In this review, we analyze selective (poly)phenol mechanisms in senescent and cancer cells to discriminate between in vitro and in vivo evidence and human applications considering (poly)phenol bioavailability, the influence of the gut microbiota, and their dose-response effects.

A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.

BACKGROUND: There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES: To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS: A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS: 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS: These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.

Change in habitual intakes of flavonoid-rich foods and mortality in US males and females.

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)], and a 13% lower risk of neurological mortality [Pooled HR: 0.87 (0.79, 0.97)], after multivariable adjustments. CONCLUSIONS: Encouraging an increased intake of specific flavonoid-rich foods and beverages, namely tea, blueberries, red wine, and peppers, even in middle age, may lower early mortality risk.

Flavonoid intake and survival after diagnosis of colorectal cancer: a prospective study in 2 US cohorts.

BACKGROUND: Although experimental evidence supports anticancer effects of flavonoids, the influence of flavonoid intake on colorectal cancer (CRC) survival remains unknown. OBJECTIVES: This study aimed to assess the association of postdiagnostic flavonoid intake with mortality. METHODS: We prospectively assessed the association of postdiagnostic flavonoid intake with CRC-specific and all-cause mortality in 2552 patients diagnosed with stage I-III CRC in 2 cohort studies-the Nurses' Health Study and the Health Professionals Follow-up Study. We assessed the intake of total flavonoids and their subclasses using validated food frequency questionnaires. We used the inverse probability-weighted multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) of mortality after adjusting for prediagnostic flavonoid intake and other potential confounders. We performed spline analysis to evaluate dose-response relationships. RESULTS: The mean [standard deviation (SD)] age of patients at diagnosis was 68.7 (9.4) y. During 31,026 person-y of follow-up, we documented 1689 deaths, of which 327 were due to CRC. The total flavonoid intake was not associated with mortality, but a higher intake of flavan-3-ols was suggestively associated with lower CRC-specific and all-cause mortality, with multivariable HR (95% CI) per 1-SD increases of 0.83 (0.69-0.99; P = 0.04) and 0.91 (0.84-0.99; P = 0.02), respectively. The spline analysis showed a linear relationship between postdiagnostic flavan-3-ol intake and CRC-specific mortality (P = 0.01 for linearity). As the major contributor to flavan-3-ol intake, tea showed an inverse association with CRC-specific and all-cause mortality, with multivariable HRs per 1 cup/d of tea of 0.86 (0.75-0.99; P = 0.03) and 0.90 (0.85-0.95; P < 0.001), respectively. No beneficial associations were found for other flavonoid subclasses. CONCLUSIONS: Higher intake of flavan-3-ol after CRC diagnosis was associated with lower CRC-specific mortality. Small, readily achievable increases in the intake of flavan-3-ol-rich foods, such as tea, may help improve survival in patients with CRC.

Association of Healthful Plant-based Diet Adherence With Risk of Mortality and Major Chronic Diseases Among Adults in the UK.

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 did not show heterogeneity across strata of sex, smoking status, body mass index, or socioeconomic status or with polygenic risk scores (specifically with regard to CVD end points). Conclusions and Relevance: The findings of this cohort study of middle-aged UK adults suggest that a diet characterized by high-quality plant-based foods and lower intakes of animal products may be beneficial for health, irrespective of established chronic disease risk factors and genetic predisposition.

Intake of dietary flavonoids and incidence of ischemic heart disease in the Danish Diet, Cancer, and Health cohort.

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.

EDESIA: Plants, Food and Health: A cross-disciplinary PhD programme from crop to clinic.

In an era where preventive medicine is increasingly important due to an ageing population and rising obesity, optimised diets are key to improving health and reducing risk of ill health. The Wellcome Trust-funded, EDESIA: Plants, Food and Health: a cross-disciplinary PhD programme from Crop to Clinic (218 467/Z/19/Z) focuses on investigating plant-based nutrition and health, from crop to clinic, drawing on the world-class interdisciplinary research expertise of partner institutions based on the Norwich Research Park (University of East Anglia, John Innes Centre, Quadram Institute and Earlham Institute). Through a rotation-based programme, EDESIA PhD students will train in a wide range of disciplines across the translational pathway of nutrition research, including analyses of epidemiological datasets, assessment of nutritional bioactives, biochemical, genetic, cell biological and functional analyses of plant metabolites, in vitro analyses in tissue and cell cultures, investigation of efficacy in animal models of disease, investigation of effects on composition and functioning of the microbiota and human intervention studies. Research rotations add a breadth of knowledge, outside of the main PhD project, which benefits the students and can be brought into project design. This comprehensive PhD training programme will allow the translation of science into guidelines for healthy eating and the production of nutritionally improved food crops, leading to innovative food products, particularly for prevention and treatment of chronic diseases where age is a major risk factor. In this article, we summarise the programme and showcase the experiences of the first cohort of students as they start their substantive PhD projects after a year of research rotations.

Urinary phthalate concentrations and mortality risk: A population-based study.

Phthalates are widely used as plasticizers. Laboratory-based mechanistic and epidemiological studies suggest that phthalates are detrimental to human health. Here, we present prospective analyses on phthalate exposure and all-cause, as well as cause-specific, mortality from the National Health and Nutrition Examination Survey (NHANES), a population-based cohort. Between 1999 and 2018, urinary concentrations of 12 phthalate metabolites were measured by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in spot urine samples of 10,881 adults aged 40-85 years, of which 2382 died over a median duration of 8.9 years after sample provision. Multivariable Cox regression analyses adjusted for a wide range of lifestyle factors and comorbidities showed that higher concentrations of mono-benzyl phthalate (MBzP) and Mono-n-butyl phthalate (MnBP) were associated with increased mortality. The hazard ratios for participants in the highest quartiles of MBzP and MnBP concentrations were at 1.27 [95% confidence interval: 1.08, 1.49; p linear trend = 0.002] and 1.35 [1.13, 1.62; p linear trend = 0.005). These findings reinforce the need for monitoring of phthalate exposure in relation to health outcomes.

Diet Patterns, the Gut Microbiome, and Alzheimer's Disease.

Given the complex bidirectional communication system that exists between the gut microbiome and the brain, there is growing interest in the gut microbiome as a novel and potentially modifiable risk factor for Alzheimer's disease (AD). Gut dysbiosis has been implicated in the pathogenesis and progression of AD by initiating and prolonging neuroinflammatory processes. The metabolites of gut microbiota appear to be critical in the mechanism of the gut-brain axis. Gut microbiota metabolites, such as trimethylamine-n-oxide, lipopolysaccharide, and short chain fatty acids, are suggested to mediate systemic inflammation and intracerebral amyloidosis via endothelial dysfunction. Emerging data suggest that the fungal microbiota (mycobiome) may also influence AD pathology. Importantly, 60% of variation in the gut microbiome is attributable to diet, therefore modulating the gut microbiome through dietary means could be an effective approach to reduce AD risk. Given that people do not eat isolated nutrients and instead consume a diverse range of foods and combinations of nutrients that are likely to be interactive, studying the effects of whole diets provides the opportunity to account for the interactions between different nutrients. Thus, dietary patterns may be more predictive of a real-life effect on gut microbiome and AD risk than foods or nutrients in isolation. Accumulating evidence from experimental and animal studies also show potential effects of gut microbiome on AD pathogenesis. However, data from human dietary interventions are lacking. Well-designed intervention studies are needed in diverse populations to determine the influence of diet on gut microbiome and inform the development of effective dietary strategies for prevention of AD.

Increased vitamin B6 turnover is associated with greater mortality risk in the general US population: A prospective biomarker study.

BACKGROUND & AIMS: Vitamin B6 status and mortality risk are inversely associated in different patient groups, while prospective studies in the general population are lacking. Here, for the first time, we evaluated the association between biomarkers of vitamin B6 status and mortality risk in a large population-based study. METHODS: The vitamin B6 vitamers pyridoxal-5'-phosphat (PLP) and 4-pyridoxic acid (4-PA) were measured by high-performance liquid chromatography in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. Participants' vital status and causes of death were recorded until December 2015. Multivariable Cox regression analyses were carried out to estimate Hazard Ratios (HRs) and 95% confidence intervals (CIs) of mortality across quintiles of PLP, 4-PA, and the ratio of 4-PA and PLP. RESULTS: Out of 15,304 study participants aged between 20 and 85 years at baseline, 1666 (7.7%) died during a median follow-up time of 7.8 years. An inverse association between PLP and mortality was found in a multivariable model adjusted for socioeconomic and lifestyle factors but became statistically non-significant upon adjustment for routine biomarkers (C-reactive protein, creatinine, albumin, and alkaline phosphatase). There was a significant linear trend for a positive association between 4-PA levels and mortality risk in the fully adjusted regression model, although a comparison of extreme quintiles (quintile 5 vs. quintile 1) did not show a significant difference (HRQ5vs.Q1 (95% CI): 1.19 (0.93, 1.51), plinear trend = 0.02). A positive association between the 4-PA/PLP ratio and all-cause mortality was observed in the multivariable model, with an HRsQ5vs.Q1 of 1.45 (95% CI: 1.14, 1.85; plinear trend<0.0001). There were no significant associations between the biomarkers and cardiovascular or cancer mortality. The association between 4-PA/PLP and mortality risk was heterogeneous across age groups, and only statistically significant among participants older than 65 years at baseline (HRQ5vs.Q1 (95% CI): 1.72 (1.29, 2.29), plinear trend<0.0001). In this group, 4-PA/PLP was also associated with cancer mortality, with an HR Q5vs.Q1 of 2.16 (1.20, 3.90), plinear trend = 0.02). CONCLUSION: Increased vitamin B6 turnover, as indicated by a higher 4-PA/PLP ratio, was associated with all-cause and cancer mortality among the older U.S. general population. Intervention trials are needed to assess whether older individuals with a high 4-PA/PLP ratio would benefit from increased vitamin B6 intake.

Flavonoid intakes inversely associate with COPD in smokers.

INTRODUCTION: Higher flavonoid intakes are beneficially associated with pulmonary function parameters; however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This study aimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) major flavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study. METHODS: This prospective cohort included 55 413 men and women without COPD, aged 50-65 years at recruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaire using Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD. Associations were modelled using restricted cubic splines within Cox proportional hazards models. RESULTS: During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 were current smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments, participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with the lowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74-0.87); a 6-22% lower risk was observed for each flavonoid subclass. The inverse association between total flavonoid intake and COPD was present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70-0.84) and former smokers (HR 0.82, 95% CI 0.69-0.97), not never-smokers. Furthermore, higher flavonoid intakes appeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity. CONCLUSION: Dietary flavonoids may be important for partially mitigating the risk of smoking-related COPD. However, smoking cessation should remain the highest priority.