[Show abstract][Hide abstract] ABSTRACT: ObjectiveA possible association between serum 25-hydroxyvitamin D and testosterone levels has been reported, however, contradictory results have emerged.DesignTo investigate a causal link between vitamin D and testosterone status, we studied the effect of vitamin D supplementation on serum testosterone concentrations in three independent intervention studies including male patients with heart failure (study 1), male nursing home residents (study 2) and male non-western immigrants in the Netherlands (study 3).Methods
In study 1, 92 subjects were randomized to either vitamin D (2000 IU cholecalciferol daily) or control. Blood was drawn at baseline, after 3 and 6 weeks. In study 2, 49 vitamin D deficient subjects received either vitamin D (600IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks. In study 3, 43 vitamin D deficient subjects received either vitamin D (1200IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks.Serum 25-hydroxyvitamin D levels were measured using LC-MS/MS or radioimmunoassay. Testosterone levels were measured using a 2nd generation immunoassay.ResultsSerum 25-hydroxyvitamin D levels significantly increased in all treatment groups (median increase of 27, 30, and 36 nmol/L in study 1, 2, 3, respectively) but not in the control groups. The documented increase in 25-hydroxyvitamin D levels, however, did not affect mean testosterone concentrations at the end of the study (median increase of 0, 0.5, and 0 nmol/L in study 1, 2, and 3, respectively) .Conclusions
In this post-hoc analysis of 3 small clinical trials of limited duration in men with normal baseline testosterone concentrations, vitamin D supplementation was not associated with an increase in circulating testosterone concentrations.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: We investigated the reliability of physical activity monitoring based on trunk accelerometry in older adults and assessed the number of measured days required to reliably assess physical activity. Seventy-nine older adults (mean age 79.1±7.9) wore an accelerometer (DynaPort MoveMonitor, McRoberts) at the lower back during two non-consecutive weeks. The duration of locomotion, lying, sitting, standing and shuffling, movement intensity, the number of locomotion bouts and transitions to standing and the median and maximum duration of locomotion were determined per day. Using data of week 2 as reference, intraclass correlations and smallest detectable differences were calculated over an increasing number of consecutive days from week 1. Reliability was good to excellent when whole weeks were assessed. Our results indicate that a minimum of 2 days of observation are required to obtain an ICC≥0.7 for most activities, except for lying and median duration of locomotion bouts, which required up to 5 days.
Journal of aging and physical activity 01/2015; 23(1):9-17. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels.
[Show abstract][Hide abstract] ABSTRACT: Objective: Vitamin D deficiency is highly prevalent among non-western immigrants in the Netherlands and associated with poor physical performance. The aim of this study was to assess the effect of vitamin D supplementation on physical performance, exercise capacity and daily physical activity in vitamin D deficient, overweight non-western immigrants. Design: Randomized, double-blind, placebo-controlled trial. Methods: A total of 130 participants were included. Eligibility criteria included overweight (BMI > 27 kg/m2), 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/l and age 20- 65 yr. The intervention group received 1200 IU vitamin D3 daily for 4 months; the control group received placebo. Both groups received 500 mg calcium daily. Outcome measures included physical performance (physical performance score), exercise capacity (6-minutes walking test) and daily physical activity (questionnaire and accelerometer). Results: There was no significant effect on physical performance, exercise capacity or physical activity in the intention to treat analysis. In an explorative post hoc analysis restricted to participants reaching a serum 25(OH)D concentration of > 60 nmol/l after intervention, there was an improvement of 19 meter in the 6-minutes walk test compared to the placebo group (p=0.053). Conclusions: Moderate dose vitamin D supplementation did not significantly improve physical performance, exercise capacity or physical activity. However, when 25(OH)D concentrations reached > 60 nmol/l after intervention there was a borderline significant improvement of exercise capacity. Although the clinical relevance is not clear, this is a promising result, since all participants were overweight and did not improve their overall activity levels.
[Show abstract][Hide abstract] ABSTRACT: The most biologically active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has well known direct effects on osteoblast growth and differentiation in vitro. The precursor 25-hydroxyvitamin D3 (25(OH)D3) can affect osteoblast function via conversion to 1,25(OH)2D3, however, it is largely unknown whether 25(OH)D3 can affect primary osteoblast function on its own. Furthermore, 25(OH)D3 is not only converted to 1,25(OH)2D3, but also to 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) which may have bioactivity as well. Therefore we used a primary human osteoblast model to examine whether 25(OH)D3 itself can affect osteoblast function using CYP27B1 silencing and to investigate whether 24R,25(OH)2D3 can affect osteoblast function. We showed that primary human osteoblasts responded to both 25(OH)D3 and 1,25(OH)2D3 by reducing their proliferation and enhancing their differentiation by the increase of alkaline phosphatase, osteocalcin and osteopontin expression. Osteoblasts expressed CYP27B1 and CYP24 and synthesized 1,25(OH)2D3 and 24R,25(OH)2D3 dose-dependently. Silencing of CYP27B1 resulted in a decline of 1,25(OH)2D3 synthesis, but we observed no significant differences in mRNA levels of differentiation markers in CYP27B1-silenced cells compared to control cells after treatment with 25(OH)D3. We demonstrated that 24R,25(OH)2D3 increased mRNA levels of alkaline phosphatase, osteocalcin and osteopontin. In addition, 24R,25(OH)2D3 strongly increased CYP24 mRNA. In conclusion, the vitamin D metabolites 25(OH)D3, 1,25(OH)2D3 and 24R,25(OH)2D3 can affect osteoblast differentiation directly or indirectly. We showed that primary human osteoblasts not only respond to 1,25(OH)2D3, but also to 24R,25(OH)2D3 by enhancing osteoblast differentiation. This suggests that 25(OH)D3 can affect osteoblast differentiation via conversion to the active metabolite 1,25(OH)2D3, but also via conversion to 24R,25(OH)2D3. Whether 25(OH)D3 has direct actions on osteoblast function needs further investigation.
PLoS ONE 10/2014; 9(10):e110283. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control.The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus.Methods/design: In a randomised double-blind placebo-controlled trial conducted in five general practices in the Netherlands three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are randomised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and six months. Secondary outcome measures include blood pressure, anthropometric parameters, lipid profile, insulin resistance, quality of life, advanced glycation end products and safety profiles. Quality of life will be measured by The Short Form (SF-36) Health Survey questionnaire. Advanced glycation end products are measured by an AGE-reader.
[Show abstract][Hide abstract] ABSTRACT: 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. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status.
[Show abstract][Hide abstract] ABSTRACT: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance.OBJECTIVE : We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes.DESIGN : The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome.RESULTS : Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040).CONCLUSIONS: Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827.
American Journal of Clinical Nutrition 06/2014; · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vitamin D status can be assessed by measuring concentrations of 25-hydroxyvitamin D (25(OH)D). Sunlight is the most important source of vitamin D and stimulates the production of vitamin D3 in the skin during the summer, depending on age, skin pigmentation, clothing style, and sunscreen use. Seasonal variation in serum 25(OH)D is between 10 and 20 nmol/L in adults and almost absent in nursing home residents. Sunscreen use decreases, but does not abolish, vitamin D production in the skin. Clothing style has a large influence on vitamin D production. Furthermore, vitamin D status can be improved by ingestion of fatty fish and the fortification of milk or orange juice. A high dietary calcium intake has a vitamin D-sparing effect, because it increases the half-life of 25(OH)D. A combination of sunlight exposure, nutrition, food fortification, and supplements is desirable to obtain sufficient vitamin D status in the population of most countries throughout the year.
Annals of the New York Academy of Sciences 05/2014; · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of osteocalcin (OC) in cardiovascular disease (CVD) is unresolved. We aimed to study the association between plasma OC concentrations and risk of non-fatal and fatal CVD. We also aimed to investigate whether such an association, if present, would be mediated by established metabolic risk factors.
Population-based longitudinal cohort study.
OC was determined in blood samples drawn in 1995/96 in n=1319 subjects aged 65-88 years participating in the Longitudinal Aging Study Amsterdam. Self-reported CVD events were collected every 3 years up to 2005/06, and CVD deaths until 1.1.2007. Cox proportional hazards regression was performed, considering potential confounders (smoking, physical activity, body mass index) and mediators (blood pressure, plasma triglycerides, total and HDL cholesterol, fructosamine and aortic calcification).
During median 4.1 years follow-up, 709 subjects (53.8%) suffered a CVD event. There was no overall association between OC and CVD: Hazard ratio (HR) 0.97 (95% CI 0.90-1.04) per nmol/l higher plasma OC, adjusted for age and sex. There was statistical interaction between plasma OC, age and sex on CVD (p=0.014). In those >=75 years, age-adjusted HRs (95% CI) were 0.86 (0.75-0.99) in men and 1.16 (1.03-1.31) in women per nmol/l higher plasma OC. Adjustment for covariates only slightly attenuated the association in older-old men, but did not affect the association in older-old women.
Higher plasma OC was associated with reduced CVD risk in older-old men, and with increased CVD risk in older-old women. We found no evidence that this was mediated by arterial calcification or metabolic risk factors.
European Journal of Endocrinology 05/2014; · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Guidelines for cross-sex hormone treatment of transsexual people are now in place. However, little attention has been paid to the issue of treatment suitability for older people. Does existing treatment need to be adapted as subjects age, and does it make a difference if treatment is only started when the subject is already older?
To assess the necessity of adapting cross-sex hormone administration for elderly transsexual people.
Risks/benefits of continued use of cross-sex hormones with regard to bone health, cardiovascular risks, and malignancies.
Due to lack of data on the subject population, sex hormone treatment of other conditions in older non-transsexual people has been taken as the best available analogy to determine the extent to which these might be applicable to comparable transsexual persons. Findings in transsexual people receiving cross-sex hormone treatment sometimes modified the above approach of applying guidelines for the elderly to the aging transsexual population.
Testosterone administration to female-to-male transsexual persons (FtoM) carries little risk with regard to cardiovascular disease and cancer. For those with high hematocrit or cardiac insufficiency the dose can be reduced. Administration of estrogens to male-to-female transsexual persons (MtoF), particularly when combined with progestins, does significantly increase the risk of developing cardiovascular disease (almost a twofold incidence compared with the general population). This may require dose adjustment or changing from oral to safer transdermal estrogens. Tumors of the breasts, prostate and pituitary may occur. In FtoM, breast cancer can occur even after breast ablation. Older subjects can commence cross-sex hormone treatment without disproportionate risks.
Cross-sex hormones may be continued into old age but monitoring for cardiovascular disease and malignancies, both of the old and new sex, is recommended. MtoF will have more health complications in old age than FtoM requiring adaptations of treatment. Gooren L and Lips P. Conjectures concerning cross-sex hormone treatment of aging transsexual persons. J Sex Med **;**:**-**.
Journal of Sexual Medicine 04/2014; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vitamin D deficiency is associated with fractures. This relationship is biologically plausible. The results of 19 randomized clinical trials with vitamin D with or without calcium show varying results: a decreased fracture incidence in 7, neutral in 10 trials, whereas 2 trials with a high dose of vitamin D once per year showed an increased fracture incidence. In three out of four well-powered trials that used recommended doses of vitamin D 700-1000 IU per day, vitamin D supplementation did not significantly influence fracture risk. In one of these trials, a statistically significant fracture reduction was observed in nursing home residents having severe vitamin D deficiency, low calcium intake and good compliance. Thirteen meta-analyses were done, and 11 of these showed a significantly decreased fracture incidence in the supplemented groups. Vitamin D alone was not effective, studies combining vitamin D and calcium showed inconsistent results. Analyses for vertebral fractures were negative in all cases. In conclusion, a vitamin D supplement of 800 IU per day in combination with calcium may decrease the incidence of non-vertebral fractures, especially in persons in the older age groups having low-baseline vitamin D status and low calcium intake and showing good compliance.
[Show abstract][Hide abstract] ABSTRACT: Vitamin D status is currently diagnosed by measuring serum 25-hydroxyvitamin D [25(OH)D].
This study aimed to develop a risk profile that can be used to easily identify older individuals at high risk of vitamin D deficiency.
This study was performed within the Longitudinal Aging Study Amsterdam, an ongoing cohort study in a representative sample of the Dutch older population (n = 1509 for the development sample and n = 1100 for the validation sample). Prediction models for serum 25(OH)D concentrations <50 and <30 nmol/L were developed by using backward logistic regression. Risk scores were calculated by dividing the individual regression coefficients by the regression coefficient with the lowest β to create simple scores.
Serum 25(OH)D concentrations <50 and <30 nmol/L were present in 46.2% and 17.5% of participants, respectively. The model for the prediction of concentrations <50 nmol/L consisted of 13 easily assessable predictors, whereas the model for concentrations <30 nmol/L contained 10 predictors. The resulting areas under the curve (AUCs) were 0.78 and 0.80, respectively. The AUC in the external validation data set was 0.71 for the <50-nmol/L model. At a cutoff of 58 in total risk score (range: 8-97), the model predicted concentrations <50 nmol/L with a sensitivity of 61% and a specificity of 82%, whereas these values were 61% and 84%, respectively, at a cutoff of 110 in the total risk score (range: 6-204) in the model for concentrations <30 nmol/L.
Two total risk scores, including 13 or 10 predictors that can easily be assessed, were developed and are able to predict serum 25(OH)D concentrations <50 and <30 nmol/L accurately. These risk scores may be useful in clinical practice to identify persons at risk of vitamin D deficiency.
American Journal of Clinical Nutrition 02/2014; · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10− 8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 × 10− 8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2 = 57%; Qhet p = 0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate which parameters of physical functioning are associated with bone quality and fracture risk and whether gender-specific differences exist within these associations. We studied 1,486 participants of the Longitudinal Aging Study Amsterdam. As measures of physical functioning, handgrip strength, physical performance, and level of physical activity were assessed. To assess bone quality, broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at baseline using quantitative ultrasound and bone mineral density (BMD) at baseline and after 3 years by dual-energy X-ray absorptiometry. In addition, fracture incidence over 6 years was assessed. After adjustment for confounders (age, serum 25[OH]D, smoking, and body weight), in men, physical performance was positively related to BUA, SOS, and BMD cross-sectionally and to BMD longitudinally. Using Cox proportional hazards model, in men higher handgrip strength and physical performance were associated with reduced fracture risk after adjustment for confounders (hazard ratio [HR] 0.96, 95 % confidence interval [CI] 0.92-0.99, and HR 0.89, 95 % CI 0.80-0.98, respectively). In women, a moderate level of physical activity was related to reduced fracture risk (HR 0.57, 95 % CI 0.33-0.99). In conclusion, in men, higher handgrip strength and physical performance are related to higher bone quality and reduced fracture risk, whereas in women, a moderate to high level of physical activity is associated with reduced fracture risk. These measurements may contribute to the identification of individuals at high fracture risk. Both the causality of and explanations for gender-specific differences in these relationships remain subject to further studies.
Calcified Tissue International 01/2014; · 2.75 Impact Factor