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The effects of vitamin D on skeletal muscle function and cellular signaling
... Therefore, it can be hypothesized that (1) interaction caveolin-1/c-Src inactivates the kinase under basal conditions and (2) when 1α,25(OH) 2 D 3 stimulates VDR translocation to the plasma membrane, it dissociates the caveolin-1/c-Src complex, allowing c-Src activation [52]. The initial activation of c-Src by 1α, 25(OH) 2 D 3 is assumed to be a gateway to the nongenomic actions in myogenic cells [53,54]. 1α,25(OH) 2 D 3 can potentially activate multiple signaling pathways, including cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), PKC, calmodulin/calmodulin-dependent kinase, protein kinase B (PKB/Akt) and multiple mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun NH 2 -terminal 1 and 2 [53]. ...
... The initial activation of c-Src by 1α, 25(OH) 2 D 3 is assumed to be a gateway to the nongenomic actions in myogenic cells [53,54]. 1α,25(OH) 2 D 3 can potentially activate multiple signaling pathways, including cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), PKC, calmodulin/calmodulin-dependent kinase, protein kinase B (PKB/Akt) and multiple mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun NH 2 -terminal 1 and 2 [53]. For example, short hairpin RNA (shRNA)-mediated silencing of VDR in C2C12 myoblasts reduces activation of c-Src, ERK1/2, p38, and Akt induced by 1α,25(OH) 2 D 3 [55,56], suggesting that 1α,25(OH) 2 D 3 exerts nongenomic actions through VDR in myogenic cells. ...
... It should be noted, however, that their relative contribution to myogenesis remains to be established. For further details on nongenomic pathways in myogenic cells, excellent reviews are available [53,54]. ...
... There is some evidence that vitamin D supplementation, particularly in people who are vitamin D deficient, can improve neuromuscular function (12,13). This has been attributed in part to the presence of vitamin D receptors (VDRs) in skeletal muscle and the brain, indicating that the active vitamin D metabolite 1-25-dihydroxyvitamin D can directly target these tissues (14,15), as well as vitamin Dmediated improvements in intracellular muscle calcium transport (16) and increased size and proportion of type II fast-twitch muscle fibers (17). There is also emerging evidence that milk fat globule membrane (MFGM), a complex structure derived from protein and lipid components of milk (18), may augment the effects of exercise on neuromuscular function (19,20). ...
... For the balance and mobility training, participants completed 3 sets of each exercise for a given number of repetitions (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) or length of time (30-60 s). Participants were asked to train at an intensity ("Rate of perceived difficulty") of 8 out of 10 ("very hard" or "very challenging"). ...
... Participants in both groups received 8 sealed cans of a supplemental dry powder and were instructed to consume a serving of 30 g (measured by scoop) twice daily by mixing it with 150 mL of cold water in a plastic shaker. The composition of the MFMD (per 30 g serving) which was sourced from cow milk was 418 kJ energy, 9.1 g protein, 0.7 g fat, 16.5 g carbohydrates, 200 mg phospholipids (from MFGM), 630 mg Ca, 7.5 μg vitamin D, 0.9 mg vitamin B-6, 0.72 μg vitamin B-12, 13.5 mg vitamin C, 2 mg vitamin E, 2 mg Zn, 88 mg Mg, and 0.1 g collagen (hydrolyzed fish). The composition of the placebo (rice powder blend) drink was 418 kJ energy, 1.6 g protein, 1.6 g fat, 25 g carbohydrates, and 30 mg Ca. ...
Background:
Multinutrient protein-enriched supplements are promoted to augment the effects of exercise on muscle mass and strength, but their effectiveness in middle-aged women, or whether there are any additional benefits to physical function, remains uncertain.
Objectives:
We aimed to evaluate whether a multinutrient-fortified milk drink (MFMD) could enhance the effects of exercise on functional muscle power (stair climbing) in middle-aged women. Secondary aims were to evaluate the intervention effects on physical function, muscle strength, lean mass (LM), fat mass (FM), bone mineral content (BMC), muscle cross-sectional area (CSA), muscle density, balance, flexibility, aerobic fitness, inflammation, oxidative stress, bone and cartilage turnover, blood pressure, and blood lipids.
Methods:
In this 4-mo, double-blind, placebo-controlled, randomized trial, 244 women (45-65 y) participated in a multimodal resistance-type exercise program 3 d/wk, with random allocation to a twice-daily MFMD containing added protein, vitamin D, calcium, milk fat globule membrane (phospholipids and other bioactives), and other micronutrients (Ex + MFMD, n = 123) or an energy-matched placebo (Ex + placebo, n = 121).
Results:
A total of 216 women (89%) completed the study. After 4 mo, both groups experienced similar 3.6%-4.3% improvements in the primary outcomes of fast-pace 5- and 10-step stair ascent power. In contrast, Ex + MFMD experienced greater improvements in 5-step regular-pace stair descent time [net difference (95% CI): -0.09 s (-0.18, 0.00 s), P = 0.045], countermovement jump height [0.5 cm (0.04, 1.0 cm), P = 0.038], total body LM [0.3 kg (0.04, 0.60 kg), P = 0.020], FM [-0.6 kg (-1.0, -0.2 kg), P = 0.004], BMC [0.4% (0.1%, 0.6%), P = 0.020], muscle CSA [thigh: 1.8% (0.6%, 2.9%), P = 0.003; lower leg: 0.9% (0.3%, 1.6%), P = 0.005], balance eyes closed [3.3 s (1.1, 5.4 s), P = 0.005], 2-min step performance [8 steps (3, 12 steps), P = 0.003], and sit-and-reach flexibility [1.4 cm (0.6, 2.2 cm), P = 0.026]. MFMD did not enhance the effects of exercise on any measures of muscle strength, gait speed, dynamic balance, reaction time, or blood lipids, and there was no effect of either intervention on blood pressure, markers of inflammation, or cartilage turnover. Ex + placebo had a greater improvement in the oxidative stress marker protein carbonyls (P < 0.01).
Conclusions:
In middle-aged women, daily consumption of an MFMD did not enhance the effects of a multimodal exercise program on the primary outcome of stair climbing ascent power, but did elicit greater improvements in multiple secondary outcomes including various other measures of functional performance, LM, muscle size, FM, balance, aerobic capacity, flexibility, and bone metabolism.This trial was registered at www.anzctr.org.au as ACTRN12617000383369.
... Besides vitamin D's fundamental role in skeletal health, the hormonally active metabolite of vitamin D, calcitriol (1α, 25-dihydroxyvitamin D), has a pivotal immune modulatory function [1]. Other extra-skeletal functions encompass cell proliferation, immune modulation, muscular functionality, skin differentiation and reproduction, safeguarding against insulin resistance, and the mediation of vascular and metabolic properties [3,4]. ...
... Given the significance of these well-established extra-skeletal immune-modulatory and metabolic functions of vitamin D, it is unsurprising that a deficiency in this vital nutrient is implicated in various abnormalities and disorders [3,4]. Notably, vitamin D deficiency has been identified in the literature as an important risk factor for numerous cardiometabolic and inflammatory diseases, such as cardiovascular disease, hypertension, susceptibility to infections and autoimmune disorders [5][6][7][8][9][10]. ...
Vitamin D's role extends beyond classical calcium and phosphate homeostasis to encompass a pivotal influence on immune modulation and metabolic health. The mechanisms by which vitamin D exerts these effects involve its conversion to hormonally active calcitriol, which binds intracellular vitamin D receptors, initiating various downstream cascades. In this review, we tease out the evidence showing the relationship between vitamin D deficiency and prediabetes within the context of subclinical inflammation, with a special focus on the novel monocyte-to-HDL ratio (MHR), a novel inflammatory marker reflecting subclinical inflammation. This was based on a thorough literature review using reputable databases covering the period from 1980 to 2024. In light of this, we discuss calcitriol's anti-inflammatory effects and consequently link vitamin D deficiency to both overt and subclinical inflammation. Additionally, the utility of several bio-markers, notably MHR, in investigating this association is also discussed. We further reviewed the role of vitamin D deficiency in precipitating prediabetes and type 2 diabetes mellitus (T2DM) via insulin resistance, decreased insulin synthesis and secretion, and subclinical inflammation. Taken together, this mini review highlights that vitamin D deficiency is significantly associated with subclinical inflammation, playing a critical role in the development of prediabetes and the progression to T2DM. Addressing vitamin D deficiency through appropriate interventions may serve as a preventative measure against the development of prediabetes and T2DM.
... According to some previous observational cohort studies, a higher concentration of 25-hydroxyvitamin D has been linked to a lower prevalence and incidence of urinary incontinence [12][13][14][15]. Other studies have not found a significant correlation [8][9][10]16]. Elin et al. found in a 2011-2014 study examining the effect of vitamin D supplementation on urinary incontinence in older women that the widespread use of moderate vitamin D supplementation did not reduce urinary incontinence [11]. ...
... Haj Ebrahimi et al. (2012) evaluated the questionnaire's validity and reliability in the Iranian context. Cronbach's alpha was 0.75, while the Pearson correlation was 0.93 [16]. ...
Background
Urinary incontinence, especially stress urinary incontinence (SUI), is one of the problems experienced by premenopausal women. Given the role of vitamin D in enhancing muscle strength and function, this study explored the effect of vitamin D3 supplementation on SUI in premenopausal women.
Methods
A randomized controlled trial was performed with 60 premenopausal women referring to Kerman gynecological clinic in 2020 and 2021. Eligible women received a 5000-unit vitamin D supplement or placebo weekly for 3 months. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) was utilized to assess SUI severity before and after the intervention. The t-test, Chi-square test, and repeated measures ANOVA were carried out in SPSS software (version 22) to analyze the data. P-values smaller than 0.05 were considered significant.
Results
Before the intervention, there was no significant difference between the intervention and control groups in SUI severity (P = 0.652) and the impact of SUI severity on premenopausal women’s lives (P = 0.804). In contrast, after 8-12 weeks of vitamin D supplementation, these scores decreased significantly in the intervention group relative to the control group (P < 0.001). In addition, after vitamin D supplementation, the number of SUI and urinary leakage symptoms decreased in the intervention group (P < 0.001).
Conclusion
Vitamin D supplementation improves SUI in premenopausal women.
Trial registration
This trial was registered with the Iranian Registry of Clinical Trials; https://fa.irct.ir/trial/53474 (IRCT20190724044318N2) on 11/02/2021.
... There is a strong association between the nutritional status of vitamin D and an optimal muscle function (Bhattoa et al., 2017). Indeed, through its binding to muscle vitamin D receptors, vitamin D mediates genomic and non-genomic effects in muscle cells, promoting muscle contractility through calcium uptake, myoblast differentiation, and the insulin sensitivity (Dirks-Naylor and Lennon-Edwards, 2011;Christakos et al., 2016;Bhattoa et al., 2017). Large cross-sectional studies underline a relationship between an insufficient level of serum 25(OH)D (<50 nmol/L) and low physical performance (Bischoff-Ferrari et al., 2004;Houston et al., 2007Houston et al., , 2011Houston et al., , 2012Dirks-Naylor and Lennon-Edwards, 2011;Toffanello et al., 2012), mobility (Bischoff-Ferrari et al., 2004;Houston et al., 2011Houston et al., , 2012Toffanello et al., 2012), muscle strength (Mowé et al., 1999;Zamboni et al., 2002;Houston et al., 2007Houston et al., , 2011Houston et al., , 2012Toffanello et al., 2012), and greater disability (Zamboni et al., 2002;Houston et al., 2011). ...
... Indeed, through its binding to muscle vitamin D receptors, vitamin D mediates genomic and non-genomic effects in muscle cells, promoting muscle contractility through calcium uptake, myoblast differentiation, and the insulin sensitivity (Dirks-Naylor and Lennon-Edwards, 2011;Christakos et al., 2016;Bhattoa et al., 2017). Large cross-sectional studies underline a relationship between an insufficient level of serum 25(OH)D (<50 nmol/L) and low physical performance (Bischoff-Ferrari et al., 2004;Houston et al., 2007Houston et al., , 2011Houston et al., , 2012Dirks-Naylor and Lennon-Edwards, 2011;Toffanello et al., 2012), mobility (Bischoff-Ferrari et al., 2004;Houston et al., 2011Houston et al., , 2012Toffanello et al., 2012), muscle strength (Mowé et al., 1999;Zamboni et al., 2002;Houston et al., 2007Houston et al., , 2011Houston et al., , 2012Toffanello et al., 2012), and greater disability (Zamboni et al., 2002;Houston et al., 2011). The importance of considering baseline serum 25(OH)D concentrations has been emphasized, since individuals with vitamin D deficiency appear to be more responsive to supplementation (Annweiler et al., 2009). ...
Carnitine palmitoyltransferase II (CPTII) deficiency is the most frequent inherited disorder regarding muscle fatty acid metabolism, resulting in a reduced mitochondrial long-chain fatty acid oxidation during endurance exercise. This condition leads to a clinical syndrome characterized by muscle fatigue and/or muscle pain with a variable annual frequency of severe rhabdomyolytic episodes. While since the CPTII deficiency discovery remarkable scientific advancements have been reached in genetic analysis, pathophysiology and diagnoses, the same cannot be said for the methods of treatments. The current recommendations remain those of following a carbohydrates-rich diet with a limited fats intake and reducing, even excluding, physical activity, without, however, taking into account the long-term consequences of this approach. Suggestions to use carnitine and medium chain triglycerides remain controversial; conversely, other potential dietary supplements able to sustain muscle metabolism and recovery from exercise have never been taken into consideration. The aim of this review is to clarify biochemical mechanisms related to nutrition and physiological aspects of muscle metabolism related to exercise in order to propose new theoretical bases of treatment which, if properly tested and validated by future trials, could be applied to improve the quality of life of these patients.
... Based on these results, there seems to be a positive association between 25(OH)D and muscle health. In fact, there is evidence demonstrating the role of Vit D on calcium uptake in muscle cells [28] and the presence of Vit D receptors in them [29], which might have effects on muscle contraction. ...
The aim was to compare changes in body composition, physical fitness, and bone biomarkers in female children and adolescent football players with different Vitamin D levels. Twenty-two players were classified into two groups according to 25(OH)D concentrations: 11 with deficient/insufficient 25(OH)D levels (IVD; <30 ng/mL) and 11 with sufficient 25(OH)D levels (SVD; ≥30 ng/mL). Body composition parameters were measured using dual-energy X-ray absorptiometry and a peripheral quantitative computed tomography scanner. The following physical fitness tests were applied: maximal isometric knee extension (MIF), long jump, 30-m sprint, and 20-m shuttle run test (VO2max). Electrochemiluminescence immunoassays were used to analyze bone biomarkers and 25(OH)D. All variables were registered at the beginning and the end of the football season. The increase in subtotal bone mineral density (BMD) was higher in players with SVD than those with IVD (p = 0.030). Only players with SVD improved their MIF of the left leg (p = 0.005); whereas, only players with IVD decreased their 30-m sprint performance (p = 0.007) and VO2max (p = 0.046). No significant between- and within-group differences were found for bone biomarkers. SVD might cause an extra improvement of subtotal BMD in female children and adolescent football players. Moreover, it seems that the 25(OH)D concentration could be an important parameter for physical fitness improvement in this population.
... Improvement in kidney function following kidney transplantation is associated with modifications in the plasma level of three important mineral metabolism hormones, which have also been linked to muscle mass: parathormone (PTH), calcitriol, and FGF23. 16,[29][30][31] Further adjusting the model for the plasma level of these hormones did not modify the association between ioGFR with CER 3 ( Table S3). The correlation between urine creatinine excretion and muscle mass can be considered a reasonably reliable assumption only in the steady state conditions. ...
Background:
Advanced chronic kidney disease is associated with muscle wasting, but how glomerular filtration rate (GFR) recovery after kidney transplantation is associated with muscle mass is unknown.
Methods:
We took advantage of the simultaneous measurement of GFR (using iohexol plasma clearance; ioGFR) and creatinine excretion rate (a surrogate marker of muscle mass; CER) performed 3 months after transplantation and at a later time point at our institution to investigate the interplay between allograft function, muscle mass, and outcome in kidney transplant recipients.
Results:
Between June 2005 and October 2019, 1319 successive kidney transplant recipients (mean age 50.4 ± 14.6; 38.7% female) underwent GFR measurement at our institution 3 months after kidney transplantation. CER (CER3 ) and ioGFR (ioGFR3 ) were 7.7 ± 2.6 μmol/min and 53 ± 17.1 mL/min/1.73 m2 , respectively. Multivariable analysis identified female gender, older donor and recipient age, reduced body mass index, coronary disease, dialysis history, proteinuria, and reduced ioGFR3 as independent predictors of low CER3 (ioGFR3 : β coefficient 0.19 [95% confidence interval 0.14 to 0.24]). A total of 1165 patients had a subsequent CER measurement after a median follow-up of 9.5 months. Of them, 373 (32%) experienced an increase in CER > 10%, while 222 (19%) showed a CER decrease of more than 10%. Multivariable analysis adjusted for CER3 and other confounders identified ioGFR3 as an independent predictor of CER at follow-up (β coefficient 0.11 [95% confidence interval 0.07 to 0.16]). In multivariable Cox analysis, reduced CER at 3 months or at follow-up were consistently associated with mortality (hazard ratio [95% confidence interval] at 3 months: 0.82 [0.74 to 0.91]; at follow-up: 0.79 [0.69 to 0.99]) but not with graft loss.
Conclusions:
Glomerular filtration rate recovery is a determinant of muscle mass variation after kidney transplantation. Early interventions targeting muscle mass gain may be beneficial for kidney transplant recipients.
... Vitamin D supports maintenance of cellular oxidation level and normal mitochondrial functions [125][126][127][128]. It has been suggested that vitamin D level can directly affect injury risk, supports recovery, bone health [129], and is essential for optimal muscle function [129][130][131][132][133][134][135]. ...
Fatigue is a phenomenon associated with decreases in both physical and cognitive performances and increases in injury occurrence. Competitive athletes are required to complete demanding training programmes with high workloads to elicit the physiological and musculoskeletal adaptations plus skill acquisition necessary for performance. High workloads, especially sudden rapid increases in training loads, are associated with the occurrence of fatigue. At present, there is limited evidence elucidating the underlying mechanisms associating the fatigue generated by higher workloads and with an increase in injury risk. The multidimensional nature and manifestation of fatigue have led to differing definitions and dichotomies of the term. Consequently, a plethora of physiological, biochemical, psychological and performance markers have been proposed to measure fatigue and recovery. Those include self-reported scales, countermovement jump performance, heart rate variability, and saliva and serum biomarker analyses. The purpose of this review is to provide an overview of the fatigue and recovery plus methods of assessments.
... One proposed explanation is an interruption of calcium deposition in collagen matrices of bone, which results in malformation of pathologically soft bone that continues to expand and exerts pressure on periosteal surfaces and subsequently on sensory pain receptors [45]. Other mechanisms that have been suggested include a reduction in nerve conduction velocity resulting in muscular atrophy and myopathy [46,47] and hyperparathyroidism by way of proteolysis of muscle leading to fatigue and muscle, bony and joint pain, however the mechanism for vitamin D deficiency in non-cyclical breast pain is unclear. Recent studies have shown that vitamin D receptors are available in almost all cells [48] and current theories around the pathogenesis of this heightened pain response implicates an exaggerated immune possibly as a reaction to infection and sensitisation of pain signalling pathways [49,[50][51][52]. ...
... The production of this active metabolite by the kidneys regulates the metabolism of calcium and phosphorus. Importantly, 25 (OH) D can be locally converted to 1,25 (OH) 2D3 in many tissues, which plays an autocrine or paracrine role in regulating various cellular processes such as cell growth, differentiation and apoptosis [4]. Every tissue in the body expresses a vitamin D receptor (VDR) that regulates both genomic and non-genomic responses to 1,25-(OH) 2D3 [5]. ...
Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.
... Second, Vitamin D increases the growth plate cells' sensitivity to growth hormone, which has an important influence on linear growth in school-aged children (9). Third, vitamin D may help muscle growth through vitamin D receptors (VDR) (37). It conducts this role by stimulation of the production of new proteins involving in muscle cell proliferation, differentiation, and contractility and the regulation of calcium transport in the sarcoplasmic reticulum (38,39). ...
Introduction: Undernutrition, defined as stunting, wasting, and underweight, still implicates millions of infants and children worldwide. Micronutrients have pivotal effects on growth rate. The outcomes of vitamin D deficiency on undernutrition indices have stayed controversial. The object of current study is to answer this question: is there any association between vitamin D status and undernutrition indices?
Methods: The international databases were used for a systematic search to identify relevant observational studies in English up to January 2021. A random-effect model was applied to combine the results of included essays.
Results: Among 3,400 citations, 7 observational studies (4 cohorts and 3 cross-sectional) were eligible to enter in meta-analysis. Analysis of the lowest 8,295 children indicated that low vs. high serum level of vitamin D is directly associated with a higher risk of wasting (Summary Risk Estimate: 1.30; 95% CI: 1.04, 1.62; I ² = 0%). However, there is no significant association between vitamin status and risk of stunting (Summary Risk Estimate: 1.10; 95% CI: 0.72, 1.70; I ² = 81.6%) and underweight (Summary Risk Estimate: 1.12; 95% CI: 0.81, 1.56; I ² = 49.2%).
Conclusion: When comparing low and high serum vitamin D concentration categories, there is an inverse link between vitamin D status and wasting, but no relationship with stunting as well as underweight. However, further prospective and trial studies are required to deepen our understanding of these associations.
... Beside the many functions of vitamin D in metabolism, recent studies in humans and mice have indicated that chronic vitamin D deficiency, which is highly prevalent in the general population, leads to muscle atrophy (particularly in type II fibers), lower strength, lower mitochondrial function, and decreased vitamin D receptor expression (34)(35)(36)(37). In addition, vitamin D deficiency may impair muscle regeneration (38) and therefore perhaps also the muscle hypertrophic response to overload. ...
Vitamin D deficiency, which is highly prevalent in the general population, exerts similar deleterious effects on skeletal muscles to those induced by cigarette smoking. We examined whether cigarette smoke (CS) exposure and/or vitamin D deficiency impairs the skeletal muscle hypertrophic response to overload. Male C57Bl/6JolaH mice on a normal or vitamin D-deficient diet were exposed to CS or room air for 18 weeks. Six weeks after initiation of CS or air exposure, sham surgery or denervation of the agonists of the left plantaris muscle was performed. The right leg served as internal control. Twelve weeks later, the hypertrophic response was assessed. CS exposure instigated loss of body and muscle mass, and increased lung inflammatory cell infiltration (p<0.05), independently of diet. Maximal exercise capacity, whole body strength, in situ plantaris muscle force and key markers of hypertrophic signaling (Akt, 4EBP1, FoxO1) were not significantly affected by smoking or diet. The increase in plantaris muscle fiber cross-sectional area in response to overload was attenuated in vitamin D-deficient CS-exposed mice (smoking x diet interaction for hypertrophy, p=0.03). In situ fatigue resistance was elevated in hypertrophied plantaris, irrespective of vitamin D deficiency and/or CS exposure. In conclusion, our data show that CS exposure or vitamin D deficiency alone did not attenuate the hypertrophic response of overloaded plantaris muscles, but this hypertrophic response was weakened when both conditions were combined. These data suggest that current smokers who also present with vitamin D deficiency may be less likely to respond to a training program.
... Another possible indirect effect of vitamin D might be defined through osteocalcin. This osteoblast-derivative bone output marker could amend beta-cell propagation, insulin secretion, and insulin sensitivity (Bouillon et al. 2008;Dirks-Naylor and Lennon-Edwards 2011;Harinarayan 2014). ...
Background
Findings of observational studies that investigated the relationship between vitamin D deficiency and abnormal glucose homeostasis were contradictory. This meta-analysis of epidemiologic studies evaluated the association of vitamin D status and risk of type-2 diabetes (T2D) and prediabetes in adults.
Methods
A systematic search was conducted on all published articles in five electronic databases (including MEDLINE/PubMed, EMBASE, Institute for Scientific Information, Scopus and Google scholar), up to August 2020. Twenty-eight prospective cohort and nested case-control studies and 83 cross-sectional and case-control investigations that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for abnormal glucose homeostasis in relation to serum vitamin D levels in adults were included in the analysis.
Results
In prospective studies, high versus low level of vitamin D was respectively associated with significant 35%, 30% and 51% decrease in risk of T2D (RR:0.65; 95%CI: 0.55–0.76; 27 effect sizes), combined T2D and pre-diabetes (RR:0.70; 95%CI: 0.52–0.95; 9 effect sizes) and pre-diabetes (RR:0.49; 95%CI: 0.26–0.93; 2 effect sizes). These inverse associations were significant in almost all subgroups. Dose–response analysis in prospective studies showed that each 10 ng/ml increase in serum vitamin D levels resulted in 12% and 11% reduced risk of T2D (RR:0.88; 95%CI: 0.83–0.94) and combined T2D and prediabetes (RR:0.89; 95%CI: 0.87–0.92), respectively. In cross-sectional and case-control studies, highest versus lowest level of serum vitamin D was linked to reduced odds of T2D (OR:0.64; 95%CI: 0.57–0.72; 42 effect sizes) and combined T2D and pre-diabetes (OR:0.79; 95%CI: 0.74–0.85; 59 effect sizes); but not pre-diabetes (OR:0.64; 95%CI: 0.17–2.37; 11 effect sizes).
Conclusion
This meta-analysis of epidemiologic studies disclosed that serum vitamin D level was reversely associated with the risk of T2D and combined T2D and prediabetes in adults, in a dose–response manner. However, the association was not remarkable for pre-diabetes.
... Vitamin D has varied functions in skeletal muscle, including calcium homeostasis, cell proliferation and differentiation, prevention of fatty degeneration, protection against insulin resistance, and arachidonic acid mobilization [81]. Multiple studies and systematic reviews have found a significant association between low levels of vitamin D and muscle dysfunction and decline in physical performance [82,83]. ...
Purpose of Review
Decades of research on nutrition and exercise on athletes and bodybuilders has yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients.
Recent Findings
For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source and supplemented with vitamin D and leucine. Agents like hydroxyl β-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandralone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes.
Summary
Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.
... According to the longterm mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription (4). According to the short-term mechanism, it affects skeletal muscle contraction through regulation of calcium-mediated secondary messengers (5). It is assumed that gradual loss of muscle mass and loss of muscle function in the elderly may also be associated with decreased VDR expression in skeletal muscle cells (6). ...
Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) µg/L, and 11.6 (11.6-34.9) µg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.
... According to the longterm mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription (4). According to the short-term mechanism, it affects skeletal muscle contraction through regulation of calcium-mediated secondary messengers (5). It is assumed that gradual loss of muscle mass and loss of muscle function in the elderly may also be associated with decreased VDR expression in skeletal muscle cells (6). ...
Context:
Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription.
Objective:
We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men.
Design:
Cross-sectional study.
Subjects and methods:
Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups.
Results:
Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05).
Conclusions:
Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.
... Although vitamin D levels were not measured herein, vitamin D may also influence both calcium levels and skeletal muscle. Considering that vitamin D regulates calcium homeostasis, 1,25-dihydroxyvitamin D3-induced calcium flux and alteration in calcium signaling may play a role in regulating muscle contractile force in differentiated muscle fibers [33]. It is also notable that the decline in muscle mass and function with age is concurrent with a decline in skeletal muscle vitamin D receptor expression [34]. ...
The aim of this study was to investigate the longitudinal change in muscle mass over 10 years according to serum calcium levels and calcium intake. A total of 1497 men and 1845 women aged 50 years and older were included. Significant muscle loss (SML) was defined as a 5% or greater loss from baseline, while time-dependent development of SML was assessed according to quartiles for corrected calcium level and daily calcium intake using Cox regression models. The incidence of SML was 6.7 and 7.7 per 100-person-years among men and women, respectively. Groups with the lowest corrected calcium levels had more prominent SML than those with higher calcium levels, regardless of sex. The relationship between SML and calcium intake was significant only among women. The hazard ratio for SML per 1 mmol/L increase in corrected calcium level was 0.236 and 0.237 for men and women, respectively. In conclusion, low serum calcium levels may predict SML among adults aged ≥ 50 years, while low calcium intake may be a predictor for muscle loss among women. Therefore, encouraging dietary calcium intake among middle-aged and older adults for preservation of muscle mass should be considered.
... In the first action pathway, vitamin D acts directly on skeletal muscle cells by accelerating the entry of Ca 2+ ions into bone tissue through the osteoblast cell membrane, which promotes bone salt deposition, increases bone calcium storage, and enhances muscle contraction (46). Furthermore, vitamin D can also act on the nucleus of intestinal mucosal cells, promotes the biosynthesis of calcium transporter, accelerates combination with calcium into a soluble complex, induces absorption of calcium, and promotes absorption of phosphorus through the calcium and phosphorus balance mechanism (47). ...
Background: Vitamin D and complement components shared some common pathophysiological pathways in the musculoskeletal system, circulation, and metabolism, which were linked to physical function. It is hypothesized that serum complement components may interact with vitamin D in respect of the physical activities of daily living (PADLs).
Objective: To investigate if serum complement components 3 (C3), complement components 4 (C4), and 25-hydroxyvitamin D [25(OH)D] associate with PADLs, and to examine whether the association between 25(OH)D levels and PADLs varies at different complement component levels among Chinese centenarians.
Methods: This study was conducted in a group of population-based centenarians. PADLs were evaluated using the Barthel Index. Multiple regressions were used to analyze the associations among 25(OH)D, complements C3 and C4, and PADLs.
Results: Among 943 participants, 672 (71.3%) had physical dependence (PD). After adjusting for potential confounders, serum 25(OH)D and C3 levels were positively correlated with PADLs, while C4 levels were negatively correlated with PADLs (Ps < 0.05). Serum 25(OH)D levels significantly interacted with both C3 (P for interaction = 0.033) and C4 (P for interaction = 0.006) levels on PADLs. At lower complement component levels, the multivariate odds ratios (ORs) of the upper tertile of vitamin D for PD were 0.32 (95% CI: 0.18–0.55) in the C3 group and 0.29 (95% CI: 0.16–0.50) in the C4 group. At higher complement component levels, the ORs in the C3 and C4 groups were not statistically significant.
Conclusions: In a group of population-based Chinese centenarians, we observed that serum complement C3 and 25(OH)D levels were positively associated with PADLs, while C4 was negatively associated with PADLs. The associations between 25(OH)D levels and PADLs were more pronounced in groups with lower serum complement component levels.
... A v.D3 aumenta força e função de fibras tipo II. Atua na homeostase do cálcio, na proliferação e diferenciação de mioblastos, na proteção contra degeneração gordurosa e RI e na redução do ácido araquidônico 12,13 . Idosos estão sob risco aumentado para deficiência de v.D3 devido a diminuição de síntese pela pele e pelos rins, exposição solar insuficiente e baixo consumo de alimentos em que ela abunde 8 . ...
RESUMO
Sarcopenia e uma sindrome caracterizada por acometimento progressivo e generalizado da musculatura esqueletica de idosos e causa sua perda de massa e funcao (forca ou desempenho). A etiologia e multifatorial e, ainda, pouco compreendida. Cursa com reducao da mobilidade e da qualidade de vida, resultando em aumento da morbimortalidade. Sua prevalencia vem aumentando gradativamente conforme a populacao envelhece, fazendo crescerem as demandas por recursos de saude. Isso torna imperioso que se estude esta patologia mais a fundo. Foi realizada revisao de artigos que abordam o tema sarcopenia, com destaque para intervencoes terapeuticas, publicados a partir de 2010 ate o primeiro semestre de 2015. Concluiu-se que o tratamento baseia-se, principalmente, em mudanca do estilo de vida, ou seja, atividade fisica e maior ingestao proteica. Adiciona-se farmacoterapia naqueles com indicacao para tal, como vitamina D e testosterona. Devem ser considerados creatina e β-hidroximetilbutirato, entre outros.
... Findings from observational studies have shown that the low levels of 25(OH)D are associated with higher a rate of general and abdominal obesity as well as muscle weakness in children and elderly subjects [60][61][62]. Vitamin D may affect muscle function through vitamin D receptor (VDR), resulting in muscle growth [63]. This induces the synthesis of new proteins affecting muscle cell contractility, proliferation, and differentiation as well as the regulation of calcium transport in the sarcoplasmic reticulum [64,65]. ...
Purpose:
Wasting is a main indicator of Child's undernutrition that is associated with several non-communicable diseases and child mortality. This is the first population-based study which evaluated the association of serum zinc and vitamin D levels with wasting in a Middle East region. We also reported the prevalence of vitamin D and zinc deficiencies among Iranian pre-school children aged 6 years.
Methods:
This was a multicenter cross-sectional study that included 425 children aged between 5 and 7 years (on average 6 years) with BMI-for-age Z-scores of < - 1 SD resident in urban and rural areas of Iran in the spring of 2012 as part of the National Integrated Micronutrient Survey 2 (NIMS-2). Anthropometric measurements and blood sampling were obtained. The prevalence of vitamin D and zinc deficiencies together with the correlations of these variables with the increase of BMI-for-age Z-scores were evaluated.
Results:
The prevalence of vitamin D and zinc deficiencies was 18.8% and 12.7%, respectively. In addition, 31.1% of children were wasted. Children in the second tertile of 25(OH)D levels were less likely to have wasting compared with those in the first tertile in both crude and adjusted models (OR 0.47, 95% CI 0.27-0.83). A significant inverse association was found between serum levels of zinc and wasting (OR 0.57, 95% CI 0.34-0.96); such that after adjusting for confounders, children in the highest tertile of serum zinc had 47% less odds of wasting compared with those in the first tertile (OR 0.53, 95% CI 0.31-0.91).
Conclusion:
The prevalence of vitamin D and zinc deficiencies among Iranian pre-school children aged 6 years was 18.8 and 12.7%, respectively. Serum levels of vitamin D and zinc were inversely associated with wasting either before or after controlling for confounders.
Level of evidence:
Level III, case-control analytic studies.
... In muscle, vitamin D activates protein kinase C, which promotes calcium release, increasing the calcium pool that is essential for muscle contraction [64]. The potential cell signalling pathways affected by vitamin D in muscle have been recently reviewed [65]. Vitamin D deficiency has long been clinically associated with impaired muscle strength [66] and is also associated with loss of muscle mass [67]. ...
... In the first mechanism, vitamin D can induce the synthesis of myogenic transcription factors and contractile proteins that affect cell proliferation and differentiation by nuclear VDR-related gene transcription in myoblasts (22,23). Effects on the nongenomic path may occur rapidly, and vitamin D may interact with the calcium system to increase signal transduction affecting skeletal muscle contraction (24). Despite animal studies that clearly define the role of vitamin D on skeletal muscle, the effects of vitamin D on human muscle remain controversial due to inconsistent clinical outcomes (10, 16,25). ...
Objective: Although there is increasing evidence about the role of vitamin D on muscle function, its relationship with grip strength is still a controversial issue. The aim of this cross-sectional clinical study was to evaluate the relationship between vitamin D and grip strength in premenopausal Turkish women.
Materials and Methods: A total of 127 women with an age range of 40–50 (44.7+-4.3) years who were premenopausal and sedentary were included in this cross-sectional descriptive study. The mean body mass index (BMI) was 30.2+-5.3 kg/m2. Dominant and nondominant grip strengths were measured by digital hand dynamometer.
Results: The mean dominant and nondominant grip strengths were 24.2+-5.9 kg and 22.5+-5.7 kg, respectively. Mean serum 25-hydroxyvitamin D (25OHD) concentration was 16.4+-9.7 ng/ml. Participants were divided into three groups as vitamin D deficiency (70.9%), insufficiency (18.1%), and sufficiency (11.0%). No statistically significant difference was found between the groups with respect to age, BMI, and dominant and nondominant grip strengths (p>0.05). Furthermore, no significant relationship was found between serum 25OHD concentration and dominant and nondominant grip strengths (p>0.05). In addition, BMI was not associated with dominant and nondominant grip strengths (p>0.05).
Conclusion: These results of this study provide evidence that vitamin D is not effective on grip strength at least in premenopausal Turkish women.
... Vitamin D deficiency may contribute to myopathy, decreased muscle tone, and imbalance and degradation of type II muscle fibers. This may have a negative impact on muscle strength, power and work [9,10]. ...
The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal cells, including skeletal muscles. Vitamin D deficiency may cause deficits in strength, and lead to fatty degeneration of type II muscle fibers, which has been found to negatively correlate with physical performance. Vitamin D supplementation has been shown to improve vitamin D status and can positively affect skeletal muscles. The purpose of this study is to summarize the current evidence of the relationship between vitamin D, skeletal muscle function and physical performance in athletes. Additionally, we will discuss the effect of vitamin D supplementation on athletic performance in players. Further studies are necessary to fully characterize the underlying mechanisms of calcitriol action in the human skeletal muscle tissue, and to understand how these actions impact the athletic performance in athletes.
... − Vitamin D favors muscle contractility through calcium inflow, myoblast differentiation, and insulin sensitivity regulation. The current RDA for vitamin D intake is 600 IU/day for persons aged 1-70 years [56, [97][98][99][100]. − N-3 Polyunsaturated Fatty Acids are noted for their antiinflammatory function. ...
INTRODUCTION
Ovarian cancer is the leading cause of death among gynecological malignancies. Its usual clinical manifestation is at advanced stages, with nutritional impairment, weight loss, and a consequent decline in skeletal muscle mass and strength (defined as sarcopenia). The relationship between sarcopenia and decreased survival was demonstrated not only in ovarian cancer but also in other cancer types, such as hepatocellular, pancreatic, lung, colon, cervical, metastatic breast, and renal cancer. The aim of this study is to review the current evidence regarding the relationship between sarcopenia and the surgical and oncological outcomes in ovarian cancer patients.
METHODS
The systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) statement. The terms “SARCOPENIA” AND “OVARIAN CANCER” were systematically used to search PubMed and Scopus databases. Original reports in English language were identified, with the purpose to include all relevant papers regarding the role of sarcopenia and indicators of skeletal muscle quality assessment in gynecological ovarian cancer.
RESULTS
A total of 9 studies were considered eligible for the present review. The strength of recommendation was moderate and the level of evidence was low in all selected articles. No prospective studies were conducted and most of the papers were case-control series comparing ovarian cancer sarcopenic population vs. non sarcopenic population.
CONCLUSIONS
Sarcopenia appears to have an important role in oncological outcomes of ovarian cancer patients. However, sarcopenia occurrence during disease history and mechanisms underlying the possible impairment in prognosis should be better investigated. Prospective trials are awaited in order to obtain a better insight in this topic.
... 11 VDR is found in the kidneys, lungs, intestines, gonads, skin, smooth muscle, heart muscle, and skeletal muscle. 1 These processes are mediated through genomic and non-genomic mechanisms. 12 Both genomic and non-genomic mechanisms are involved in regulating metabolic processes, transcription, and gene expression in skeletal muscles by stimulating intracellular calcium control (calcium channel membrance regulation), myocytic differentiation, contraction of protein expression, hypertrophy, and improved mitochondrial function. It has been suggested that vitamin D can improve contraction, growth, and muscle strength. ...
Introduction
Vitamin D is a potent secosteroid hormone that provides many health benefits. The ubiquitous nature of vitamin D receptor (VDR) suggests widespread effect.
Purpose
The purpose of this study was to investigate the relationship between 25-hydroxyvitamin D (25OHD) levels and muscle strength, maximal oxygen consumption (VO2max), and body mass index (BMI) in Iranian young and middle adulthood women.
Participants and methods
A cross-sectional descriptive study was conducted in 182 healthy Iranian women within the age range of 26–60 years. Body weight and height were measured, and BMI was calculated. VO2max was determined by the Rockport test. Muscle strength was determined by the chest press, leg press, and hand grip test. Also, circulating levels of 25OHD were evaluated.
Results
Results showed a significant relationship between 25OHD levels and BMI, VO2max, and muscle strength (chest press, leg press, hand grip dominant hand [HGDH], and hand grip nondominant hand [HGNDH]) in young and middle adulthood women (BMI in young and middle adulthood: r=−0.48, P<0.001 and r=−0.27, P=0.01, respectively; VO2max in young and middle adulthood women: r=0.69, P<0.001 and r=0.57, P<0.001, respectively; chest press, leg press, HGDH, and HGNDH in young adulthood: r=0.58, r=0.59, r=0.65, and r=0.42, respectively, P<0.001; and in middle adulthood: r=0.73, r=0.34, r=0.66, and r=0.55, respectively, P≤0.001). Multiple linear regression analysis showed that higher levels of VO2max, HGDH, and chest press predicted higher 25OHD levels in the young adulthood women (R²=0.75; β=0.39, β=0.35, and β=0.30, respectively; P<0.001). Moreover, VO2max and HGDH were the strongest predictor of 25OHD levels in the middle adulthood women (R²=0.71; β=0.35, β=0.40, respectively; P<0.001).
Conclusion
Based on the results, it could be concluded that VO2max and strength are useful indirect marker for 25OHD levels in the young and middle adulthood women. It also seems that VO2max and HGDH strength had stronger associations with 25OHD levels in the young adulthood women, and chest press and HGDH had stronger associations with 25OHD levels in the middle adulthood women.
... Other mechanisms that have been suggested include a reduction in nerve conduction velocity resulting in muscular atrophy and myopathy [33,34] and hyperparathyroidism by way of proteolysis of muscle leading to fatigue and muscle, bony and joint pain, however the mechanism for vitamin D deficiency in non-cyclical breast pain is unclear. Recent studies have shown that vitamin D receptors are available in almost all cells [35] and current theories around the pathogenesis of this heightened pain response implicates an exaggerated immune possibly as a reaction to infection and sensitisation of pain signalling pathways [19,[36][37][38]. This would reflect how vitamin D deficiency is linked to a number of multi-organ disease states and could be the underlying mechanism by which vitamin D deficiency results in breast tissue tenderness. ...
Objective: Non-cyclical mastalgia is a common presenting complaint, poorly understood and difficult to manage. Vitamin D deficiency has been linked with breast and musculoskeletal pain in both non-Caucasians populations as well as breast cancer patients receiving aromatase inhibitor treatment. Our catchment has a high proportion of non- Caucasian inhabitants and in the temperate climate of the UK, they are at high risk of Vitamin D deficiency. This study aims to investigate if supplementation can improve non-cyclical mastalgia.Methods: Prospective pilot survey of all patients with non-cyclical mastalgia and Vitamin D deficiency seen at one centre within a two year period. All patients with low Vitamin D levels were referred to their general practitioners (GPs) for appropriate management. A follow up questionnaire was then sent to analyse treatment response.Results: A total of 68 out of 110 patients completed questionnaires. 63% of patients were prescribed Vitamin D by their GP and complied with the therapy. 51% of these noted complete or near complete remission of symptoms following therapy. 26% noted a pain score of <5 following therapy. 23% noted a residual pain score of >5 despite therapy. 3 out of the 18 patients who did not receive Vitamin D noted spontaneous improvement in pain.Conclusion: This pilot study shows a correlation between Vitamin-D deficiency and non-cyclical mastalgia. Improvement of symptoms was seen in 77% of patients following supplementation and only 17% of spontaneous improvement without treatment (p<0.01). Further study by way of a blinded randomized control trial is required to quantify this correlation.
Aims
Cross‐sectional studies demonstrate an association between low serum levels of vitamin D and slower gait speed in older individuals. However, longitudinal studies remain inconclusive. This study investigates whether vitamin D deficiency and insufficiency are risk factors for the incidence of slowness.
Materials and Methods
A total of 2815 participants from the English Longitudinal Study of Ageing (ELSA), aged ≥60 years and with a baseline gait speed >0.8 m/s, were followed for six years. Baseline serum levels of vitamin D [25(OH)D] were categorized as “sufficiency” (>50 nmol/L), “insufficiency” (>30 and ≤50 nmol/L) or “deficiency” (≤30 nmol/L). Gait speed was reassessed at four and six years of follow‐up to identify incident cases of slowness (walking speed ≤0.8 m/s). A Poisson regression model, adjusted for sociodemographic, behavioural and clinical characteristics at baseline, was conducted to determine the association between serum 25(OH)D levels and the risk of slowness.
Results
The incidence densities of slowness per 1000 person‐years were 67.4 (95% CI: 60.93–74.64) for sufficiency, 76.7 (95% CI: 68.30–86.22) for insufficiency and 90.7 (95% CI: 78.46–104.92) for deficiency. Serum 25(OH)D deficiency was associated with a 22% increase in the risk of slowness (IRR: 1.22; 95% CI: 1.01–1.49) compared with serum 25(OH)D sufficiency. No significant association was observed for serum 25(OH)D insufficiency.
Conclusions
Serum 25(OH)D deficiency is a risk factor for the incidence of slowness in older individuals, suggesting that maintaining sufficient 25(OH)D levels could be a strategic approach to minimise long‐term mobility impairment.
Cardiovascular parameters and cardiorespiratory fitness in adolescents may be influenced by eating habits. The aim was to evaluate the association between the levels of some nutrients and micronutrients with blood pressure and VO 2max in adolescents. A total of 60 adolescents (15.77 ± 0.96 years old) participated in the study, of whom 35 were girls and 25 were boys. Eating habits were assessed frequency questionnaire (FFQ). Before and after a cardiorespiratory fitness test (YOYO TEST), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected. A backward elimination method of multiple regression was performed to analyse the data. A positive association was found between VO 2max and the intake of iron ( ), vitamin D ( ), vitamin B6 ( ) and vitamin B12 ( ) for girls. Additionally, no significant associations were found between sugar, fibre and fat intake and VO 2max . There was a positive association between SBP and sugar intake ( ) for girls and negative association between DBP after exertion and fibre intake ( ) and body mass index ( ) for boys. There is a positive association between the intake of iron, vitamins and VO 2max in girls and intake of sugar with SBP for girls and negative association between fibres and DBP after exertion for boys.
Background:
This study explores the association between vitamin D deficiency and distal biceps tendon injuries, illustrating that, although vitamin D deficiency is associated with prolonged hospital stays and various musculoskeletal problems, its connection to distal biceps tendon injuries is unknown.
Hypothesis:
Vitamin D deficiency is associated with an elevated risk of distal biceps injury but not with increased rates of subsequent surgery or revision surgery.
Study Design:
Case-control study.
Level of Evidence:
Level 3.
Methods:
A 1:1 matched retrospective comparative study of 336,320 vitamin-D-deficient patients was performed using PearlDiver data (between January 1, 2011 and October 31, 2018). Cohorts, with a mean age of 55.7 ± 13.2 years, underwent multivariate logistic regression to calculate distal biceps tendon injury and surgical repair incidence according to age and sex, while controlling for demographics and comorbidities.
Results:
The 1-year incidence of distal biceps tendinopathy in vitamin-D-deficient patients was 118 per 100,000 person-years (95% CI) compared with 44.3 per 100,000 person-years in matched controls. Male patients with vitamin D deficiency were at a greater risk for distal biceps tendinopathy after 1 and 2 years (adjusted odds ratio [aOR] = 2.81, 2.08-3.83; aOR = 2.80, 2.21-3.56). Female patients were also at a greater risk after both years (aOR = 1.69, 1.27-2.27; aOR = 1.57, 1.26-1.96). Vitamin D deficiency was not associated with an elevated risk of surgical repair or revision surgery.
Conclusion:
In a nationwide cohort, a diagnosis of vitamin D deficiency elevated the risk of distal biceps tendinopathy but did not raise the rate of surgical repair or revision. As a result, prevention strategies in the form of vitamin supplementation should be increased for athletes.
Clinical Relevance: These findings emphasize the clinical relevance of monitoring vitamin D levels in patients at risk for musculoskeletal injuries, and providing adequate care to those involved in high-demand physical activities.
Context
Although several investigations have been conducted on the association between serum vitamin D levels and prediabetes and type 2 diabetes mellitus (T2DM) in children and adolescents, their findings are inconsistent.
Objective
We conducted a systematic review and dose-response meta-analysis to summarize this subject.
Data Sources
The electronic databases of ISI Web of Science, Scopus, PubMed, and motor engineering of Google Scholar were comprehensively searched up to May 2023.
Data Extraction
Epidemiologic studies that investigated the risk of hyperglycemia and insulin resistance in relation to serum 25-hydroxy vitamin D levels in children and adolescents were included.
Data Analysis
Twenty-two investigations, with a total of 38 622 participants, were systematically reviewed. Meta-analysis of 15 studies (n = 32 720 participants) showed that participants with the highest serum vitamin D levels had 42% lower risk of hyperglycemia, compared with those in the lowest category of serum vitamin D levels (relative risk [RR] = 0.58; 95%CI, 0.48, 0.71). Moreover, pooling 8 studies (n = 10 465 participants) illustrated that highest serum vitamin D level was associated with a 44% lower risk of insulin resistance compared with the lowest serum vitamin D level (RR = 0.56; 95%CI, 0.37, 0.83). Based on linear dose-response analysis, each 10 nmol/L increment in serum 25-hydroxy vitamin D was associated with a 6% decreased risk of hyperglycemia and insulin resistance in children. Furthermore, nonlinear dose-response analysis revealed that increasing serum vitamin D concentration from 40 nmol/L to sufficient values (>50 nmol/L) was associated with a decreasing trend in risk of hyperglycemia and insulin resistance.
Conclusion
This meta-analysis revealed inverse associations between serum vitamin D levels and hyperglycemia and insulin resistance in children and adolescents, in a dose-response manner. Increasing serum vitamin D concentration from 40 nmol/L to sufficient values (>50 nmol/L) was associated with a decreasing trend in hyperglycemia and insulin resistance risk. Systematic Review Registration: PROSPERO registration no. CRD42023458155.
The aim of the study was to assess the level of vitamin D and nitric oxide metabolites, and to search for the relationship between them in cross-country skiers at various stages of the training cycle. During the year, two groups of men (20–26 years old, inhabitants of the Komi Republic) were examined four times: cross-country skiers who are active members of the national teams of the Komi Republic/Russia (n = 11) and office workers (n = 10). It was shown that skiers had higher vitamin D levels duration the year compared to office workers. The fluctuations in the levels of vitamin D, calcium and phosphorus detected in cross-country skiers were seasonal, which could lead to significant changes in the synthesis of nitric oxide and the work of the endothelial system. The greatest number of correlations between the studied metabolites in cross-country skiers was revealed at the beginning and end of the annual training season. A significant imbalance in the levels of vitamin D and nitric oxide metabolites found in them in March may negatively affect the success of performance at important competitions.
Background:
Vitamin D deficiency is common in postmenopausal women and is associated with low vitamin D intake, increased age, decreased absorption. Especially at advanced age, vitamin D deficiency may increase muscle weakness and disbalance resulting in increased risk of fracture.
Objectives:
This study aims to explore the correlation between 25(OH) vitamin D3 levels and quadriceps muscle strength in postmenopausal women.
Methods:
We evaluated bilateral qadriceps muscle strength in postmenopausal women with isokinetic test. We evaluated the correlation of muscle power with measurements of parathormone, vitamin D, Calcium, creatinine, alanine transaminase, alkaline phosphatase, total creatine kinase.
Results:
The mean vitamin D level of 95 participants included in the study was 18.24 ± 8.94 ng/ml. Vitamin D levels were found to be deficient (< 10 ng/ml) in 23 (24.1%), insufficient in 62 (65.26%) and normal in 10 (10.53%) of the 95 participants. A weak negative correlation was observed between participants' vitamin D levels and PT values (r=-0.271, p= 0.012). A moderate negative correlation was found between ALP and vitamin D levels (r=-0.317, p= 0.002). However, there was no significant correlation between vitamin D levels and the 60∘ and 90∘ flexion and extension peak torque values (All p values > 0.05).
Conclusions:
Vitamin D levels and muscle strength weren't statistically significant. Few studies are available in the related literature, highlighting the need for further research to achieve a clearer consensus.
Fibroblasts play a pivotal role in fibrogenesis after skeletal muscle injury. Excess fibrous formation can disrupt contractile functions and delay functional recovery. Although vitamin D receptor (VDR) is expressed explicitly in regenerating muscle compared with uninjured muscle, how calcitriol [1α,25(OH) 2 D 3 ] directly regulates skeletal muscle primary fibroblast proliferation, the transition to myofibroblasts, and Smad signalling-associated fibrogenesis is currently unknown. Herein, the effects of calcitriol on cultured skeletal muscle primary fibroblasts of male C57BL/6 mice (aged 1 month old) were investigated. The percentage of BrdU ⁺ nuclei in primary fibroblasts was significantly decreased after calcitriol treatment; however, the antiproliferative effect of calcitriol was diminished after TGF-β1 stimulation to induce fibroblast to myofibroblast transition. This suppressive effect was associated with significantly decreased VDR expression in TGF-β1-treated cells. In addition, Vdr siRNA transfection abolished the effects of calcitriol on the suppression of α-SMA expression and Smad2/3 signalling in myofibroblasts, supporting that its antifibrogenic effect requires VDR activation. Compared with calcitriol, the antifibrotic agent suramin could inhibit fibroblast/myofibroblast proliferation and suppress the expression of TCF-4, which regulates fibrogenic determination. Collectively, these findings suggest that profibrotic stimulation and VDR-dependent activation could modulate the effects of calcitriol on skeletal muscle fibroblast proliferation and fibrogenesis processes. Therefore, TGF-β1 and VDR expression levels are crucial determinants for the antifibrogenic effect of calcitriol on skeletal muscle after injury.
Мета. Проаналізувати сучасний стан проблеми та висвітлити питання участі вітаміну D у збереженні структурно-функціонального стану опорно-рухового апарату. Методи. Аналіз та узагальнення даних сучасної спеціальної та науково-методичної літератури. Результати. В оглядовій статті розглянуто питання ролі вітаміну D у функціонуванні опорнорухового опарату. Оскільки цей мікронутрієнт бере участь у формуванні та розвитку скелета, недостатність або дефіцит вітаміну D призводить до порушення абсорбції кальцію і фосфору в тонкому кишечнику, що погіршує мінералізацію кісткової тканини та підвищує ризик виникнення остеопорозу і переломів напруження. У м’язах вітамін D впливає на кількість і розмір м’язових волокон, а відтак і на силу та аеробну працездатність м’язів. Також показано взаємозв’язок між статусом вітаміну D та функціями скелетних м’язів, а також фізичною працездатністю осіб різних вікових груп. При цьому у м’язах кальцитріол може діяти як ендокринним шляхом, так і автокринним або паракринним, позаяк у міоцитах важливим є наявність ферменту, який перетворює кальцидіол на гормонально активну форму. Оскільки дані багатьох досліджень свідчать, що вітамін D є не тільки вітаміном, а й гормонально активною речовиною, в огляді висвітлено сучасні уявлення про механізми його дії. Для здійснення біологічного ефекту кальцитріол зв’язується з ядерними та позаядерними рецепторами, локалізованими практично в усіх органах та тканинах. Відповідно до цього він може здійснювати свій вплив як геномним шляхом, так і негеномним. До геномних ефектів належать зміна рівня транскрипції генів та синтез білків de novo, а до негеномних – активація різних шляхів сигнальної трансдукції, що сприяє забезпеченню щоденних метаболічних потреб організму. Також наведено дані щодо причин виникнення дефіциту і недостатності вітаміну D та рекомендації щодо їх профілактики. Висновки. Оптимальний рівень вітаміну D у крові (понад 30 нг ∙ мл –1 ) є одним з ключових факторів збереження здоров’я опорнорухового апарату. Тому в умовах недостатності надходження цього вітаміну з їжею або за відсутності сонячного опромінення більшість фахівців Міжнародного ендокринологічного товариства і Європейського товариства з клінічних та економічних наслідків остеопорозу і остеоартрозу рекомендують населенню країн Центральної Європи щоденно вживати підтримуючі або профілактичні дози цього мікронутрієнта.
Objective:
This study aimed to evaluate the prevalence of dynapenia and factors related to low dominant handgrip strength (HGS) in postmenopausal women.
Methods:
A cross-sectional study was performed on 249 postmenopausal women aged 50 to 84 years. The following variables were recorded: age, age at menopause, smoking status, and the HGS measured with a digital dynamometer, body mass index, and adiposity assessed by bioelectric impedance. The physical activity level was evaluated by using the International Physical Activity Questionnaire. Bone mineral density was reported as T-scores, and blood biochemical parameters (calcium, phosphorus, vitamin D, and parathormone levels) were measured.
Results:
31.3% of women had dynapenia, and those aged ≥65 years had lower HGS (P < 0.001). Age at menopause was also associated with HGS, with those with menopause < 51 showing lower HGS (P = 0.005). Likewise, fat content ≥ 40%, and osteopenia/osteoporosis were also related to lower strength (P < 0.001). There was no statistically significant difference among HGS with respect to body mass index, smoking status, and plasma levels of vitamin D. A logistic regression model with lower Akaine Information Criterion showed that for every year in age and for each 1% of adiposity, women were more likely to have dynapenia with odd ratio (OR): 1.09; 95% and confidence interval (CI): 1.04 to 1.14 and OR: 1.06; 95% CI: 1.00 to 1.13, respectively. Conversely, women with higher femoral neck T-score were less likely to have dynapenia (OR: 0.53; 95% CI: 0.35-0.78).
Conclusions:
HGS was associated with age at menopause, bone mineral density, and adiposity adjusted by age. The age and adiposity were significantly associated with a higher risk of dynapenia, whereas women with higher femoral neck T-score were less likely to have dynapenia.
Poor physical function and muscle weakness are associated with higher mortality in chronic kidney disease and end-stage renal disease patients. Studies have tested therapeutic agents to prevent and mitigate muscle wasting with the hope of maintaining or even increasing physical function. Anabolic pathways in muscle largely signal through the insulin-like growth factor-1/PI3K/Akt system. Several therapeutic agents have been found to stimulate this pathway, such as testosterone, growth hormone (GH), and vitamin D. The ubiquitin–proteasome system is the major catabolic pathway in skeletal muscle. This pathway is stimulated by myostatin, which decreases anabolic signaling and induces catabolic signaling. Several therapeutic agents have been developed to counter myostatin action. In this chapter, we review the history, molecular mechanisms, in vitro and in vivo data, and clinical trial data for each of these therapeutic agents: testosterone, GH, vitamin D, and antimyostatin antibodies.
Overuse injuries in sports are common and include stress fracture and musculoskeletal inflammation. Vitamin D is important in bone metabolism and exerts anti‐inflammatory effects, and it may be protective against those injuries. The objective was to evaluate the association between vitamin D status and sport injuries. This systematic review was conducted according to the PRISMA statement. We used systematic literature search in PubMed, Embase, Cochrane and Sportdiscus until the 28th of June 2020. We included observational and randomised studies assessing vitamin D status. Sport injuries were defined as stress fractures or musculoskeletal injuries. A meta‐analysis was performed with stress fracture as outcome. In total 16 articles were included, 7 investigating stress fractures and 9 investigating musculoskeletal injuries. Regarding stress fractures, serum vitamin D levels below 30ng/ml appeared to be associated with an increased risk of stress fractures, and the meta‐analysis showed increased odds ratio for stress fracture with vitamin D insufficiency. Regarding musculoskeletal injuries only two studies found that low serum vitamin D levels were associated with musculoskeletal injuries. Low serum vitamin D levels are associated with an enhanced risk of stress fractures, while no conclusion can be made regarding musculoskeletal injuries.
Le rôle principal de la vitamine D est de contrôler l'homéostasie phosphocalcique de l’organisme. Les études observationnelles récentes ont montré que la vitamine D est également capable de réguler la sécrétion d'insuline et la sensibilité à l'insuline, jouant ainsi un rôle important dans la régulation de l'homéostasie du glucose. De plus, il a été montré que la vitamine D exerce un effet sur la santé musculaire. A titre d’exemple, un déficit en vitamine D influence négativement la masse et la fonction musculaires chez les personnes âgées. Il est à noter que selon certaines études, la correction d’une déficience en vitamine D est capable d’améliorer la fonction contractile et la force musculaires dans cette population. En outre, le niveau d'activité physique diminue avec l'âge, ce qui affecte négativement la masse et les capacités musculaires, et conduit à une prise de poids, principalement sous forme de masse grasse. Or, des études ont révélé que les personnes âgées en surpoids étaient caractérisées par des concentrations sanguines de vitamine D plus basses, une masse et une force musculaire plus faibles comparativement à une population de référence de même âge.Aussi l’objectif principal de la thèse était d’évaluer les effets d’un apport complémentaire de vitamine D sur l’homéostasie du glucose et l’indice de résistance à l’insuline, ainsi que sur la masse musculaire appendiculaire (ASMM) et la force musculaire chez des personnes âgées normo-pondérales ou en surpoids. Ces travaux sont basés sur un essai contrôlé randomisé, réalisé en simple aveugle. En termes de résultats, nous avons montré qu’un apport de vitamine D chez des sujets âgés normo-pondéraux ou en surpoids ayant de faibles statuts a permis d’améliorer à court terme la glycémie à jeun et les marqueurs de résistance à l'insuline. L’augmentation du taux sérique de 25-hydroxyvitamine D [25 (OH) D] après la complémentation a entraîné une baisse significative des taux d’insuline à jeun et de l’indice HOMA-IR. Nous avons pu identifier une corrélation entre de faibles concentrations sériques de [25 (OH) D] et une diminution de la tolérance au glucose et un risque accru de diabète de type 2.Concernant les marqueurs musculaires, nous avons observé qu'une complémentation en vitamine D influençait bénéfiquement la masse musculaire appendiculaire et la masse grasse chez les hommes et les femmes âgés en surpoids. Cependant, nous n'avons trouvé aucun effet significatif sur la force musculaire. Nous avons également relevé que les sujets âgés sarcopéniques en surpoids étaient caractérisés par un taux sérique de [25 (OH) D] inférieur au départ de l’étude. De plus, l’augmentation de la masse musculaire après un apport de vitamine D restait inférieure à celle des sujets normo-pondéraux.Ce travail de thèse montre qu’il semble nécessaire de surveiller le statut en vitamine D chez le sujet âgé surtout lorsqu’il est en surpoids.
Extra-renal expression of Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) has been well recognized and reflects the importance of intracrine/paracrine vitamin D signaling in different tissues under physiological and pathological conditions. In a prior RNA sequencing project, we identified CYP27B1 mRNA as upregulated in muscle samples from patients with amyotrophic lateral sclerosis (ALS) compared to normal controls. Our aims here were: (1) to validate this finding in a larger sample set including disease controls, (2) to determine which cell type is expressing CYP27B1 protein in muscle tissue, (3) to correlate CYP27B1 mRNA expression with disease progression in the SOD1G93A ALS mouse and in ALS patients. We assessed CYP27B1 expression by qPCR, western blot, and immunohistochemistry in a repository of muscle samples from ALS, disease controls (myopathy and non-ALS neuropathic disease), normal subjects, and muscle samples from the SOD1G93A mouse. Eight ALS patients were studied prospectively over 6-12 months with serial muscle biopsies. We found that CYP27B1 mRNA and protein levels were significantly increased in ALS versus normal and myopathy muscle samples. Neuropathy samples had increased CYP27B1 mRNA and protein expression but at a lower level than the ALS group. Immunohistochemistry showed that CYP27B1 localized to myofibers, especially those with features of denervation. In the SOD1G93A mouse, CYP27B1 mRNA and protein were detected in skeletal muscle in early pre-symptomatic stages and increased through end-stage. In the human study, increases in CYP27B1 mRNA in muscle biopsies correlated with disease progression rates over the same time period. In summary, we show for the first time that CYP27B1 mRNA and protein expression are elevated in muscle fibers in denervating disease, especially ALS, where mRNA levels can potentially serve as a surrogate marker for tracking disease progression. Its upregulation may reflect a local perturbation of vitamin D signaling, and further characterization of this pathway may provide insight into underlying molecular processes linked to muscle denervation.
Objectives:
Vitamin D is important for the muscular tone and bone metabolism. Due to the high prevalence of vitamin D deficiency in Iranian women, this study aimed to investigate the difference in vitamin D levels between patients with and without pelvic floor disorder (PFD) to assess the possible effect of vitamin D on PFD.
Materials and Methods:
The present case-control study examined 209 women referring to Ayatollah Rouhani hospital of Babol in 2017. Patients were explored for prolapse and those with at least one disorder or without PFD were categorized as the case (n= 104) or control (n= 105) groups, respectively. Then, the serum level of 25-hydroxy vitamin D was compared between the groups.
Results:
The mean age and abdominal circumference of the patients were significantly higher in the case group (P< 0.001 & P= 0.046, respectively) as compared to the control group. Meanwhile, the total mean±SD serum level of vitamin D was 20.03±17.88 ng/mL and significantly higher in the case group (24.58±20.75 ng/mL) than that of the control group (15.53±13.11 ng/mL), especially in patients with stress and urgency urinary incontinence (SIU/UIU)(both with a significance level of P< 0.001).
Conclusions:
As a result of PFD, the group with UI, especially the one with SIU or UIU had the highest vitamin D level compared to the control and other groups. Nonetheless, the mean age and educational level were significantly higher and lower in this group, respectively. These results could be due to the multifactorial nature of vitamin D level, that is, it varies based on nutrition, place of residence, and other factors.
Objectives: Vitamin D is important for the muscular tone and bone metabolism. Due to the high prevalence of vitamin D deficiency in Iranian women, this study aimed to investigate the difference in vitamin D levels between patients with and without pelvic floor disorder (PFD) to assess the possible effect of vitamin D on PFD. Materials and Methods: The present case-control study examined 209 women referring to Ayatollah Rouhani hospital of Babol in 2017. Patients were explored for prolapse and those with at least one disorder or without PFD were categorized as the case (n = 104) or control (n = 105) groups, respectively. Then, the serum level of 25-hydroxy vitamin D was compared between the groups. Results: The mean age and abdominal circumference of the patients were significantly higher in the case group (P < 0.001 & P = 0.046, respectively) as compared to the control group. Meanwhile, the total mean ± SD serum level of vitamin D was 20.03±17.88 ng/ mL and significantly higher in the case group (24.58 ± 20.75 ng/mL) than that of the control group (15.53±13.11 ng/mL), especially in patients with stress and urgency urinary incontinence (SIU/UIU) (both with a significance level of P < 0.001). Conclusions: As a result of PFD, the group with UI, especially the one with SIU or UIU had the highest vitamin D level compared to the control and other groups. Nonetheless, the mean age and educational level were significantly higher and lower in this group, respectively. These results could be due to the multifactorial nature of vitamin D level, that is, it varies based on nutrition, place of residence, and other factors.
Previous studies have shown that improving vitamin D status among the elderly may lead to an improvement in muscle mass and muscle strength. In our study, vitamin D supplementation showed significant improvements in vitamin D concentrations as well as appendicular muscle mass in pre-sarcopenic older Lebanese people. However, we found no significant effect on muscle strength.
Introduction
Improving vitamin D status might improve muscle function and muscle mass that lead to sarcopenia in older subjects. The aim of this randomized, controlled, double-blind study was to examine the effect of vitamin D supplementation on handgrip strength and appendicular skeletal muscle mass in pre-sarcopenic older Lebanese subjects. We also examined whether this effect differs in normal vs. obese subjects.
Methods
Participants (n = 128; 62 men and 66 women) deficient in vitamin D (25(OH)D = 12.92 ± 4.3 ng/ml) were recruited from Saint Charles Hospital, Beirut, Lebanon. The participants were given a supplement of 10,000 IU of cholecalciferol (vitamin D group; n = 64) to be taken three times a week or a placebo tablet (placebo group; n = 64) for 6 months. One hundred fifteen subjects completed the study: 59 had normal weight, while 56 were obese. Strength and functional assessment and biochemical analysis were performed at the start and after 6 months.
Results
Compared to placebo, the vitamin D supplemented group showed significant improvements in appendicular skeletal muscle mass (ASMM) (P < 0.001) but not in handgrip strength (P = 0.2901). ANCOVA for ASMM adjusting for obesity and including the interaction between obesity and vitamin D showed a significant interaction. The increase in ASMM with vitamin D in normal-weight subjects was higher than that of obese subjects (B = 35.09 vs. B = 2.19).
Conclusion
Treatment with vitamin D showed beneficial effects on appendicular muscle mass in pre-sarcopenic older Lebanese men and women. However, it had no effect on muscle strength relative to placebo. This trial was registered at isrctn.org as ISRCTN16665940.
In skeletal muscle cells the steroid hormone 1α,25-dihydroxy-vitamin-D3(1,25(OH)2D3) nongenomically promotes Ca²⁺ release from intracellular stores and cation influx through both l-type and store-operated Ca²⁺(SOC) channels. In the present work we evaluated the regulation and kinetics of the 1,25(OH)2D3-stimulated SOC influx in chick muscle cells. Stimulation with 10⁻⁹m 1,25(OH)2D3 in Ca²⁺-free medium resulted in a rapid (40–60 s) but transient [Ca²⁺]i rise, which correlated with sterol-dependent inositol 1,4,5-trisphosphate production. The SOC influx stimulated by the hormone was insensitive to bothl-type channel antagonists and polyphosphoinositide-specific phospholipase C (PPI-PLC) inhibitors but was fully inhibitable by La³⁺ and Ni²⁺. PPI-PLC blockade prior to 1,25(OH)2D3 stimulation suppressed both the [Ca²⁺]i transient and the SOC influx. 1,25(OH)2D3-induced SOC entry was markedly increased after 3 min of treatment (30% above basal) and then rapidly reached a steady-state level. The sterol-stimulated SOC influx was prevented by protein kinase C and tyrosine kinase inhibitors but unaffected by blockade of the protein kinase A pathway. None of these inhibitors altered the thapsigargin-induced SOC entry, suggesting the operation of a signaling mechanism different from that for sterol-dependent SOC influx. The present results indicate that 1,25(OH)2D3-induced activation of PPI-PLC is upstream to Ca²⁺ influx through SOC channels and point for a role of both protein kinase C and tyrosine kinases but not protein kinase A in the regulation of the sterol-dependent SOCE pathway.
Purpose of review:
Vitamin D is best known for its role in regulating calcium homeostasis and in strengthening bone. However, it has become increasingly clear that it also has important beneficial effects beyond the skeleton, including muscle. This review summarizes current knowledge about the role of vitamin D in skeletal muscle tissue and physical performance.
Recent findings:
Molecular mechanisms of vitamin D action in muscle tissue include genomic and nongenomic effects via a receptor present in muscle cells. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Vitamin D status is positively associated with physical performance and inversely associated with risk of falling. Vitamin D supplementation has been shown to improve tests of muscle performance, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults.
Summary:
Further studies are needed to fully characterize the underlying mechanisms of vitamin D action in human muscle tissue, to understand how these actions translate into changes in muscle cell morphology and improvements in physical performance, and to define the 25-hydroxyvitamin D level at which to achieve these beneficial effects in muscle.
SummaryThis review describes the vitamin D status in different regions of the world with the objective of understanding the scope
of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and
fragility fractures.
IntroductionVitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders.
The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and
to identify the common and significant determinants of hypovitaminosis D.
MethodsSix regions of the world were reviewed—Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania—through
a survey of published literature.
ResultsThe definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D,
vary between studies. However, serum 25(OH)D levels below 75nmol/L are prevalent in every region studied whilst levels below
25nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter
season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main
factors that are significantly associated with lower 25(OH)D levels.
ConclusionReports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.
Objective To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals.
Data sources We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary.
Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D3 (1α-hydroxycalciferol) or 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion.
Results Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D3 concentration (25(OH)D concentration: <60 nmol/l v ≥60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94).
Conclusions Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.
In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly.
The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men.
Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ).
Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%.
Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.
The objectives were to characterize the vitamin D status of black and white adolescents residing in the southeastern United States (latitude: approximately 33 degrees N) and to investigate relationships with adiposity.
Plasma 25-hydroxyvitamin D levels were measured with liquid chromatography-tandem mass spectroscopy for 559 adolescents 14 to 18 years of age (45% black and 49% female). Fat tissues, physical activity, and cardiovascular fitness also were measured.
The overall prevalences of vitamin D insufficiency (<75 nmol/L) and deficiency (< or = 50 nmol/L) were 56.4% and 28.8%, respectively. Black versus white subjects had significantly lower plasma 25-hydroxyvitamin D levels in every season (winter, 35.9 + or - 2.5 vs 77.4 + or - 2.7 nmol/L; spring, 46.4 + or - 3.5 vs 101.3 + or - 3.5 nmol/L; summer, 50.7 + or - 4.0 vs 104.3 + or - 4.0 nmol/L; autumn, 54.4 + or - 4.0 vs 96.8 + or - 2.7 nmol/L). With adjustment for age, gender, race, season, height, and sexual maturation, there were significant inverse correlations between 25-hydroxyvitamin D levels and all adiposity measurements, including BMI percentile (P = .02), waist circumference (P < .01), total fat mass (P < .01), percentage of body fat (P < .01), visceral adipose tissue (P = .015), and subcutaneous abdominal adipose tissue (P = .039). There were significant positive associations between 25-hydroxyvitamin D levels and vigorous physical activity (P < .01) and cardiovascular fitness (P = .025).
Low vitamin D status is prevalent among adolescents living in a year-round sunny climate, particularly among black youths. The relationships between 25-hydroxyvitamin D levels, adiposity, physical activity, and fitness seem to be present in adolescence.
Ecologic and observational studies have suggested an association between serum 25-hydroxyvitamin D (25(OH)D) levels and cardiovascular disease (CVD) risk factors, CVD mortality, and cancer mortality. Based on this, low serum 25(OH)D levels should be associated with higher all-cause mortality in a general population. This hypothesis was tested in the present study.
The Tromsø study is a longitudinal population-based multipurpose study initiated in 1974 with focus on lifestyle-related diseases. Our data are based on the fourth Tromsø study carried out in 1994-1995.
Information about death and cause of death was registered by obtaining information from the National Directory of Residents and the Death Cause Registry. Serum 25(OH)D was measured in 7161 participants in the fourth Tromsø study. Results are presented for smokers (n=2410) and non-smokers (n=4751) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers.
During a mean 11.7 years of follow-up, 1359 (19.0%) participants died. In multivariate regression models, there was a significantly increased risk of all-cause mortality (hazard ratio (HR) 1.32, confidence interval (CI) 1.07-1.62) among non-smoking participants in the lowest 25(OH)D quartile when compared with participants in the highest quartile. Equivalent results for smokers were not significant (HR 1.06, CI 0.83-1.35).
Low serum 25(OH)D levels were associated with increased all-cause mortality for non-smokers, but the results did not reach statistical significance for smokers. However, low 25(OH)D levels are known to be associated with impaired general health, and randomized controlled studies are needed to address the question of causality.
Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both under-performance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.
To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals.
We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion.
Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94).
Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.
To determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents.
With a nationally representative sample of children aged 1 to 21 years in the National Health and Nutrition Examination Survey 2001-2004 (n = 6275), we measured serum 25(OH)D deficiency and insufficiency (25[OH]D <15 ng/mL and 15-29 ng/mL, respectively) and cardiovascular risk factors.
Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 61%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient. Only 4% had taken 400 IU of vitamin D per day for the past 30 days. After multivariable adjustment, those who were older (odds ratio [OR]: 1.16 [95% confidence interval (CI): 1.12 to 1.20] per year of age), girls (OR: 1.9 [1.6 to 2.4]), non-Hispanic black (OR: 21.9 [13.4 to 35.7]) or Mexican-American (OR: 3.5 [1.9 to 6.4]) compared with non-Hispanic white, obese (OR: 1.9 [1.5 to 2.5]), and those who drank milk less than once a week (OR: 2.9 [2.1 to 3.9]) or used >4 hours of television, video, or computers per day (OR: 1.6 [1.1 to 2.3]) were more likely to be 25(OH)D deficient. Those who used vitamin D supplementation were less likely (OR: 0.4 [0.2 to 0.8]) to be 25(OH)D deficient. Also, after multivariable adjustment, 25(OH)D deficiency was associated with elevated parathyroid hormone levels (OR: 3.6; [1.8 to 7.1]), higher systolic blood pressure (OR: 2.24 mmHg [0.98 to 3.50 mmHg]), and lower serum calcium (OR: -0.10 mg/dL [-0.15 to -0.04 mg/dL]) and high-density lipoprotein cholesterol (OR: -3.03 mg/dL [-5.02 to -1.04]) levels compared with those with 25(OH)D levels > or =30 ng/mL.
25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.
The growing incidence of prediabetes and clinical type 2 diabetes, in part characterised by insulin resistance, is a critical health problem with consequent devastating personal and health-care costs. Vitamin D status, assessed by serum 25-hydroxyvitamin D levels, is inversely associated with diabetes in epidemiological studies. Several clinical intervention studies also support that vitamin D, or its active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D), improves insulin sensitivity, even in subjects with glucose metabolism parameters classified within normal ranges. The mechanisms proposed which may underlie this effect include potential relationships with improvements in lean mass, regulation of insulin release, altered insulin receptor expression and specific effects on insulin action. These actions may be mediated by systemic or local production of 1,25(OH)2D or by suppression of parathyroid hormone, which may function to negatively affect insulin sensitivity. Thus, substantial evidence supports a relationship between vitamin D status and insulin sensitivity; however, the underlying mechanisms require further exploration.
Our goal in this cross-sectional study was to investigate the influence of low-vitamin D status on bone mass, bone turnover, and muscle strength in 301 healthy Chinese adolescent girls. Blood plasma 25-hydroxyvitamin D [25(OH)D] was measured by RIA and plasma and urine biomarkers of bone turnover were measured. Bone mineral content (BMC) and density and bone area for the whole body and the distal and proximal forearm were measured by dual energy X-ray absorptiometry. When vitamin D deficiency was defined as a serum 25(OH)D concentration of < or =50 nmol/L and severe deficiency as <25 nmol/L, 57.8% of subjects were vitamin D deficient and 31.2% were severely deficient. Multivariate analysis shows that girls with adequate vitamin D status had higher size-adjusted BMC for the whole body (P < 0.001), distal forearm (P < 0.001), and proximal forearm (P < 0.01) than those with poorer vitamin D status after adjusting for body size, handgrip strength, physical activity, and dietary intakes of calcium and vitamin D. Similar results were also found for handgrip muscle strength. Participants with adequate vitamin D status had significantly lower concentrations of bone alkaline phosphatase in plasma and deoxypyridinoline:creatinine ratio in urine compared with those of the vitamin D-deficient girls. Adolescent girls with adequate vitamin D status had significantly higher bone mass and muscle strength compared with those with poor vitamin D status. This may be attributed in part to a lower rate of bone remodeling with adequate vitamin D status. These findings suggest that adequate vitamin D status during adolescence is important for optimizing bone mass, which may lead to higher peak bone mass at maturity. Poor vitamin D status also compromises forearm muscle strength.
Vitamin D insufficiency is associated with suboptimal health. The prevalence of vitamin D insufficiency may be rising, but population-based trends are uncertain. We sought to evaluate US population trends in vitamin D insufficiency.
We compared serum 25-hydroxyvitamin D (25[OH]D) levels from the Third National Health and Nutrition Examination Survey (NHANES III), collected during 1988 through 1994, with NHANES data collected from 2001 through 2004 (NHANES 2001-2004). Complete data were available for 18 883 participants in NHANES III and 13 369 participants in NHANES 2001-2004.
The mean serum 25(OH)D level was 30 (95% confidence interval [CI], 29-30) ng/mL during NHANES III and decreased to 24 (23-25) ng/mL during NHANES 2001-2004. Accordingly, the prevalence of 25(OH)D levels of less than 10 ng/mL increased from 2% (95% CI, 2%-2%) to 6% (5%-8%), and 25(OH)D levels of 30 ng/mL or more decreased from 45% (43%-47%) to 23% (20%-26%). The prevalence of 25(OH)D levels of less than 10 ng/mL in non-Hispanic blacks rose from 9% during NHANES III to 29% during NHANES 2001-2004, with a corresponding decrease in the prevalence of levels of 30 ng/mL or more from 12% to 3%. Differences by age strata (mean serum 25[OH]D levels ranging from 28-32 ng/mL) and sex (28 ng/mL for women and 32 ng/mL for men) during NHANES III equalized during NHANES 2001-2004 (24 vs 24 ng/mL for age and 24 vs 24 ng/mL for sex).
National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.
There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied.
Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force.
This was a cross-sectional study.
The study was community based in a secondary school.
A total of 99 post-menarchal 12- to 14-yr-old females was included in the study.
Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured.
Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04).
From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.
The factors that influence vitamin D status were investigated in 125 patients with hip fracture and in 74 elderly control subjects. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] varied with sunshine score and were paralleled by serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The control subjects showed a higher sunshine score and higher serum 24(OH)D levels than the patients with hip fracture. Dietary vitamin D intake was similar in both groups (mean 115 IU/d). A positive correlation between vitamin D intake and serum 25(OH)D was observed in the patients with low sunshine exposure. It appeared from this relation that dietary vitamin D intake should be approximately 300 IU/d to maintain an adequate serum (25(OH)D concentration. Vitamin D status was very poor in patients who were institutionalized before hip fracture. Multiple regression analysis on serum 25(OH)D confirmed the primary role of sunshine exposure as determinant of vitamin D status. The principal determinants of serum 1,25(OH)2D were serum 25(OH)D, serum creatinine, and serum phosphate.
Background: Obesity is associated with vitamin D insufficiency and secondary hyperparathyroidism.
Objective: This study assessed whether obesity alters the cutaneous production of vitamin D3 (cholecalciferol) or the intestinal absorption of vitamin D2 (ergocalciferol).
Design: Healthy, white, obese [body mass index (BMI; in kg/m²) ≥ 30] and matched lean control subjects (BMI ≤ 25) received either whole-body ultraviolet radiation or a pharmacologic dose of vitamin D2 orally.
Results: Obese subjects had significantly lower basal 25-hydroxyvitamin D concentrations and higher parathyroid hormone concentrations than did age-matched control subjects. Evaluation of blood vitamin D3 concentrations 24 h after whole-body irradiation showed that the incremental increase in vitamin D3 was 57% lower in obese than in nonobese subjects. The content of the vitamin D3 precursor 7-dehydrocholesterol in the skin of obese and nonobese subjects did not differ significantly between groups nor did its conversion to previtamin D3 after irradiation in vitro. The obese and nonobese subjects received an oral dose of 50000 IU (1.25 mg) vitamin D2. BMI was inversely correlated with serum vitamin D3 concentrations after irradiation (r = −0.55, P = 0.003) and with peak serum vitamin D2 concentrations after vitamin D2 intake (r = −0.56, P = 0.007).
Conclusions: Obesity-associated vitamin D insufficiency is likely due to the decreased bioavailability of vitamin D3 from cutaneous and dietary sources because of its deposition in body fat compartments.
Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
Context: VitaminDinsufficiency hasnowreached epidemic proportions and has been linked to low
bone mineral density, increased risk of fracture, and obesity in adults. However, this relationship
has not been well characterized in young adults.
Objective: The objective of the study was to examine the relationship between serum 25-hydroxyvitamin
D (25OHD), anthropometric measures, body fat (BF), and bone structure at the time
of peak bone mass.
Design: This was a cross-sectional study.
Outcome Measures and Subjects: Anthropometric measures, serum 25OHD radioimmunoassay
values, and computed tomography and dual-energy x-ray absorptiometry values of BF and bone
structure in 90 postpubertal females, aged 16–22 yr, residing in California were measured.
Results: Approximately 59% of subjects were 25OHD insufficient (�29 ng/ml), and 41% were
sufficient (�30 ng/ml). Strong negative relationships were present between serum 25OHD and
computedtomography measures of visceralandsc fatanddual-energy x-ray absorptiometry values
of BF. In addition, weight, body mass, and imaging measures of adiposity at all sites were significantly
lower in women with normal serum 25OHD concentrations than women with insufficient
levels. In contrast, no relationship was observed between circulating 25OHD concentrations and
measures of bone mineral density at any site. Unexpectedly, there was a positive correlation
between 25OHD levels and height.
Conclusions: We found that vitamin D insufficiency is associated with increased BF and decreased
height but not changes in peak bone mass. (J Clin Endocrinol Metab 94: 67–73, 2009)
Background: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking.
Objective: The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types.
Design: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4°N. Subjects were randomly assigned to receive 1400–1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo.
Results: When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk.
Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170.
Objective: The objective of this study was to systematically review all the published articles examining the effects of low serum vitamin D concentration and vitamin D supplementation on muscle, balance and gait performance among people aged 65 and older. Methods: An English and French Medline search ranging from January 2004 to November 2008 indexed under the Medical Subject Heading (MeSH) terms "aged OR aged, 80 and over" AND "Vitamin D OR Vitamin D Deficiency" combined with the terms "Gait" OR "Gait Apraxia" OR "Gait Disorders, Neurologic" OR "Walking" OR "Mobility Limitation" OR "Polyneuropathy" OR "Proprioception" OR "Ataxia" OR "Accidental Falls" was performed. Results: Of the 102 selected studies, 16 met the selection criteria and were included in the final analysis. There were 8 observational studies and 8 interventional studies. The number of participants ranged from 24 to 33067. A majority of studies examined community-dwelling older women. Five observational studies showed a significant positive association, whereas three studies did not. Four of the 5 studies and two of the 3 studies which tested the vitamin D supplementation effect, respectively on balance and gait, showed no significant effect. Four studies showed a significant effect on muscle strength, while this effect was not observed in three others studies. In addition, there was no significant association between vitamin D supplementation and an improvement of the sit-to-stand test results in 50% of the studies. Conclusions: The findings show that the association between vitamin D and physical performance remains controversial. Observational studies and clinical trials yielded divergent results, which highlights the complex and to date still poorly understood association between serum vitamin D concentration or vitamin D supplementation and physical performance.
Background: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis. Methods: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed. Results: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI 0.40 to 1.12; p for trend 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of 400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI 0.38 to 0.91; p for trend 0.006). No association was found between vitamin D from food and MS incidence. Conclusion: These results support a protective effect of vitamin D intake on risk of developing MS. NEUROLOGY 2004;62:60 -65
We have previously demonstrated that the steroid hormone 1α,25(OH)2-vitamin D3[1α,25(OH)2D3] stimulates the production of inositol trisphosphate (InsP3), the breakdown product of phosphatidylinositol 4,5-biphosphate (PtdInsP2) by phospholipase C (PtdIns-PLC), and activates the cytosolic tyrosine kinase c-Src in skeletal muscle cells. In the present study we examined whether 1α,25(OH)2D3 induces the phosphorylation and membrane translocation of PLCγ and the mechanism involved in this isozyme activation. We found that the steroid hormone triggers a significant phosphorylation on tyrosine residues of PLCγ and induces a rapid increase in membrane-associated PLCγ immunoreactivity with a time course that correlates with that of phosphorylation in muscle cells. Genistein, a tyrosine kinase inhibitor, blocked the phosphorylation of PLCγ. Inhibition of 1α,25(OH)2D3-induced c-Src activity by its specific inhibitor PP1 or muscle cell transfection with an antisense oligodeoxynucleotide directed against c-Src mRNA, prevented hormone stimulation of PLCγ tyrosine phosphorylation. The isozyme phosphorylation is also blocked by both wortmannin and LY294002, two structurally different inhibitors of phosphatidyl inositol 3-kinase (PtdIns3K), the enzyme that produces PtdInsP3 known to activate PLCγ isozymes specifically by interacting with their SH2 and pleckstrin homology domains. The hormone also increases the physical association of c-Src and PtdIns3K with PLCγ and induces a c-Src-dependent tyrosine phosphorylation of the p85 regulatory subunit of PtdIns3K. The time course of hormone-dependent PLCγ phosphorylation closely correlates with the time course of its redistribution to the membrane, suggesting that phosphorylation and redistribution to the membrane of PLCγ are two interdependent events. 1α,25(OH)2D3-induced membrane translocation of PLCγ was prevented to a great extent by c-Src and PtdIns3K inhibitors, PP1 and LY294002. Taken together, the present data indicates that the cytosolic tyrosine kinase c-Src and PtdIns 3-kinase play indispensable roles in 1α,25(OH)2D3 signal transduction cascades leading to PLCγ activation.
The calciotropic hormone 1α,25-dihydroxy-vitamin D3 (1,25(OH)2D3) has been shown to stimulate both rat and chick myoblast 45Ca2+ uptake via modulation of dihydropyridine-sensitive L-type calcium channels through phosphorylation by the cAMP/protein kinase A pathway. We further investigated the involvement of protein kinases in 1,25(OH)2D3-signal transduction on cultured myoblasts. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) was found to rapidly stimulate myoblast 45Ca2+ uptake, mimicking 1,25(OH)2D3. The effects of PMA were time- (1–5 min) and dose (50–100 nM)-dependent, were mimicked by 1,2-dioctanoylglycerol (DOG) and were specific, since the inactive analogue 4α-phorbol was without effect. Analogously to the hormone, PMA-enhanced 45Ca2+ uptake was suppressed by the Ca2+-channel blocker nifedipine (5 μM). 1-(5-isoquinolynsulfonyl)-2-methyl-piperazine (H-7), a PKC inhibitor, and down-regulation of PKC by prolonged exposure to PMA (1 μM, 24 h), abolished both PMA and hormone effects on rat and chick cells. As in chick myoblasts, 1,25(OH)22D3 activated PKC in rat myoblasts, with translocation of activity from the cytosol to the cell membrane. Treatment of myoblasts with PMA (100 nM) plus 1,25(OH)2D3 (1 nM) greatly potentiated 45Ca2+ uptake than either agent alone. PMA also increased myoblast cAMP content.These results suggest the involvement of PKC in the mechanism by which 1,255(OH)2D3 rapidly stimulates calcium uptake in both mammalian and avian myoblasts.
Changes in morphology and DNA synthesis in cultured myoblasts in response to 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] have previously suggested that the vitamin D hormone may affect muscle cell proliferation and differentiation. However, this interpretation was not substantiated by measurement of specific biochemical markers of myogenesis. To study the effect of 1,25(OH)2D3 on muscle development, chicken embryo myoblasts were cultured for 1–6 days in the presence or absence of 1,25(OH)2D3 (10−9 M). The hormone increased DNA synthesis and decreased creatine kinase activity, indicating stimulation of cell proliferation and inhibition of myogenesis, in undifferentiated myoblasts (1 day of culture). At longer culture intervals, when myoblasts elongate and fuse to form differentiated myotubes, 1,25(OH)2D3 promoted myogenesis, as indicated by an inhibition of DNA synthesis and an increase in specific muscle differentiation markers as creatine kinase activity and myosin expression. The role of protein kinase C (PKC) in mediating the effects of hormone and the likely PKC isoform involved were also investigated. Increased PKC activity was observed during 1,25(OH)2D3 stimulation of myoblast proliferation whereas inhibition of PKC activity accompanied the effects of the hormone on myoblast differentiation. The specific PKC inhibitor calphostin suppressed hormone potentiation of DNA synthesis in proliferating myoblasts. 1,25(OH)2D3-dependent changes in the expression of PKC isoforms α, β, δ, ε and ζ during myogenesis were investigated by Western blot analysis. The early stimulation of myoblast proliferation by the hormone mainly correlated to increased PKC α expression whereas decreased PKC α levels were observed during the subsequent activation of myoblast differentiation. These results support that 1,25(OH)2D3 has a function in embryonic muscle growth and maturation, and PKC α may participate in the signal transduction pathway which mediates the response to the hormone.
1,25-Dihydroxy vitamin D3[1,25(OH)2D3] an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation1−3, which are thought to be mediated by the 1,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily4−6. However, the molecular basis for the actions of 1,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density7 are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D−dependent rickets type II (refs 8,9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D−deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.
Purpose: Activated vitamin D (calcitriol) is a pluripotent pleiotropic secosteroid hormone. As a steroid hormone, which regulates more than 1000 vitamin D-responsive human genes, calcitriol may influence athletic performance. Recent research indicates that intracellular calcitriol levels in numerous human tissues, including nerve and muscle tissue, are increased when inputs of its substrate, the prehormone vitamin D, are increased.
Methods: We reviewed the world's literature for evidence that vitamin D affects physical and athletic performance.
Results: Numerous studies, particularly in the German literature in the 1950s, show vitamin D-producing ultraviolet light improves athletic performance. Furthermore, a consistent literature indicates physical and athletic performance is seasonal; it peaks when 25-hydroxy-vitamin D [25(OH)D] levels peak, declines as they decline, and reaches its nadir when 25(OH)D levels are at their lowest. Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance.
Conclusions: Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25(OH)D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng·mL-1. Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions.
We have previously demonstrated that the steroid hormone 1α,25(OH)2-vitamin D3[1α,25(OH)2D3] stimulates the production of inositol trisphosphate (InsP3), the breakdown product of phosphatidylinositol 4,5-biphosphate (PtdInsP2) by phospholipase C (PtdIns-PLC), and activates the cytosolic tyrosine kinase c-Src in skeletal muscle cells. In the present study we examined whether 1α,25(OH)2D3 induces the phosphorylation and membrane translocation of PLCγ and the mechanism involved in this isozyme activation. We found that the steroid hormone triggers a significant phosphorylation on tyrosine residues of PLCγ and induces a rapid increase in membrane-associated PLCγ immunoreactivity with a time course that correlates with that of phosphorylation in muscle cells. Genistein, a tyrosine kinase inhibitor, blocked the phosphorylation of PLCγ. Inhibition of 1α,25(OH)2D3-induced c-Src activity by its specific inhibitor PP1 or muscle cell transfection with an antisense oligodeoxynucleotide directed against c-Src mRNA, prevented hormone stimulation of PLCγ tyrosine phosphorylation. The isozyme phosphorylation is also blocked by both wortmannin and LY294002, two structurally different inhibitors of phosphatidyl inositol 3-kinase (PtdIns3K), the enzyme that produces PtdInsP3 known to activate PLCγ isozymes specifically by interacting with their SH2 and pleckstrin homology domains. The hormone also increases the physical association of c-Src and PtdIns3K with PLCγ and induces a c-Src-dependent tyrosine phosphorylation of the p85 regulatory subunit of PtdIns3K. The time course of hormone-dependent PLCγ phosphorylation closely correlates with the time course of its redistribution to the membrane, suggesting that phosphorylation and redistribution to the membrane of PLCγ are two interdependent events. 1α,25(OH)2D3-induced membrane translocation of PLCγ was prevented to a great extent by c-Src and PtdIns3K inhibitors, PP1 and LY294002. Taken together, the present data indicates that the cytosolic tyrosine kinase c-Src and PtdIns 3-kinase play indispensable roles in 1α,25(OH)2D3 signal transduction cascades leading to PLCγ activation.
The identification of vitamin D receptor expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been the focus of several studies
To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.
Multicenter, randomized, controlled trial with a factorial design.
Five hospitals in Auckland, New Zealand, and Sydney, Australia.
Two hundred forty-three frail older people.
Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.
The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.
There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.
Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.
Originally regarded as just membrane constituents and energy storing molecules, lipids are now recognised as potent signalling molecules that regulate a multitude of cellular responses via receptor-mediated pathways, including cell growth and death, and inflammation/infection. Derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), each lipid displays unique properties, thus making their role in inflammation distinct from that of other lipids derived from the same PUFA. The diversity of their actions arises because such metabolites are synthesised via discrete enzymatic pathways and because they elicit their response via different receptors. This review will collate the bioactive lipid research to date and summarise the findings in terms of the major pathways involved in their biosynthesis and their role in inflammation and its resolution. It will include lipids derived from AA (prostanoids, leukotrienes, 5-oxo-6,8,11,14-eicosatetraenoic acid, lipoxins and epoxyeicosatrienoic acids), EPA (E-series resolvins), and DHA (D-series resolvins, protectins and maresins).
Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.
We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants.
Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile.
Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency.
Full funding sources listed at end of paper (see Acknowledgments).
A deficiency of vitamin D results in muscle weakness as well as rickets in children and osteomalacia in the adult. To study the basis for this weakness, severe vitamin D deficiency was produced in rats as revealed by a low level or absence of 25-hydroxyvitamin D(3) in the serum. Vitamin D deficiency was achieved by feeding purified diets to weanlings for 16 weeks. Muscle force, peak contraction (P), time-to-half contraction (T(1/2)), time-to-peak contraction (T(P)), and time-to-half recovery (T(1/2r)) were measured. A significant reduction in muscle force was found when vitamin D deficiency was accompanied by hypophosphatemia. Within 2 days of correcting the hypophosphatemia, muscle strength was normalized. When serum calcium and serum phosphorus were maintained in the normal range in vitamin D-deficient rats, muscle weakness did not develop. Further, hypocalcemia together with vitamin D deficiency did not produce muscle weakness. These results strongly suggest that muscle weakness noted in rachitic patients is the result of the hypophosphatemia of vitamin D deficiency.
Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals.
To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals.
Forty healthy volunteers (24 M/16 F, mean age (SD) 31.5 ± 5.0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60,000 IU D3/week for 8 weeks followed by 60,000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months.
Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on (31) P magnetic resonance spectroscopy were assessed at baseline and after 6 months.
The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25.4 ± 9.9, 94.5 ± 53.8 and 56.0 ± 17.0 nm, and 21.1 ± 9.4, 32.8 ± 14.4 and 29.7 ± 15.0 nm, respectively. The supplemented group gained a handgrip strength of 2.4 kg (95% C.I. = 1.2-3.6); gastro-soleus strength of 3.0 Nm (95% C.I. = 0.1-5.9) and walking distance of 15.9 m (95% C.I. = 6.3-25.5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months.
Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60,000 IU per month could not maintain 25(OH)D levels in the sufficient range.
We previously reported that 1alpha,25(OH)2D3 induces non-transcriptional rapid responses through activation of MAPKs in C2C12 skeletal muscle cells. However, there is little information on the molecular mechanism underlying the initiation of 1alpha,25(OH)2D3 signaling through this pathway. Plasma membrane components have been involved in some non-genomic effects. In this work, we investigated the role of caveolae and caveolin-1 (cav-1) in 1alpha,25(OH)2D3-stimulation of c-Src and MAPKs. When proliferating cells were pretreated with methyl beta cyclodextrin (MbetaCD), a caveolae disrupting agent, under conditions in which cell morphology is not affected and no signs of apoptosis are observed, 1alpha,25(OH)2D3-dependent activation of ERK1/2, p38 MAPK and c-Src was suppressed. Similar results were obtained by siRNA technology whereby silencing of cav-1 expression abolished activation of c-Src and MAPKs induced by the hormone. By confocal immunocytochemistry it was observed that cav-1 colocalizes with c-Src in the periplasma membrane zone at basal conditions. Hormone treatment disrupted the colocalization of these proteins and redistributed them into cytoplasm and nucleus. Co-immunoprecipitation assays corroborated these observations. Changes in VDR localization after 1alpha,25(OH)2D3 exposure were also investigated. Confocal microscopy images showed that the hormone induces VDR translocation to the plasma membrane, and this effect is abolished by MbetaCD. Altogether, these data suggest that caveolae is involved upstream in c-Src-MAPKs activation by 1alpha,25(OH)2D3 and that VDR and cav-1 participate in the rapid signaling elicited by the hormone.
The purpose of this study was to study the relationship between fatty degeneration of thigh muscles and vitamin D status in elderly adults.
For six months, 121 patients 65 years old or older were evaluated. Myopathy, muscular impairment, and conditions influencing vitamin D status other than diet and sunlight were exclusion criteria. Twenty patients (10 men and 10 women; mean age, 77.6 years) underwent MRI. Thigh muscles were scanned from the hip to the knee with T1- and T2-weighted spin-echo sequences. Skeletal muscles were evaluated for fatty degeneration and atrophy from grade 0 to 3 (grade 0 = normal appearance, grade 3 = severe changes). The relationship between muscular fatty degeneration, 25-hydroxyvitamin D (25-OHD) levels, and scores on Tinetti scales for balance and gait were examined.
In the evaluation of the extensor muscles for fatty degeneration and atrophy, grade 0 was present in three patients (15%), grade 1 in 11 (55%), and grade 2 in six (30%). In the flexor muscles, grade 0 was found in one patient (5%), grade 1 in five (25%), and grade 2 in 14 (70%); grade 3 changes were not seen. Muscular fatty degeneration negatively correlated with 25-OHD levels (r = -0.50, p < 0.01) and the Tinetti scores (balance: r = -0.40, p < 0.05; gait: r = -0.50, p < 0.05). In 11 vitamin D-deficient patients (55%), there was selective complete atrophy of at least one thigh muscle. The gracilis and sartorius muscles were spared.
In elderly adults, fatty degeneration of thigh muscles was associated with vitamin D deficiency and impaired balance and gait. Selective complete fatty degeneration of single muscles was observed.
This study examined the role of vitamin D as a factor accounting for fatty degeneration and muscle function in the rotator cuff. There were 366 patients with disorders of the shoulder. A total of 228 patients had a full-thickness tear (group 1) and 138 patients had no tear (group 2). All underwent magnetic resonance arthrography and an isokinetic muscle performance test. The serum concentrations of vitamin D (25(OH)D 3 ) were measured.
In general, a lower serum level of vitamin D was related to higher fatty degeneration in the muscles of the cuff. Spearman’s correlation coefficients were 0.173 (p = 0.001), −0.181 (p = 0.001), and −0.117 (p = 0.026) for supraspinatus, infraspinatus and subscapularis, respectively. In group 1, multivariate linear regression analysis revealed that the serum level of vitamin D was an independent variable for fatty degeneration of the supraspinatus and infraspinatus.
The serum vitamin D level has a significant negative correlation with the fatty degeneration of the cuff muscle and a positive correlation with isokinetic muscle torque.
The objective of this study was to systematically review all the published articles examining the effects of low serum vitamin D concentration and vitamin D supplementation on muscle, balance and gait performance among people aged 65 and older.
An English and French Medline search ranging from January 2004 to November 2008 indexed under the Medical Subject Heading (MeSH) terms "aged OR aged, 80 and over" AND "Vitamin D OR Vitamin D Deficiency" combined with the terms "Gait" OR "Gait Apraxia" OR "Gait Disorders, Neurologic" OR "Walking" OR "Mobility Limitation" OR "Polyneuropathy" OR "Proprioception" OR "Ataxia" OR "Accidental Falls" was performed.
Of the 102 selected studies, 16 met the selection criteria and were included in the final analysis. There were 8 observational studies and 8 interventional studies. The number of participants ranged from 24 to 33067. A majority of studies examined community-dwelling older women. Five observational studies showed a significant positive association, whereas three studies did not. Four of the 5 studies and two of the 3 studies which tested the vitamin D supplementation effect, respectively on balance and gait, showed no significant effect. Four studies showed a significant effect on muscle strength, while this effect was not observed in three others studies. In addition, there was no significant association between vitamin D supplementation and an improvement of the sit-to-stand test results in 50% of the studies.
The findings show that the association between vitamin D and physical performance remains controversial. Observational studies and clinical trials yielded divergent results, which highlights the complex and to date still poorly understood association between serum vitamin D concentration or vitamin D supplementation and physical performance.
Hypervitaminosis vitamin D(3) has been recently implicated in premature aging through the regulation of 1alpha hydroxylase expression by klotho and fibroblast growth factor-23 (Fgf-23). Here we examined whether the lack of hormonal function of vitamin D(3) in mice is linked to aging phenomena. For this, we used vitamin D(3) receptor (VDR) "Tokyo" knockout (KO) mice (fed with a special rescue diet) and analyzed their growth, skin and cerebellar morphology, as well as overall motor performance. We also studied the expression of aging-related genes, such as Fgf-23, nuclear factor kappaB (NF-kappaB), p53, insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), in liver, as well as klotho in liver, kidney and prostate tissues. Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts. There was no difference either in the structure of cerebellum or in the number of Purkinje cells. Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging.
The vitamin D endocrine system is essential for calcium and bone homeostasis. Vitamin D deficits are associated with muscle weakness and osteoporosis, whereas vitamin D supplementation may improve muscle function, body sway and frequency of falls, growth and mineral homeostasis of bones. The loss of muscle strength and mass, as well as deficits in bone formation, lead to poor balance. Poor balance is one of the main causes of falls, and may lead to dangerous injuries. Here we examine balance functions in vitamin D receptor deficient (VDR-/-) mice, an animal model of vitamin D-dependent rickets type II, and in 1alpha-hydroxylase deficient (1alpha-OHase-/-) mice, an animal model of pseudovitamin D-deficiency rickets. Recently developed methods (tilting box, rotating tube test), swim test, and modified accelerating rotarod protocol were used to examine whether the absence of functional VDR, or the lack of a key vitamin D-activating enzyme, could lead to mouse vestibular dysfunctions. Overall, VDR-/- mice, but not 1alpha-OHase-/- mice, showed shorter latency to fall from the rotarod, smaller fall angle in the tilting box test, and aberrant poor swimming. These data suggest that VDR deficiency in mice is associated with decreased balance function, and may be relevant to poorer balance/posture control in humans with low levels of vitamin D.
Vitamin D insufficiency has now reached epidemic proportions and has been linked to low bone mineral density, increased risk of fracture, and obesity in adults. However, this relationship has not been well characterized in young adults. Objective: The objective of the study was to examine the relationship between serum 25-hydroxyvitamin D (25OHD), anthropometric measures, body fat (BF), and bone structure at the time of peak bone mass.
This was a cross-sectional study. OUTCOME MEASURES AND SUBJECTS: Anthropometric measures, serum 25OHD radioimmunoassay values, and computed tomography and dual-energy x-ray absorptiometry values of BF and bone structure in 90 postpubertal females, aged 16-22 yr, residing in California were measured.
Approximately 59% of subjects were 25OHD insufficient (<or=29 ng/ml), and 41% were sufficient (>or=30 ng/ml). Strong negative relationships were present between serum 25OHD and computed tomography measures of visceral and sc fat and dual-energy x-ray absorptiometry values of BF. In addition, weight, body mass, and imaging measures of adiposity at all sites were significantly lower in women with normal serum 25OHD concentrations than women with insufficient levels. In contrast, no relationship was observed between circulating 25OHD concentrations and measures of bone mineral density at any site. Unexpectedly, there was a positive correlation between 25OHD levels and height.
We found that vitamin D insufficiency is associated with increased BF and decreased height but not changes in peak bone mass.
Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, macrophages and skin among other organs have the enzymatic machinery to produce 1,25-dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes.
Although skeletal muscle is a major calcium-regulated organ, there remains uncertainty about whether muscle is a target organ for the action of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In this study we examine pure populations of clonally derived human muscle cells for the presence of 1,25-(OH)2D3 receptors and direct responses to the hormone. All of the clones tested exhibited specific [3H]1,25-(OH)2D3 binding, with values ranging from 5-70 fmol/mg protein. Scatchard analysis of binding data revealed a dissociation constant (approximately 100 pM) comparable to that of classical receptors in other target organs. The 1,25-(OH)2D3 receptors sedimented at 3.3S on hypertonic sucrose gradients. Specificity for [3H]1,25-(OH)2D3 was demonstrated on gradients by substantially better competition by 1,25-(OH)2D3 than 25-hydroxyvitamin D3 for the 3.3S receptor binding peak. The 1,25-(OH)2D3 receptor complex bound to DNA-cellulose and eluted as a single peak at 0.2 M KCl. Myoblasts and myotubes did not show significant differences in either the amount or characteristics of the 1,25-(OH)2D3 receptor. In addition to the presence of receptors, cells were tested for functional responsiveness to 1,25-(OH)2D3. Both cell types exhibited a dose-dependent induction of 25-hydroxyvitamin D3-24-hydroxylase enzyme activity after treatment of monolayers with 1,25-(OH)2D3. Incorporation of both leucine and thymidine into growing myoblasts and fused myotubes was inhibited in a dose-dependent fashion after treatment with 1,25-(OH)2D3. In summary, cloned human skeletal muscle cells contain a binding protein compatible with classical 1,25-(OH)2D3 receptors as well as functional responsiveness to 1,25-(OH)2D3 at physiological concentrations of hormone.
I. Introduction VITAMIN D plays an essential role in vertebrates. In concert with the two peptide hormones PTH and calcitonin, vitamin D mediates calcium and phosphorus metabolism at target tissues, including intestine, bone, and kidney. The sterol must be metabolically activated before exerting its action. Vitamin D derived from the diet or generated in the skin by photometabolism of 7-dehydrocholesterol or ergosterol undergoes 25-hydroxylation in the liver. In the kidney, 25-hydroxyvitamin D (25OHD) is further metabolized to lα,25-dihydroxyvitamin D [1,25-(OH)2D] and 24,25-dihydroxyvitamin D [24,25-(OH2)D]. The most biologically active form of vitamin D is 1,25-(OH)2D. 1,25-(OH)2D functions in a classical endocrine fashion. Its production in the kidney is under a complex regulatory system so that more of the metabolite is available when demand for calcium is high. Moreover, there is substantial evidence which indicates that, analogous to classic steroid hormones, 1,25-(OH)2D elicits its biological respo...
To determine the effect of increased skin pigment on the cutaneous production of vitamin D3, circulating vitamin D concentrations were determined in two lightly pigmented Caucasian and three heavily pigmented Negro volunteers after exposure to a single standard dose of ultraviolet radiation (UVR). Exposure of Caucasian subjects to 1 minimal erythemal dose of UVR greatly increased serum vitamin-D concentrations by up to 60-fold 24-48 h after exposure, whereas this dose did not significantly change serum vitamin-D concentrations in Negro subjects. Re-exposure of one Negro subject to a dose of UVR six times larger than the standard dose increased circulating vitamin D to concentrations similar to those recorded in Caucasian subjects after exposure to the lower dose. These results indicate that increased skin pigment can greatly reduce the UVR-mediated synthesis of vitamin D.
Vitamin D status decreases with age, mainly as a result of restricted sunlight exposure, reduced capacity of the skin to produce vitamin D, and reduced dietary vitamin D intake. We measured wintertime serum 25-hydroxyvitamin D [25(OH)D] concentrations in 824 elderly people from 11 European countries. 36% of men and 47% of women had 25(OH)D concentrations below 30 nmol/L. Users of vitamin D supplements and/or sunlamps had higher 25(OH)D (median 54 nmol/L) than non users (median 31 nmol/L). Surprisingly, lowest mean 25(OH)D concentrations were seen in southern European countries. Low 25(OH)D concentrations could largely be explained by attitudes towards sunlight exposure and factors of physical health status, after exclusion of users of vitamin D supplements or sunlamps. Problems with daily living activities and wearing clothes with long sleeves during periods of sunshine were strong predictors of low wintertime serum 25(OH)D concentrations. These findings show that free-living elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter and that dietary enrichment or supplementation with vitamin D should be seriously considered during this season.