Dietary flavonoids among children and adolescents in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study: intake, food sources and trends from 1985 until 2016.

Flavonoids are suggested to reduce disease risk. Since dietary habits are acquired during early life, describing age and time trends of flavonoid intake and major food sources are important for monitoring and disease prevention in later life. We aimed to describe total flavonoid intake and food sources and to investigate age and time trends of flavonoid intake in 3-18-year-olds, from the Dortmund Nutritional and Anthropometric Longitudinally Designed study from 1985 to 2016. Intake was assessed annually using 3-d weighed food records (WFR). Flavonoid values were assigned using the United States Department of Agriculture database. Foods contributing to intake were determined. Age and time trends in total flavonoid and isoflavone density were analysed by sex with PROC MIXED. In total, 1312 children completed 10 758 WFR. Across all ages, daily mean total flavonoid density was lower in boys compared with girls (134 v. 146 mg/4184 kJ) and no difference in median isoflavone density (0·04 mg/4184 kJ per d) was found. The top five foods contributing to total flavonoid intake were apple with peel (15·0/17·1 %), strawberries (5·9/6·1 %), chocolate spread (3·9/3·5 %), orange juice (3·5/3·4 %) and pasta (3·5/3·4 %) for boys and girls, respectively. Overall, in boys, total flavonoid density decreased over the course of age and time. In girls, there was no association with age or time. In both sexes, isoflavone density followed a U-shaped age trend with no change over time. From a public health perspective, the overall observed downwards trend of flavonoid intake in boys deserves attention. Future initiatives should be tailored at maintaining a high flavonoid density as children age, specifically among boys.

Dietary patterns associated with inflammatory biomarkers in a Northern German population.

PURPOSE: The aim of the present study was to derive overall and sex-specific dietary patterns associated with inflammatory biomarkers in a general population sample from Northern Germany. METHODS: The present analysis included 1158 participants (477 men, 681 women, mean age: 53.1 years; mean body mass index: 26.2 kg/m2) of the Food Chain Plus (FoCus) cohort in Kiel, Germany. Participants completed a semi-quantitative food frequency questionnaire and provided blood samples. Reduced rank regression with C-reactive protein (CRP) and Interleukin 6 (IL-6) as response variables was used to derive dietary patterns. After a mean follow-up of 1.7 years, a second blood sample was obtained in a subsample of 112 individuals. Multiple regression models were used to examine the association between dietary patterns at baseline and inflammatory biomarkers at follow-up. RESULTS: The overall pattern characterised by high intakes of soft drinks, meat, potatoes and sauce, and low intakes of other cereals (except pasta/rice), wine, nuts, seeds, vegetarian dishes, vegetable oil, and fish was positively associated with CRP (OR 2.20; 95% CI 1.12, 4.35) and IL-6 (OR 3.14; 95% CI 1.26, 7.87) at follow-up. In men, the dietary pattern was higher in soft drinks, processed meat and low in cereals and plant-based fats. In women, the pattern was characterised by soft drinks, meat, vegetables and low in other cereals, wine, nuts, and seeds. The association between sex-specific patterns with inflammatory biomarkers was weaker for CRP. CONCLUSION: We identified dietary patterns positively associated with established biomarkers of chronic low-grade inflammation.

Flavonoid intake from fruit and vegetables during adolescence is prospectively associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

PURPOSE: Flavonoid consumption during adolescence could contribute to preventing adult onset of type 2 diabetes mellitus. We investigated the prospective association between habitual intake of flavonoids from fruit and vegetables (FlavFV) during adolescence and risk markers of type 2 diabetes in early adulthood. METHODS: This analysis included participants of the DONALD Study, who had provided a fasting blood sample in adulthood (18-39 years), data on FlavFV-intake during adolescence (females: 9-15 years, males: 10-16 years) and relevant covariates. Habitual FlavFV-intake was either estimated using repeated 3-day weighed dietary records (n = 268), or the validated biomarker hippuric acid (uHA)-excretion in repeated 24-h urine samples (n = 241). Multivariable linear regressions were performed to analyse the prospective associations of FlavFV or uHA with homeostasis model assessment insulin sensitivity (HOMA2-%S), hepatic steatosis index (HSI), fatty liver index (FLI) and a pro-inflammatory score. RESULTS: Higher FlavFV-intake was independently related to higher HOMA2-%S among females (Ptrend = 0.03), but not among males. Both FlavFV-intake and uHA-excretion were inversely associated with HSI (Ptrend < 0.0001 and Ptrend = 0.02, respectively) and the pro-inflammatory score (Ptrend = 0.02 and Ptrend = 0.008, respectively), but not with FLI. CONCLUSIONS: Our data indicate that flavonoid consumption from fruit and vegetables during adolescence is associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

Lifestyle Indices and Cardiovascular Disease Risk: A Meta-analysis.

CONTEXT: Several studies investigated lifestyle indices to account for interrelations between lifestyle behaviors and cardiovascular disease risk. So far, no systematic review has been conducted. Thus, the aim is to summarize the evidence of associations between lifestyle indices and cardiovascular disease risk in observational prospective studies. EVIDENCE ACQUISITION: A systematic literature search was conducted in two databases in February 2018. Multivariable-adjusted risk estimates were combined using random effects models comparing the highest with the lowest healthy lifestyle score. Additionally, meta-analyses for cardiovascular disease types, such as stroke and heart failure, were conducted. Heterogeneity was assessed using I2 index. EVIDENCE SYNTHESIS: The search identified 27 studies, of which 22 were included in the meta-analyses. Most lifestyle indices included physical activity, smoking, diet, alcohol consumption, and body weight. A healthy lifestyle was associated with a reduced risk of 66% for cardiovascular disease (95% CI=0.28, 0.41, I2=79.1%), 60% for stroke, and 69% for heart failure. A dose-response effect for adherence to an increasing number of healthy behaviors and cardiovascular disease risk was observed. Statistical heterogeneity was found, suggesting that the definition of the lifestyle indices and components varied substantially between the studies. CONCLUSIONS: Adherence to several healthy lifestyle behaviors simultaneously was associated with a 66% reduced cardiovascular disease risk compared with adopting none or only one behavior. Despite heterogeneity of indices, consistent inverse associations across studies underscore the relevance of adopting healthy behaviors at all. More research on other lifestyle behaviors, such as sleep duration or sedentary behavior in combination, is warranted.

Polyphenol exposure and risk of type 2 diabetes: dose-response meta-analyses and systematic review of prospective cohort studies.

Background: Type 2 diabetes is characterized by impaired glucose metabolism. Bioactive compounds in fruits and vegetables such as polyphenols have been suggested to influence glucose metabolism. Objective: The aim of the current study was to systematically review the literature and conduct dose-response meta-analyses to summarize evidence of polyphenol exposure in association with incident type 2 diabetes. Design: Prospective epidemiologic studies published before January 2018 were searched through 2 databases. Log-transformed multivariable adjusted hazard and odds ratios were combined in a random-effects model. Meta-analyses comparing extreme quantiles of polyphenol exposure were further explored with the use of linear and nonlinear dose-response meta-analyses. Results: Eighteen studies investigated the association between polyphenols (51 different compounds in total) and type 2 diabetes. A comparison of extreme quantiles revealed inverse associations for intakes of polyphenols (HR: 0.56; 95% CI: 0.34, 0.93), flavonoids (HR: 0.88; 95% CI: 0.81, 0.96), flavonols (HR: 0.92; 95% CI: 0.85, 0.98), flavan-3-ols (HR: 0.89; 95% CI: 0.81, 0.99), catechins (HR: 0.86; 95% CI: 0.75, 0.97), anthocyanidins (HR: 0.86; 95% CI: 0.81, 0.91), isoflavones (HR: 0.92; 0.86, 0.97), daidzein (HR: 0.89; 95% CI: 0.83, 0.95), genistein (HR: 0.92; 95% CI: 0.86, 0.99), and stilbenes (HR: 0.44; 95% CI: 0.26, 0.72), and biomarkers of daidzein (HR: 0.81; 95% CI: 0.66, 0.99) and genistein (HR: 0.79; 95% CI: 0.62, 0.99). In the dose-response meta-analysis, nonlinear associations were observed for intakes of polyphenols, flavonoids, flavanones, anthocyanidins, anthocyanins, and biomarkers of genistein. A linear dose-response association was observed for phenolic acids. Conclusions: This study adds to the evidence showing that diets rich in polyphenols, and particularly flavonoids, play a role in the prevention of type 2 diabetes. For most associations evidence for nonlinearity was found, suggesting a recommendable amount of intake associated with the lowest risk of type 2 diabetes. Therefore, future studies are warranted in which nonlinear associations are further explored.

Habitual Flavonoid Intake from Fruit and Vegetables during Adolescence and Serum Lipid Levels in Early Adulthood: A Prospective Analysis.

Flavonoids have been implicated in the prevention of cardiovascular diseases (CVD). In a prospective approach, we investigated whether habitual flavonoid intake from fruit, vegetables and juices (FlavFVJ) during adolescence is associated with adult levels of serum lipids, one of the main CVD risk factors. This analysis included healthy participants from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study, who had provided a fasting blood sample in adulthood (aged 18-39 years), data on FlavFVJ intake during adolescence (females: 9-15 years, males: 10-16 years)-estimated either from multiple 3-day weighed dietary records (n = 257), or from validated biomarker hippuric acid (uHA) excretion from multiple 24-h urine samples (n = 233)-together with information on relevant covariates. In multivariable linear regression analyses, a higher FlavFVJ intake during adolescence was independently associated with higher serum high-density lipoprotein cholesterol (HDL-C) levels among males (Ptrend = 0.038); however, the inclusion of adult waist circumference attenuated this association (Ptrend = 0.053). FlavFVJ was not associated with triglycerides (TG), total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C; all Ptrend ≥ 0.1), nor was uHA excretion with any serum lipid outcome among males (all Ptrend ≥ 0.5). Neither FlavFVJ intake nor uHA excretion was associated with serum lipids among women (all Ptrend ≥ 0.1). However, a higher flavonoid intake from fruit and vegetables was independently related to lower LDL-C levels (Ptrend = 0.021), while a higher intake from juices was associated with higher LDL-C levels (Ptrend = 0.016) among females. In conclusion, a higher flavonoid intake from fruit, vegetables and/or juices during adolescence may be linked to cholesterol levels in early adulthood in a sex- and food source-specific manner.

Association of isoflavone biomarkers with risk of chronic disease and mortality: a systematic review and meta-analysis of observational studies.

CONTEXT: Isoflavones have been suggested to play a role in disease prevention. The accuracy of assessing exposure to isoflavones might be improved by using them as biomarkers. OBJECTIVE: A systematic review of observational studies on the association of isoflavone biomarkers with the risk of chronic disease and mortality was conducted. Meta-analyses of specific biomarker and disease combinations were performed. DATA SOURCES: PubMed and Web of Science databases were searched. DATA EXTRACTION: Two authors screened the titles and abstracts of candidate publications. The third author was consulted to resolve discrepancies. Forty studies were included and their quality assessed. PRISMA-P guidelines were followed. DATA ANALYSIS: Eight different isoflavone biomarkers were investigated in association with cancer (26 studies), mortality (2 studies), cardiovascular disease (3 studies), metabolic syndrome risk factors (7 studies), and other outcomes (2 studies). Meta-analyses of studies on individual isoflavonic compounds were conducted for breast and prostate cancer and type 2 diabetes. Higher daidzein and genistein concentrations were associated with lower risk of breast cancer and diabetes. Only daidzein concentrations were inversely associated with risk of prostate cancer. For the remaining endpoints, evidence for associations was inconsistent and scarce, perhaps owing to heterogeneity in study exposures and outcomes. CONCLUSIONS: Further research using biomarker information is warranted.

Association of Polyphenol Biomarkers with Cardiovascular Disease and Mortality Risk: A Systematic Review and Meta-Analysis of Observational Studies.

Epidemiologic studies have suggested an inverse association between flavonoids and cardiovascular disease (CVD). However, the results might have been influenced by the use of dietary assessment methods, which are error prone. The aim of this paper was to systematically review and analyse the literature for evidence of associations between polyphenol biomarkers and CVD and mortality risk in observational studies. Eligible studies were identified through PubMed, Web of Science, and reference lists. Multivariable adjusted associations were extracted. Data were log-transformed and pooled using the random effects model. In total, eight studies were included, investigating 16 different polyphenol biomarkers in association with CVD and mortality. Blood and urine were used as biospecimens, and enterolactone, a lignan metabolite, was most often investigated. Three meta-analyses were conducted investigating the association between enterolactone, and all-cause and CVD mortality, and non-fatal myocardial infarction. A 30% and 45% reduced all-cause and CVD mortality risk were revealed at higher enterolactone concentrations. Furthermore, inverse associations were observed between polyphenol biomarkers and all-cause mortality, kaempferol, and acute coronary syndrome. There is evidence to suggest that enterolactone is associated with a lower CVD mortality risk. This emphasises the importance of the role of the microbiota in disease prevention. To strengthen the evidence, more studies are warranted.