The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts.

PURPOSE: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. METHODS: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). MAIN OUTCOME MEASURES: Corneal-compensated IOP. RESULTS: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). CONCLUSIONS: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank.

PURPOSE: We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP. DESIGN: Cross-sectional study in the UK Biobank. PARTICIPANTS: We included 121 374 participants (baseline ages, 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009-2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls). METHODS: We evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP. MAIN OUTCOME MEASURES: Intraocular pressure and glaucoma. RESULTS: Mendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P > 0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (≥232 mg/day) versus lowest (<87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (Ptrend = 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming > 480 mg/day versus < 80 mg/day was associated with a 0.35-mmHg higher IOP (Pinteraction = 0.01). The relationship between caffeine intake and glaucoma was null (P ≥ 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ≥ 321 mg/day showed a 3.90-fold higher glaucoma prevalence (Pinteraction = 0.0003). CONCLUSIONS: Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence.

Changes in waist circumference and risk of all-cause and CVD mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.

BACKGROUND: Measures of abdominal adiposity are strongly associated with all-cause mortality and cardiovascular disease (CVD). However, data are limited and conflicting regarding the consequences of changes in body fat distribution. The main aims of this paper are to investigate the association between changes in waist circumference (WC) and all-cause and CVD mortality and to examine these changes in relation to concurrent changes in weight. METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study recruited 25,639 participants between 1993 and 1997, aged 39-79, a number of whom also attended a second examination (1998-2000), and were followed up to 2016 for mortality. Participants were eligible for inclusion if they had WC, weight and height measurements at both time-points; those with a self-reported history of CVD or cancer, body mass index < 18.5 kg/m2 or missing data on covariates were excluded, leaving 12,337 participants for analyses. The median (IQR) follow-up time was 16.4 (15.7, 17.2) years. Hazard Ratios (HRs) for all-cause (2866 deaths) and CVD mortality (822 deaths), by categories of WC change, were determined using Cox proportional hazards analyses. RESULTS: After multivariable adjustment, the HRs (95% CIs) for all-cause mortality for men and women with a WC gain (WCG) >  5 cm were 1.51 (1.29-1.75) and 1.25 (1.06-1.46) respectively. For CVD mortality in men and women with a WCG >  5 cm, the HRs were 1.84 (1.39-2.43) and 1.15 (0.85-1.55) respectively. In analyses of concurrent changes in WC and weight, the greatest risk (HRs) (95% CIs) in men occurred with weight loss and WCG: 1.80 (1.13-2.86) for all-cause and 2.22 (1.03-4.82) for CVD mortality. In women, the greatest risk for both all-cause (HR 1.50 (1.16-1.95)) and CVD mortality (HR 1.81 (1.15-2.85)) was observed in those with weight loss and maintenance of WC (WCM). CONCLUSIONS: Objectively measured WCG > 5 cm, was associated with subsequent higher total mortality risk and higher CVD mortality risk in men. Interventions focusing on preventing increase in central adiposity rather than lowering weight per se in later life may potentially have greater health benefits.

FEV1 and total Cardiovascular mortality and morbidity over an 18 years follow-up Population-Based Prospective EPIC-NORFOLK Study.

BACKGROUND: Our study aimed to determine the association between forced expiratory volume in one second (FEV1) and subsequent fatal and non-fatal events in a general population. METHODS: The Norfolk (UK) based European Prospective Investigation into Cancer (EPIC-Norfolk) recruited 25,639 participants between 1993 and 1997. FEV1 measured by portable spirometry, was categorized into sex-specific quintiles. Mortality and morbidity from all causes, cardiovascular disease (CVD) and respiratory disease were collected from 1997 up to 2015. Cox proportional hazard regression analysis was used with adjustment for socio-economic factors, physical activity and co-morbidities. RESULTS: Mean age of the population was 58.7 ± 9.3 years, mean FEV1 for men was 294± 74 cL/s and 214± 52 cL/s for women. The adjusted hazard ratios for all-cause mortality for participants in the highest fifth of the FEV1 category was 0.63 (0.52, 0.76) for men and 0.62 (0.51, 0.76) for women compared to the lowest quintile. Adjusted HRs for every 70 cL/s increase in FEV1 among men and women were 0.77 (p < 0.001) and 0.68 (p < 0.001) for total mortality, 0.85 (p<0.001) and 0.77 (p<0.001) for CVD and 0.52 (p <0.001) and 0.42 (p <0.001) for respiratory disease. CONCLUSIONS: Participants with higher FEV1 levels had a lower risk of CVD and all-cause mortality. Measuring the FEV1 with a portable handheld spirometry measurement may be used as a surrogate marker for cardiovascular risk. Every effort should be made to identify those with poorer lung function even in the absence of cardiovascular disease as they are at greater risk of total and CV mortality.

Correcting for measurement error in fractional polynomial models using Bayesian modelling and regression calibration, with an application to alcohol and mortality.

Exposure measurement error can result in a biased estimate of the association between an exposure and outcome. When the exposure-outcome relationship is linear on the appropriate scale (e.g. linear, logistic) and the measurement error is classical, that is the result of random noise, the result is attenuation of the effect. When the relationship is non-linear, measurement error distorts the true shape of the association. Regression calibration is a commonly used method for correcting for measurement error, in which each individual's unknown true exposure in the outcome regression model is replaced by its expectation conditional on the error-prone measure and any fully measured covariates. Regression calibration is simple to execute when the exposure is untransformed in the linear predictor of the outcome regression model, but less straightforward when non-linear transformations of the exposure are used. We describe a method for applying regression calibration in models in which a non-linear association is modelled by transforming the exposure using a fractional polynomial model. It is shown that taking a Bayesian estimation approach is advantageous. By use of Markov chain Monte Carlo algorithms, one can sample from the distribution of the true exposure for each individual. Transformations of the sampled values can then be performed directly and used to find the expectation of the transformed exposure required for regression calibration. A simulation study shows that the proposed approach performs well. We apply the method to investigate the relationship between usual alcohol intake and subsequent all-cause mortality using an error model that adjusts for the episodic nature of alcohol consumption.

Mediterranean Diet Reduces Risk of Incident Stroke in a Population With Varying Cardiovascular Disease Risk Profiles.

Background and Purpose­: Although some evidence has found that the Mediterranean diet (MD) is protective for stroke risk, few studies have investigated whether this relationship differs by sex or cardiovascular disease risk. Methods­: We investigated the relationship between adherence to the MD score, estimated using 7-day dietary diaries and risk of incident stroke in an observational prospective population-based cohort study of 23 232 men and women (54.5% women) aged 40 to 77 years who participated in the European Prospective Investigation into Cancer study in Norfolk, United Kingdom. Risk of incident stroke was calculated using multivariable Cox regression, in the whole population, and also stratified by sex and cardiovascular disease risk profile, using the Framingham risk score. Results­: During 17.0 years of follow-up (395 048 total person-years), 2009 incident strokes occurred. Risk of stroke was significantly reduced with greater adherence to the MD score (quartile 4 versus quartile 1 hazard ratio [HR], 0.83; 95% CI, 0.74-0.94; P-trend <0.01) in the whole population and in women (quartile 4 versus quartile 1 HR, 0.78; 95% CI, 0.65, 0.93; P-trend <0.01) but not in men (quartile 4 versus quartile 1 HR, 0.94; 95% CI, 0.79-1.12; P-trend =0.55). There was reduced risk of stroke in those at high risk of cardiovascular disease and across categories of the MD score (quartile 4 versus quartile 1 HR, 0.87; 95% CI, 0.76-0.99; P-trend =0.04). However, this was driven by the associations in women (quartile 4 versus quartile 1 HR, 0.80; 95% CI, 0.65-0.97; P-trend =0.02). Conclusions­: Greater adherence to the MD was associated with lower risk of stroke in a UK white population. For the first time in the literature, we also investigated the associations between the MD score in those at both low and high risk of cardiovascular disease. Although the findings in our study were driven by the associations in women, they have implications for the general public and clinicians for prevention of stroke.

Weight change and 15 year mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.

Studies have reported a higher mortality risk associated with weight loss, particularly in middle-aged and older adults, although some of these studies did find that gaining weight was also associated with an increased mortality risk. We examined changes in weight in relation to mortality in a prospective population-based cohort study of men and women, resident in Norfolk, UK. Participants were assessed at baseline (1993-1997) and at a second examination (1998-2000), as part of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, and followed up to 2015 for mortality. Participants with a self-reported history of cancer or cardiovascular disease, body mass index < 18.5 kg/m2 or missing data on adjustment variables, at either time-point were excluded, leaving 12,580 participants, aged 39-78 in 1993-1997, eligible for analyses. Cox proportional hazards models were used to determine Hazard Ratios (HRs) for all-cause (2603 deaths), cardiovascular (749 deaths), cancer (981 deaths), respiratory (226 deaths) and other causes of mortality (647 deaths) by categories of weight change. After multivariate adjustment, the HRs (95% CIs) for all-cause mortality for men and women who lost more than 5 kg were 1.85 (1.48-2.31) and 1.64 (1.31-2.05) respectively. Higher hazards were also found for specific causes of mortality and weight loss > 5 kg. Similar associations were observed after excluding deaths in the first 5 years of follow-up. Results for weight gain were inconclusive. We conclude that objectively measured weight loss, but not weight gain, was associated with subsequent higher mortality risk in this population-based study of middle-aged and elderly men and women. However, undiagnosed, pre-existing disease and the inability to account for weight cycling need to be remembered when interpreting these results. Unravelling the causal pathways underlying this association will require more detailed studies, including that of changes in body composition.

Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort.

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), ß-carotene intake (P=0·003), ß-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and ß-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.

Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages.

AIMS/HYPOTHESIS: This study aimed to evaluate the association of types of sugar-sweetened beverages (SSB) (soft drinks, sweetened-milk beverages, sweetened tea/coffee), artificially sweetened beverages (ASB) and fruit juice with incident type 2 diabetes and determine the effects of substituting non-SSB for SSB and the population-attributable fraction of type 2 diabetes due to total sweet beverages. METHODS: Beverage consumption of 25,639 UK-resident adults without diabetes at baseline (1993-1997) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study was assessed using 7-day food diaries. During 10.8 years of follow-up 847 incident type 2 diabetes cases were verified. RESULTS: In adjusted Cox regression analyses there were positive associations (HR [95% CI] per serving/day]) for soft drinks 1.21 (1.05, 1.39), sweetened-milk beverages 1.22 (1.05, 1.43) and ASB 1.22 (1.11, 1.33), but not for sweetened tea/coffee 0.98 (0.94, 1.02) or fruit juice 1.01 (0.88, 1.15). Further adjustment for adiposity attenuated the association of ASB, HR 1.06 (0.93, 1.20). There was a positive dose-response relationship with total sweet beverages: HR per 5% energy 1.18 (1.11, 1.26). Substituting ASB for any SSB did not reduce the incidence in analyses accounting for energy intake and adiposity. Substituting one serving/day of water or unsweetened tea/coffee for soft drinks and for sweetened-milk beverages reduced the incidence by 14%-25%. If sweet beverage consumers reduced intake to below 2% energy, 15% of incident diabetes might be prevented. CONCLUSIONS/INTERPRETATION: The consumption of soft drinks, sweetened-milk beverages and energy from total sweet beverages was associated with higher type 2 diabetes risk independently of adiposity. Water or unsweetened tea/coffee appear to be suitable alternatives to SSB for diabetes prevention. These findings support the implementation of population-based interventions to reduce SSB consumption and increase the consumption of suitable alternatives.

Opposites don't attract: high spouse concordance for dietary supplement use in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.

OBJECTIVE: Dietary supplements are commonly consumed but may not be beneficial for everyone. It is known that supplement users have healthy behaviour characteristics but until now concordance between spouses living in the same household has not been investigated and concordance may be an important behavioural determinant. DESIGN: Prospective cohort study, cross-sectional data analysis. SETTING: European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) in the UK, recruitment between 1993 and 1998. SUBJECTS: Married (or living as married) participants sharing a household, who attended a health examination and completed a 7 d diet diary were included in the analysis (n 11 060). The age range was 39-79 years. RESULTS: Nearly 75 % of the households in EPIC-Norfolk were concordant in their supplement use, with 46·7 % not using supplements and 27·0 % using supplements. Concordance increased with age; the percentage of concordant couples varied less by other sociodemographic characteristics. Participants who had a spouse who used a supplement were nearly nine times more likely to use a supplement (unadjusted). Depending on participants' sex and type of supplement used, odds ratios for 'supplement use by spouse' in the prediction of participants' supplement use varied between 6·2 and 11·7 adjusted for participants' age, smoking status, BMI, social class, education level and physical activity. CONCLUSIONS: 'Supplement use by spouse' is an independent and the strongest predictor of participants' supplement use. This phenomenon can be useful in the design of studies and health interventions; or when assessing risk of excessive intake from dietary supplements.

Association between sucrose intake and risk of overweight and obesity in a prospective sub-cohort of the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk).

OBJECTIVE: The objective of the present study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). DESIGN: Prospective cohort study. SETTING: EPIC-Norfolk in the UK, recruitment between 1993 and 1997. SUBJECTS: Men and women (n 1734) aged 39-77 years. Sucrose intake was assessed using 7 d diet diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as a biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI>25·0 kg/m2 after three years of follow-up. RESULTS: After three years of follow-up, mean BMI was 26·8 kg/m2. Self-reported sucrose intake was significantly positively associated with the biomarker. Associations between the biomarker and BMI were positive (ß=0·25; 95 % CI 0·08, 0·43), while they were inverse when using self-reported dietary data (ß=-1·40; 95 % CI -1·81, -0·99). The age- and sex-adjusted OR for BMI>25·0 kg/m2 in participants in the fifth v. first quintile was 1·54 (95 % CI 1·12, 2·12; P trend=0·003) when using biomarker and 0·56 (95 % CI 0·40, 0·77; P trend<0·001) with self-reported dietary data. CONCLUSIONS: Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with BMI. Future studies should consider the use of objective biomarkers of sucrose intake.

Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary.

AIM/HYPOTHESIS: The aim of this study was to investigate the association between total and types of dairy product intake and risk of developing incident type 2 diabetes, using a food diary. METHODS: A nested case-cohort within the EPIC-Norfolk Study was examined, including a random subcohort (n = 4,000) and cases of incident diabetes (n = 892, including 143 cases in the subcohort) followed-up for 11 years. Diet was assessed using a prospective 7-day food diary. Total dairy intake (g/day) was estimated and categorised into high-fat (≥3.9%) and low-fat (<3.9% fat) dairy, and by subtype into yoghurt, cheese and milk. Combined fermented dairy product intake (yoghurt, cheese, sour cream) was estimated and categorised into high- and low-fat. Prentice-weighted Cox regression HRs were calculated. RESULTS: Total dairy, high-fat dairy, milk, cheese and high-fat fermented dairy product intakes were not associated with the development of incident diabetes. Low-fat dairy intake was inversely associated with diabetes in age- and sex-adjusted analyses (tertile [T] 3 vs T1, HR 0.81 [95% CI 0.66, 0.98]), but further adjustment for anthropometric, dietary and diabetes risk factors attenuated this association. In addition, an inverse association was found between diabetes and low-fat fermented dairy product intake (T3 vs T1, HR 0.76 [95% CI 0.60, 0.99]; p(trend) = 0.049) and specifically with yoghurt intake (HR 0.72 [95% CI 0.55, 0.95]; p(trend) = 0.017) in multivariable adjusted analyses. CONCLUSIONS/INTERPRETATION: Greater low-fat fermented dairy product intake, largely driven by yoghurt intake, was associated with a decreased risk of type 2 diabetes development in prospective analyses. These findings suggest that the consumption of specific dairy types may be beneficial for the prevention of diabetes, highlighting the importance of food group subtypes for public health messages.

Dietary intake measurement using 7 d diet diaries in British men and women in the European Prospective Investigation into Cancer-Norfolk study: a focus on methodological issues.

The aim of the present study was to describe the energy, nutrient and crude v. disaggregated food intake measured using 7 d diet diaries (7dDD) for the full baseline Norfolk cohort recruited for the European Prospective Investigation into Cancer (EPIC-Norfolk) study, with emphasis on methodological issues. The first data collection took place between 1993 and 1998 in Norfolk, East Anglia (UK). Of the 30,445 men and women, aged 40-79 years, registered with a general practitioner invited to participate in the study, 25,639 came for a health examination and were asked to complete a 7dDD. Data from diaries with data recorded for at least 1 d were obtained for 99% members of the cohort; 10,354 (89·8%) of the men and 12,779 (91·5%) of the women completed the diet diaries for all 7 d. Mean energy intake (EI) was 9·44 (SD 2·22) MJ/d and 7·15 (SD 1·66) MJ/d, respectively. EI remained approximately stable across the days, but there was apparent under-reporting among the participants, especially among those with BMI >25 kg/m². Micronutrient density was higher among women than among men. In conclusion, under-reporting is an issue, but not more so than that found in national surveys. How foods were grouped (crude or disaggregated) made a difference to the estimates obtained, and comparison of intakes showed wide limits of agreement. The choice of variables influences estimates obtained from the food group data; while this may not alter the ranking of individuals within studies, this issue may be relevant when comparing absolute food intakes between studies.

Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European Union.

Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18-64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62%), pome fruits (11%), berries (3%) and cocoa products (3%). Tea was the major single contributor to monomer intake (75%), followed by pome fruits (6%). Pome fruits were also the main source of PA (28%). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.

Estimated dietary intakes and sources of flavanols in the German population (German National Nutrition Survey II).

BACKGROUND/OBJECTIVES: Data from intervention studies suggest a beneficial effect of flavanols on vascular health. However, insufficient data on their intake have delayed the assessment of their health benefits. The aim of this study was to estimate intake of flavanols and their main sources among people living in Germany. SUBJECTS/METHODS: Data from diet history interviews of the German National Nutrition Survey II for 15,371 people across Germany aged 14-80 years were analyzed. The FLAVIOLA Flavanol Food Composition Database was compiled using the latest US Department of Agriculture and Phenol-Explorer Databases and expanded to include recipes and retention factors. RESULTS: Mean intake of total flavanols, flavan-3-ol monomers, proanthocyanidins (PA), and theaflavins in Germany was 386, 120, 196, and 70 mg/day, respectively. Women had higher intakes of total flavanols (399 mg/day) than men (372 mg/day) in all age groups, with the exception of the elderly. Similar results were observed for monomers (108 mg/day for men, 131 mg/day for women) and PA (190 mg/day; 203 mg/day), although intake of theaflavins was higher in men (74 mg/day; 66 mg/day). There was an age gradient with an increase in total flavanols, monomers, and theaflavins across the age groups. The major contributor of total flavanols in all subjects was pome fruits (27%) followed by black tea (25%). CONCLUSIONS: This study demonstrated age- and sex-related variations in the intake and sources of dietary flavanols in Germany. The current analysis will provide a valuable tool in clarifying and confirming the potential health benefits of flavanols.

Hospital-treated infections and subsequent Parkinson's disease risk: a register-based sibling comparison study.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database.

OBJECTIVE: A diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group. DESIGN: Development of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a populationbased study. SETTING: Men and women, aged 40­79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries. SUBJECTS: A subset of 20 437 participants. RESULTS: The median daily phyto-oestrogen intake for all men was 1199 mg (interquartile range 934­1537mg; mean 1504mg, SD 1502mg) and 888mg for all women (interquartile range 710­1135 mg; mean 1205 mg, SD 1701mg). In soya consumers, median daily intakes were higher: 2861 mg in men (interquartile range 1304­7269mg; mean 5051mg, SD 5031mg) and 3142 mg in women (interquartile range 1089­7327mg; mean 5396 mg, SD 6092 mg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake ­ 40?8% and 35?6%, respectively. In soya consumers, vegetable dishes and soya/goat's/sheep's milks were the main contributors ­ 45?7% and 21?3% in men and 38?4% and 33?7% in women, respectively. CONCLUSIONS: The ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial.

Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 µg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 µg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank.

PURPOSE: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). METHODS: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. RESULTS: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 µm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. CONCLUSIONS: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.