scholarly journals The Effect of Yearly-Dose Vitamin D Supplementation on Muscle Function in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1097 ◽  
Author(s):  
Alan Hayes ◽  
Emma Rybalka ◽  
Danielle A. Debruin ◽  
Erik D. Hanson ◽  
David Scott ◽  
...  
Keyword(s):  
Vitamin D ◽  
Muscle Function ◽  
Vitamin D Supplementation ◽  
Fatigue Properties ◽  
Direct Result ◽  
High Dose ◽  
Early Recovery ◽  
Increased Risk ◽  
Risk Of Falls ◽  
Yearly Dose

Supplementation with vitamin D helps to alleviate weakness and fatigue seen with deficiency. However, large bolus doses appear to worsen the risk of falls. Whether this occurs as a direct result of muscle weakness is currently unknown. Thus, the aims of this study were to examine the muscle function following administration of high doses of vitamin D. Given the safety issues associated with bolus doses, experiments were conducted on C57BL6 mice. Mice at eight weeks of age with otherwise normal levels of vitamin D were supplemented for four weeks with a high dose (HIGH; n = 12) of vitamin D (20000 IU/kg food) designed to provide a year’s worth of vitamin D. These mice were compared to another group who received that same yearly dose in a single bolus i.p. injection (YEAR; n = 12). Mice provided with standard mouse chow, which contained 1000 IU/kg food, and injected with the vitamin D vehicle were used as controls (CON; n = 16). Force and fatigue properties of hind limb fast- and slow-twitch muscles were measured. CON animals ingested vitamin D consistent with typical human supplementation. HIGH animals consumed significantly more food than the CON animals, such that they ingested more than a year’s worth of vitamin D in four weeks. Despite this, there were few differences in the muscle function compared with CON. YEAR animals demonstrated lower absolute and relative forces in both muscles compared to the HIGH animals, as well as lower force during fatigue and early recovery. Large bolus doses of vitamin D appear to have detrimental effects on the skeletal muscle function, likely being a contributor to increased risk of falls observed with similar doses in humans. Mice ingesting the same amount over four weeks did not demonstrate the same deleterious effects, suggesting this may be a safe way to provide high vitamin D if required.

scholarly journals Design and Main Results of STURDY: A Randomized Clinical Trial of Four Vitamin D3 Doses to Prevent Falls in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 759-759
Author(s):  
Lawrence Appel ◽  
Jennifer Schrack ◽  
Erin Michos ◽  
Christine Mitchell ◽  
Stephen Juraschek ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Primary Outcome ◽  
Vitamin D Supplementation ◽  
Dose Finding ◽  
High Dose ◽  
Hazard Ratios ◽  
Risk Of Falls ◽  
Event Rates ◽  
And Control

Abstract STURDY was a Bayesian, response-adaptive trial with dose-finding and confirmatory stages. Participants (n=688; ≥70years with serum 25(OH)D of 10-29ng/mL) were randomized to 200 (control), 1000, 2000, or 4000 IU/day of vitamin D3. The primary outcome was time to first fall or death over 2 years. During dose-finding, the best non-control dose was determined to be 1000IU/day based on higher primary outcome event rates in the 2000 and 4000IU/day doses than the 1000IU/day dose (posterior probability of being best dose=0.90; hazard ratios[HR] were 1.86 [95%CI: 1.16-2.97] and 1.68 [95%CI: 1.05-2.69], respectively). Participants were then switched from other non-control doses to 1000IU/day, and event rates did not differ between the pooled higher doses and control groups (HR=1.02, P=0.84). There was no heterogeneity by baseline 25(OHD). In conclusion, high-dose vitamin D supplementation ≥1000IU/day did not prevent falls. Whether vitamin D doses >2000IU/day increase the risk of falls is uncertain.

scholarly journals Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

2012 ◽  
Vol 109 (38) ◽  
pp. 15449-15454 ◽  
Author(s):  
Anna K. Coussens ◽  
Robert J. Wilkinson ◽  
Yasmeen Hanifa ◽  
Vladyslav Nikolayevskyy ◽  
Paul T. Elkington ◽  
...  
Keyword(s):  
Vitamin D ◽  
Antimicrobial Therapy ◽  
Potential Role ◽  
Inflammatory Responses ◽  
Vitamin D Supplementation ◽  
Tuberculosis Treatment ◽  
Sputum Smear ◽  
High Dose ◽  
Increased Risk

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial

2019 ◽  
Vol 71 (2) ◽  
pp. 311-317 ◽  
Author(s):  
Carlos A Camargo ◽  
John Sluyter ◽  
Alistair W Stewart ◽  
Kay-Tee Khaw ◽  
Carlene M M Lawes ◽  
...  
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Randomized Controlled ◽  
Increased Risk ◽  
High Dose Vitamin

Abstract Background Although adults with low vitamin D status are at increased risk of acute respiratory infection (ARI), randomized controlled trials of vitamin D supplementation have provided inconsistent results. Methods We performed a randomized, double-blinded, placebo-controlled trial of 5110 adults aged 50–84 years. In 2011–2012, participants were randomized to an initial oral dose of 200 000 IU vitamin D3 followed by 100 000 IU monthly (n = 2558) or placebo (n = 2552) until late 2013 (median follow-up, 1.6 years). Participants reported upper and lower ARIs on monthly questionnaires. Cox models analyzed time to first ARI (upper or lower) by treatment group. Results Participants’ mean age was 66 years and 58% were male; 83% were of European/other ethnicity, with the rest Maori, Polynesian, or South Asian. Mean (SD) baseline blood 25-hydroxyvitamin D [25(OH)D] level was 63 (24) nmol/L; 25% were <50 nmol/L. In a random sample (n = 441), vitamin D supplementation increased mean 25(OH)D to 135 nmol/L at 3 years, while those on placebo remained at 63 nmol/L. During follow-up, 3737 participants reported ≥1 ARI: 74.1% in the vitamin D group versus 73.7% in the placebo group. The hazard ratio for vitamin D compared with placebo was 1.01 (95% CI, 0.94, 1.07). Similar results were seen in most subgroups, including those with baseline 25(OH)D <50 nmol/L and in analyses of the upper/lower components of the ARI outcome. Conclusions Monthly high-dose vitamin D supplementation does not prevent ARI in older adults with a low prevalence of profound vitamin D deficiency at baseline. Whether effects of daily or weekly dosing differ requires further study. Clinical Trials Registration Australian New Zealand Clinical Trials Registry, identifier ACTRN12611000402943.

24 A Retrospective Review of Vitamin D Levels and Dosing in Burn Center Patients

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S21-S21
Author(s):  
Sara Calder ◽  
Asia N Quan ◽  
Suzanne C Osborn ◽  
Karen J Richey ◽  
Curt Bay ◽  
...  
Keyword(s):  
Vitamin D ◽  
Retrospective Chart Review ◽  
Vitamin D Insufficiency ◽  
Infectious Complications ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Weekly Dose ◽  
Burn Patients ◽  
Increased Risk ◽  
Vitamin D Levels

Abstract Introduction The potential consequences of vitamin D insufficiency/deficiency (I/D), include increases in ICU length of stay, organ dysfunction, infectious complications, and mortality. Burn patients, in particular, may be at increased risk of vitamin D I/D due to bleeding, systemic inflammatory response syndrome, increased utilization of vitamin D by injured tissues, compromised vascular integrity, fluid shifts, and leakage of vitamin D binding protein (VDBP) and albumin. The purpose of this study is to determine the incidence of vitamin D I/D and evaluate the institutional vitamin D dosing regimen. Methods A retrospective chart review was performed of all adult patients from January 1, 2018 through December 31, 2019 who received cholecalciferol and had at least one vitamin D hydroxy level during their hospitalization. Vitamin D level was drawn on admission, then weekly thereafter. Patients found to be I/D were initiated on high dose vitamin D supplementation and then adjusted based on the weekly levels. The therapeutic goal for vitamin D supplementation was set at 50 ng/ml. Results Three hundred and sixteen patients met criteria for review. Of those patients, 293 patients (93%) were vitamin D I/D. The magnitude of vitamin D deficiency was strongly positively correlated with %TBSA burn size (p< 0.001). Mean time to reach therapeutic vitamin D levels following initiation of supplementation was 19 days with an average weekly dose of 142,877 international units cholecalciferol. Many patients were discharged prior to reaching therapeutic levels. Time to reach therapeutic levels was also positively correlated with increasing burn size (p< 0.05). Conclusions Vitamin D I/D is present is over 90% of burn patients and the degree of I/D was profound. Additionally, vitamin D I/D was not easily corrected, taking almost 3 weeks to reach therapeutic levels using an aggressive supplementation regimen. Further studies documenting the clinical consequences of vitamin D I/D and development of evidence-based supplementation dosing regimens are warranted.

scholarly journals Vitamin D induces myogenic differentiation in skeletal muscle derived stem cells

2017 ◽  
Vol 6 (3) ◽  
pp. 139-150 ◽  
Author(s):  
Melissa Braga ◽  
Zena Simmons ◽  
Keith C Norris ◽  
Monica G Ferrini ◽  
Jorge N Artaza
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Vitamin D ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Myogenic Differentiation ◽  
Vitamin D Supplementation ◽  
Increased Risk ◽  
Risk Of Falls

Skeletal muscle wasting is a serious disorder associated with health conditions such as aging, chronic kidney disease and AIDS. Vitamin D is most widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance. Recently, vitamin D supplementation has been shown to improve muscle performance and reduce the risk of falls in vitamin D deficient older adults. However, little is known of the underlying molecular mechanism(s) or the role it plays in myogenic differentiation. We examined the effect of 1,25-D3 on myogenic cell differentiation in skeletal muscle derived stem cells. Primary cultures of skeletal muscle satellite cells were isolated from the tibialis anterior, soleus and gastrocnemius muscles of 8-week-old C57/BL6 male mice and then treated with 1,25-D3. The efficiency of satellite cells isolation determined by PAX7+ cells was 81%, and they expressed VDR. Incubation of satellite cells with 1,25-D3 induces increased expression of: (i) MYOD, (ii) MYOG, (iii) MYC2, (iv) skeletal muscle fast troponin I and T, (v) MYH1, (vi) IGF1 and 2, (vii) FGF1 and 2, (viii) BMP4, (ix) MMP9 and (x) FST. It also promotes myotube formation and decreases the expression of MSTN. In conclusion, 1,25-D3 promoted a robust myogenic effect on satellite cells responsible for the regeneration of muscle after injury or muscle waste. This study provides a mechanistic justification for vitamin D supplementation in conditions characterized by loss of muscle mass and also in vitamin D deficient older adults with reduced muscle mass and strength, and increased risk of falls.

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