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Indian Journal of Pediatrics Aug 2012Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and... (Review)
Review
Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children (CKiD) and the Cardiovascular Comorbidity in Children with CKD (4 C) should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes.
Topics: Child; Cholecalciferol; Dietary Supplements; Ergocalciferols; Growth Disorders; Humans; Hyperparathyroidism, Secondary; Kidney; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 22544696
DOI: 10.1007/s12098-012-0765-1 -
Critical Reviews in Food Science and... 2015There has been renewed interest in vitamin D since numerous recent studies have suggested that besides its well-established roles in bone metabolism and immunity,... (Review)
Review
There has been renewed interest in vitamin D since numerous recent studies have suggested that besides its well-established roles in bone metabolism and immunity, vitamin D status is inversely associated with the incidence of several diseases, e.g., cancers, cardio-vascular diseases, and neurodegenerative diseases. Surprisingly, there is very little data on factors that affect absorption of this fat-soluble vitamin, although it is acknowledged that dietary vitamin D could help to fight against the subdeficient vitamin D status that is common in several populations. This review describes the state of the art concerning the fate of vitamin D in the human upper gastrointestinal tract and on the factors assumed to affect its absorption efficiency. The main conclusions are: (i) ergocalciferol (vitamin D2), the form mostly used in supplements and fortified foods, is apparently absorbed with similar efficiency to cholecalciferol (vitamin D3, the main dietary form), (ii) 25-hydroxyvitamin D (25OHD), the metabolite produced in the liver, and which can be found in foods, is better absorbed than the nonhydroxy vitamin D forms cholecalciferol and ergocalciferol, (iii) the amount of fat with which vitamin D is ingested does not seem to significantly modify the bioavailability of vitamin D3, (iv) the food matrix has apparently little effect on vitamin D bioavailability, (v) sucrose polyesters (Olestra) and tetrahydrolipstatin (orlistat) probably diminish vitamin D absorption, and (vi) there is apparently no effect of aging on vitamin D absorption efficiency. We also find that there is insufficient, or even no data on the following factors suspected of affecting vitamin D bioavailability: (i) effect of type and amount of dietary fiber, (ii) effect of vitamin D status, and (iii) effect of genetic variation in proteins involved in its intestinal absorption. In conclusion, further studies are needed to improve our knowledge of factors affecting vitamin D absorption efficiency. Clinical studies with labeled vitamin D, e.g., deuterated or (13)C, are needed to accurately and definitively assess the effect of various factors on its bioavailability.
Topics: Aging; Biological Availability; Cholecalciferol; Dietary Supplements; Ergocalciferols; Fatty Acids; Food, Fortified; Humans; Intestinal Absorption; Lactones; Orlistat; Risk Factors; Sucrose; Vitamin D
PubMed: 24915331
DOI: 10.1080/10408398.2012.688897 -
Current Rheumatology Reports Apr 2008Vitamin D is known for its role in calcium homeostasis for optimal skeletal health. It was previously believed that only elderly or hospitalized patients were at risk... (Review)
Review
Vitamin D is known for its role in calcium homeostasis for optimal skeletal health. It was previously believed that only elderly or hospitalized patients were at risk for vitamin D insufficiency, but many people in the general US population have insufficient levels of 25-hydroxyvitamin D (25D). According to the Third National Health and Nutrition Examination Survey, 61% of white and 91% of black Americans suffer from vitamin D insufficiency (25D < 32 ng/mL). Recent studies have demonstrated that a minimum 25(OH)D level of 32 ng/mL is necessary for optimal protection from fracture and intestinal absorption of calcium. Recently, vitamin D has been recognized as important for extraskeletal functions such as immune function, cancer prevention, and hypertension prevention. We review the role of vitamin D in skeletal health and present data on vitamin D in other extraskeletal diseases, with special emphasis on the rheumatology patient.
Topics: Accidental Falls; Bone Density Conservation Agents; Calcium; Ergocalciferols; Fractures, Bone; Humans; Osteogenesis; Rheumatic Diseases; Vitamin D Deficiency
PubMed: 18460265
DOI: 10.1007/s11926-008-0020-y -
BMJ (Clinical Research Ed.) Aug 2019To investigate whether vitamin D supplementation is associated with lower mortality in adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate whether vitamin D supplementation is associated with lower mortality in adults.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.
MAIN OUTCOME MEASURES
All cause mortality.
RESULTS
52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D supplementation than in trials with vitamin D supplementation (P for interaction=0.04); neither vitamin D nor vitamin D was associated with a statistically significant reduction in all cause mortality.
CONCLUSIONS
Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D supplementation is associated with lower all cause mortality.
STUDY REGISTRATION
PROSPERO registration number CRD42018117823.
Topics: Cholecalciferol; Dietary Supplements; Ergocalciferols; Humans; Mortality; Neoplasms; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 31405892
DOI: 10.1136/bmj.l4673 -
The American Journal of Clinical... Aug 2008Although researchers first identified the fat-soluble vitamin cholecalciferol almost a century ago and studies have now largely elucidated the transcriptional mechanism... (Review)
Review
Although researchers first identified the fat-soluble vitamin cholecalciferol almost a century ago and studies have now largely elucidated the transcriptional mechanism of action of its hormonal form, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], we know surprisingly little about mechanisms of vitamin D toxicity. The lipophilic nature of vitamin D explains its adipose tissue distribution and its slow turnover in the body (half-life approximately 2 mo). Its main transported metabolite, 25-hydroxyvitamin D(3) [25(OH)D(3)], shows a half-life of approximately 15 d and circulates at a concentration of 25-200 nmol/L, whereas the hormone 1alpha,25(OH)(2)D(3) has a half-life of approximately 15 h. Animal experiments involving vitamin D(3) intoxication have established that 25(OH)D(3) can reach concentrations up to 2.5 mumol/L, at which it is accompanied by hypercalcemia and other pathological sequelae resulting from a high Ca/PO(4) product. The rise in 25(OH)D(3) is accompanied by elevations of its precursor, vitamin D(3), as well as by rises in many of its dihydroxy- metabolites [24,25(OH)(2)D(3); 25,26(OH)(2)D(3); and 25(OH)D(3)-26,23-lactone] but not 1alpha,25(OH)(2)D(3). Early assumptions that 1alpha,25(OH)(2)D(3) might cause hypercalcemia in vitamin D toxicity have been replaced by the theories that 25(OH)D(3) at pharmacologic concentrations can overcome vitamin D receptor affinity disadvantages to directly stimulate transcription or that total vitamin D metabolite concentrations displace 1alpha,25(OH)(2)D from vitamin D binding, increasing its free concentration and thus increasing gene transcription. Occasional anecdotal reports from humans intoxicated with vitamin D appear to support the latter mechanism. Although current data support the viewpoint that the biomarker plasma 25(OH)D concentration must rise above 750 nmol/L to produce vitamin D toxicity, the more prudent upper limit of 250 nmol/L might be retained to ensure a wide safety margin.
Topics: Animals; Bone Density Conservation Agents; Ergocalciferols; Half-Life; Humans; Hypercalcemia; Metabolic Clearance Rate; Risk Factors; Toxicology; Vitamin D
PubMed: 18689406
DOI: 10.1093/ajcn/88.2.582S -
The American Journal of Clinical... Jun 2012Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D].
OBJECTIVE
The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans.
DESIGN
The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials.
RESULTS
A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation.
CONCLUSIONS
This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.
Topics: Cholecalciferol; Dietary Supplements; Drug Administration Schedule; Ergocalciferols; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 22552031
DOI: 10.3945/ajcn.111.031070 -
International Journal of Molecular... Feb 2023Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D and vitamin D [...].
Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D and vitamin D [...].
Topics: Cholecalciferol; Ergocalciferols; Vitamin D; Vitamin D-Binding Protein
PubMed: 36902073
DOI: 10.3390/ijms24054642 -
Nutrients Mar 2017Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to... (Review)
Review
Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue. As in the general population, this condition is associated with increased morbidity and poor outcomes. Together with the progressive decline of serum calcitriol, vitamin D deficiency leads to secondary hyperparathyroidism (SHPT) and its complications, tertiary hyperparathyroidism and hypercalcemia, which require surgical parathyroidectomy or calcimimetics. Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease Improving Global Outcomes (KDIGO) experts have recognized that vitamin D insufficiency and deficiency should be avoided in CKD and dialysis patients by using supplementation to prevent SHPT. Many vitamin D supplementation regimens using either ergocalciferol or cholecalciferol daily, weekly or monthly have been reported. The benefit of native vitamin D supplementation remains debatable because observational studies suggest that vitamin D receptor activator (VDRA) use is associated with better outcomes and it is more efficient for decreasing the serum parathormone (PTH) levels. Vitamin D has pleiotropic effects on the immune, cardiovascular and neurological systems and on antineoplastic activity. Extra-renal organs possess the enzymatic capacity to convert 25(OH)D to 1,25(OH)₂D. Despite many unanswered questions, much data support vitamin D use in renal patients. This article emphasizes the role of native vitamin D replacement during all-phases of CKD together with VDRA when SHPT persists.
Topics: Cholecalciferol; Dialysis; Dietary Supplements; Ergocalciferols; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Parathyroid Hormone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin D Deficiency
PubMed: 28346348
DOI: 10.3390/nu9040328 -
The Cochrane Database of Systematic... Sep 2018This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation.
OBJECTIVES
To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs).
MAIN RESULTS
We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D₃, and one trial tested vitamin D₂. Vitamin D₃ had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D₃ reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms.
AUTHORS' CONCLUSIONS
To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.
Topics: Cholecalciferol; Ergocalciferols; Fatigue; Humans; Multiple Sclerosis; Quality of Life; Randomized Controlled Trials as Topic; Vitamins
PubMed: 30246874
DOI: 10.1002/14651858.CD008422.pub3 -
The Israel Medical Association Journal... Jul 2017Vitamin D deficiency is becoming an increasing problem worldwide. It should not be underestimated, not only due to the well-known consequences vitamin D deficiency has... (Review)
Review
Vitamin D deficiency is becoming an increasing problem worldwide. It should not be underestimated, not only due to the well-known consequences vitamin D deficiency has on bone health, but primarily because recent studies have shown how the biologically active form of vitamin D - 1,25(OH)2D - is involved in many biological processes, including immune system modulation. Moreover, the presence of a vitamin D receptor was discovered in almost all immune cells and some of its polymorphisms were found to be associated with increased incidence of autoimmune diseases. This finding led to a proposed link between vitamin D deficiency and autoimmune diseases. Patients affected by various autoimmune diseases showed low levels of vitamin D. However, it is not always clear whether vitamin D deficiency is the cause or rather a consequence of the disease. Limitations of the studies, such as the small number of patients, heterogeneity of selected groups, environmental conditions, methods used to measure vitamin D serum concentration and other confounding factors do not lead to unequivocal results to demonstrate a direct link between low vitamin D levels and autoimmune disease. Therefore, randomized trials are needed to clarify conflicting results.
Topics: Autoimmune Diseases; Ergocalciferols; Humans; Polymorphism, Genetic; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency
PubMed: 28786260
DOI: No ID Found