A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Gepner, Adam D.; Ramamurthy, Rekha; Krueger, Diane; Korcarz, Claudia E.; Binkley, Neil; Stein, James H.

doi:10.1371/journal.pone.0036617

Cited by 166 publications

(141 citation statements)

References 45 publications

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“…A couple of cross-sectional studies in healthy adults show lower serum levels of 25(OH)D to be associated with endothelial dysfunction (91,92) . A few trials show an improvement in flow-mediated dilation with vitamin D supplementation (93)(94)(95) , but most show no effect (79,(96)(97)(98) ( Table 2).…”

Section: Endothelial Functionmentioning

confidence: 99%

Vitamin D and risk of CVD: a review of the evidence

Fry

Sanders

2015

Proc. Nutr. Soc.

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This review summarises evidence for an association between vitamin D status and CVD and the mechanisms involved. Vitamin D 3 is predominantly provided by the action of UVB from sunlight on skin. Average UK diets supply 2-3 μg/d vitamin D but diets containing at least one portion of oily fish per week supply about 7 μg/d. Pharmacological doses of vitamin D 2 (bolus injection of 7500 μg or intakes >50 μg/d) result in a smaller increase in plasma 25 (OH)D than those of D 3 but physiological doses 5-25 μg/d seem equivalent. Plasma 25 (OH)D concentrations are also influenced by clothing, obesity and skin pigmentation. Up to 40 % of the population have plasma 25(OH)D concentrations <25 nmol/l in the winter compared with <10 % in the summer. The relative risk of CVD death is 1·41 (95 % CI 1·18, 1·68) greater in the lowest quintile of plasma 25(OH)D according to meta-analysis of prospective cohort studies. Acute deficiency may inhibit insulin secretion and promote inflammation thus increasing the risk of plaque rupture and arterial thrombosis. Chronic insufficiency may increase arterial stiffness. There is no evidence to support claims of reduced CVD from existing trials with bone-related health outcomes where vitamin D was usually co-administered with calcium. Although several trials with cardiovascular endpoints are in progress, these are using pharmacological doses. In view of the potential toxicity of pharmacological doses, there remains a need for long-term trials of physiological doses of D 2 and D 3 with CVD incidence as the primary outcome. Ergocalciferol: Cholecalciferol: Cardiovascular riskVitamin D deficiency causes rickets in children and osteomalacia in adults and may contribute to the causation of CVD. Cholecalciferol (vitamin D 3 ) is made by the action of UVB light on the skin but is also provided in the diet from foods of animal origin (eggs, oily fish and meat). Ergocalciferol (vitamin D 2 ) is present in fungi that have been exposed to UVB irradiation. Both forms of vitamin D undergo 25-hydroxylation in the liver to form 25(OH) metabolites, most of which circulate in plasma bound to the vitamin D binding protein (VDBP). In the kidney, 25 hydroxyvitamin D (25(OH)D) is converted to the biologically active metabolite 1,25 dihydroxyvitamin D (1,25 (OH) 2 D) by the action of 1α-hydroxylase (Fig. 1). This then binds to the vitamin D receptor, which is a highaffinity nuclear hormone receptor that regulates gene expression (1) . Measurement of serum 25(OH)D to assess vitamin D status has predominantly used immunoassays, which show lower sensitivity (about 30 %) to D 2 metabolites than gold-standard methods such as HPLC/tandem MS. Formerly, a lack of standardisation of methods and appropriate quality control made comparisons between studies difficult (2) . The situation has been remedied by the availability (3) of standard reference serum (SRM 972, National Institute of Standards and Technology) and a quality control programme in the UK organised by the Vitamin D External Quality Assessment Scheme (4) . It has...

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Section: Endothelial Functionmentioning

confidence: 99%

Vitamin D and risk of CVD: a review of the evidence

Fry

Sanders

2015

Proc. Nutr. Soc.

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“…However, there is evidence indicating that preeclampsia is associated with vitamin D deficiency [1][2][3]. Indeed, vitamin D plays important roles not only in bone health, but also in both cardiovascular and immune systems alterations during pregnancy [4][5][6][7][8]. Vitamin D undergoes hydroxylation in the maternal liver to form 25-OH-vitamin D (25OH-D), which is an inactive form of this hormone [9].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

et al. 2012

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Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P [ 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P [ 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

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“…Clinical trials exploring the effects of treatment with vitamin D in non-diabetic patients on blood pressure and vascular function have shown benefits in some (154,155), but not all studies (156,157). A recent large meta-analysis did not find a reduced risk for cardiovascular disease or mortality after administration of vitamin D (158).…”

Section: Vitamin D Metabolismmentioning

confidence: 99%

Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D

Jennersjö

2016

Linköping University Medical Dissertations

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Background Type 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes. Methods Data from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of sagittal abdominal diameter. Results Paper 1: Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure. Paper 2: The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV. Paper 3: At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up. Paper 4: Low vitamin D levels were associated with significantly increased risk for premature mortalit...

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A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Cited by 166 publications

References 45 publications

Vitamin D and risk of CVD: a review of the evidence

Vitamin D and risk of CVD: a review of the evidence

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D

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