Vitamin D Deficiency in Adults: When to Test and How to Treat

Recent evidence for the nonskeletal effects of vitamin D, coupled with recognition that vitamin D deficiency is common, has revived interest in this hormone. Vitamin D is produced by skin exposed to ultraviolet B radiation or obtained from dietary sources, including supplements. Persons commonly at risk for vitamin D deficiency include those with inadequate sun exposure, limited oral intake, or impaired intestinal absorption. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D concentration in the blood. Average daily vitamin D intake in the population at large and current dietary reference intake values are often inadequate to maintain optimal vitamin D levels. Clinicians may recommend supplementation but be unsure how to choose the optimal dose and type of vitamin D and how to use testing to monitor therapy. This review outlines strategies to prevent, diagnose, and treat vitamin D deficiency in adults.AI = adequate intake; CKD = chronic kidney disease; D2 = vitamin D₂; D3 = vitamin D₃; 1,25(OH)2D = 1,25-dihydroxyvitamin D; HPT = hyperparathyroidism; 25(OH)D = 25-hydroxyvitamin D; PTH = parathyroid hormone; UVB = ultraviolet BVitamin D has been appreciated for its role in calcium homeostasis and bone health since its identification in 1921.¹ Even so, 25% to 50% or more of patients commonly encountered in clinical practice are deficient in vitamin D. Recent advances in biochemical assessment, therapeutic goals for vitamin D nutrition for optimal bone health, and the association of vitamin D deficiency with nonskeletal disease have revived interest in this hormone.Vitamin D consists of 2 bioequivalent forms. Vitamin D₂ (D₂), also known as ergocalciferol, is obtained from dietary vegetable sources and oral supplements. Vitamin D₃ (D₃), also known as cholecalciferol, is obtained primarily from skin exposure to ultraviolet B (UVB) radiation in sunlight, ingestion of food sources such as oily fish and variably fortified foods (milk, juices, margarines, yogurts, cereals, and soy), and oral supplements. Aside from rich sources such as oily fish, the vitamin D content of most foods is between 50 and 200 IU per serving. This value varies greatly by region of the world because fortification markedly improves the availability of vitamin D through diet. Both D₂ and D₃ are biologically inert. Once absorbed from the intestine, they are metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], composed of 25(OH)D₂ and 25(OH)D₃; 25(OH)D (also called calcidiol) is subsequently converted to 1,25-dihydroxyvitamin D [1,25(OH)₂D], also known as calcitriol, in the kidney and select other tissues by the action of the 1α-hydroxylase enzyme. The predominant effects of vitamin D are exerted through the endocrine and autocrine actions of calcitriol via activation of the vitamin D receptor in cells.     

Effects of Vitamin D Supplementation on Bone Health and Bone-related Parameters in HIV-infected Patients: A Systematic Review and Meta-analysis

PurposeThere is growing evidence that bone health is decreased in individuals with HIV infection. Vitamin D deficiency is also highly prevalent among HIV-infected patients. The literature was systematically reviewed to determine whether bone health and bone-related parameters may improve with vitamin D supplementation in HIV-infected individuals.MethodsFour databases were systematically searched for randomized clinical trials of vitamin D supplementation in HIV infection, published from January 1990 to September 2021. No language or publication restrictions were applied. Standardized mean differences (SMD) with 95% CIs are reported. A random-effects model was used to perform meta-analysis.FindingsTen studies met the inclusion criteria (N = 733 participants at study completion). The mean ages of the patients in the included trials ranged from 10 to 49 years. The meta-analysis indicated that with vitamin D supplementation, serum 25-hydroxy vitamin D (25[OH]D) level was significantly increased (SMD, 1.86; 95% CI, 1.02 to 2.70; I² = 94.4%), but there were no significant effects on levels of serum 1,25-dihydroxy vitamin D (1,25-[OH]₂D) (SMD, 0.29; 95% CI, –0.07 to 0.64; I² = 67.4%), total bone mineral density (SMD, 0.07; 95% CI, –0.23 to 0.37; I² = 00.0%), spine bone mineral density (SMD, 0.15; 95% CI, –0.19 to 0.49; I² = 17.3%), and parathyroid hormone level (SMD, –0.18; 95% CI, –0.37 to 0.02; I² = 1.2%) in HIV-infected patients.ImplicationsThis study showed that vitamin D supplementation can improve serum 25(OH)D in HIV-infected patients. The effects of vitamin D supplementation on other bone health–related parameters such as bone mineral density and parathyroid hormone in HIV-infected patients need to be further investigated in larger-scale, well-designed randomized, controlled trials.     

Vitamin D for Health: A Global Perspective

It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases. However, there remains cynicism about the lack of randomized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by searching English-language studies published up to April 1, 2013, in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials (search terms: vitamin D and supplementation) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources, supplements, and sun exposure. The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life. There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses, including some cancers, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and mortality.     

Vitamin D status is associated with bone mineral density and functional exercise capacity in patients with chronic obstructive pulmonary disease

Background. Chronic obstructive pulmonary disease (COPD) is associated with several extrapulmonary effects that contribute to the severity of the disease. Vitamin D is suggested to play a role in COPD and its related extrapulmonary effects. Aims. To determine the prevalence of vitamin D deficiency and its relation with bone density, muscle strength, and exercise capacity in patients with COPD. Methods. Our cross-sectional study included patients with moderate to very severe COPD. We collected data on lung function, body composition, bone density, quadriceps muscle strength, 6-minute walking distance, and plasma 25-hydroxyvitamin D (25(OH)D) concentration. Vitamin D deficiency was defined as plasma 25(OH)D concentration below 50 nmol/L. Results. In total, 151 COPD patients were included; 87 patients (58%) had vitamin D deficiency. Plasma 25(OH)D concentration was positively associated with bone density (P =?0.005) and 6-minute walking distance (P <?0.001) after adjustment for potential confounders. Plasma 25(OH)D concentration was not associated with quadriceps muscle strength. Conclusions. The majority of COPD patients had vitamin D deficiency. Plasma 25(OH)D concentration was positively associated with bone density and exercise capacity. Intervention studies are necessary to determine whether vitamin D supplementation is of benefit in the prevention or treatment of osteoporosis and poor exercise capacity in patients with COPD.     

The influence of maternal vitamin D supplementation on infant vitamin D status: A systematic review and meta-analyses

BackgroundInconsistencies exist with regard to effect of maternal vitamin D supplementation on infant vitamin D status. The inconsistencies could be attributed to numerous factors, such as duration of intervention and dosage, among others. In this work, we conducted a systematic review and meta-analysis to determine the influence of maternal vitamin D supplementation on infant vitamin D status.MethodsA comprehensive systematic search was performed in Scopus, EMBASE, Web of Science, and PubMed/MEDLINE, by investigators, from database inception until November 2019, without using any restrictions. Weighted mean difference (WMD) with the 95 % CI was used for assessing the effects of maternal vitamin D supplementation on 25(OH) D levels in infants.ResultsOverall results from 14 studies revealed a non-significant effect of maternal vitamin D administration on the level of 25(OH) D in breastfeeding infants (WMD: -0.464 ng/mL, 95 % CI: -6.68 to 5.75, p = 0.884, I² = 98 %). Subgroup analyses demonstrated that vitamin D supplementation dosage ≥2000 IU/day (WMD: 9 ng/mL, 95 % CI: 8.19, 9.82, I² = 99 %) and intervention duration ≥20 weeks (WMD: 16.20 ng/mL, 95 % CI: 14.89, 17.50, I² = 99 %) significantly increased 25(OH) D.ConclusionsThe main results indicate a non-significant increase in infant vitamin D following maternal vitamin D supplementation. Additionally, vitamin D supplementation dosage ≥2000 IU/day and intervention duration ≥20 weeks significantly increased infant 25(OH) D.     

Vitamin D intakes and health outcomes in infants and preschool children: Summary of an evidence report

BackgroundA systematic review was commissioned to support an international expert group charged to update the Food and Agriculture Organisation of the United Nations (FAO)/World Health Organisation (WHO)’s vitamin D intake recommendations for children aged 0–4 years.Materials and methodsMultiple electronic databases were searched to capture studies published from database inception to the 2^nd week of June 2020 according to key questions formulated by the FAO/WHO. Relevant studies were summarised and synthesised by key questions and by health outcomes using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach.ResultsThe 146 included studies examined the effects of different vitamin D intake levels on a variety of health outcomes (e.g. infectious disease, growth, neurodevelopment, rickets, and bone mineral density), and on outcomes for setting vitamin D upper limits (e.g. hypercalcemia, hypercalciuria, and nephrocalcinosis). For most outcomes, the strength of evidence was low or very low. Evidence was rated moderate for the effect of daily vitamin D supplementation on raising serum 25(OH)D concentrations, and a random-effects meta-regression analysis of 28 randomised controlled trials (mostly in infants 0–12 months) showed that each 100 IU/d increase in vitamin D supplementation was associated with an average of 1.92 (95% CI 0.28, 3.56) nmol/L increase in achieved 25-hydroxy-vitaminn D (25[OH]D) concentration (n = 53 intervention arms; p = .022) with large residual heterogeneity (I² = 99.39%). Evidence was very low on two of the upper limit outcomes – hypercalcemia and hypercalciuria.ConclusionsThe evidence report provided the expert group with a foundation and core set of data to begin their work to set vitamin D nutrient reference values. To move the field forward, future studies should use standardised 25(OH)D assay measurements and should examine the relationship between long-term vitamin D status and health outcomes.

Key Messages

• Results of a large complex systematic review suggest the current totality of evidence from trials and prospective observational studies do not reach sufficient certainty level to support a causal relationship between vitamin D intake and asthma, wheeze, eczema, infectious diseases, or rickets (most trials reported no rickets) in generally healthy infants and young children.
• In this systematic review, the only body of evidence that reached a moderate level of certainty was regarding the effect of daily vitamin D supplementation (vitamin D₃ or D₂ supplements to infants/children) on increasing serum 25(OH)D concentrations. However, currently there is no consensus on the definitions of vitamin D status, e.g. deficiency, insufficiency, sufficiency and toxicity, based on serum 25(OH)D concentrations.
• This systematic review provided an international expert group a foundation and core set of data through intake-response modelling to help set vitamin D nutrient reference values for infants and children up to 4 years of age.

     

Relationship Between Vitamin D Level and Mortality in Adults With Psoriasis: A Retrospective Cohort Study of NHANES Data

PurposeStudies have shown an increased risk for mortality in patients with psoriasis. Furthermore, research has demonstrated an inverse relationship between 25-hydroxyvitamin D (25[OH]D) level and all-cause mortality. This study investigated the association between 25(OH)D level and all-cause mortality in US adults with psoriasis.MethodsData from NHANES (1999–2014 and mortality data through December 31, 2015) were analyzed. Quartiles of 25(OH)D level were created based on 25(OH)D levels among patients. Cox proportional hazards models were used for estimating hazard ratios (95% CI) for all-cause mortality.FindingsA total of 82,091 participants were enrolled in the NHANES study from 1999 to 2014. Overall, 610 patients with psoriasis were identified in NHANES. The mean (SD) duration of follow-up was 5.61 (3.38) years (3427.92 person-years). The hazard ratio for mortality in the fully adjusted model was 0.12 (95% CI, 0.02–0.60; P_trend = 0.01) in patients with a high 25(OH)D concentration compared to those with 25(OH)D deficiency.ImplicationsThe 25(OH)D concentration was significantly inversely associated with all-cause mortality among these patients with psoriasis. Studies have shown an increased risk for mortality in patients with psoriasis compared to the general population. Vitamin D is not regularly metabolized in patients with psoriasis due to their skin abnormality. Vitamin D supplementation has been associated with a reduced mortality in patients with psoriasis. In practice, attention to vitamin D level is crucial, as is the use of vitamin D supplementation, for improving the health of these patients.     

High-dose cholecalciferol supplementation for vitamin D deficiency in haemodialysis patients

Vitamin D deficiency, which is a recognized problem in haemodialysis (HD) patients, has been associated with higher all-cause mortality. There are no guidelines concerning vitamin D supplementation in HD patients. This study aimed to assess the effects of once-monthly supplementation with high-dose cholecalciferol (vitamin D(3)) in HD patients. Patients with 25-hydroxy vitamin D (25[OH]D) levels of < 75 nmol/l received 40,000 IU of cholecalciferol oncemonthly for 3 months in succession. Every 4 months, 25(OH)D levels were measured and, based on the findings, cholecalciferol therapy was continued for another cycle if necessary. Six cycles were completed in the 24-month study period. The majority of HD patients had mild or severe vitamin D deficiency at baseline. Monthly supplementation with cholecalciferol at 40,000 IU was well tolerated, safe and inexpensive. The treatment regime was effective for vitamin D insufficiency but did not prove to be enough to restore 25(OH)D levels in HD patients with mild or severe vitamin D deficiency.     

Vitamin D supplementation and pain-related emergency department visits in children with sickle cell disease

ObjectivesSickle cell disease (SCD) is the most prevalent inherited hematological disorder and affects 100,000 individuals in the United States. Pain is the most common cause of emergency department (ED) visits in the SCD population, which profoundly affects quality of life. Vitamin D supplementation is a potential target for reducing pain. Thus, the goal of the present study was to identify the prevalence of vitamin D deficiency and explore the relationship between vitamin D supplementation and ED visits in pediatric patients with SCD.DesignWe conducted a retrospective chart review of 110 patients with SCD aged 8–16 years who had at least one ED visit for SCD pain during the 6-year study period. Patients were categorized into three vitamin D supplementation groups: patients who did not receive supplementation, patients supplemented with 25-hydroxyvitamin D levels (< 30 ng/mL), and patients supplemented with at least one sufficient 25-hydroxyvitamin D level (≥ 30 ng/mL).ResultsOverall, 45 % of patients were vitamin D deficient. Only 20 % of patients had sufficient vitamin D levels. This number increased to 55 % when examining only patients who did not receive vitamin D supplementation. For patients supplemented with vitamin D, the number of ED visits was significantly lower after they reached the sufficient range (≥ 30 ng/mL), p = 0.03.ConclusionsOur findings indicate that reductions in the number of pain-related ED visits may be achieved by normalizing 25-hydroxyvitamin D levels with supplementation. In addition, findings highlight the need for screening and vitamin D supplementation being incorporated into routine care for pediatric patients with SCD.     

Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D,calculated free 25-hydroxyvitamin D and vitamin D binding protein

Backgroundvitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels.ObjectiveTo assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism.To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children.DesignProspective cohort study.SettingJanuary and February 2017 in a Mediterranean population.Patientshealthy children.Measurementsm-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle.Resultsm-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula.Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (β:0.156, p:0.026) and total 25(OH)D (β:0.043, p < .001).The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798–0.958); p < .001; sensitivity:72.7% (95%CI: 49.8–89.3); specificity: 95.5% (95%CI: 84.5–99.4)).ConclusionsDirectly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children.     

The effect of intramuscular megadose of vitamin D injections on E-selectin,CRP and biochemical parameters in vitamin D-deficient patients with type-2 diabetes mellitus: A randomized controlled trial

Background and aimsInflammatory processes has been shown to be associated with the development of type 2 diabetes mellitus (T2DM) in which vitamin D supplementation might exert beneficial outcomes. We examined the effects of vitamin D supplement on inflammatory and cell adhesion molecule in patients with T2DM.MethodsThis study consisted of 50 patients with T2DM who had vitamin D deficiency. Participants were randomized into two groups of 25 in which the intervention group received two intramuscular injections of a 200000-IU vitamin D supplement, one at week 0 and another at week 4. The concentrations of fasting blood glucose (FBG), lipid profiles, liver enzymes, E-selectin, C-reactive protein (CRP), calcium, phosphorus, serum 25-hydroxyvitamin D [25(OH)D] and anthropometric indices were obtained before and after 8 weeks.ResultsVitamin D resulted in significant reductions in CRP(P = 0.01) and gamma glutamyl transferase (GGT) levels(P = 0.03) and significant increases in 25(OH)D concentrations(P = 0.01) in the intervention group compared with the control. Within-group comparisons showed that FBG decreased significantly in the intervention group(P = 0.04). No significant changes were observed regarding within- and between-group comparisons of the other markers.ConclusionVitamin D had beneficial effects on the levels of CRP, serum 25(OH)D and GGT among vitamin D deficient patients with T2DM. (http://www.irct.ir: IRCT2017100336539N1).     

Risk factors for vitamin D inadequacy among women with osteoporosis: an international epidemiological study

A serum 25-hydroxyvitamin D [25(OH)D] level of 75 nmol/l (30 ng/ml) has been proposed as the minimum for adequate vitamin D nutrition as lower levels are associated with increases in serum parathyroid hormone in otherwise healthy adults. Amongst 2589 community-dwelling, postmenopausal women with osteoporosis from 18 countries, recruited to determine risk factors for vitamin D inadequacy, 64% had vitamin D inadequacy. General health, education, ethnicity, sun exposure, skin reactivity, diet, recent travel to sunny climates, vitamin D supplementation, body mass index (BMI), season and latitude were assessed using logistic regression models. Asian ethnicity, BMI >or=30 kg/m(2), living in non-equatorial countries, inadequate vitamin D supplementation, poor/fair health, no education about vitamin D, skin reactivity and no recent travel to sunny areas were significant predictors. Several modifiable risk factors are associated with vitamin D inadequacy worldwide, suggesting potentially simple ways to increase vitamin D and improve bone health in postmenopausal women.     

Vitamin D inadequacy among post-menopausal women: a systematic review

BACKGROUND: Vitamin D inadequacy has been studied extensively, due to concerns about ageing populations, associations with osteoporosis and other disorders (including non-musculoskeletal), and high prevalence. AIM: To review recent reports on the prevalence of vitamin D inadequacy among post-menopausal women with and without osteoporosis and/or other musculoskeletal diseases. DESIGN: Systematic review. METHODS: We reviewed publications in the past 10 years reporting prevalence estimates for vitamin D inadequacy, reported as serum 25(OH)D values below various levels. Thirty published studies in the English language were identified, from January 1994 through April 2004. RESULTS: In osteoporotic populations, the prevalence of 25(OH) vitamin D concentration <12 ng/ml ranged from 12.5% to 76%, while prevalence rates reached 50% to 70% of patients with a history of fracture(s) using a cut-off of 15 ng/ml. In post-menopausal women, the prevalence of 25(OH) vitamin D concentrations 相似文献   

Low serum 25-hydroxyvitamin D levels are associated with perennial allergic rhinitis but not disease severity

BackgroundVitamin D deficiency plays an essential role in allergic rhinitis(AR), but the role of vitamin D deficiency in perennial allergic rhinitis (pAR) remains unclear. Therefore, our study explored 25(OH)D levels in patients with pAR and healthy individuals in a single center in China for three years.MethodsA total of 655 patients with pAR and 682 healthy controls were enrolled in this study from 2015 to 2017. Patients'' clinical history and symptoms were recorded. sIgE tests were performed using the allergen detection system (UniCAP), and the ADVIA centaur XP system (SIEMENS) was used to measure serum 25(OH)D levels.ResultsSerum 25(OH)D levels were significantly different between the pAR group and control group over the three‐year study period(all P < .05). Specifically, 25(OH)D levels were decreased in the pAR groups over three years. Serum25(OH)D deficiency, insufficiency, and sufficiency were noted in 66.9% ~71.9%, 22.5% ~29.4%, and 2.5%~5.6%, respectively, of patients in the pAR group and 53.2%~60.7%, 31.4%~36.6%, and 7.9% ~11.4%, respectively, of participants in the control group. We did not identify significant associations between serum 25(OH)D levels and clinical characteristics of patients with pAR over the three‐year period (all P > .05) after adjusting for sex, age, duration of disease, total nasal symptom score (TNSS), sIgE levels, number of positive allergens, and family history.ConclusionpAR patients exhibited lower serum 25(OH)D levels compared with healthy people with a high prevalence of 25(OH)D deficiency or insufficiency. We did not identify a significant correlation between 25(OH)D and pAR associated factors.     

Vitamin D insufficiency

Vitamin D deficiency, which classically manifests as bone disease (either rickets or osteomalacia), is characterized by impaired bone mineralization. More recently, the term vitamin D insufficiency has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with other disease outcomes. Reliance on a single cutoff value to define vitamin D deficiency or insufficiency is problematic because of the wide individual variability of the functional effects of vitamin D and interaction with calcium intakes. In adults, vitamin D supplementation reduces the risk of fractures and falls. The evidence for other purported beneficial effects of vitamin D is primarily based on observational studies. We selected studies with the strongest level of evidence for clinical decision making related to vitamin D and health outcomes from our personal libraries of the vitamin D literature and from a search of the PubMed database using the term vitamin D in combination with the following terms related to the potential nonskeletal benefits of vitamin D: mortality, cardiovascular, diabetes mellitus, cancer, multiple sclerosis, allergy, asthma, infection, depression, psychiatric, and pain. Conclusive demonstration of these benefits awaits the outcome of controlled clinical trials.     

Potential benefit of vitamin D supplementation in people with respiratory illnesses,during the COVID‐19 pandemic

This review describes the evidence for the potential benefit of vitamin D supplementation in people with respiratory diseases who may have a higher susceptibility to coronavirus disease 2019 (COVID‐19) infection and its consequences. Clinical evidence indicates that vitamin D may reduce the risk of both upper and lower respiratory tract infections and offers benefit particularly in people with vitamin D deficiency. Some evidence exists for a higher incidence of active tuberculosis (TB) in patients who are deficient in vitamin D. An association between low levels of 25(OH)D (the active form of vitamin D) and COVID‐19 severity of illness and mortality has also been reported. In addition, low 25(OH)D levels are associated with poor outcomes in acute respiratory distress syndrome (ARDS). The cytokine storm experienced in severe COVID‐19 infections results from excessive release of pro‐inflammatory cytokines. Due to its immunomodulatory effects, adequate vitamin D levels may cause a decrease in the pro‐inflammatory cytokines and an increase in the anti‐inflammatory cytokines during COVID‐19 infections. Vitamin D deficiency was found in 82.2% of hospitalized COVID‐19 cases and 47.2% of population‐based controls (p < 0.0001). The available evidence warrants an evaluation of vitamin D supplementation in susceptible populations with respiratory diseases, such as TB, and particularly in those who are deficient in vitamin D. This may mitigate against serious complications of COVID‐19 infections or reduce the impact of ARDS in those who have been infected.     

A high prevalence of prediabetes and vitamin D deficiency are more closely associated in women: results of a cross-sectional study

ObjectiveMany studies have shown that vitamin D deficiency is associated with insulin resistance and metabolic syndrome. However, few studies have shown independent associations between vitamin D deficiency and the metabolic characteristics of prediabetes. We aimed to evaluate the relationship between serum vitamin D concentration and metabolic risk factors in adults with prediabetes.MethodsWe enrolled 161 patients aged 25 to 75 years in a cross-sectional study and collected clinical and biochemical data, including 25-hydroxyvitamin D (25[OH]D) status and fasting glucose concentration. Vitamin D status was defined as follows: deficiency (25[OH]D <49.9 ng/mL), insufficiency (49.9 to 74.9 nmol/L) or sufficiency (>74.9 nmol/L). Prediabetes was defined using fasting plasma glucose concentrations of 5.55 to 6.49 mmol/L.ResultsThe prevalences of vitamin D deficiency and insufficiency were 49.7% and 24.8%, respectively. Participants with vitamin D deficiency had a higher prevalence of prediabetes than those without (53.8% vs. 32.1%), and there was a significant relationship between female sex and vitamin D status (odds ratio: 1.382; 95% confidence interval: 0.335–5.693).ConclusionVitamin D deficiency is more closely associated with a high prevalence of prediabetes in women than in men. Further studies are needed to elucidate the explanation for this association.     

The Effect of Vitamin D Supplementation on Treatment-Induced Pain in Cancer Patients: A Systematic Review

ObjectivesDespite the widespread use of complementary and alternative medicine by patients and physicians alike, there is no accurate evidence regarding the effects of vitamin D supplementation on treatment-induced pain in cancer patients. Thus, the aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the impact of vitamin D administration on therapy-related pain in subjects diagnosed with malignant disorders.Review analysis methodsWe searched the Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases up to October 2020 to identify published RCTs that investigated the use of vitamin D in the management of treatment-induced pain in individuals with cancer.ResultsNine RCTs were detected. The median duration of the intervention was of 24 weeks (range 12-52 weeks) and dose of vitamin D employed was 2000-50000 IU of vitamin D3 weekly orally each day. Six RCTs reported a significant reduction in pain, whereas three did not detect a notable decrease of this variable. Of the six studies that reported an alleviation of pain, an RCT which recruited 60 participants and lasted for 24 weeks consisted of supplementation with high doses of vitamin D2 weekly for 8 weeks in women receiving anastrozole as adjuvant therapy, then supplementation with vitamin D2 monthly for 4 months, effectively alleviated the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). The results of the same RCT also suggested a beneficial effect of vitamin D on musculoskeletal pain.ConclusionsOur results suggest that the supplementation with high doses of vitamin D in cancer patients with low serum levels of vitamin D, can be effective in reducing treatment-related pain.     

Extraskeletal effects of vitamin D in older adults: Cardiovascular disease,mortality, mood,and cognition

Background: Vitamin D insufficiency is prevalent among older adults and may be associated with higher risk for cardiovascular (CV) disease, mortality, depression, and cognitive deficits.Objective: The aim of this article was to review published observational and experimental studies that explored the association between vitamin D insufficiency and CV disease, mortality, mood, and cognition with an emphasis on older adults.Methods: PubMed and Web of Science databases were searched for English-language articles from January 1966 through June 2009 relating to vitamin D, using the following MeSH terms: aged, vitamin D deficiency, physiopathology, drug therapy, cardiovascular diseases, blood pressure, mortality, delirium, dementia, cognitive disorders, depression, depressive disorder, seasonal affective disorder, mental disorders, and vitamin D/therapeutic use. Publications had to include patients ≥65 years of age who had ≥1 recorded measurement of 25-hydroxyvitamin D (25[OH]D) or were receiving vitamin D supplementation. All case-control, cohort, and randomized studies were reviewed.Results: Forty-two case-control, cohort, and randomized trials were identified and included in the review. Based on these publications, the prevalence of vitamin D insufficiency (25[OH]D concentration <30 ng/mL) in communitydwelling older adults (≥65 years of age) ranged from 40% to 100%. Epidemiologic data and several small randomized trials found a potential association between vitamin D deficiency (25[OH]D concentration <10 ng/mL) and CV disease, including hypertension and ischemic heart disease. Although subgroup analyses of data from the Women's Health Initiative Randomized Trial (the largest randomized, placebo-controlled trial of vitamin D plus calcium therapy) did not find reductions in blood pressure, myocardial infarction, or CV disease-related deaths, intervention contamination limited the findings. Observational studies and a meta-analysis of randomized controlled trials found a mortality benefit associated with higher serum 25(OH)D concentrations or vitamin D₂ or D₃ supplementation (mean dose, 528 IU/d). Observational and small randomized trials found a potential benefit of sunlight or vitamin D on symptoms of depression and cognition, but the findings were limited by methodologic problems.Conclusions: Vitamin D insufficiency appears to be highly prevalent among older adults. Evidence from epidemiologic studies and small clinical trials suggests an association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality. The Women's Health Initiative Randomized Trial did not find a benefit of vitamin D supplementation on blood pressure, myocardial infarction, or mortality in postmenopausal women.     

Vitamin D deficiency and high serum levels of vitamin A increase the risk of osteoporosis evaluated by Quantitative Ultrasound Measurements (QUS) in postmenopausal Spanish women

ObjectivesAssociation between vitamin D deficiency and excess of vitamin A as a potential risk factor of osteoporosis and fracture has been evaluated.Design and methods232 healthy postmenopausal women were studied. Serum parameters were analyzed by standard methods and fat-soluble vitamins by an own HPLC method. QUS measurement of the calcaneal bone was carried out by Sahara.Results124 patients were considered non-osteoporotic and 101 (44.9%) were osteoporotic. The prevalence of high serum levels of retinol was 36.4% and vitamin D deficiency was 70.1%. 60.4% of women with vitamin D deficiency have high serum levels of retinol.In the whole population, the increased risk of osteoporosis was up to three times higher for the highest retinol quintile, as compared with the lowest retinol quintile. Whereas in women with vitamin D deficiency the risk of osteoporosis increased was up 5 times higher than women in the lowest quintile of retinol.ConclusionsOur results show that high retinol levels together with vitamin D deficiency are hitherto an overlooked risk factor for osteoporosis.