Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts.

OBJECTIVE: We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professionals Follow-Up Study (1986-2016). Dietary data were collected every 2-4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance-weighted fixed-effects meta-analyses. RESULTS: During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00-1.11]) but not after additional adjustment for red meat intake (1.04 [0.99-1.10]). No evidence of association was observed between intakes of folate and diabetes. CONCLUSIONS: The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.

Towards a Swiss health study with human biomonitoring: Learnings from the pilot phase about participation and design.

BACKGROUND: A large-scale national cohort aiming at investigating the health status and determinants in the general population is essential for high-quality public health research and regulatory decision-making. We present the protocol and first results of the pilot phase to a Swiss national cohort aiming at establishing the study procedures, evaluating feasibility, and assessing participation and willingness to participate. METHODS: The pilot phase 2020/21 included 3 components recruited via different channels: a population-based cross-sectional study targeting the adult population (20-69 years) of the Vaud and Bern cantons via personal invitation, a sub-study on selenium in a convenience sample of vegans and vegetarians via non-personal invitation in vegan/vegetarian networks, and a self-selected sample via news promotion (restricted protocol). Along with a participatory approach and participation, we tested the study procedures including online questionnaires, onsite health examination, food intake, physical activity assessments and biosample collection following high-quality standards. RESULTS: The population-based study and the selenium sub-study had 638 (participation rate: 14%) and 109 participants, respectively, both with an over-representation of women. Of altogether 1349 recruited participants over 90% expressed interest in participating to a national health study, over 75% to contribute to medicine progress and help improving others' health, whereas about one third expressed concerns over data protection and data misuse. CONCLUSIONS: Publicly accessible high-quality public health data and human biomonitoring samples were collected. There is high interest of the general population in taking part in a national cohort on health. Challenges reside in achieving a higher participation rate and external validity. For project management clear governance is key.

Epidemiology and prevalence of tobacco use in Tehran; a report from the recruitment phase of Tehran cohort study.

INTRODUCTION: Tobacco use is a major health concern worldwide, especially in low/middle-income countries. We aimed to assess the prevalence of cigarette smoking, waterpipe, and pipe use in Tehran, Iran. METHODS: We used data from 8272 participants of the Tehran Cohort Study recruitment phase. Tobacco use was defined as a positive answer to using cigarettes, waterpipes, or pipes. Participants who did not report tobacco use during the interview but had a previous smoking history were categorized as former users. Age- and sex-weighted prevalence rates were calculated based on the national census data, and characteristics of current and former tobacco users were analyzed. RESULTS: Age- and sex-weighted prevalence of current tobacco users, cigarette smokers, waterpipe, and pipe users in Tehran was 19.8%, 14.9%, 6.1%, and 0.5%, respectively. Current tobacco use was higher in younger individuals (35-45 years: 23.4% vs. ≥ 75 years: 10.4%, P < 0.001) and men compared to women (32.9% vs. 7.7% P < 0.001). The prevalence of tobacco use increased with more years of education (> 12 years: 19.3% vs. illiterate: 9.7%, P < 0.001), lower body mass index (< 20 kg/m2: 31.3% vs. ≥ 35 kg/m2: 13.8%, P < 0.001), higher physical activity (high: 23.0% vs. low: 16.4%, P < 0.001), opium (user: 66.6% vs. non-user: 16.5%, P < 0.001), and alcohol use (drinker: 57.5% vs. non-drinker: 15.4%, P < 0.001). Waterpipe users were younger (46.1 vs. 53.2 years) and had a narrower gender gap in prevalence than cigarette smokers (male/female ratio in waterpipe users: 2.39 vs. cigarette smokers: 5.47). Opium (OR = 5.557, P < 0.001) and alcohol consumption (OR = 4.737, P < 0.001) were strongly associated with tobacco use. Hypertension was negatively associated with tobacco use (OR = 0.774, P = 0.005). CONCLUSION: The concerning prevalence of tobacco use in Tehran and its large gender gap for cigarette and waterpipe use warrant tailored preventive policies.

The European Academy of Neurology Brain Health Strategy: One brain, one life, one approach.

BACKGROUND AND PURPOSE: Brain health is essential for health, well-being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations. METHODS: The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non-disease-, non-age-centred holistic and positive approach ('one brain, one life, one approach') to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage. RESULTS: The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people-centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health. CONCLUSIONS: By adopting this 'one brain, one life, one approach' strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well-being of individuals is enhanced by maintaining brain health through the life course.

Effects of phytoestrogen supplementation on intermediate cardiovascular disease risk factors among postmenopausal women: a meta-analysis of randomized controlled trials.

IMPORTANCE: Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women. OBJECTIVE: Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women. EVIDENCE REVIEW: Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form. FINDINGS: In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27 mmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25 mmol/L [-0.37 to -0.13]), triglycerides (-0.20 mmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13 g/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86 ng/mL [-30.06 to -7.65]) and E-selectin (-2.32 ng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 µm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled. CONCLUSIONS AND RELEVANCE: Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health. : Video Summary: http://links.lww.com/MENO/A593.

Video Summary: http://links.lww.com/MENO/A593.

Associations between Phytoestrogens, Glucose Homeostasis, and Risk of Diabetes in Women: A Systematic Review and Meta-Analysis.

Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.

Phytoestrogen supplementation and body composition in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

Phytoestrogen-based medications are commonly used by menopausal women, and especially by obese postmenopausal women, to relieve menopausal symptoms. Substitution of animal with soy protein is often used in weight loss regimens, yet the effect of phytoestrogens, the main constituent of soy foods, on body composition is not completely understood. We conducted a systematic review and meta-analysis to investigate the associations between phytoestrogen supplementation and body weight and the main parameters of body composition in postmenopausal women. A literature search was done using 5 electronic databases from inception to April 2018. Randomized controlled trials (RCTs) with postmenopausal women comparing phytoestrogen supplementation followed by usual diet and placebo were included in the present meta-analysis. From 5932 references, we identified 23 RCTs that met our inclusion criteria, with a total of 1880 postmenopausal women. No association was observed between phytoestrogen supplementation and body weight, body mass index, waist and hip circumference, total fat mass or percentage of body fat. However, the use of phytoestrogens supplementation was associated with a slight decrease in waist-hip ratio; the pooled mean difference was -0.01 cm (95%CI: -0.01 to -0.006). In subgroup analysis, we found a modest decrease in body weight with phytoestrogens supplementation compared with placebo in healthy postmenopausal women [pooled mean difference of changes -0.28 kg (95%CI: -0.52 to -0.04)] and in RCTs with a median number of participants of 66 or less [pooled mean difference of changes -0.49 kg (95%CI: -0.87 to -0.11)]. In contrast, phytoestrogen supplementation was associated with increased body weight in postmenopausal women with preexisting metabolic disorders (prediabetes, type 2 diabetes, prehypertension and hyperlipidemia) [pooled mean difference of changes: 0.78 kg (95%CI: 0.53-1.03)]. In addition, there were some indications that some types of phytoestrogens, such as daidzein, but not soy products or isoflavone mix, could lead to modest adverse changes in body composition in menopausal women. Therefore, future studies should investigate the potential adverse effects of phytoestrogen supplementation on body composition among postmenopausal women.

Dietary patterns in an elderly population and their relation with bone mineral density: the Rotterdam Study.

PURPOSE: Our aim was to identify dietary patterns that are associated with bone mineral density (BMD) against a background of relatively high dairy intake in elderly Dutch subjects. METHODS: Participants were 55 years of age and older (n = 5144) who were enrolled in The Rotterdam Study, a population-based prospective cohort study. Baseline intake of 28 pre-defined food groups was determined using a validated food frequency questionnaire. Dietary patterns were identified using principal component analysis. BMD was measured using dual-energy X-ray absorptiometry at baseline and at three subsequent visits (between 1993 and 2004). Linear mixed modelling was used to longitudinally analyse associations of adherence to each pattern with repeatedly measured BMD (both in Z scores). RESULTS: After adjustment for confounders, two dietary patterns were associated with high BMD: a "Traditional" pattern, characterized by high intake of potatoes, meat and fat (ß = 0.06; 95 % CI 0.03, 0.09) and a "Health conscious" pattern, characterized by high intake of fruits, vegetables, poultry and fish (ß = 0.06; 95 % CI 0.04, 0.08). The "Processed" pattern, characterized by high intake of processed meat and alcohol, was associated with low BMD (ß = -0.03; 95 % CI -0.06, -0.01). Associations of adherence to the "Health conscious" and "Processed" pattern with BMD were independent of body weight and height, whereas the association between adherence to the "Traditional" pattern with BMD was not. CONCLUSIONS: Against a background of high dairy intake and independent of anthropometrics, a "Health conscious" dietary pattern may have benefits for BMD, whereas a "Processed" dietary pattern may pose a risk for low BMD.

A priori and a posteriori derived dietary patterns in infancy and cardiometabolic health in childhood: The role of body composition.

BACKGROUND & AIMS: Cardiometabolic risk has its origins in early life. However, it is unclear whether diet during early childhood is associated with cardiometabolic health, and what the role is of obesity. We aimed to study whether overall diet during early childhood is associated with cardiometabolic health and to examine if difference in body composition explain this association. METHODS: We examined associations of different types of dietary patterns in infancy with cardiometabolic health at school age among 2026 Dutch children participating in a population-based cohort in the Netherlands. Food intake at the age of 1 year was assessed with a food-frequency questionnaire. Three dietary pattern approaches were used: 1) An a priori-defined diet quality score; 2) dietary patterns based on variation in food intake, derived from principal component analysis (PCA); and 3) dietary patterns based on variations in fat and fat-free mass index, derived with reduced-rank regression (RRR). At the children's age of 6 years, we measured their body composition, systolic and diastolic blood pressure, and serum concentrations of insulin, triglycerides, and HDL-cholesterol, which we combined in a cardiometabolic risk-factor score. RESULTS: We observed that, after adjustment for confounders, children with higher adherence to a 'Health-conscious' PCA-derived pattern had a lower cardiometabolic risk-factor score (-0.07 SD (95%CI -0.12; -0.02) per SD). This association did not change after adjustment for fat and fat-free mass index. The RRR-derived dietary patterns based on variations in body composition were not associated with the cardiometabolic risk-factor score. CONCLUSIONS: Our results suggest that diet in early childhood may affect cardiometabolic health independent of differences in body composition.

Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: The Rotterdam study.

BACKGROUND & AIMS: Coffee and tea have been proposed to limit the progression of liver fibrosis in established liver disease, but it is unknown if this is also true for subclinical fibrosis. We therefore aimed to evaluate whether coffee and tea consumption are associated with liver stiffness in the general population. METHODS: The Rotterdam Study is an ongoing prospective population-based cohort. We included participants who underwent transient elastography, ultrasound and completed a food frequency questionnaire. Coffee and tea consumption were categorized into no, moderate (>0-3), or frequent (⩾3) intake (cups/day), and tea further into green, black and herbal tea (no/any). Significant fibrosis was defined as liver stiffness measurements (LSM) ⩾8.0kPa. We performed regression analyses relating coffee and tea intake with fibrosis, steatosis and log-transformed LSM and adjusted for energy, sugar and creamer intake, age, gender, BMI, steatosis/LSM, HOMA-IR, ALT, alcohol, smoking, soda, healthy diet index and physical activity. RESULTS: We included 2,424 participants (age 66.5±7.4; 43% male) of whom 5.2% had LSM ⩾8.0kPa and 34.6% steatosis. Proportion of LSM ⩾8.0kPa decreased with higher coffee consumption (7.8%, 6.9% and 4.1% for no, moderate and frequent respectively; Ptrend=0.006). This inverse association was confirmed in multivariable regression (ORmod 0.75, 95% CI 0.33-1.67; ORfreq 0.39, 95% CI 0.18-0.86; p=0.005). Amongst tea consumers, only herbal tea consumers (36.3%) had lower log-transformed LSM after adjustment (Beta-0.05, 95% CI-0.08;-0.02, p=0.001). Subtypes of tea were associated with steatosis in univariate but not multivariable analysis. CONCLUSIONS: In the general population, frequent coffee and herbal tea consumption were inversely related with liver stiffness but not steatosis. Longitudinal analyses, as well as studies validating and unravelling underlying mechanisms are needed. LAY SUMMARY: The Rotterdam Study is a large ongoing population study of suburban inhabitants of Rotterdam in whom data on liver stiffness, as proxy for liver fibrosis, presence of fatty liver on ultrasound and detailed information on coffee and tea consumption were obtained in 2,424 participants. The consumption of herbal tea and daily consumption of three or more cups of coffee was related to the presence of lower liver stiffness, independent of a great number of other lifestyle and environmental factors. Previous studies have found a protective effect of coffee on established liver disease and we now show for the first time that this effect is already measurable in the general population.

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Dietary mineral intake and lung cancer risk: the Rotterdam Study.

OBJECTIVE: Limited data are available on the role of mineral intake in the development of lung cancer (LC). We investigated whether dietary calcium, copper, iron, magnesium, selenium and zinc intake were associated with LC risk. METHODS: We analyzed data from 5435 participants of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years and older. At baseline (1990-1993), diet was measured by a validated food frequency questionnaire. LC events were diagnosed on the basis of pathology data and medical records. Hazard ratios (HRs) on LC for energy-adjusted mineral intake were calculated using Cox regression models while adjusting for potential confounders. RESULTS: During a follow-up period of 22 years, we identified 211 incident cases of LC. A higher zinc intake was associated with 42 % reduction in risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.35; 0.94, P-for trend = 0.039). Similarly, high intake of iron was associated with reduced risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.37; 0.92, P-for trend = 0.021). There was no association between dietary intake of calcium, copper, magnesium and selenium and LC risk. CONCLUSIONS: Our results suggest that dietary zinc and iron intake are associated with reduced risk of LC. No evidence was found for an association between calcium, copper, magnesium and selenium intake and LC risk.

Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.

AIMS/HYPOTHESIS: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. METHODS: We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. RESULTS: During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. CONCLUSIONS/INTERPRETATION: DHEA serum levels might be an independent marker of type 2 diabetes.

Maternal weight status, diet, and supplement use as determinants of breastfeeding and complementary feeding: a systematic review and meta-analysis.

CONTEXT: Infant feeding practices are influenced by maternal factors. OBJECTIVE: The aim of this review is to examine the associations between maternal weight status or dietary characteristics and breastfeeding or complementary feeding. DATA SOURCES: A systematic literature search of the Embase, Cochrane Library, Google Scholar, MEDLINE, PubMed, and Web of Science databases was performed. STUDY SELECTION: Interventional and cohort studies in healthy mothers and infants that reported on maternal weight status, diet, or supplement use were selected. DATA EXTRACTION: Outcomes assessed included delayed onset of lactogenesis; initiation, exclusivity, duration, and cessation of breastfeeding; and timing of complementary feeding. DATA ANALYSIS: Eighty-one studies were included. Maternal underweight, diet, and supplement use were not associated with infant feeding practices. Obese women had a relative risk of failure to initiate breastfeeding (risk ratio [RR] = 1.23; 95%CI, 1.03-1.47) and a delayed onset of lactogenesis (RR  =  2.06; 95%CI, 1.18-3.61). The RR for breastfeeding cessation was 1.11 (95%CI, 1.07-1.15) per increase in category of body mass index. CONCLUSIONS: Prevention of obesity in women of reproductive age, as well as counseling of obese women after delivery, could be targeted to improve infant feeding practices.

Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis.

IMPORTANCE: Between 40% and 50% of women in Western countries use complementary therapies to manage menopausal symptoms. OBJECTIVE: To determine the association of plant-based therapies with menopausal symptoms, including hot flashes, night sweats, and vaginal dryness. DATA SOURCES: The electronic databases Ovid MEDLINE, EMBASE, and Cochrane Central were systematically searched to identify eligible studies published before March 27, 2016. Reference lists of the included studies were searched for further identification of relevant studies. STUDY SELECTION: Randomized clinical trials that assessed plant-based therapies and the presence of hot flashes, night sweats, and vaginal dryness. DATA EXTRACTION: Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN OUTCOMES AND MEASURES: Hot flashes, night sweats, and vaginal dryness. RESULTS: In total, 62 studies were identified, including 6653 individual women. Use of phytoestrogens was associated with a decrease in the number of daily hot flashes (pooled mean difference of changes, -1.31 [95% CI, -2.02 to -0.61]) and vaginal dryness score (pooled mean difference of changes, -0.31 [95% CI, -0.52 to -0.10]) between the treatment groups but not in the number of night sweats (pooled mean difference of changes, -2.14 [95% CI, -5.57 to 1.29]). Individual phytoestrogen interventions such as dietary and supplemental soy isoflavones were associated with improvement in daily hot flashes (pooled mean difference of changes, -0.79 [-1.35 to -0.23]) and vaginal dryness score (pooled mean difference of changes, -0.26 [-0.48 to -0.04]). Several herbal remedies, but not Chinese medicinal herbs, were associated with an overall decrease in the frequency of vasomotor symptoms. There was substantial heterogeneity in quality across the available studies, and 46 (74%) of the included randomized clinical trials demonstrated a high risk of bias within 3 or more areas of study quality. CONCLUSIONS AND RELEVANCE: This meta-analysis of clinical trials suggests that composite and specific phytoestrogen supplementations were associated with modest reductions in the frequency of hot flashes and vaginal dryness but no significant reduction in night sweats. However, because of general suboptimal quality and the heterogeneous nature of the current evidence, further rigorous studies are needed to determine the association of plant-based and natural therapies with menopausal health.

Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age.

OBJECTIVE: The associations of maternal caffeine intake during pregnancy with offspring growth patterns and body fat and insulin levels at school age were examined. METHODS: In a population-based birth cohort among 7,857 mothers and their children, maternal caffeine intake during pregnancy was assessed by questionnaires. Growth characteristics were measured from birth onward. At 6 years, body fat and insulin levels were measured. RESULTS: Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years, and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. CONCLUSIONS: These results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution.

Associations of breast-feeding patterns and introduction of solid foods with childhood bone mass: The Generation R Study.

Breast-feeding has been associated with later bone health, but results from previous studies are inconsistent. We examined the associations of breast-feeding patterns and timing of introduction of solids with bone mass at the age of 6 years in a prospective cohort study among 4919 children. We collected information about duration and exclusiveness of breast-feeding and timing of introduction of any solids with postnatal questionnaires. A total body dual-energy X-ray absorptiometry scan was performed at 6 years of age, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC) and bone area (BA) were analysed. Compared with children who were ever breast-fed, those never breast-fed had lower BMD (-4·62 mg/cm2; 95 % CI -8·28, -0·97), BMC (-8·08 g; 95 % CI -12·45, -3·71) and BA (-7·03 cm2; 95 % CI -12·55, -1·52) at 6 years of age. Among all breast-fed children, those who were breast-fed non-exclusively in the first 4 months had higher BMD (2·91 mg/cm2; 95 % CI 0·41, 5·41) and aBMC (3·97 g; 95 % CI 1·30, 6·64) and lower BA (-4·45 cm2; 95 % CI -8·28, -0·61) compared with children breast-fed exclusively for at least 4 months. Compared with introduction of solids between 4 and 5 months, introduction <4 months was associated with higher BMD and aBMC, whereas introduction between 5 and 6 months was associated with lower aBMC and higher BA. Additional adjustment for infant vitamin D supplementation did not change the results. In conclusion, results from the present study suggest that ever breast-feeding compared with never breast-feeding is associated with higher bone mass in 6-year-old children, but exclusive breast-feeding for 4 months or longer was not positively associated with bone outcomes.

Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns.

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.

Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study.

BACKGROUND: It remains unclear whether serum total cholesterol is associated with colorectal cancer (CRC) risk. Interplay between dietary fatty acids and serum total cholesterol on CRC risk may be present as well. We aimed to investigate the association between serum total cholesterol with CRC. Furthermore, we investigated whether this association was modified by intake of dietary polyunsaturated fatty acids (PUFAs). METHODS: We analysed data from 6628 participants of the Rotterdam Study, a prospective population-based follow-up study among patients aged 55 years and older. Serum total cholesterol was measured at baseline. During a mean follow-up time of 12.9 years, we identified 248 new CRC cases based on pathology data and medical records. Multivariable HRs were calculated using Cox regression models. RESULTS: After adjustment, serum total cholesterol levels were associated with a higher risk of CRC (HR 1.49; 95% CI 1.08 to 2.06 for highest vs lowest tertile). Statistically significant effect modification was present for PUFAs intake (P-interaction=0.04). After stratification by median PUFAs intake, an increased risk with increasing tertiles of serum total cholesterol was observed among patients with low PUFAs intake (3rd tertile vs 1st tertile: HR 2.43; 95% CI 1.41 to 4.18), whereas no association was observed among patients with high PUFAs intake (3rd tertile vs 1st tertile: HR 0.93; 95% CI 0.55 to 1.58). CONCLUSIONS: Taken together, these findings suggest that high levels of serum total cholesterol increase CRC risk, but this risk may be reduced by high dietary PUFAs intake.

The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis.

BACKGROUND: The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated. OBJECTIVE: We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages. DESIGN: This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles. RESULTS: Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids. CONCLUSIONS: Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce.