Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives

Osteoarthritis is a debilitating and degenerative disease which affects millions of people worldwide. The causes and mechanisms of osteoarthritis remain to be fully understood. Vitamin D has been hypothesised to play essential roles in a number of diseases including osteoarthritis. Many cell types within osteoarthritic joints appear to experience negative effects often at increased sensitivity to vitamin D. These findings contrast clinical research which has identified vitamin D deficiency to have a worryingly high prevalence among osteoarthritis patients. Randomised-controlled trial is considered to be the most rigorous way of determining the effects of vitamin D supplementation on the development of osteoarthritis. Studies into the effects of low vitamin D levels on pain and joint function have to date yielded controversial results. Due to the apparent conflicting effects of vitamin D in knee osteoarthritis, further research is required to fully elucidate its role in the development and progression of the disease as well as assess the efficacy and safety of vitamin D supplementation as a therapeutic strategy.

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VITALITY trial: protocol for a randomised controlled trial to establish the role of postnatal vitamin D supplementation in infant immune health

BMJ Open ◽

10.1136/bmjopen-2015-009377 ◽

2015 ◽

Vol 5 (12) ◽

pp. e009377 ◽

Cited By ~ 25

Author(s):

Katrina J Allen ◽

Mary Panjari ◽

Jennifer J Koplin ◽

Anne-Louise Ponsonby ◽

Peter Vuillermin ◽

...

Keyword(s):

Vitamin D ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Trial Protocol ◽

Immune Health ◽

Randomised Controlled

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Optimal Vitamin D Supplementation Levels for Cardiovascular Disease Protection

Disease Markers ◽

10.1155/2015/864370 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Sebastian T. Lugg ◽

Phillip A. Howells ◽

David R. Thickett

Keyword(s):

Cardiovascular Disease ◽

Vitamin D ◽

Current Knowledge ◽

Experimental Studies ◽

Vitamin D Supplementation ◽

Disease Marker ◽

Vitamin D Levels ◽

Artery Disease ◽

Randomised Controlled

First described in relation to musculoskeletal disease, there is accumulating data to suggest that vitamin D may play an important role in cardiovascular disease (CVD). In this review we aim to provide an overview of the role of vitamin D status as both a marker of and potentially causative agent of hypertension, coronary artery disease, heart failure, atrial fibrillation, stroke, and peripheral vascular disease. The role of vitamin D levels as a disease marker for all-cause mortality is also discussed. We review the current knowledge gathered from experimental studies, observational studies, randomised controlled trials, and subsequent systematic reviews in order to suggest the optimal vitamin D level for CVD protection.

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Prevalence of Vitamin D Deficiency and Its Relationship with Clinical Outcomes in Patients with Fibromyalgia: a Systematic Review of the Literature

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-021-01105-w ◽

2022 ◽

Vol 4 (1) ◽

Author(s):

Omar M. E. Ali

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Patient Flow ◽

Controlled Trial ◽

Cost Effective ◽

Therapeutic Benefit ◽

Vitamin D Supplementation ◽

Effective Interventions ◽

Randomised Controlled ◽

And Control

Abstract Fibromyalgia is a debilitating chronic condition which poses a therapeutic challenge to the clinician. With a large backlog in patient flow subsequent to the COVID-19 pandemic and rising numbers of patients with post-acute sequelae of COVID-19 (PASC) presenting with fibromyalgia-like clinical features, there is an increasingly pressing need to identify broad cost-effective interventions. Low levels of vitamin D have previously been reported in patients with fibromyalgia, though any causative link has been difficult to establish. A systematic literature review on the association between vitamin D deficiency and fibromyalgia was performed examining retrospective evidence both for and against an association between vitamin D deficiency (VDD) and fibromyalgia and evaluating the therapeutic benefit from supplementation. A group of six studies were selected based on relevance, use of controls, quality of research and citations. Four primary studies assessing the prevalence of VDD in fibromyalgia patients versus controls were evaluated with a total 3,496 subjects. Three included females only and one larger study assessed males. Two (n = 313) concluded the presence of a statistically significant association, and two (n = 161) found none. Two randomised controlled trials assessing the effect of vitamin D supplementation in a total of 80 subjects found conflicting results, with pain reduction in one and none in the other. It is likely there exists an association between VDD deficiency and fibromyalgia in a large subset of patients, although establishing primary causation is difficult. There is a need for larger randomised controlled trial designs with more effective comparison with healthy subjects and control for confounding factors. Given VDD is a major problem in the general population, we recommend supplementation be recommended by healthcare professionals to fibromyalgia patients for the purpose of maintaining bone health given their potentially increased susceptibility to developing deficiency and its sequelae.

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Role of Vitamin D in Reducing the Frequency of Asthma Attacks in Patients with Frequent Exacerbation of Asthma

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i53b33675 ◽

2021 ◽

pp. 11-16

Author(s):

Mubeen Ahmed Memon ◽

Sheeba Faryal Ansari ◽

Mumtaz Ali Lakho ◽

Mukhtiar Hussain Jaffery ◽

Syed Zulfiquar Ali Shah ◽

...

Keyword(s):

Vitamin D ◽

Corticosteroid Treatment ◽

Vitamin D Supplementation ◽

The Body ◽

P Value ◽

Care Hospital ◽

Asthma Exacerbations ◽

Vitamin D Levels ◽

Interventional Group

Introduction: Vitamin D deficiency is common among asthmatics with literature suggesting that its low levels in the body may trigger exacerbations and decrease the response to corticosteroid treatment. It has also shown to inhibit the production of cytokines, which in turn enhances the body’s response to corticosteroid treatment during an exacerbation. Therefore, maintenance of adequate levels of vitamin D in patients with asthma may reduce the risk of exacerbation and improve their general health. This study aims to explore the role of vitamin D supplementation in preventing asthma exacerbations. Methods: This single blind parallel arm interventional study was conducted in the pulmonology ward in a tertiary care hospital from June 2018 to April 2020. Two hundred (n= 200) participants with a history of frequent acute exacerbation of asthma were enrolled in the study via consecutive convenient non-probability technique. Participants were divided into two groups; the placebo and the interventional group that received 200,000 IU of vitamin D capsule. Results: Compared to day 0, mean episodes of exacerbation in the interventional group were significantly lower after 180 days (1.1 ± 0.4 vs. 0.61 ± 0.3; p-value <0.0001). Similarly, number of asthma attacks in past 7 days was significantly lower in intervention group after 180 days (4.4 ± 2.7 vs. 3.1 ± 1.5; p-value 0.0001) Conclusion: Vitamin D supplementation is a safe and cost-friendly approach to reducing asthma exacerbations. It may also help to improve the condition in severe asthmatics with low vitamin D levels.

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The Effect of High-Dose Postpartum Maternal Vitamin D Supplementation Alone Compared with Maternal Plus Infant Vitamin D Supplementation in Breastfeeding Infants in a High-Risk Population. A Randomized Controlled Trial

Nutrients ◽

10.3390/nu11071632 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1632 ◽

Cited By ~ 12

Author(s):

Adekunle Dawodu ◽

Khalil M. Salameh ◽

Najah S. Al-Janahi ◽

Abdulbari Bener ◽

Naser Elkum

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Calcium ◽

Vitamin D3 ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Urine Calcium ◽

Randomized Controlled ◽

High Prevalence ◽

Maternal Supplementation

In view of continuing reports of high prevalence of severe vitamin D deficiency and low rate of infant vitamin D supplementation, an alternative strategy for prevention of vitamin D deficiency in infants warrants further study. The aim of this randomized controlled trial among 95 exclusively breastfeeding mother–infant pairs with high prevalence of vitamin D deficiency was to compare the effect of six-month post-partum vitamin D3 maternal supplementation of 6000 IU/day alone with maternal supplementation of 600 IU/day plus infant supplementation of 400 IU/day on the vitamin D status of breastfeeding infants in Doha, Qatar. Serum calcium, parathyroid hormone, maternal urine calcium/creatinine ratio and breast milk vitamin D content were measured. At baseline, the mean serum 25-hydroxyvitamin D (25(OH)D) of mothers on 6000 IU and 600 IU (35.1 vs. 35.7 nmol/L) and in their infants (31.9 vs. 29.6) respectively were low but similar. At the end of the six month supplementation, mothers on 6000 IU achieved higher serum 25(OH)D mean ± SD of 98 ± 35 nmol/L than 52 ± 20 nmol/L in mothers on 600 IU (p < 0.0001). Of mothers on 6000 IU, 96% achieved adequate serum 25(OH)D (≥50 nmol/L) compared with 52%in mothers on 600 IU (p < 0.0001). Infants of mothers on 600 IU and also supplemented with 400 IU vitamin D3 had slightly higher serum 25(OH)D than infants of mothers on 6000 IU alone (109 vs. 92 nmol/L, p = 0.03); however, similar percentage of infants in both groups achieved adequate serum 25(OH)D ≥50 nmol/L (91% vs. 89%, p = 0.75). Mothers on 6000 IU vitamin D3/day also had higher human milk vitamin D content. Safety measurements, including serum calcium and urine calcium/creatinine ratios in the mother and serum calcium levels in the infants were similar in both groups. Maternal 6000 IU/day vitamin D3 supplementation alone safely optimizes maternal vitamin D status, improves milk vitamin D to maintain adequate infant serum 25(OH)D. It thus provides an alternative option to prevent the burden of vitamin D deficiency in exclusively breastfeeding infants in high-risk populations and warrants further study of the effective dose.

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Effects of sunlight exposure and vitamin D supplementation on vitamin D levels in postmenopausal women in rural Thailand: A randomized controlled trial

Complementary Therapies in Medicine ◽

10.1016/j.ctim.2018.06.004 ◽

2018 ◽

Vol 40 ◽

pp. 243-247 ◽

Cited By ~ 2

Author(s):

Waranya Watcharanon ◽

Srinaree Kaewrudee ◽

Sukree Soontrapa ◽

Woraluk Somboonporn ◽

Prasopsuk Srisaenpang ◽

...

Keyword(s):

Vitamin D ◽

Randomized Controlled Trial ◽

Postmenopausal Women ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Sunlight Exposure ◽

Randomized Controlled ◽

Vitamin D Levels ◽

Rural Thailand

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O13 Pregnancy vitamin D supplementation leads to greater offspring bone mineral density at 4 years: the MAVIDOS randomised placebo controlled trial

Rheumatology ◽

10.1093/rheumatology/keaa110.012 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Elizabeth M Curtis ◽

Rebecca J Moon ◽

Stefania D'Angelo ◽

Sarah R Crozier ◽

Nicholas J Bishop ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Bone Mass ◽

Bone Mineral ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Whole Body ◽

Mineral Density ◽

Double Blind ◽

Randomised Controlled

Abstract Background Observational studies have demonstrated associations between maternal gestational vitamin D status and offspring bone health. We have recently shown, in a randomised controlled trial, that pregnancy vitamin D supplementation leads to improved offspring bone mass at birth amongst winter deliveries (when background 25(OH)-vitamin D levels are lowest). In the present analysis, we aimed to evaluate whether the beneficial effect of pregnancy vitamin D supplementation on neonatal bone mass is sustained into early childhood, with bone indices assessed at age 4 years in a subset of participants of the MAVIDOS trial. Methods Pregnant women were randomised in Southampton, Oxford and Sheffield, in a double-blind design, to 1000 IU/day cholecalciferol or matched placebo from 14 weeks’ gestation to birth. At 4 years of age (Southampton participants only, n = 723 births), offspring assessments included anthropometry, whole-body dual-energy x-ray absorptiometry (DXA) [Hologic Horizon, yielding whole body less head (WBLH) bone mineral content (BMC), bone mineral density (BMD), bone area (BA) and lean mass (LM)], and a maternal questionnaire. Linear regression was used to estimate the mean difference (represented by β) in outcomes between the two randomisation arms, adjusted for sex and age at DXA. Further models were additionally adjusted for gestational age, maternal BMI, and child’s sedentary time. All outcomes were standardised to a standard deviation scale, for ease of comparison. Full ethics and MHRA approvals were granted. Results 564 children attended the 4-year visit; 452 had a useable DXA with minimal movement artefact. Maternal pregnancy vitamin D supplementation led to greater offspring indices of bone mass compared with placebo, irrespective of season. For example, WBLH BMD at age 4 years was greater in the offspring of supplemented mothers [β = 0.18 SD (95%CI: 0.00, 0.35), p = 0.047]; there was also evidence of greater LM in the intervention group [β = 0.15 SD (95%CI: -0.02, 0.31), p = 0.081]. In fully adjusted models associations were consistent for lumbar spine indices and for BA and BMC. In keeping with the offspring findings, maternal vitamin D supplementation led to significantly higher maternal plasma 25(OH)D concentrations in late pregnancy (34 weeks’ gestation): placebo group (median(IQR)): 42.4 nmol/l (23.3, 56.4); vitamin D group: 67.4 nmol/l (56.2, 80.3); p < 0.001. Conclusion This is the first ever demonstration in a large placebo-controlled, double-blind randomised controlled trial that maternal pregnancy vitamin D supplementation leads to improved bone and lean mass in children. Our findings suggest that maternal cholecalciferol supplementation may have lasting benefits for offspring musculoskeletal health and thus represent an important public health message. This work was supported by grants from Versus Arthritis 17702, Medical Research Council (MRC #405050259; #U105960371), Bupa Foundation, NIHR Southampton Biomedical Research Centre (BRC), University of Southampton, and NIHR Oxford BRC, University of Oxford. EC was supported by the Wellcome Trust (#201268/Z/16/Z). Disclosures E.M. Curtis None. R.J. Moon None. S. D'Angelo None. S.R. Crozier None. N.J. Bishop None. S. Gopal- Kothandapani None. S. Kennedy None. A.T. Papageorghiou None. R. Fraser None. S.V. Gandhi None. I. Schoenmakers None. A. Prentice None. H.M. Inskip None. K.M. Godfrey None. K. Javaid None. R. Eastell None. C. Cooper None. N.C. Harvey None.

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0809 A Randomized Double-blind, Placebo Controlled Trial With Cross-over, To Assess The Efficacy Of Correcting Vitamin D Deficiency In Improving The Symptoms Of Restless Legs Syndrome (RLS)

SLEEP ◽

10.1093/sleep/zsaa056.805 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A307-A308

Author(s):

J Wong ◽

D Gupta ◽

A Nadhim ◽

S Bhat ◽

P Polos

Keyword(s):

Vitamin D ◽

Iron Deficiency ◽

Vitamin D Deficiency ◽

Controlled Trial ◽

Activity Count ◽

Double Blind ◽

Vitamin D Levels ◽

Effect Of Treatment ◽

B Vitamin

Abstract Introduction Recent studies have shown an association of low Vitamin D levels and severity of RLS symptoms. However, effect of treatment of Vit D deficiency on RLS symptoms was not reported, nor were other exacerbating factors for RLS such as iron deficiency or OSA addressed in prior studies, but have been addressed in our study. Methods This is an ongoing study at the JFKMC Sleep Clinic. Eligible Patients with RLS include those with vitamin D 25,hydroxy deficiency (<20 ng/ml), or insufficiency (<30 ng/ml). Such patients will be enrolled in the study after comorbid conditions like iron deficiency and OSA have been adequately corrected. Randomization of the patients will be done by the JFK pharmacy so the patient and provider are blinded to the substance. Substance A or B could be either Vitamin D3 Capsule 50,000 IU, or placebo. Each patient takes A for 6 weeks and then crosses over to B for 6 weeks. Weekly iRLS questionnaires will be collected. Actiwatch Device, to assess activity count per minute, will be worn on the ankle at night for one week time periods: at baseline, at end of 6 weeks of taking A and then at the end of 6 weeks of taking B. Vitamin D levels will also be assessed after each course of supplementation and correlated with subjective and objective findings. Results Between July 7, 2019 to current, 50 consecutive patients seen in sleep clinic with RLS were assessed for vitamin D levels. Ages ranged from 23-86 years. 27 patients were female (54%). Two patients met inclusion criteria and have started their 13-week study. Conclusion This study will help to establish the role of Vitamin D deficiency as a risk factor for RLS, independent of ferritin levels, and comorbid OSA, in affected individuals. This may help to discover a potentially treatable form of RLS. Support No financial support.

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