Exploring the association of physical activity with the plasma and urine metabolome in adolescents and young adults.

BACKGROUND: Regular physical activity elicits many health benefits. However, the underlying molecular mechanisms through which physical activity influences overall health are less understood. Untargeted metabolomics enables system-wide mapping of molecular perturbations which may lend insights into physiological responses to regular physical activity. In this study, we investigated the associations of habitual physical activity with plasma and urine metabolome in adolescents and young adults. METHODS: This cross-sectional study included participants from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study with plasma samples n = 365 (median age: 18.4 (18.1, 25.0) years, 58% females) and 24 h urine samples n = 215 (median age: 18.1 (17.1, 18.2) years, 51% females). Habitual physical activity was assessed using a validated Adolescent Physical Activity Recall Questionnaire. Plasma and urine metabolite concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) methods. In a sex-stratified analysis, we conducted principal component analysis (PCA) to reduce the dimensionality of metabolite data and to create metabolite patterns. Multivariable linear regression models were then applied to assess the associations between self-reported physical activity (metabolic equivalent of task (MET)-hours per week) with single metabolites and metabolite patterns, adjusted for potential confounders and controlling the false discovery rate (FDR) at 5% for each set of regressions. RESULTS: Habitual physical activity was positively associated with the "lipid, amino acids and xenometabolite" pattern in the plasma samples of male participants only (ß = 1.02; 95% CI: 1.01, 1.04, p = 0.001, adjusted p = 0.042). In both sexes, no association of physical activity with single metabolites in plasma and urine and metabolite patterns in urine was found (all adjusted p > 0.05). CONCLUSIONS: Our explorative study suggests that habitual physical activity is associated with alterations of a group of metabolites reflected in the plasma metabolite pattern in males. These perturbations may lend insights into some of underlying mechanisms that modulate effects of physical activity.

Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value).

This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value.

Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis.

Endogenous and exogenous metabolite concentrations may be susceptible to variation over time. This variability can lead to misclassification of exposure levels and in turn to biased results. To assess the reproducibility of metabolites, the intraclass correlation coefficient (ICC) is computed. A literature search in three databases from 2000 to May 2021 was conducted to identify studies reporting ICCs for blood and urine metabolites. This review includes 192 studies, of which 31 studies are included in the meta-analyses. The ICCs of 359 single metabolites are reported, and the ICCs of 10 metabolites were meta-analyzed. The reproducibility of the single metabolites ranges from poor to excellent and is highly compound-dependent. The reproducibility of bisphenol A (BPA), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), methylparaben, and propylparaben is poor to moderate (ICC median: 0.32; range: 0.15-0.49), and for 25-hydroxyvitamin D [25(OH)D], it is excellent (ICC: 0.95; 95% CI, 0.90-0.99). Pharmacokinetics, mainly the half-life of elimination and exposure patterns, can explain reproducibility. This review describes the reproducibility of the blood and urine exposome, provides a vast dataset of ICC estimates, and hence constitutes a valuable resource for future reproducibility and clinical epidemiologic studies.

Assessment of Fruit and Vegetables Intake with Biomarkers in Children and Adolescents and Their Level of Validation: A Systematic Review.

Fruit and vegetables (FV) are part of a healthy diet and should be frequently consumed already at a young age. However, intake of FV is difficult to assess in children and adolescents due to various misreporting aspects. Thus, measurement of dietary biomarkers may be a promising alternative to assess FV intake more objectively at young age. To date, dietary biomarkers have been primarily studied in adults, and research focused on their usefulness in children is scarce. However, clinical studies have revealed important differences between children and adults, most importantly in their gut microbiome composition, resulting in differences in postprandial metabolism, as well as in food choices and meal compositions that may influence individual biomarker levels. Therefore, the present review aimed to identify biomarkers of FV intake (BFVI) currently available in children and adolescents and to explore whether there are any differences in the BFVI profile above between children and adolescents and adults. In addition, the current level of validation of BFVI in children and adolescents was examined. In total, 28 studies were eligible for this review, and 18 compounds were identified as potential biomarkers for FV intake in children and adolescents. Carotenoid concentration in skin was a valuable biomarker for total FV intake for both children and adult populations. Common BFVI in blood in adults (e.g., carotenoids and vitamin C) showed inconsistent results in children and adolescents. Biomarkers particularly useful in children included urinary hippuric acid as a biomarker of polyphenolic compound intake originating from FV and the combination of N-methylnicotinic acid and acetylornithine as a biomarker of bean intake. Further studies are needed to assess their kinetics, dose-response, and other validation aspects. There is limited evidence so far regarding valid BFVI in children and adolescents. Thus, to put BFVI into practice in children and adolescents, further studies, particularly based on metabolomics, are needed to identify and validate BFVI that can be used in future epidemiological studies.

Changing dietary patterns is necessary to improve the sustainability of Western diets from a One Health perspective.

Western diets are associated with multiple environmental impacts and risks to human health. European countries are gradually taking action towards the Farm to Fork Strategy, embracing a Life Cycle Assessment (LCA) perspective to promote the sustainability of food production and consumption. Although LCA enables the comprehensive assessment of environmental impacts, diet-related human health and animal welfare impacts are often underrepresented. This study proposes integrating additional indicators into LCA to evaluate the sustainability of diets under the One Health (OH) approach, which holistically considers interlinked complex health issues between humans, animals and the environment. Human health loss is estimated according to risk factors for non-communicable diseases; while animal welfare is measured as animal life years suffered, loss of animal lives and loss of morally-adjusted animal lives. The extended LCA framework is applied to men and women's reference diets in the German federal state of North Rhine-Westphalia (NRW); compared to three optimized dietary scenarios under nutritional constraints: 1) the national dietary guidelines, 2) a vegan diet (VD) and 3) a Mediterranean diet (MD). Men's reference diet causes greater impacts than women's across OH dimensions due to the higher food consumption, especially of ready-to-eat meals, sausages, meat, and sweetened and alcoholic beverages. Both reference diets are associated with risk factors for cardiovascular diseases, diabetes, stroke and neoplasms. Besides meat, consumption of honey, fish and seafood has the greatest impact on animal welfare, because of the high number of individuals involved. Alternative diets improve the sustainability of food consumption in NRW, although trade-offs arise: MD worsens animal suffering due to the higher fish intake; water use increases in both VD and MD due the higher intake of nuts and vegetables. Results highlight the importance of including animal welfare and human health indicators in LCA to better elucidate the potential impacts of diets characterized by the high intake of animal products, from a OH perspective.

Post-diagnostic reliance on plant-compared with animal-based foods and all-cause mortality in omnivorous long-term colorectal cancer survivors.

BACKGROUND: Plant-rich diets are associated with lower cardiometabolic risks and longer survival in the general population, but their association with mortality in cancer survivors is still unclear. OBJECTIVES: We aimed to examine the associations of 3 postdiagnostic plant-based diet indices with all-cause mortality in omnivorous long-term colorectal cancer (CRC) survivors. METHODS: Diet was assessed with FFQs at a median of 6 years after diagnosis in 1404 CRC survivors (56% male; median age, 69 years) in a Northern German prospective cohort study. An overall, a healthful plant-based, and an unhealthful plant-based diet index were derived by scoring intakes of animal foods reversely and intakes of healthy (whole grains, vegetables, fruits, legumes, nuts, oils, tea/coffee) and less healthy plant foods (refined grains, fruit juices, sugar-sweetened beverages, potatoes, sweets/desserts) positively or reversely, depending on the index. Vital status follow-up was conducted via population registries. Cox proportional hazards regression was applied to estimate HRs for all-cause mortality according to plant-based diet adherence. RESULTS: Within 7 years (median) after diet assessment, 204 deaths occurred. The overall plant-based diet index displayed a significant, inverse association with all-cause mortality (HR per 10-point increase in diet index, 0.72; 95% CI, 0.57-0.91). Although not statistically significant, higher healthful plant-based diet scores showed a strong tendency towards lower mortality (HR, 0.82; 95% CI, 0.67-1.01). The unhealthful plant-based diet index was associated with higher mortality, but lost statistical significance after multivariable adjustment (HR, 1.19; 95% CI, 0.96-1.48). A subgroup analysis revealed that the tendency towards a positive association of the unhealthful plant-based diet with mortality was restricted to less physically active individuals (<95 metabolic equivalent of task hours/week). CONCLUSIONS: An overall plant-based diet was inversely associated with all-cause mortality in long-term CRC survivors. However, more research is needed to further disentangle the impacts of different qualities of plant-based diets on cancer survivors' health.

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Adherence to healthy lifestyles and incidence of diabetes and mortality among individuals with diabetes: a systematic review and meta-analysis of prospective studies.

INTRODUCTION: Lifestyle factors in combination have been hypothesised to be associated with the prevention of type 2 diabetes (T2D) and mortality among individuals with T2D. The aim was to conduct a systematic review and meta-analysis to quantify the association between lifestyle indices and incident T2D as well as mortality in individuals with T2D. METHODS: PubMed and Web of Science were searched up to September 2019. We included prospective cohort studies investigating at least three lifestyle factors in association with T2D, or all-cause mortality in individuals with diabetes. We conducted pairwise and dose-response meta-analyses to calculate summary relative risks (SRR) by using random effects model. RESULTS: In total, 19 studies were included. Adhering to a healthy lifestyle (mostly favourable diet, physical activity, non-smoking, moderate alcohol intake and normal weight) was associated with a reduced SRR of 78% for T2D (SRR: 0.22; 95% CI: 0.16 to 0.32; n=14) and 57% for mortality (SRR: 0.43; 95% CI: 0.31 to 0.58; n=5) compared with low adherence to a healthy lifestyle. In dose-response analyses, the adherence to every additional healthy lifestyle factor was associated with a reduced relative risk of 32% (95% CI: 28% to 36%) for T2D and 21% (95% CI: 15% to 26%) for mortality. CONCLUSIONS: Our findings underline the importance of the joint adherence to healthy lifestyle factors to prevent T2D and improve survival among individuals with diabetes. Adherence to every additional health lifestyle factor play a role in the T2D prevention and progression. PROSPERO REGISTRATION NUMBER: CRD42018091409.

Dietary Patterns Are Associated with Serum Metabolite Patterns and Their Association Is Influenced by Gut Bacteria among Older German Adults.

BACKGROUND: Although dietary intakes and dietary intake patterns (DPs) have been associated with single metabolites, it is unclear whether DPs are also reflected in specific metabolite patterns (MPs). Moreover, the influence of groups of gut bacteria on the relationship between DPs and MPs is underexplored. OBJECTIVES: We aimed to investigate the association of DPs and serum MPs and also the modifying effect of the gut bacteria compositional patterns (BCPs). METHODS: This is a cross-sectional investigation among 225 individuals (median age: 63 y; 53% women) from the European Prospective Investigation into Cancer and Nutrition study. Dietary intakes were assessed by three 24-h dietary recalls, gut bacteria composition was quantified by 16S rRNA gene sequencing, and the serum metabolome was profiled by an untargeted approach. We identified DPs and BCPs by the treelet transform analysis. We modeled associations between DPs and 8 previously published MPs and the modifying effect of BCPs by fitting generalized linear models using DataSHIELD R. RESULTS: We identified 5 DPs and 7 BCPs. The "bread, margarine, and processed meat" and "fruiting vegetables and vegetable oils" DPs were positively associated with the "amino acids" (ß = 0.35; 95% CI: 0.02, 0.69; P = 0.03) and "fatty acids" MPs (ß = 0.45; 95% CI: 0.16, 0.74; P = 0.01), respectively. The "tea and miscellaneous" was inversely associated with the "amino acids" (ß = -0.28; 95% CI: -0.52, -0.05; P = 0.02) and "amino acid derivatives" MPs (ß = -0.21; 95% CI: -0.39, -0.02; P = 0.03). One BCP negatively modified the association between the "bread, margarine, and processed meat" DP and the "amino acids" MP (P-interaction = 0.01). CONCLUSIONS: In older German adults, DPs are reflected in MPs, and the gut bacteria attenuate 1 DP-MP association. These MPs should be explored as biomarkers of these jointly consumed foods while taking into account a potentially modifying role of the gut bacteria.

The Association between Alcohol Consumption and Serum Metabolites and the Modifying Effect of Smoking.

Alcohol consumption is an important lifestyle factor that is associated with several health conditions and a behavioral link with smoking is well established. Metabolic alterations after alcohol consumption have yet to be comprehensively investigated. We studied the association of alcohol consumption with metabolite patterns (MPs) among 2433 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, and a potential modification by smoking. Alcohol consumption was self-reported through dietary questionnaires and serum metabolites were measured by a targeted approach. The metabolites were summarized as MPs using the treelet transform analysis (TT). We fitted linear models with alcohol consumption continuously and in five categories. We stratified the continuously modelled alcohol consumption by smoking status. All models were adjusted for potential confounders. Among men, alcohol consumption was positively associated with six MPs and negatively associated with one MP. In women, alcohol consumption was inversely associated with one MP. Heavy consumers differed from other consumers with respect to the "Long and short chain acylcarnitines" MP. Our findings suggest that long and short chain acylcarnitines might play an important role in the adverse effects of heavy alcohol consumption on chronic diseases. The relations seem to depend on gender and smoking status.

Developmental trajectories of body mass index from childhood into late adolescence and subsequent late adolescence-young adulthood cardiometabolic risk markers.

BACKGROUND: Reports on body mass index (BMI) trajectories from childhood into late adolescence, their determinants, and subsequent cardiometabolic risk markers, particularly among European populations have been few. Moreover, sex-specific investigation is necessary considering the sex difference in BMI, and the sex-specific association between BMI and some cardiometabolic risk markers. METHODS: Using a sample from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study, we explored sex-specific trajectories of the BMI standard deviation score (SDS) from 4 to 18 years of age in 354 males and 335 females by latent (class) growth models. The determinants of trajectory were assessed by logistic regression. We identified cardiometabolic risk markers that were highly associated with BMI SDS trajectory by random forest regression, and finally we used generalized linear models to investigate differences in the identified cardiometabolic risk markers between pairs of trajectories. RESULTS: We observed four: 'low-normal weight', 'mid-normal weight', 'high-normal weight', and 'overweight', and three: ''low-normal weight', 'mid-normal weight', and 'high-normal weight' trajectories in males and females, respectively. Higher maternal prepregnancy BMI was associated with the 'overweight' trajectory, and with 'high-normal weight' trajectory in both sexes. In addition, employed mothers and first-born status were associated with 'high-normal weight' trajectory in females. BMI SDS trajectory was associated with high-density lipoprotein-cholesterol and interleukin-18 (IL-18) in males, and diastolic blood pressure and interleukin-6 (IL-6) in females. However, only males following the 'overweight' trajectory had significantly higher IL-18 when compared to their 'low-normal weight' counterpart. CONCLUSIONS: We identified sex-specific distinct trajectories of BMI SDS from childhood into late adolescence, higher maternal prepregnancy BMI as a common determinant of the 'high-normal weight' and 'overweight' trajectories, and 'overweight' trajectory being associated with elevated IL-18 in late adolescence-young adulthood. This study emphasizes the role of maternal prepregnancy BMI in overweight, and highlights IL-18 as a cardiometabolic signature of overweight across life.

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Association between the dietary inflammatory index and all-cause mortality in colorectal cancer long-term survivors.

Pro-inflammatory dietary factors have been shown to be associated with the incidence of a range of cancers. However, there are many fewer studies on the association between the inflammatory potential of diet and survival after cancer diagnosis. We examined the association between post-diagnosis dietary inflammatory index (DII®) scores and all-cause mortality in long-term survivors of colorectal cancer (CRC). DII scores were calculated from dietary data of 1,404 CRC survivors collected at a median of 6 years after CRC diagnosis. Using multivariable-adjusted Cox proportional hazards regression models, hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the association of DII scores, modeled continuous and in quartiles, with all-cause mortality. After a median follow-up time of 7 years (after dietary assessment), 204 study participants had died. Overall, in the fully adjusted model there was a suggestion of a positive association between DII score and all-cause mortality (HRDIIquartile4vs1 : 1.36; 95% CI: 0.88-2.09 and HRDIIcontinuous : 1.08; 95% CI: 0.97-1.20). However, in subgroup analyses, we found significant differences in individuals with metastatic disease (HRDIIcontinuous : 1.34; 95% CI: 1.07-1.67) and the absence of stoma (HRDIIcontinuous : 1.15; 95% CI: 1.02-1.29). Overall, the post-diagnosis DII was not statistically significantly associated with all-cause mortality in CRC long-term survivors; however, there was suggestive evidence of an association in select subgroups.

Health-related quality of life in long-term survivors of colorectal cancer and its association with all-cause mortality: a German cohort study.

BACKGROUND: The group of colorectal cancer (CRC) survivors continues to grow worldwide. Understanding health-related quality of life (HRQOL) determinants and consequences of HRQOL impairments in long-term CRC survivors may help to individualize survivorship care plans. We aimed to i) examine the HRQOL status of CRC long-term survivors, ii) identify cross-sectional sociodemographic and clinical correlates of HRQOL, and iii) investigate the prospective association of HRQOL after CRC diagnosis with all-cause mortality. METHODS: We assessed HRQOL within a Northern German cohort of 1294 CRC survivors at a median of 6 years after CRC diagnosis using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Cross-sectional correlates of different HRQOL dimensions were analyzed using multivariable-adjusted logistic regression models with HRQOL as a binary variable. With multivariable-adjusted Cox proportional hazards regression models, hazard ratios (HR) of all-cause mortality were estimated per 10-point-increments of an HRQOL summary score, a global quality of life scale, and HRQOL functioning and symptom domains. RESULTS: The median HRQOL summary score was 87 (interquartile range: 75-94). Sex, age, education, tumor location, metastases, other cancers, type of therapy, and current stoma were identified as correlates of different HRQOL scales. After a median follow-up time of 7 years after HRQOL assessment, 175 participants had died. Nearly all HRQOL domains, except for cognitive functioning and diarrhea, were significantly associated with all-cause mortality. A 10-point-increment in the summary score decreased the risk of death by 24% (HR: 0.76; 95% CI: 0.70-0.82). CONCLUSIONS: HRQOL in CRC survivors appeared to be relatively high in the long term. Various clinical and sociodemographic factors were cross-sectionally associated with HRQOL in long-term CRC survivors. Lower HRQOL was associated with increased all-cause mortality. Individualized healthcare programs for CRC survivors (including psychosocial screening and interventions) are needed to detect decreased HRQOL and to further improve long-term HRQOL and survival.

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.

Joint Data Analysis in Nutritional Epidemiology: Identification of Observational Studies and Minimal Requirements.

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition.

Determinants of diet and physical activity (DEDIPAC): a summary of findings.

The establishment of the Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub, 2013-2016, was the first action taken by the 'Healthy Diet for a Healthy Life' European Joint Programming Initiative. DEDIPAC aimed to provide better insight into the determinants of diet, physical activity and sedentary behaviour across the life course, i.e. insight into the causes of the causes of important, non-communicable diseases across Europe and beyond. DEDIPAC was launched in late 2013, and delivered its final report in late 2016. In this paper we give an overview of what was achieved in terms of furthering measurement and monitoring, providing overviews of the state-of-the-art in the field, and building toolboxes for further research and practice. Additionally, we propose some of the next steps that are now required to move forward in this field, arguing in favour of 1) sustaining the Knowledge Hub and developing it into a European virtual research institute and knowledge centre for determinants of behavioural nutrition and physical activity with close links to other parts of the world; 2) establishing a cohort study of families across all regions of Europe focusing specifically on the individual and contextual determinants of major, non-communicable disease; and 3) furthering DEDIPAC's work on nutrition, physical activity, and sedentary behaviour policy evaluation and benchmarking across Europe by aligning with other international initiatives and by supporting harmonisation of pan-European surveillance.

Postdiagnostic physical activity, sleep duration, and TV watching and all-cause mortality among long-term colorectal cancer survivors: a prospective cohort study.

BACKGROUND: Lifestyle recommendations for cancer survivors are warranted to improve survival. In this study, we aimed to examine the association of total physical activity, different types of physical activity, hours of sleeping at day and night, and hours spent watching television (TV) with all-cause mortality in long-term colorectal cancer (CRC) survivors. METHODS: We assessed physical activity in 1376 CRC survivors (44% women; median age, 69 years) at median 6 years after CRC diagnosis using a validated questionnaire. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) for all-cause mortality according to categories of physical activities, sleep duration, and TV watching. RESULTS: During a median follow-up time of 7 years, 200 participants had died. Higher total physical activity was significantly associated with lower all-cause mortality (HR: 0.53; 95% CI: 0.36-0.80, 4th vs. 1st quartile). Specifically, sports, walking, and gardening showed a significant inverse association with all-cause mortality (HR: 0.34; 95% CI: 0.20-0.59, HR: 0.65; 95% CI: 0.43-1.00, and HR: 0.62; 95% CI: 0.42-0.91, respectively for highest versus lowest category). Individuals with ≥2 h of sleep during the day had a significantly increased risk of all-cause mortality compared to individuals with no sleep at day (HR: 2.22; 95% CI: 1.43-3.44). TV viewing of ≥4 h per day displayed a significant 45% (95% CI: 1.02-2.06) higher risk of dying compared to ≤2 h per day of watching TV. CONCLUSIONS: Physical activity was inversely related to all-cause mortality; specific activity types might be primarily responsible for this association. More hours of sleep during the day and a higher amount of TV viewing were each associated with higher all-cause mortality. Based on available evidence, it is reasonable to recommend CRC survivors to engage in regular physical activity.

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.