Publications by authors named "Elisabeth Stöcklin"

9 Publications

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Vitamin D, an essential nutrient with versatile functions in nearly all organs.

Int J Vitam Nutr Res 2013 ;83(2):92-100

DSM Nutritional Products Ltd., Kaiseraugst, Switzerland.

For decades, vitamin D has been known to be essential in the development, function, and maintenance of healthy bones through the regulation of calcium homeostasis throughout life. Sufficient vitamin D prevents the occurrence of rickets in children and osteomalacia in adults. The adequate nutritional intake of vitamin D and calcium are the basis for the prevention and management of osteoporosis, a disease producing brittle bones that are prone to fractures. Vitamin D has been implicated in the regulation of neuromuscular function and in reducing the risk of falls, a major cause of bone fractures. Thus vitamin D may be a central component of musculoskeletal health through its beneficial effects on muscle function and bone stability. The action of vitamin D by the active metabolite 1,25-dihydroxyvitamin D [1,25(OH)2D], however, is not limited to its endocrine function in bone metabolism. The active metabolite behaves as a hormone and binds to the vitamin D receptor (VDR) present in nearly all tissues of the human body. In addition, the 1-alpha-hydroxylase enzyme is present not only in the kidney but also in many other organs. Both vitamin and enzyme exert their biological effects via paracrine/autocrine actions related to cardiovascular disease, diabetes, cancer, and the immune system. Thus vitamin D may show favorable effects in many organs and play a significant role in the maintenance of general health.
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http://dx.doi.org/10.1024/0300-9831/a000151DOI Listing
May 2014

Relative effectiveness of oral 25-hydroxyvitamin D3 and vitamin D3 in raising wintertime serum 25-hydroxyvitamin D in older adults.

Am J Clin Nutr 2012 Jun 2;95(6):1350-6. Epub 2012 May 2.

School of Food and Nutritional Sciences, Department of Medicine, University College Cork, Cork, Ireland.

Background: The relative potency of 25-hydroxyvitamin D3 to vitamin D3 needs to be better defined so that food-composition tables can better reflect the true vitamin D nutritive value of certain foods.

Objective: We performed a randomized, controlled intervention study in apparently healthy, free-living adults to investigate whether the intake of 25-hydroxyvitamin D3 is 5 times more potent in raising serum 25-hydroxyvitamin D [25(OH)D] during winter compared with an equivalent amount of vitamin D3.

Design: A randomized, placebo-controlled, double-blind intervention study was conducted in adults aged ≥50 y (n = 56) who consumed a placebo, 20 μg vitamin D3, or 7 or 20 μg 25-hydroxyvitamin D3 daily throughout 10 wk of winter. Serum 25(OH)D was measured by using an enzyme-linked immunoassay, and serum albumin-corrected calcium (S-Ca) was assessed colorimetrically at the baseline, midpoint, and endpoint of the study.

Results: The mean (±SD) increases (per microgram of vitamin D compound) in serum 25(OH)D concentrations over baseline after 10 wk of supplementation were 0.96 ± 0.62, 4.02 ± 1.27, and 4.77 ± 1.04 nmol · L(-1) · μg intake(-1) for the 20-μg vitamin D3/d and 7- and 20-μg 25-hydroxyvitamin D3/d groups, respectively. A comparison of the 7- and 20-μg 25-hydroxyvitamin D3/d groups with the 20-μg vitamin D3/d group yielded conversion factors of 4.2 and 5, respectively. There was no effect of treatment on S-Ca concentrations and no incidence of hypercalcemia (S-Ca >2.6 nmol/L).

Conclusions: Each microgram of orally consumed 25-hydroxyvitamin D3 was about 5 times more effective in raising serum 25(OH)D in older adults in winter than an equivalent amount of vitamin D3. This conversion factor could be used in food-compositional tables for relevant foods. This study was registered at clinicaltrials.gov as NCT01398202.
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http://dx.doi.org/10.3945/ajcn.111.031427DOI Listing
June 2012

Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity.

J Bone Miner Res 2012 Jan;27(1):160-9

Centre on Aging and Mobility, University of Zurich and Waid City Hospital Zurich, Zurich, Switzerland.

To test the effect of 25(OH)D(3) (HyD) compared to vitamin D(3) on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D(3) per day in a double-blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]-8, IL-12, interferon gamma-induced protein 10 kDa [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta [MIP-1β], and "Regulated upon Activation, Normal T-cell Expressed, and Secreted" [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D(3) group. Women on HyD compared with vitamin D(3) had a 2.8-fold increased odds of maintained or improved lower extremity function (odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.18-6.58), and a 5.7-mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1, and MIP-1 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D(3).
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http://dx.doi.org/10.1002/jbmr.551DOI Listing
January 2012

Differential gene expression in skeletal muscle of rats with vitamin E deficiency.

IUBMB Life 2006 Sep;58(9):540-8

Physiological Flow Studies Group, Department of Bioengineering, Imperial College London, London, UK.

Vitamin E (VE) deficiency is accompanied by myopathy in various animal species including man. Although gene expression profiles related to degenerative and regenerative processes in different kinds of myopathies have been studied, no global expression profile for skeletal muscle subject to VE deficiency has previously been reported. In the present study, Affymetrix GeneChip technology was used to obtain such a profile. Two groups of male rats were fed with either a diet deficient in VE or a control diet. Differential gene expression was monitored at five time-points over 430 days, with all animals individually profiled. Out of approximately 7000 genes represented on the Genechip, 56 were found to be up-regulated in response to VE deficiency in at least four consecutive time-points from as early as 91 days of deficiency. Up-regulated genes included muscle structure and extra cellular matrix genes, as well as anti-oxidative, anti-inflammatory and anti-fibrotic genes. Our data show that molecular transcription might provide a very early marker to detect oncoming degenerative conditions in VE deficiency. They provide further insight into possible molecular mechanisms underlying VE deficiency in skeletal muscle, and reveal the activation of an intensive protection program that can explain the long maintenance of muscle structure during deficiency.
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http://dx.doi.org/10.1080/15216540600871100DOI Listing
September 2006

Alpha-tocopherol affects androgen metabolism in male rat.

Ann N Y Acad Sci 2004 Dec;1031:334-6

DSM Nutritional Products, Research and Development, Human Nutrition and Health, CH-4303 Kaiseraugst, Switzerland.

The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study has provided the first evidence implicating vitamin E in hormone synthesis. The effect of vitamin E on stereoidogenesis in testes and adrenal glands was assessed in growing rats using Affymetrix gene-chip technology. Dietary supplementation of rats with vitamin E (60 mg/kg feed) for a period of 429 days caused a significant repression of genes encoding for proteins centrally involved in the uptake (low-density lipoprotein receptor) and de novo synthesis (for example, 7-dehydrocholesterol reductase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, isopentenyl-diphosphate delta-isomerase, and farnesyl pyrophosphate synthetase) of cholesterol, the precursor of all steroid hormones. The present investigation indicates that dietary vitamin E may induce changes in stereoidogenesis by affecting cholesterol homeostasis.
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http://dx.doi.org/10.1196/annals.1331.036DOI Listing
December 2004

Dietary alpha-tocopherol affects differential gene expression in rat testes.

IUBMB Life 2004 May;56(5):277-80

Hugh Sinclar Human Nutrition Unit, School of Food Biosciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK.

Gene-chip technology was employed to study the effect of dietary vitamin E (VE) on gene expression in rat testes. Male albino rats were fed with either a diet deficient in VE or a standard diet containing VE. Differential gene expression was monitored at five individual time-points over a period of 14 months with all animals individually profiled. Low VE intake resulted in the consistent up-regulation of 7-dehydrocholesterol reductase and GATA binding protein 4, both involved in testosterone synthesis. Cyclin D3, important in cell cycle progression and Wilms tumor 1, related to cancer development, were also up-regulated in the vitamin E deficient animals. This study demonstrates that low dietary VE intake has long-term effects on gene expression in the testes. Our data provides insights into the possible molecular mechanisms underlying the beneficial effects of vitamin E on the male reproductive organ.
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http://dx.doi.org/10.1080/15216540410001724133DOI Listing
May 2004

Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health.

Eur J Nutr 2004 Dec 5;43(6):325-35. Epub 2004 Feb 5.

Dept. of Biochemistry, University of Maastricht, P. O. Box 616, 6200 MD Maastricht, The Netherlands.

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. During recent years vitamin K-dependent proteins were discovered to be of vital importance for bone and vascular health. Recommendations for dietary vitamin K intake have been made on the basis of the hepatic requirements for the synthesis of blood coagulation factors. Accumulating evidence suggests that the requirements for other functions than blood coagulation may be higher. This paper is the result of a closed workshop (Paris, November 2002) in which a number of European vitamin K experts reviewed the available data and formulated their standpoint with respect to recommended dietary vitamin K intake and the use of vitamin K-containing supplements.
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http://dx.doi.org/10.1007/s00394-004-0480-4DOI Listing
December 2004

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects.

Blood 2004 Nov 1;104(9):2682-9. Epub 2004 Jul 1.

Cardiovascular Research Institute Maastricht and VitaK BV, Maastricht, The Netherlands.

Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 microg-500 microg) of vitamin K(1) supplements (K(1)) taken daily for 7 days. The threshold K(1) dose causing a statistically significant lowering of the INR was 150 microg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 microg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 microg K(1)/day compared with 100 microg K(1)/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic gamma-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K(1) is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 microg/day of vitamin K(1) do not significantly interfere with oral anticoagulant therapy.
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http://dx.doi.org/10.1182/blood-2004-04-1525DOI Listing
November 2004

Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats.

Biochim Biophys Acta 2004 May;1689(1):66-74

DSM Nutritional Products (registered as Roche Vitamins Ltd), Human Nutrition and Health, P O Box 3255, CH-4002 Basel, Switzerland.

The recent discovery that vitamin E (VE) regulates gene activity at the transcriptional level indicates that VE may exert part of its biological effects by mechanisms which may be independent of its well-recognised antioxidant function. The objective of this study was the identification of hepatic vitamin E-sensitive genes and examination of the effects of VE on their corresponding biological endpoints. Two groups of male rats were randomly assigned to either a VE-sufficient diet or to a control diet deficient in VE for 290 days. High-density oligonucleotide microarrays comprising over 7000 genes were used to assess the transcriptional response of the liver. Differential gene expression was monitored over a period of 9 months, at four different time-points, and rats were individually profiled. This experimental strategy identified several VE-sensitive genes, which were chronically altered by dietary VE. VE supplementation down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase was significantly up-regulated. Measurement of the corresponding biological endpoints such as activated partial thromboplastin time, plasma dihydrotestosterone and hepatic glutathione substantiated the gene chip data which indicated that dietary VE plays an important role in a range of metabolic processes within the liver.
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http://dx.doi.org/10.1016/j.bbadis.2004.02.002DOI Listing
May 2004