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Degenerative lumbar disease is a significant contributor to acute or chronic musculoskeletal issues in the elderly, often associated with low serum 25‐hydroxyvitamin D (25(OH)D) levels. The effect of vitamin D2 supplementation on muscle mass, strength, and physical performance remains unclear. This study aimed to determine the effect of vitamin D2 supplementation on these parameters in patients with degenerative lumbar disease and low vitamin D status. A total of 115 patients with serum 25(OH)D levels < 30 ng/mL were administered 40,000 IU of vitamin D2 (ergocalciferol) weekly for 6 months. Body composition, serum 25(OH)D, parathyroid hormone (PTH) levels, muscle strength, and physical performance were examined before and after 6 months of vitamin D2 supplementation. Baseline median serum 25(OH)D was 24.9 ng/mL; 79.1% had vitamin D insufficiency, and 20.9% had vitamin D deficiency. After supplementation, median 25(OH)D increased to 43.1 ng/mL (p < 0.001), with a significant reduction in PTH (p < 0.001). Significant improvements were observed in muscle mass (p = 0.04), balance test (p = 0.01), gait speed (p = 0.009), chair stand test (p < 0.001), short physical performance (p < 0.001), Oswestry disability index (p < 0.001), and visual analog scale (VAS) scores (p < 0.001). Post‐supplementation 25(OH)D levels correlated negatively with body mass index (ρ = −0.187, p = 0.045), fat mass (ρ = −0.219, p = 0.019), fat percentage (ρ = −0.199, p = 0.033), and VAS score (ρ = −0.313, p < 0.001). Six months of vitamin D2 supplementation significantly improved vitamin D status, muscle mass, physical performance, and quality of life in patients with degenerative lumbar disease.

Abstract Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined “empiric supplementation” as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

AbstractObjectiveTo investigate whether vitamin D supplementation is associated with lower mortality in adults.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.Eligibility criteria for selecting studiesRandomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.Main outcome measuresAll cause mortality.Results50 trials with a total of 74 655 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.85, 0.74 to 0.97, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.ConclusionsVitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 15%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.Study registrationPROSPERO registration number CRD42018117823.

Modest and even severe vitamin D deficiency is widely prevalent around the world. There is consensus that a good vitamin D status is necessary for bone and general health. Similarly, a better vitamin D status is essential for optimal efficacy of antiresorptive treatments. Supplementation of food with vitamin D or using vitamin D supplements is the most widely used strategy to improve the vitamin status. Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) are the most widely used compounds and the relative use of both products depends on historical or practical reasons. Oral intake of calcifediol (25OHD3) rather than vitamin D itself should also be considered for oral supplementation. We reviewed all publications dealing with a comparison of oral cholecalciferol with oral calcifediol as to define the relative efficacy of both compounds for improving the vitamin D status. First, oral calcifediol results in a more rapid increase in serum 25OHD compared to oral cholecalciferol. Second, oral calcifediol is more potent than cholecalciferol, so that lower dosages are needed. Based on the results of nine RCTs comparing physiologic doses of oral cholecalciferol with oral calcifediol, calcifediol was 3.2-fold more potent than oral cholecalciferol. Indeed, when using dosages ≤ 25 μg/day, serum 25OHD increased by 1.5 ± 0.9 nmol/l for each 1 μg cholecalciferol, whereas this was 4.8 ± 1.2 nmol/l for oral calcifediol. Third, oral calcifediol has a higher rate of intestinal absorption and this may have important advantages in case of decreased intestinal absorption capacity due to a variety of diseases. A potential additional advantage of oral calcifediol is a linear dose-response curve, irrespective of baseline serum 25OHD, whereas the rise in serum 25OHD is lower after oral cholecalciferol, when baseline serum 25OHD is higher. Finally, intermittent intake of calcifediol results in fairly stable serum 25OHD compared with greater fluctuations after intermittent oral cholecalciferol.

Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances.Design Systematic review and meta-analysis of observational studies and randomised controlled trials.Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators.Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes.Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics.Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods.Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.

Vitamin D deficiency has long been associated with reduced immune function that can lead to viral infection. Several studies have shown that Vitamin D deficiency is associated with increases the risk of infection with COVID-19. However, it is unknown if treatment with Vitamin D can reduce the associated risk of COVID-19 infection, which is the focus of this study. In the population of US veterans, we show that Vitamin D 2 and D 3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively [(D 3 Hazard Ratio (HR) = 0.80, [95% CI 0.77, 0.83]), D 2 HR = 0.72, [95% CI 0.65, 0.79]]. Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D 3 and 25% lower with D 2 (D 3 HR = 0.67, [95% CI 0.59, 0.75]; D 2 HR = 0.75, [95% CI 0.55, 1.04]). We also find that after controlling for vitamin D blood levels, veterans receiving higher dosages of Vitamin D obtained greater benefits from supplementation than veterans receiving lower dosages. Veterans with Vitamin D blood levels between 0 and 19 ng/ml exhibited the largest decrease in COVID-19 infection following supplementation. Black veterans received greater associated COVID-19 risk reductions with supplementation than White veterans. As a safe, widely available, and affordable treatment, Vitamin D may help to reduce the severity of the COVID-19 pandemic.

Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.