The Lifelines Cohort (Lifelines) is a large population-based multidisciplinary dynamic cohort and biobank designed to unravel the determinants of healthy ageing. Lifelines continuously generates deep pheno- and genotypic data to enable research on the development of chronic and rare diseases and their risk factors with the ultimate goal to contribute to healthy ageing, public health and precision medicine. Between 2006 and 2013, 10% (around 167 000) of the northern population of The Netherlands aged 0 to 93 years was enrolled using a three-generation recruitment design, as described previously. ¹ Data are collected through questionnaires (all ages) and measurements (age 8 years and older) on physical and mental health, lifestyle and the exposome. Furthermore, the Lifelines biobank has samples (blood, plasma, serum, hair, urine and feces) stored in a freezer warehouse (from age 8 years and older). Lifelines allows analyses at multiple levels, ranging from genetic and molecular domains through clinical, psychosocial and environmental determinants of health and disease, which allows for analyses within specific domains and also inter- and multidisciplinary analyses. All participants are invited for follow-up assessments every 5 years including a comprehensive questionnaire, and will be followed for at least 30 years ( Figure 1). In between assessments, follow-up questionnaires are completed approximately once every 1.5–2.5 years.

To investigate the association between dietary patterns and prevalence and incidence 3 years later of depressive symptoms using data from the mid-aged cohort in the Australian Longitudinal Study on Women’s Health. Participants (aged 50–55 years) completed a food frequency questionnaire in 2001. Depressive symptoms were measured in 2001 and 2004 using the validated 10-item Centre for Epidemiologic Studies Depression scale. Multiple logistic regression was used for cross-sectional analysis (8369 women) and longitudinal analysis (7588) to assess the associations between dietary patterns and prevalence of depressive symptoms, and then for longitudinal analysis (6060) on their associations with the incidence of depressive symptoms in 2004, while adjusting for sociodemographic and lifestyle factors. Six dietary patterns were identified from factor analysis: cooked vegetables, fruit, Mediterranean style, meat and processed meat, dairy, and high fat and sugar. A higher consumption of the Mediterranean-style diet had a cross-sectional association with lower prevalence of depressive symptoms in 2001, adjusted odds ratio 0.82 (95% confidence interval 0.77–0.88); and longitudinally with lower incidence of depressive symptoms in 2004, adjusted odds ratio 0.83 (0.75–0.91). None of the associations found for other dietary patterns remained statistically significant after adjustment for confounders. A dose–response relationship was found cross-sectionally when women were grouped according to quintiles of Mediterranean-style diet (P-value for trend <0.001). Consumption of a ‘Mediterranean-style’ dietary pattern by mid-aged women may have a protective influence against the onset of depressive symptoms. These findings suggest that dietary patterns have a potential role in the prevention and management of depressive symptoms.

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. 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. 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. 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. 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.

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.

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. 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. PubMed and Web of Science databases were searched. 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. 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. Further research using biomarker information is warranted.