No independent associations between preconception paternal dietary patterns and embryonic growth; the Predict Study.

Background & Aim: Several studies show the importance of periconceptional maternal dietary patterns on human embryonic growth. Healthy paternal nutrition has been associated with better semen quality and fecundability, however, evidence on the impact on pregnancy outcome is limited. Therefore, the aim of this study was to investigate the association between preconception paternal dietary patterns and first trimester embryonic growth using the parameters longitudinal crown-rump length (CRL) and embryonic volume (EV).

Use of Selective Serotonin Reuptake Inhibitors and Bone Mineral Density Change: A Population-Based Longitudinal Study in Middle-Aged and Elderly Individuals.

Background: Longitudinal studies showed conflicting results regarding the association between use of selective serotonin reuptake inhibitors (SSRIs) and bone mineral density (BMD). Therefore, we investigate the association between-duration of-SSRI use and BMD, and change in BMD ([INCREMENT]BMD).

Methods: Data from the population-based Rotterdam Study cohort (1991-2008) were used.

Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis.

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide.

Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis.

Aims: To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk.

Methods: Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively.

CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis.

Objective: To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk.

Design: Three prospective studies; the Rotterdam Study, B-PROOF, and LASA.

Setting: Community-dwelling individuals living in or near five Dutch cities.

Effects of Two-Year Vitamin B and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT.

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants ( = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B and 400 µg folic acid daily or placebo for two years.

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.

A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study.

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial.

Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study.

Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults.

Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial.

Introduction: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients.

Methods: The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50  μmol/l), treated with B-vitamins (500  μg vitamin B12 and 400  μg folic acid) or placebo for 2 years.

Cognitive Performance: A Cross-Sectional Study on Serum Vitamin D and Its Interplay With Glucose Homeostasis in Dutch Older Adults.

Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance.

Design, Setting, And Participants: Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older.

Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters.

Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial.

Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk.

Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals.

Medication-related fall incidents in an older, ambulant population: the B-PROOF study.

Background: Medication use is a potentially modifiable risk factor for falling; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk. However, evidence is mainly based on studies that recorded falls retrospectively and/or did not determine medication use at the time of the fall. Therefore, we investigated the associations indicated in the literature between medication use and falls, using prospectively recorded falls and medication use determined at the time of the fall.

Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT.

Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels.

Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet.

Non-linear associations between serum 25-OH vitamin D and indices of arterial stiffness and arteriosclerosis in an older population.

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population.

Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF Study.

Background: Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive.

Homocysteine level is associated with aortic stiffness in elderly: cross-sectional results from the B-PROOF study.

Objective: Homocysteine has been shown to be a more accurate predictor of cardiovascular mortality in very old persons than models based on classical risk factors. Arterial stiffening is a structural abnormality involved in the pathway of cardiovascular disease. We expect this underlying pathophysiology to be a possible explanation for the association between homocysteine and cardiovascular risk, particularly in older populations.