Table 2 - uploaded by Michael F Holick
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Causes of Vitamin D Deficiency.* Cause Effect Reduced skin synthesis Sunscreen use -absorption of UVB radiation by sunscreen 1-3,7,85 Reduces vitamin D 3 synthesis -SPF 8 by 92.5%, SPF 15 by 99% Skin pigment -absorption of UVB radiation by melanin 1-3,7,85 Reduces vitamin D 3 synthesis by as much as 99% 

Causes of Vitamin D Deficiency.* Cause Effect Reduced skin synthesis Sunscreen use -absorption of UVB radiation by sunscreen 1-3,7,85 Reduces vitamin D 3 synthesis -SPF 8 by 92.5%, SPF 15 by 99% Skin pigment -absorption of UVB radiation by melanin 1-3,7,85 Reduces vitamin D 3 synthesis by as much as 99% 

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... Vitamin D serum level below 7 ng/ml was considered as severe deficiency. Comparison of vitamin D level between both groups was made along with subgroup analysis [9,10]. ...
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Background This prospective case-control study was conducted from June 2018 to October 2019 in a tertiary referral hospital to investigate the correlation between otitis media with effusion (OME) and serum vitamin D level in children. The study population included 50 children with adenotonsillar hypertrophy and OME (group A) who underwent adenotonsillectomy with tympanostomy tubes insertion compared to 50 children free from any medical or surgical disease (control group). Serum 25-hydroxy vitamin D was measured using electrochemiluminescence technique for both groups. Results The mean age in group A was 53.4 ± 9.2 months whereas in group B (control group) it was 65.0 ± 13.2 months ( P <0.001). In group A, there were 29 (58 %) male children and 21 (42%) female children while in group B, there were 27 (54%) male children and 23 (46%) female children ( P = 0.689). The mean vitamin D level in group A was 16.0 ± 6.1 ng/mL with a minimum of 7 ng/mL and a maximum of 32.10 ng/mL. In group B, the mean vitamin D level was 15.7 ± 5.3ng/mL with a minimum of 7.38 ng/mL and a maximum of 27.90 ng/mL. The statistical analysis showed that there was no significant difference in the level of vitamin D level between both groups ( P = 0.770). Conclusion In this study, the mean level of serum vitamin D was low in children suffering from OME with adenotonsillar hypertrophy and in children without any medical or surgical disease; however, there was no statistically significant difference in the mean serum level of vitamin D between both groups. Therefore, a further study on a larger sample is needed.
... International Journal of Implant Dentistry (BIC) [1,2]. New bone formation can be both enhanced [3] or decelerated [4,5] due to vitamin D, depending on its level. Vitamin D deficiency is associated with a variety of diseases, such as parodontitis [6,7], early tooth loss [8], a catabolic metabolism, osteoporotic fractures [5] and compromised fracture healing [9,10]. ...
... New bone formation can be both enhanced [3] or decelerated [4,5] due to vitamin D, depending on its level. Vitamin D deficiency is associated with a variety of diseases, such as parodontitis [6,7], early tooth loss [8], a catabolic metabolism, osteoporotic fractures [5] and compromised fracture healing [9,10]. Vitamin D is a steroid hormone which can be synthesized in the skin when sun irradiation is sufficient (290-315 nm) and successfully converted in the liver and kidneys [11]. ...
... It plays an important role in the mineral homeostasis by stimulating intestinal absorption of calcium and phosphate [15]. It also regulates the bone metabolism and bone mineralization by activating osteoclasts and osteoblasts [5,16,17]. Vitamin D is available in different sources and, therefore, has different versions. Ergocalciferol (Vitamin D 2 ) is the versions contained in plants and Cholecalciferol (Vitamin D 3 ) in animals and humans [18,19] (Fig. 1). ...
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Purpose The aim of this study was to systematically review the available evidence to evaluate the efficacy of vitamin D supplementation or vitamin D depletion on the osseointegration of implants in animals and humans. Methods The focus questions addressed were “Do vitamin D deficient subjects treated with (dental) implants have an inferior osseointegration than subjects with adequate serum vitamin D level?” and “Do vitamin D supplemented subjects treated with (dental) implants have a superior osseointegration than subjects with adequate serum vitamin D level?” Humans and animals were considered as subjects in this study. Databases were searched from 1969 up to and including March 2021 using different combination of the following terms: “implant”, “bone to implant contact”, “vitamin D” and “osseointegration”. Letters to the editor, historic reviews, commentaries and articles published in languages other than English and German were excluded. The pattern of the present systematic review was customize to primarily summarize the pertinent data. Results Thirteen experimental studies with animals as subject, two clinical studies and three case reports, with humans as subjects, were included. The amount of inserted titanium implants ranged between 24 and 1740. Results from three animal studies showed that vitamin D deficiency has a negative effect on new bone formation and/or bone to implant contact (BIC). Eight animal studies showed that vitamin D supplementation has a enhancing effect on BIC and/or new bone formation around implants. Furthermore, enhancing the impact of vitamin D supplementation on the osseointegration of implants in subjects with diabetes mellitus, osteoporosis and chronic kidney disease (CKD) were assessed. Studies and case reports involving human subjects showed that patients with a low serum vitamin D level have a higher tendency to exhibit an early dental implant failure. When supplemented with vitamin D the osseointegration was successful in the case reports and a beneficial impact on the changes in the bone level during the osseointegration were determined. Conclusions Vitamin D deficiency seems to have a negative effect on the osseointegration of implants in animals. The supplementation of vitamin D appears to improve the osseointegration in animals with systemic diseases, such as vitamin D deficiency, diabetes mellitus, osteoporosis, and CKD. Slight evidence supports the hypothesis that humans similarly benefit from vitamin D supplementation in terms of osseointegration. Further investigation is required to maintain these assumptions.
... Deficient or excess vitamin D is linked to various disorders, such as rickets, osteomalacia, cardiovascular diseases, neurodegenerative diseases, diabetes, and even cancer. Vitamin D has been used as a biomarker for the early diagnosis of many disorders (Holick 2007;Holick and Chen 2008). In particular, 25-hydroxycholecalciferol (25(OH)D 3 ) has been used as a clinical biomarker for monitoring vitamin D status owing to its direct link to the vitamin D substrate, a long half-life, and a high concentration in blood (Ding et al. 2010;Zerwekh 2008). ...
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Vitamin D deficiency is associated with various disorders and is diagnosed based on the concentration of 25-hydroxy vitamin D3 (25(OH)D 3 ) in serum. The parylene matrix chip was fabricated to reduce the matrix background noise, and the homogenous distribution of the matrix was retained for the quantitative analysis of 25(OH)D 3 . The Amplex Red assay was performed to confirm that the sample-matrix mixing zone of the parylene matrix chip was formed below the surface of the parylene-N film. The homogeneous distribution of the matrix was verified from the fluorescence image. For effective analysis using a parylene matrix chip, 25(OH)D 3 was modified through the nucleophilic addition of betaine aldehyde (BA) to form a hemiacetal salt. Such modified 25(OH)D 3 with a positive charge from BA could be effectively analyzed using MALDI-TOF mass spectrometry. Serum 25(OH)D 3 was extracted by liquid–liquid extraction (LLE) and quantified using MALDI-TOF mass spectrometry based on the parylene matrix chip. The intensity of the mass peak of 25(OH)D 3 was linearly correlated ( r ² = 0.992) with the concentration of 25(OH)D 3 spiked in serum, and the LOD was 0.0056 pmol/μL. Energy drinks and vitamin D 3 tablets were also employed for the real sample analysis. Finally, the results of the chemiluminescence binding assay and MALDI-TOF mass spectrometry were statistically analyzed to determine the applicability of the method using the Bland–Altman test and Passing–Bablok regression.
... VitD also has structural and functional effects on skin, subcutaneous fat, muscle, and many other tissues [2]. VitD levels are affected by various factors such as skin type, gender, body mass index (BMI), physical activity, alcohol intake, latitude, season, and VitD receptor polymorphism [2,4,5] whereby < 20 ng/ml is generally accepted as deficiency [2][3][4]. ...
... Current 25-OH VitD values were recorded from the medical records. According to the relevant literature, subjects were classified into two groups according to their 25-OH VitD levels; deficient group (< 20 ng/ml) and normal/control group (≥ 20 ng/ml) [3,4]. Weight, height, and waist/hip circumferences were measured (to the nearest 0.1 kg and 1 cm, where appropriate). ...
... According to our results, VitD deficiency was present in about 60% in both genders. Vitamin D deficiency is reported around 40% in the USA and Europe [3,20,21]. Regardless of our rate being higher than the literature, it is noteworthy that VitD deficiency is high in the adult population [21]. Herein, individual differences might stem from clothing, working, and living conditions in different countries, as well as from the current pandemic [22]. ...
Article
Vitamin D deficiency is still an important subject due to its significant effects on various tissues and functions. We found a relationship between vitamin D deficiency and increase in adipose tissue thicknesses. This situation reveals the importance of vitamin D supplementation, the harms of weight gain and obesity, and the importance of a balanced diet. Purpose: Although the relationship between vitamin D (VitD) levels with body composition and physical/cognitive functions have been investigated in various studies, however, there is no study evaluating all these parameters together. In accordance with, we aimed to evaluate the relationship between VitD deficiency with body composition (i.e., skin, subcutaneous fat, and muscle thicknesses) and physical/cognitive functions. Methods: A total of 203 adults (78 M, 125 F, aged 19-91 years) who had recent 25-OH-vitamin D measurements were included. Ultrasonographic (US) measurements (skin, subcutaneous fat, and muscle thicknesses) were made from the dorsum of the hand, and anterior sides of forearm, arm, and thigh. Handgrip strength, gait speed, Timed Up and Go Test, and Chair Stand Test were evaluated. Additionally, cognitive status was also evaluated with Mini-Mental State Exam. Results: Subjects were classified as VitD deficient group (< 20 ng/ml, N = 125) and control group (≥ 20 ng/ml, N = 78). The groups were not significantly different as regards age, gender, and anthropometric measurements (all p > 0.05). Subcutaneous fat tissues were thicker in the VitD deficient group (all p < 0.05). All the other US measurements and functional/cognitive tests were not significantly different between the groups (all p > 0.05). According to linear regression analyses, body mass index (BMI) was independently related with all subcutaneous fat thicknesses in both genders, and VitD deficiency was related with all subcutaneous fat thicknesses in females and anterior forearm subcutaneous fat thickness in males (all p < 0.05). Conclusion: We imply that together with BMI, VitD deficiency is independently related with increased regional subcutaneous fat tissue. We also underscore the role of US measurements for evaluation of body composition in related clinical scenarios.
... Vitamin D consists of a group of fat-soluble steroid-based prohormones essential for health through their role in the uptake of calcium and other micronutrients 14,15 . Vitamin D is available to humans in the form of vitamin D2 (ergocalciferol) and D3 (cholecalciferol) which are obtained from food ingestion or ultraviolet ray-induced dermal synthesis. ...
... www.nature.com/scientificreports/ in the liver, which is converted in the kidneys to produce 1,25-dihydroxyvitamin D [1,25(OH) 2 D]-the biologically active metabolite of vitamin D 15 . Due to its structural stability and long half-time in circulation, serum or plasma concentration of 25(OH)D is the preferred indicator of vitamin D status 16 . ...
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Chronic and harmful substance use is associated with a cluster of harms to health, including micronutrient deficiencies. Maintaining adequate levels of vitamin D is important for musculoskeletal and other aspects of health. In this prospective longitudinal cohort study, 666 participants drawn from outpatient opioid agonist therapy (OAT) clinics and community care clinics for substance use disorder in Western Norway were assessed annually for determination of serum 25-hydroxyvitamin D [s-25(OH)D] levels. Fifty-seven percent were deficient at baseline (s-25(OH)D < 50 nmol/l), and 19% were severely deficient (s-25(OH)D < 25 nmol/l). Among those deficient/severely deficient at baseline, 70% remained deficient/severely deficient at the last measurement (mean duration 714 days). Substance use patterns and dosage of opioids for OAT were not associated with vitamin D levels. One exception was found for cannabis, where consumption on a minimum weekly basis was associated with lower levels at baseline (mean difference: −5.2 nmol/l, 95% confidence interval [CI]: −9.1, − 1.3), but without clear time trends (mean change per year: 1.4 nmol/l, CI: − 0.86, 3.7). The high prevalence of sustained vitamin D deficiency in this cohort highlights the need for targeted monitoring and supplementation for this and similar at-risk populations.
... Metabolism; metabolism of this vitamin takes place in the liver to (25(OH)D) (Haddad et al. 1993). Next, 25(OH)D is metabolized by 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) in the kidneys into the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D) (Holick 2007). Excretion; vitamin D3 is mainly excreted through the bile into the feces. ...
Article
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Vitamin D is one of the essential vitamins and has recently been demonstrated to be much more important for the appropriate functioning of the human body and well-being than initially believed. Although vitamin D is mainly known for its link with bone fractures and bone diseases, recent studies revealed that vitamin D and its analogues have revealed many pharmacological actions covering the regulation of cell growth, inhibition of inflammation, and improvement of neuromuscular function and immune function. Moreover, vitamin D and its analogues are reported to have role in different types of cancers, skin diseases, diabetes mellitus and infections caused by different bacterial and viral pathogens including SARS-CoV-2. The goal of this study is to evaluate the scientific literature on therapeutic uses of vitamin D and its analogues against different diseases and health condition. Special attention has been given to COVID-19 infection, cancer, skin diseases, and diabetes. The molecular mechanisms involved are also explored.
... Vitamin D is synthesized in the skin after exposure to natural sunlight or absorbed through the dietary and supplemental intake. The vitamin D status depends on several factors such as pigmentation of the skin, amount of sun exposure, the latitude of living, season, vitamin D intake, age, sex, overweight/obesity, malabsorption, and medication such as corticosteroids [14]. Receptors for vitamin D are expressed in many types of tissues and cells, indicating a potential influence on several biological processes, such as modification of the adaptive and innate immune system, with anti-microbial and antiinflammatory effects, and suppression of autoimmune responses [15,16]. ...
... However, inadequate vitamin D levels appear to be common among young individuals with JIA [31]. Serum vitamin D levels, JIA activity, and oral health conditions might be affected by ethnicity, lifestyle, dietary habits, socio-economic and environmental factors, and also genetics [3,14,32,33]. ...
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Background Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics. Methods This multi-center, cross-sectional study, included individuals with JIA aged 4–16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufficiency was defined as < 50 nmol/L. A clinical oral examination was performed applying commonly used indices in epidemiological studies of dental caries, dental erosion, enamel defects, gingival bleeding, and oral hygiene. Serum vitamin D was used as exposure variable in multivariable regression analyses to estimate the associations between insufficient vitamin D level, JIA disease status, and oral conditions, with adjustments for age, sex, geographical region, BMI, seasonal blood sampling, and parental education. Results Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufficient levels. Vitamin D levels did not differ between sexes, but between regions, iso-BMI categories, age groups, and seasons for blood sampling. Insufficient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43–5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10–5.01). No associations were found with active JIA disease or more severe disease characteristics. Conclusion In our study, nearly 30% had vitamin D insufficiency, with a particularly high prevalence among adolescents. Vitamin D insufficiency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health.
... 1,25(OH) 2 D 3 , in addition to regulating calcium homeostasis, has important pleiotropic effects affecting almost all body functions. This action is mediated through interactions with vitamin D receptor (VDR), belonging to a subfamily of nuclear receptors [57][58][59][61][62][63]. VDR heterodimerizes with the retinoid X receptor (RXR) and functions as a ligand-activated transcription factor, after binding to the promoter regions of VDR responsive element (VDRE) to influence the expression of responsive genes [58,63,64]. ...
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Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.
... Considering whether prenatal vitamin D deficiency is associated with maternal morbidity seems reasonable. The findings from several studies suggest an increasing prevalence of vitamin D deficiency in pregnancy and its associated adverse outcomes [81][82][83][84][85]. To further understand the role of vitamin D in pregnancy and the seemingly associated adverse outcomes, interventional and observational studies are needed. ...
Article
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Vitamin D has well-defined classical functions related to metabolism and bone health but also has non-classical effects that may influence pregnancy. Maternal morbidity remains a significant health care concern worldwide, despite efforts to improve maternal health. Nutritional deficiencies of vitamin D during pregnancy are related to adverse pregnancy outcomes, but the evidence base is difficult to navigate. The primary purpose of this review is to map the evidence on the effects of deficiencies of vitamin D on pregnancy outcome and the dosage used in such studies. A systematic search was performed for studies on vitamin D status during pregnancy and maternal outcomes. A total of 50 studies came from PubMed, 15 studies came from Cochrane, and 150 studies came from Embase, for a total of 215 articles. After screening, 34 were identified as candidate studies for inclusion. Finally, 28 articles met the inclusion criteria, which originated from 15 countries. The studies included 14 original research studies and 13 review studies conducted between 2012 and 2021. This review was finally limited to the 14 original studies. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the quality and strength of the evidence was evaluated using the Navigation Guide Systematic Review Methodology (SING). We found evidence that supports the idea that supplementary vitamin D for pregnant women is important for reducing the risk of gestational diabetes, hypertension, preeclampsia, early labor, and other complications. The data retrieved from this review are consistent with the hypothesis that adequate vitamin D levels might contribute to a healthy pregnancy.
... Vitamin D is strongly involved in the structural maintenance and functional integrity of intestinal mucosal cells and exerts antimicrobial effects [152]. In addition, vitamin D-VDR signaling has been shown to regulate immunity to gut pathogens [153][154][155][156][157]. Data from animal studies have shown that vitamin D deficiency or a defect in vitamin D-related signaling pathways impairs the gut's innate immunity, including the downregulation of defensins expressed on Paneth cells, leading to intestinal dysbiosis, endotoxemia, and low-grade systemic inflammation, which in turn promotes the development of insulin resistance and metabolic disorders [117,158]. ...
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There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.