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Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

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Challenges to Quantify Total Vitamin Activity: How to Combine the Contribution of Diverse Vitamers?
Jakobsen, Jette ; Melse-Boonstra, Alida ; Rychlik, Michael - \ 2019
Current Developments in Nutrition 3 (2019)10. - ISSN 2475-2991
folate - foods - total vitamin activity - vitamer - Vitamin A - Vitamin D

This state-of-the-art review aims to highlight the challenges in quantifying vitamin activity in foods that contain several vitamers of a group, using as examples the fat-soluble vitamins A and D as well as the water-soluble folate. The absorption, metabolism, and physiology of these examples are described along with the current analytical methodology, with an emphasis on approaches to standardization. Moreover, the major food sources for the vitamins are numerated. The article focuses particularly on outlining the so-called SLAMENGHI factors influencing a vitamer's' ability to act as a vitamin, that is, molecular species, linkage, amount, matrix, effectors of absorption, nutrition status, genetics, host-related factors, and the interaction of these. After summarizing the current approaches to estimating the total content of each vitamin group, the review concludes by outlining the research gaps and future perspectives in vitamin analysis. There are no standardized methods for the quantification of the vitamers of vitamin A, vitamin D, and folate in foods. For folate and β-carotene, a difference in vitamer activity between foods and supplements has been confirmed, whereas no difference has been observed for vitamin D. For differences in vitamer activity between provitamin A carotenoids and retinol, and between 25-hydroxyvitamin D and vitamin D, international consensus is lacking. The challenges facing each of the specific vitamin communities are the gaps in knowledge about bioaccessibility and bioavailability for each of the various vitamers. The differences between the vitamins make it difficult to formulate a common strategy for assessing the quantitative differences between the vitamers. In the future, optimized stationary digestive models and the more advanced dynamic digestive models combined with in vitro models for bioavailability could more closely resemble in vivo results. New knowledge will enable us to transfer nutrient recommendations into improved dietary advice to increase public health throughout the human life cycle.

Vitamin D-related genes, blood vitamin D levels and colorectal cancer risk in western european populations
Fedirko, Veronika ; Mandle, Hannah B. ; Zhu, Wanzhe ; Hughes, David J. ; Siddiq, Afshan ; Ferrari, Pietro ; Romieu, Isabelle ; Riboli, Elio ; Bueno-de-Mesquita, Bas ; Duijnhoven, Fränzel J.B. Van; Siersema, Peter D. ; Tjønneland, Anne ; Olsen, Anja ; Perduca, Vittorio ; Carbonnel, Franck ; Boutron-Ruault, Marie Christine ; Kühn, Tilman ; Johnson, Theron ; Krasimira, Aleksandrova ; Trichopoulou, Antonia ; Makrythanasis, Periklis ; Thanos, Dimitris ; Panico, Salvatore ; Krogh, Vittorio ; Sacerdote, Carlotta ; Skeie, Guri ; Weiderpass, Elisabete ; Colorado-Yohar, Sandra ; Sala, Núria ; Barricarte, Aurelio ; Sanchez, Maria Jose ; Quirós, Ramón ; Amiano, Pilar ; Gylling, Björn ; Harlid, Sophia ; Perez-Cornago, Aurora ; Heath, Alicia K. ; Tsilidis, Konstantinos K. ; Aune, Dagfinn ; Freisling, Heinz ; Murphy, Neil ; Gunter, Marc J. ; Jenab, Mazda - \ 2019
Nutrients 11 (2019)8. - ISSN 2072-6643
Colorectal neoplasms - Incidence - Single nucleotide polymorphism (SNP) - Vitamin D

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β(TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults
Hangelbroek, Roland W.J. ; Vaes, Anouk M.M. ; Boekschoten, Mark V. ; Verdijk, Lex B. ; Hooiveld, Guido J.E.J. ; Loon, Luc J.C. van; Groot, Lisette C.P.G.M. De; Kersten, Sander - \ 2019
BMC Geriatrics 19 (2019). - ISSN 1471-2318
25-hydroxyvitamin D - older adults - skeletal muscle - transcriptomics - Vitamin D

Objective: Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. Methods: A double-blind placebo-controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group and the calcifediol group (10 μg per day). Muscle biopsies were obtained before and after 6 months of calcifediol (n = 10) or placebo (n = 12) supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Results: Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies, with Ct values exceeding 30. Blood 25-hydroxycholecalciferol levels were significantly higher after calcifediol supplementation (87.3 ± 20.6 nmol/L) than after placebo (43.8 ± 14.1 nmol/L). No significant difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak, as indicated by the fact that correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any reasonable cut-offs (all q-values ~ 1). P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Conclusion: Calcifediol supplementation did not significantly affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults. Trial registration: This study was registered at as NCT02349282 on January 28, 2015.

Calcifediol supplementation to reduce pulse pressure in a limited sample of vitamin D deficient older adults with elevated parathyroid hormone levels
Grootswagers, Pol ; Vaes, Anouk M.M. ; Tieland, Michael ; Groot, Lisette C.P.G.M. de - \ 2019
Clinical Nutrition Experimental 24 (2019). - ISSN 2352-9393 - p. 77 - 82.
Older adults - Parathyroid hormone - Pulse pressure - Randomized clinical trial - Vitamin D

Vitamin D is proposed as an antihypertensive agent, but current evidence is inconclusive. Calcifediol is more potent in raising vitamin D status. It might, therefore, be more effective in lowering pulse pressure than cholecalciferol especially in patients with low vitamin D status and high levels of parathyroid hormone (PTH). This study investigated the efficacy of calcifediol on pulse pressure in older adults with vitamin D deficiency and elevated PTH levels. Supplementation with 15 μg calcifediol resulted in lower pulse pressure (Δ 35.4 mm Hg, 95%CI: 4.8, 66.1 mm Hg, P = 0.021) and PTH levels (Δ 1.83 pmol/l, 95%CI: −0.1, 3.7 pmol/l, P = 0.065) compared to 5 μg calcifediol. These effects were observed in a limited sample size of 16 older adults and therefore need confirmation in a larger trial. In conclusion, supplementation with 15 μg calcifediol might be an effective way to reduce pulse pressure in elderly with vitamin D deficiency and elevated PTH levels.

Bovine lactoferrin enhances TLR7-mediated responses in plasmacytoid dendritic cells in elderly women : Results from a nutritional intervention study with bovine lactoferrin, GOS and Vitamin D
Splunter, Marloes van; Perdijk, Olaf ; Fick-Brinkhof, Henriëtte ; Feitsma, Anouk L. ; Floris-Vollenbroek, Esther G. ; Meijer, Ben ; Brugman, Sylvia ; Savelkoul, Huub F.J. ; Hoffen, Els van; Neerven, R.J.J. van - \ 2018
Frontiers in Immunology 9 (2018). - ISSN 1664-3224
aging - bovine lactoferrin - GOS - inflammation - mDCs - pDCs - TLR stimulation - Vitamin D

During aging the immune system is dysregulated. Especially plasmacytoid dendritic cells (pDCs) and myeloid DCs (mDCs) have reduced Toll like receptor (TLR)-mediated responses resulting in increased susceptibility to infections. Consumption of bovine lactoferrin (bLF) has been shown to reduce infections with viruses. Galacto-oligosacharides (GOS) and Vitamin D are associated with reduced pro-inflammatory cytokine levels in serum, and increased TLR7/8 responses, respectively. A double-blind placebo-controlled nutritional intervention study in elderly women was performed, to investigate the potential of bLF, GOS, and Vitamin D to restore TLR responsiveness of pDCs and mDCs and to reduce inflammatory markers in serum. The nutritional intervention group (n = 15) received bLF for 3 weeks, followed by 3 weeks of bLF + GOS, and subsequently 3 weeks of bLF + GOS + Vitamin D. The placebo group (n = 15) received maltodextrin for 9 weeks. Every 3 weeks, blood was collected and TLR responses of pDCs and mDCs, and inflammation-related markers in serum were measured. After 3 weeks of bLF supplementation, increased TLR7/8 and TLR1/2 responses were observed in pDCs of the nutritional intervention group compared to the placebo group. When the effects of the entire nutritional intervention were investigated, increased TLR1/2 mediated responses in mDCs were observed, and in serum sVCAM tended to decrease. Finally, based on the RAND-36 questionnaire physical function tended to improve in the intervention group. Since especially TLR7-mediated responses in pDCs were enhanced after bLF supplementation compared to placebo, this suggests that bLF may contribute to antiviral responses mediated by pDC in elderly women.

Prediagnostic serum Vitamin D levels and the risk of Crohn's disease and ulcerative colitis in european populations : A nested case-control study
Opstelten, Jorrit L. ; Chan, Simon S.M. ; Hart, Andrew R. ; Schaik, Fiona D.M. Van; Siersema, Peter D. ; Lentjes, Eef G.W.M. ; Khaw, Kay Tee ; Luben, Robert ; Key, Timothy J. ; Boeing, Heiner ; Bergmann, Manuela M. ; Overvad, Kim ; Palli, Domenico ; Masala, Giovanna ; Racine, Antoine ; Carbonnel, Franck ; Boutron-Ruault, Marie Christine ; Tjønneland, Anne ; Olsen, Anja ; Andersen, Vibeke ; Kaaks, Rudolf ; Kuhn, Tilman ; Tumino, Rosario ; Trichopoulou, Antonia ; Peeters, Petra H.M. ; Verschuren, W.M.M. ; Witteman, Ben J.M. ; Oldenburg, Bas - \ 2018
Inflammatory Bowel Diseases 24 (2018)3. - ISSN 1078-0998 - p. 633 - 640.
Crohn's disease - etiology - inflammatory bowel disease - ulcerative colitis - Vitamin D

Background A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.

Supplement use and dietary sources of folate, vitamin D, and n-3 fatty acids during preconception : The GLIMP2 study
Looman, Moniek ; Berg, Claudia van den; Geelen, Anouk ; Samlal, Rahul A.K. ; Heijligenberg, Rik ; Klein Gunnewiek, Jacqueline M.T. ; Balvers, Michiel G.J. ; Leendertz-Eggen, Caroline L. ; Wijnberger, Lia D.E. ; Feskens, Edith J.M. ; Brouwer-Brolsma, Elske M. - \ 2018
Nutrients 10 (2018)8. - ISSN 2072-6643
Diet - Folate - N-3 fatty acids - Preconception - Supplements - Vitamin D

An adequate nutritional status during the preconception period is important, particularly for folate, vitamin D, and n-3 fatty acids (i.e., EPA+DHA). We aimed to determine supplement intake and the main dietary sources of folate, vitamin D, and EPA+DHA using the data of 66 Dutch women aged 18–40 years who wished to become pregnant. Additionally, associations of these intakes with their blood levels were examined. Dietary intake was assessed with a validated food frequency questionnaire, and supplement use with a structured questionnaire. 25-hydroxyvitamin D levels were determined in serum and folate and phospholipid EPA+DHA levels in plasma. Partial Spearman’s correlations, restricted cubic splines and trend analyses over tertiles of nutrient intakes were performed to examine intake-status associations. A large proportion of women did not meet the Dutch recommended intakes of folate (50%), vitamin D (67%), and EPA+DHA (52%). Vegetables were the main contributor to dietary folate intake (25%), oils and fats to dietary vitamin D intake (39%), and fish to dietary EPA+DHA intake (69%). Fourteen percent of the women had an inadequate folate status and 23% an inadequate vitamin D status. Supplemental folate intake, supplemental and dietary vitamin D intake and dietary EPA+DHA intake were significantly associated with their blood levels. In conclusion, even in our highly educated population, a large proportion did not achieve recommended folate, vitamin D and n-3 fatty acid intakes. Promotion of folate and vitamin D supplement use and fish consumption is needed to improve intakes and blood levels of these nutrients in women who wish to become pregnant.

Single nucleotide polymorphisms in the vitamin D receptor gene (VDR) may have an impact on acute pancreatitis (AP) development : A prospective study in populations of AP patients and alcohol-abuse controls
Cieślińska, Anna ; Kostyra, Elżbieta ; Fiedorowicz, Ewa ; Snarska, Jadwiga ; Kordulewska, Natalia ; Kiper, Krzysztof ; Savelkoul, Huub F.J. - \ 2018
International Journal of Molecular Sciences 19 (2018)7. - ISSN 1661-6596
Acute pancreatitis - Polymorphism - SNP analysis - Vitamin D - Vitamin D receptor

Vitamin D imbalance is suggested to be associated with the development of pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but not yet in pancreatitis. The aim of this study was to explore possible associations of the four SNPs in the VDR receptor gene in a population of acute pancreatitis patients and alcohol-abuse controls, and to investigate the association with acute pancreatitis (AP) susceptibility. The study population (n = 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse control group (n = 110). All patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI: 1.68–4.03; p < 0.0001) to be almost three times more frequent in the AP group compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in the vitamin D receptor may have an impact on the development of acute pancreatitis due to the lack of the protective role of vitamin D.

The association between 25-hydroxyvitamin D concentration, physical performance and frailty status in older adults
Vaes, Anouk M.M. ; Brouwer-Brolsma, Elske M. ; Toussaint, Nicole ; Regt, Margot de; Tieland, Michael ; Loon, Luc J.C. van; Groot, Lisette C.P.G.M. de - \ 2018
European Journal of Nutrition 58 (2018). - ISSN 1436-6207 - p. 1173 - 1181.
25-Hydroxyvitamin D - Frailty - Muscle strength - Physical performance - Vitamin D
Purpose: Sufficient 25-hydroxyvitamin D (25(OH)D) concentrations might prevent a decline in physical performance, and are considered important for the prevention of frailty. This study investigates the association of serum 25(OH)D concentration with physical performance and frailty status in Dutch older adults. Methods: This cross-sectional study included 756 men and women, aged ≥ 65 years. Serum 25(OH)D concentration and frailty status (Fried criteria) were assessed in the total population. Screening for frailty status included functional tests of gait speed and hand grip strength. In a subgroup (n = 494), the Timed Up and Go test (TUG) and knee-extension strength were measured. Associations of serum 25(OH)D status with physical performance were examined by multiple linear regression. Prevalence ratios (PR) were used to quantify associations between serum 25(OH)D deficiency (< 50 nmol/L) and frailty. Results: In total, 45% of the participants were vitamin D deficient. Participants with vitamin D status < 50 and 50–75 nmol/L had significantly lower scores on the TUG and gait speed test, compared to participants with vitamin D status > 75 nmol/L. No significant associations with serum 25(OH)D concentrations were observed for handgrip strength or knee-extension strength. Participants with serum 25(OH)D status < 50 nmol/L were about two times more likely to be frail compared to participants with serum 25(OH)D status ≥ 50 nmol/L. No significant associations were observed between the pre-frail state and serum 25(OH)D status. Conclusion: In this study, serum 25(OH)D concentrations were significantly associated with frailty status and measures of physical performance, including gait speed and TUG, but not with strength-related outcomes.
Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
Duijnhoven, Fränzel J.B. van; Jenab, Mazda ; Hveem, Kristian ; Siersema, Peter D. ; Fedirko, Veronika ; Duell, Eric J. ; Kampman, Ellen ; Halfweeg, Anouk ; Kranen, Henk J. van; Ouweland, Jody M.W. van den; Weiderpass, Elisabete ; Murphy, Neil ; Langhammer, Arnulf ; Ness-Jensen, Eivind ; Olsen, Anja ; Tjønneland, Anne ; Overvad, Kim ; Cadeau, Claire ; Kvaskoff, Marina ; Boutron-Ruault, Marie Christine ; Katzke, Verena A. ; Kühn, Tilman ; Boeing, Heiner ; Trichopoulou, Antonia ; Kotanidou, Anastasia ; Kritikou, Maria ; Palli, Domenico ; Agnoli, Claudia ; Tumino, Rosario ; Panico, Salvatore ; Matullo, Giuseppe ; Peeters, Petra ; Brustad, Magritt ; Olsen, Karina Standahl ; Lasheras, Cristina ; Obón-Santacana, Mireia ; Sánchez, María José ; Dorronsoro, Miren ; Chirlaque, Maria Dolores ; Barricarte, Aurelio ; Manjer, Jonas ; Almquist, Martin ; Renström, Frida ; Ye, Weimin ; Wareham, Nick ; Khaw, Kay Tee ; Bradbury, Kathryn E. ; Freisling, Heinz ; Aune, Dagfinn ; Norat, Teresa ; Riboli, Elio ; Bueno-de-Mesquita, H.B. - \ 2018
International Journal of Cancer 142 (2018)6. - ISSN 0020-7136 - p. 1189 - 1201.
Cancer epidemiology - Nested case-control study - Pancreatic cancer - Vitamin D
Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
Supplemental protein from dairy products increases body weight and vitamin D improves physical performance in older adults : a systematic review and meta-analysis
Dewansingh, Priya ; Melse-Boonstra, Alida ; Krijnen, Wim P. ; Schans, Cees P. van der; Jager-Wittenaar, Harriët ; Heuvel, Ellen G.H.M. van den - \ 2018
Nutrition Research 49 (2018). - ISSN 0271-5317 - p. 1 - 22.
Aged - Nutritional status - Physical fitness - Protein - Vitamin D
The purpose of these systematic review and meta-analysis was to assess the effectiveness of dairy components on nutritional status and physical fitness in older adults, as evidence for efficacy of the supplementation of these components is inconclusive. Scopus and MEDLINE were searched. Main inclusion criteria for articles were as follows: double-blind, randomized, placebo-controlled trials including participants aged ≥55 years who received dairy components or a placebo. Outcome measures were nutrient status (body weight and body mass index) and physical fitness (body composition, muscle strength, and physical performance). Thirty-six trials with 4947participants were included. Most trials investigated protein and vitamin D supplementation and showed no effect on the outcomes. Meta-analysis on the effect of protein on body weight showed a significant increase in mean difference of 1.13 kg (95% confidence interval, 0.59-1.67). This effect increased by selecting trials with study a duration of 6 months in which less nourished and physically fit participants were included. Trials where the participants were (pre-)frail, inactive older adults or when supplementing ≥20 g of protein per day tended to increase lean body mass. Only small significant effects of vitamin D supplementation on Timed Up and Go (mean difference –0.75 seconds; 95% confidence interval –1.44 to −0.07) were determined. This effect increased when vitamin D doses ranged between 400 and 1000 IU. Additional large randomized controlled trials of ≥6 months are needed regarding the effect of dairy components containing an adequate amount of vitamin D (400-1000 IU) and/or protein (≥20 g) on nutritional status and physical fitness in malnourished or frail older adults.
A comparison of UVb compact lamps in enabling cutaneous vitamin D synthesis in growing bearded dragons
Diehl, J.J.E. ; Baines, F.M. ; Heijboer, A.C. ; Leeuwen, J.P. van; Kik, M. ; Hendriks, W.H. ; Oonincx, D.G.A.B. - \ 2018
Journal of Animal Physiology and Animal Nutrition 102 (2018)1. - ISSN 0931-2439 - p. 308 - 316.
25(OH)D - Lizard - Pogona vitticeps - Reptile - Ultraviolet light - Vitamin D - Vitamin D metabolites

The effect of exposure to different UVb compact lamps on the vitamin D status of growing bearded dragons (Pogona vitticeps) was studied. Forty-two newly hatched bearded dragons (<24 h old) were allocated to six treatment groups (n = 7 per group). Five groups were exposed to different UVb compact lamps for two hours per day, with a control group not exposed to UVb radiation. At 120 days of age, blood samples were obtained and concentrations of 25(OH)D3, Ca, P and uric acid were determined. In addition, plasma 25(OH)D3 concentration was determined in free-living adult bearded dragons to provide a reference level. Only one treatment resulted in elevated levels of 25(OH)D3 compared to the control group (41.0 ± 12.85 vs. 2.0 ± 0.0 nmol/L). All UVb-exposed groups had low 25(OH)D3 plasma levels compared to earlier studies on captive bearded dragons as well as in comparison with the free-living adult bearded dragons (409 ± 56 nmol/L). Spectral analysis indicated that all treatment lamps emitted UVb wavelengths effective for some cutaneous vitamin D synthesis. None of these lamps, under this regime, appeared to have provided a sufficient UVb dose to enable synthesis of plasma 25(OH)D3 levels similar to those of free-living bearded dragons in their native habitat.

Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites : A randomized controlled trial in older adults
Vaes, Anouk M.M. ; Tieland, Michael ; Regt, Margot F. de; Wittwer, Jonas ; Loon, Luc J.C. van; Groot, Lisette C.P.G.M. de - \ 2018
Clinical Nutrition 37 (2018)3. - ISSN 0261-5614 - p. 808 - 814.
25-Hydroxyvitamin D - Calcifediol - Dose-response - PTH - Supplementation - Vitamin D

Background & aims: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. Methods: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. Results: Supplementation with 20 μg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. Conclusions: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. Trial registration number: NCT01868945.

Vitamin D receptor gene polymorphisms associated with childhood autism
Ciéslińska, Anna ; Kostyra, Elzbieta ; Chwała, Barbara ; Moszyńska-Dumara, Małgorzata ; Fiedorowicz, Ewa ; Teodorowicz, Gosia ; Savelkoul, Huub F.J. - \ 2017
Brain Sciences 7 (2017)9. - ISSN 2076-3425
Autism - Polymorphism - Receptor - SNP analysis - Vitamin D
Background: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Methods: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. Results: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3concentration in serum of ASD children. Conclusion: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3metabolism, while vitamin D3levels were not significantly different between ASD and non-ASD children.
Evidence-Based Reptile Housing and Nutrition
Oonincx, Dennis ; Leeuwen, Jeroen van - \ 2017
Veterinary Clinics of North America - Exotic Animal Practice 20 (2017)3. - ISSN 1094-9194 - p. 885 - 898.
Enrichment - Nutrition - Reptiles - Ultraviolet light - Vitamin D - Welfare - 017-4031
The provision of a good light source is important for reptiles. For instance, ultraviolet light is used in social interactions and used for vitamin D synthesis. With respect to housing, most reptilians are best kept pairwise or individually. Environmental enrichment can be effective but depends on the form and the species to which it is applied. Temperature gradients around preferred body temperatures allow accurate thermoregulation, which is essential for reptiles. Natural distributions indicate suitable ambient temperatures, but microclimatic conditions are at least as important. Because the nutrient requirements of reptiles are largely unknown, facilitating self-selection from various dietary items is preferable.
Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
Manousaki, Despoina ; Dudding, Tom ; Haworth, Simon ; Hsu, Yi Hsiang ; Liu, Ching Ti ; Medina-Gómez, Carolina ; Voortman, Trudy ; Velde, Nathalie Van Der; Melhus, Håkan ; Vandenput, Liesbeth ; Noordam, Raymond ; Forgetta, Vincenzo ; Greenwood, Celia M.T. ; Biggs, Mary L. ; Psaty, Bruce M. ; Rotter, Jerome I. ; Zemel, Babette S. ; Mitchell, Jonathan A. ; Taylor, Bruce ; Lorentzon, Mattias ; Karlsson, Magnus ; Jaddoe, Vincent W.V. ; Tiemeier, Henning ; Campos-Obando, Natalia ; Franco, Oscar H. ; Utterlinden, Andre G. ; Broer, Linda ; Schoor, Natasja M. van; Ham, Annelies C. ; Ikram, Arfan M.A. ; Karasik, David ; Mutsert, Renée De; Rosendaal, Frits R. ; Heijer, Martin den; Wang, Thomas J. ; Lind, Lars ; Orwoll, Eric S. ; Mook-Kanamori, Dennis O. ; Michaëlsson, Karl ; Kestenbaum, Bryan ; Ohlsson, Claes ; Mellström, Dan ; Groot, Lisette C.P.G.M. de; Grant, Struan F.A. ; Kiel, Douglas P. ; Zillikens, M.C. ; Rivadeneira, Fernando ; Sawcer, Stephen ; Timpson, Nicholas J. ; Richards, J.B. - \ 2017
American Journal of Human Genetics 101 (2017)2. - ISSN 0002-9297 - p. 227 - 238.
GWAS - Low-frequency genetic variants - Multiple sclerosis - Vitamin D
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. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10-88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 × 10-12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 × 10-5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
The impact of maternal vitamin D status on offspring brain development and function : A systematic review
Pet, Milou A. ; Brouwer-Brolsma, Elske M. - \ 2016
Advances in Nutrition 7 (2016)4. - ISSN 2161-8313 - p. 665 - 678.
25(OH)D - Brain - Cognition - Developmental - Maternal - Neuropsychological - Prenatal - Vitamin D

Various studies have examined associations between maternal vitamin D (VD) deficiency and offspring health, including offspring brain health. The purpose of this review was to summarize current evidence concerning the impact of maternal VD deficiency on brain development and function in offspring. A systematic search was conducted within Medline (on Ovid) for studies published through 7 May 2015. Animal and human studies that examined associations between maternal VD status or developmental VD deficiency and offspring brain development and function were included. A total of 26 animal studies and 10 human studies met the inclusion criteria. Several animal studies confirmed the hypothesis that low prenatal VD status may affect brain morphology and physiology as well as behavioral outcomes. In humans, subtle cognitive and psychological impairments in offspring of VD-deficient mothers were observed. However, data obtained from animal and human studies provide inconclusive evidence, and results seem to depend on strain or race and age of offspring. To conclude, prenatal VD status is thought to play an important role in brain development, cognitive function, and psychological function. However, results are inconclusive; validation of these findings and investigation of underlying mechanisms are required. Thus, more investigation is needed before recommending supplementation of VD during pregnancy to promote brain health of offspring.

Vitamin D deficiency as adverse drug reaction? A cross-sectional study in Dutch geriatric outpatients
Orten-Luiten, A.C.B. van; Janse, A. ; Dhonukshe-Rutten, R.A.M. ; Witkamp, R.F. - \ 2016
European Journal of Clinical Pharmacology (2016). - ISSN 0031-6970 - p. 605 - 614.
Adverse drug reaction - Drug-food interaction - Elderly - Polypharmacy - Vitamin D

Purpose: Adverse drug reactions as well as vitamin D deficiency are issues of public health concern in older people. However, relatively little is known about the impact of drug use on vitamin D status. Our primary aim is to explore associations between drug use and vitamin D status in older people. Furthermore, prevalences of drug use and vitamin D deficiency are estimated. Methods: In a population of 873 community-dwelling Dutch geriatric outpatients, we explored the cross-sectional relationships of polypharmacy (≥5 medications concomitantly used), severe polypharmacy (≥10 medications), and use of twenty-one specific drug groups, with serum 25-hydroxyvitamin D (25(OH)D) by analysis of covariance. Results: Overall prevalence of polypharmacy was 65 %, of severe polypharmacy 22 %. Depending on the cut-off value, prevalence of vitamin D deficiency was 49 % (

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