Objective: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. Participants: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Conclusions: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recomme...

/pdf/evaluation-treatment-and-prevention-of-vitamin-d-deficiency-4wt9apc7iy.pdf

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline

OBJECTIVE\nThe objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency.\n\n\nPARTICIPANTS\nThe Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration.\n\n\nCONSENSUS PROCESS\nConsensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes.\n\n\nCONCLUSIONS\nConsidering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline (Journal of Clinical Endocrinology and Metabolism (2011) 96, (1911-1930))

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

/pdf/vitamin-d-metabolism-molecular-mechanism-of-action-and-1rmxk5ppvb.pdf

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

Much has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as “cf” is used when speaking of specific segments of the arterial circulation.

The ability to measure arterial stiffness has been present for many years, but the measurement was invasive in the early times. The improvement in technologies to enable repeated, minimal-risk, reproducible measures of this aspect of circulatory physiology led to its incorporation into longitudinal cohort studies spanning a variety of clinical populations, including those at extreme cardiovascular risk (patients on dialysis), those with comorbidities such as diabetes mellitus (DM) and hypertension, healthy elders, and general populations.

In the ≈3 decades of clinical use of PWV measures in humans, we have learned much about the importance of this parameter. PWV has proven to have independent predictive utility when evaluated in conjunction with standard risk factors for death and cardiovascular disease (CVD). However, the field of arterial stiffness investigation, which has exploded over the past 20 years, has proliferated without logistical guidance for clinical and …

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association

It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases. However, there remains cynicism about the lack of randomized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by searching English-language studies published up to April 1, 2013, in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials (search terms: vitamin D and supplementation) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources, supplements, and sun exposure. The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life. There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses, including some cancers, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and mortality.

/pdf/vitamin-d-for-health-a-global-perspective-36p410gca6.pdf

Vitamin D for Health: A Global Perspective

Context: Vitamin D insufficiency/deficiency is commonly observed in black youth.Objective: The aim was to determine 25-hydroxyvitaminD[25(OH)D] in response to 2000 IU vitaminD supplementation over time; to evaluate the relation between 25(OH)D concentrations and totalbody fat mass by dual-energy x-ray absorptiometry; and to determine whether vitamin D supplementation improves arterial stiffness measured by pulse wave velocity (PWV).Design: We conducted a randomized, blinded, controlled clinical trial.Setting and Participants: Forty-nine normotensive black boys and girls, aged 16.3 1.4 yr, wererandomly assigned to either the control group (400 IU/d; n 24) or the experimental group (2000IU/d; n 25).Results: Plasma 25(OH)D values at baseline and at 4, 8, and 16 wk were 34.010.6, 44.99.4, 51.211.1, and 59.818.2 nmol/liter, respectively, for the control group; and 33.18.7, 55.011.8, 70.922.0, and 85.730.1 nmol/liter, respectively, for the experimental group. The experimental group vs.the control group reached significantly higher 25(OH)D concentrations at 8 and 16 wk, respectively.Partial correlation analyses indicated that totalbodyfatmassat baselinewassignificantlyandinverselyassociated with 25(OH)D concentrations in response to the 2000-IU supplement across time. Furthermore, carotid-femoralPWVincreased from baseline (5.380.53 m/sec) to posttest (5.710.75 m/sec) in the control group (P 0.016), whereas in the experimental group carotid-femoral PWV decreased from baseline (5.41 0.73 m/sec) to posttest (5.33 0.79 m/sec) (P 0.031).Conclusion: Daily 2000 IU vitamin D supplementation may be effective in optimizing vitamin Dstatus and counteracting the progression of aortic stiffness in black youth. Plasma 25(OH)D concentrations in response to the 2000 IU/d supplementation are negatively modulated by adiposity.

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A 16-Week Randomized Clinical Trial of 2000 International Units Daily Vitamin D3 Supplementation in Black Youth: 25-Hydroxyvitamin D, Adiposity, and Arterial Stiffness

Overactivity of the epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In an open-labeled, nonplacebo-controlled clinical trial (Clinicaltrials.gov: NCT-01308983), the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). The mean body mass index of participants was 28.45±1.30 kg/m(2) . Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.

Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.

/pdf/arterial-stiffness-supplementation-in-black-youth-25-29vo13gx5g.pdf

Arterial Stiffness Supplementation in Black Youth: 25-Hydroxyvitamin D, Adiposity, and 3 D A 16-Week Randomized Clinical Trial of 2000 International Units Daily Vitamin

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A 16-Week Randomized Clinical Trial of 2000 International Units Daily Vitamin D3 Supplementation in Black Youth: 25-Hydroxyvitamin D, Adiposity, and Arterial Stiffness

Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.

Arterial Stiffness Supplementation in Black Youth: 25-Hydroxyvitamin D, Adiposity, and 3 D A 16-Week Randomized Clinical Trial of 2000 International Units Daily Vitamin