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Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

Background Vitamin D deficiency is now recognized as an independent risk factor and is involved in the pathogenesis of carpal tunnel syndrome (CTS). The purpose of this study was to evaluate the effects of vitamin D3 supplementation on functional and symptomatic outcomes in CTS patients with vitamin D deficiency. Methods This was a prospective, single-arm study with a pretreatment or posttreatment quasi-experimental design. Carpal tunnel syndrome patients with vitamin D deficiency were treated with vitamin D3 (60 000 IU/week) plus standard treatment for a period of 3 months. Carpal tunnel syndrome–related pain and functional and symptomatic outcomes were assessed at baseline and at 3 months posttreatment using the Visual Analogue Scale (VAS) and the Boston Carpal Tunnel Questionnaire, respectively, along with serum vitamin D. Results A total of 42 patients were analyzed. At 3 months posttreatment, there was a significant reduction in the severity of pain (VAS score) from baseline ( Z = −5.71, P < .001). Similarly, the functional and symptomatic outcomes (Boston symptoms severity scale [SSS] and Boston functional status scale [FSS] score) at 3 months posttreatment significantly improved in comparison with baseline (Boston SSS: Z = −5.66, P < .001; Boston FSS: Z = −5.68, P < .001). Conclusions Vitamin D3 supplementation was associated with improvement in functional and symptomatic outcomes and CTS-related pain in CTS with vitamin deficiency. However, further robust randomized controlled trials are warranted to validate the results.

With a well-established role in inflammation and immune function, vitamin D status has emerged as a potential factor for coronavirus disease-2019 (COVID-19).The purpose of this study was to evaluate the moderating effect of race on the relationship between vitamin D status and the risk of COVID-19 test positivity, and to compare propensity score (PS) model results to those obtained from classical bivariate and multivariable models, which have primarily comprised the literature to date.Electronic health record (EHR) data from TriNetX (unmatched n = 21,629; matched n = 16,602) were used to investigate the effect of vitamin D status, as measured by 25-hydroxyvitamin D [25(OH)D], on the odds of experiencing a positive COVID-19 test using multivariable logistic regression models with and without PS methodology.Having normal (Models which use weighting and matching methods resulted in smaller estimated effect sizes than models which do not use weighting or matching. These findings suggest a minimal protective effect of vitamin D status on COVID-19 test positivity in White individuals and no protective effect in Black individuals.

Background: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin- B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin- D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, vitamin-C and vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

Vitamin D (25OHD) deficiency is associated with poor outcomes in intensive care populations. The primary objective of this 7-center study was to determine if 25OHD deficiency is associated with infectious outcomes in adult burn patients. Generalized linear mixed modeling was used to control for center effect, percent total body surface area burn (% TBSA), age, and presence of inhalation injury. A total of 1147 patients were initially included (admitted January 2016 through August 2019). After exclusions, 234 (56.8%) in the deficient (25OHD20 ng/mL) and 178 in the non-deficient group (25OHD ≥ 20 ng/mL) remained, surpassing a priori power requirements. The non-deficient group had their concentration drawn earlier (p 0.001), were more likely to be male (p = 0.006), Caucasian (p 0.001), have lower body mass index (p = 0.009), lower % TBSA (p = 0.002), and taking a 25OHD supplement prior to admission (p 0.001). Deficient patients were more likely to have an infectious outcome (52.1% vs 36.0%, p = 0.002), acute kidney injury with renal replacement therapy (p = 0.009), less ventilator free days in the first 28 days (p 0.001), and vasopressors (p = 0.01). After controlling for center, % TBSA, age, and inhalation injury the best model also included presence of deficiency (OR 2.425 [CI 1.206-4.876]), days until 25OHD supplement initiation (OR 1.139 [CI 1.035-1.252]), and choice of cholecalciferol over ergocalciferol (OR 2.112 [CI 1.151-3.877]). To the authors' knowledge, this is the first multicenter study to evaluate the relationship between 25OHD and infectious complications in burn patients.

Choline, folic acid, and Vitamin D are essential for fetal brain development that may be the first steps in the pathogenesis of the psychotic spectrum. Micronutrient deficiencies have been associated with changes in fetal brain development, manifest as early problems in childhood behavior, and cognition, and later as increased incidence of psychotic and autism spectrum disorders. Micronutrient supplements may not only prevent deficiency, but they may also positively affect brain development in the context of other maternal risk factors, including maternal infection, stress, inflammation, and substance abuse. Many genes associated with later psychotic illness are highly expressed in the fetal brain, where they are responsible for various neurodevelopmental mechanisms. Interaction of micronutrient vitamins with these genetically programmed mechanisms to prevent pathological brain development associated with later psychosis is under active investigation. In addition to their effects on brain development, micronutrient vitamins have effects on other aspects of gestation and fetal development, including the prevention of premature delivery and other developmental abnormalities. Supplemental micronutrient vitamins should be part of good prenatal care, as has already happened for folic acid and Vitamin D and is now advocated by the American Medical Association for choline. The benefits of these micronutrient supplements include protection of brain development and the possibility of decreased risk for future psychotic disorders in those children who are either genetically or environmentally vulnerable. The purpose of this review is to present the current evidence supporting the safety and effectiveness of micronutrients in gestation and to suggest areas for future research.

Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.

Hypervolemia and vitamin D deficiency occur frequently in patients receiving peritoneal dialysis and may contribute to left ventricular (LV) hypertrophy. The effect of bioelectrical impedance analysis (BIA)-guided volume management or vitamin D supplementation on LV mass among those receiving peritoneal dialysis is uncertain.Two-by-two factorial randomized controlled trial.Sixty-five patients receiving maintenance peritoneal dialysis.BIA-guided volume management versus usual care and oral cholecalciferol 50,000 U weekly for 8 weeks followed by 10,000 U weekly for 44 weeks or matching placebo.Change in LV mass at 1 year measured by cardiac magnetic resonance imaging.Total body water decreased by 0.9 + 2.4 (SD) L in the BIA group compared with a 1.5 ± 3.4 L increase in the usual care group (adjusted between-group difference: -2.4 [95% CI, -4.1 to -0.68] L, P = 0.01). LV mass increased by 1.3 ± 14.3 g in the BIA group and decreased by 2.4 ± 37.7 g in the usual care group (between-group difference: +2.2 [95% CI, -13.9 to 18.3] g, P = 0.8). Serum 25-hydroxyvitamin D concentration increased by a mean of 17.2 ± 30.8 nmol/L in the cholecalciferol group and declined by 8.2 ± 24.3 nmol/L in the placebo group (between-group difference: 28.3 [95% CI, 17.2-39.4] nmol/L, P 0.001). LV mass decreased by 3.0 ± 28.1 g in the cholecalciferol group and increased by 2.0 ± 31.2 g in the placebo group (between-group difference: -4.5 [95% CI, -20.4 to 11.5] g, P = 0.6).Relatively small sample size with larger than expected variation in change in LV mass.BIA-guided volume management had a modest impact on volume status with no effect on the change in LV mass. Vitamin D supplementation increased serum vitamin D concentration but had no effect on LV mass.Unrestricted Baxter International extramural grant and the Kidney Foundation of Canada.Registered at ClinicalTrials.gov with study number NCT01045980.

espanolIntroduccion: La diabetes mellitus gestacional (DMG) afecta a entre el 5 y el 40% de mujeres embarazadas. Recientemente se han evaluado diferentes intervenciones con suplementos nutricionales para prevenir la DMG. Objetivo: Realizar una sintesis de la evidencia sobre eficacia de suplementos nutricionales (mioinositol, probioticos y vitamina D) para prevenir DMG. Metodo: Se realizo una busqueda sistematica en PubMed y la biblioteca Cochrane, se incluyeron revisiones sistematicas de estudios clinicos aleatorizados (ECAs), publicados en idioma ingles o espanol hasta mayo de 2020; se utilizaron las palabras clave: “prevencion”, “diabetes gestacional”, “hiperglicemia y embarazo”, “suplementacion”, “probioticos”, “mio-inositol” y “vitamina D”. Resultados: Se analizaron 10 revisiones sistematicas que cumplieron los criterios de inclusion. La suplementacion con mioinositol comparado con placebo disminuyo la incidencia de DMG (RR: 0.44; IC 95%: 0.27-0.87; cinco ECAs). Si bien la suplementacion con vitamina D o probioticos durante el embarazo podria disminuir la incidencia de DMG, la evidencia es limitada. Conclusiones: La suplementacion con mioinositol es efectiva para prevenir DMG en mujeres de alto riesgo. La suplementacion con vitamina D o probioticos probablemente disminuye la incidencia de DMG. EnglishIntroduction: Gestational diabetes mellitus (GDM) affects between 5 and 40% of pregnant women. Recently different interventions with nutritional supplements have been evaluated for prevention of GDM. Aim: To perform a synthesis of the evidence on the efficacy of nutritional supplements (myo-inositol, probiotics, and vitamin D) in the prevention of GDM. Methods: A systematic search in PubMed and Cochrane library was performed, including systematic reviews of randomized clinical trials (RCTs), published in English or Spanish until May 2020, using the keywords: “prevention”, “gestational diabetes”, “hyperglycemia and pregnancy”, “supplementation”, “probiotics”, “myo-inositol” and “vitamin D”. Results: 10 systematic reviews that met the inclusion criteria were analyzed. Myo-inositol supplementation compared to placebo decreased the incidence of GDM (RR: 0.44 [0.27-0.87]; five RCTs), low quality of evidence. Although the supplementation with vitamin D or probiotics during pregnancy could reduce the incidence of GDM the evidence is limited. Conclusions: Myo-inositol supplementation is effective for prevention of GDM in high-risk women. Supplementation with vitamin D or probiotics probably decreases the incidence of GDM.

New evidence shows that up to 40% of rheumatoid arthritis (RA) cases are attributable to exposure to potentially modifiable factors. We can now identify people at higher risk of RA (pre-RA) through their family history, risk factors, autoantibodies and symptoms. Counselling these patients to act to modify factors known to be associated with RA risk could prevent the development of RA, and evidence shows that informing individuals of their risk and of ways to reduce it leads to positive behavioural change and is not harmful. This consumer-focussed narrative review is targeted at primary care providers and physicians to describe 11 changes that can be made, based on current evidence linking potentially modifiable factors to RA risk. These evidence-based recommendations are: (i) cease smoking; (ii) reduce exposure to inhaled silica, dusts and occupational risks; (iii) maintain a healthy weight; (iv) increase leisure time physical activity; (v) maintain good dental hygiene; (vi) maximise breastfeeding if able; (vii) maximise dietary quality and avoid high-salt diets; (viii) consume high levels of omega-3 fatty acids and fish; (ix) reduce consumption of sugar-sweetened soft drinks; (x) consume moderate levels of alcohol; and (xi) remain vitamin D replete.

Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI). Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12–2.19; p = 0.36), a lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23–1.37; I 2 = 74%; p = 0.20), the rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06–0.54; I 2 = 77%; p = 0.002) as well as rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16–0.80; I 2 = 0.48; p = 0.01). Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.

The aim of the study was to determine the effect of pregabalin as monotherapy on biochemical markers and bone mineral density. 40 patients diagnosed with neuropathic pain or fibromyalgia syndrome who were using pregabalin for at least 6 months and age and sex matched 40 healthy individuals were recruited for this cross-sectional study. Bone mineral density of both groups were measured by dual energy x ray absorbsiometry(DXA), bone biochemical markers, serum calcium, and vitamin D levels were investigated. Association between pregabalin use and bone biochemical markers, serum calcium, vitamin D levels were evaluated. The mean age of 40 patients (27 females, 13 males) was 40.6 ± 7.1 years and the mean age of 40 healthy individuals (27 females, 13 males) was 40.4 ± 7.3 years. The other demographic data were similar. There were no significant differences in lumbar and femur neck BMD scores between 2 groups. Also, there were no associations neither between pregabalin use and biochemical markers including serum calcium levels nor between pregabalin use and vitamin D levels. However, the patients who had been used pregabalin less than 24 months had low lumbar t and z scores than patients who had been used pregabalin more than 24 months. This effect was more prominent in male patients. Although no negative effect of pregabalin was found on bone metabolism in these group of patients, we have suggested that further prospective controlled studies with large sample size in different age groups could provide new data about the effects of pregabalin on bone metabolism. We suggest to investigate the bone metabolism especially in male patients on pregabalin treatment who had been used pregabalin treatment less than 24 months.

Vitamin D deficiency impairs prognosis in many types of cancer; however, its significance in each subtype of hematological malignancies is unclear. In addition, data on the association between pretransplant vitamin D levels and outcomes of hematopoietic stem cell transplantation (HSCT) are inconsistent. This systematic review and meta-analysis aimed to elucidate the impact of vitamin D levels at diagnosis or pre-HSCT on the prognosis of hematological malignancies. Thirty articles and abstracts were extracted from PubMed, Embase, and Cochrane Library databases and conference proceedings. Fixed and random effect models were used to analyze primary outcomes: overall survival (OS) and progression-free survival (PFS). Lower vitamin D level was significantly associated with poorer OS and PFS in myeloid malignancies (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.06-1.82 and HR, 2.03; 95% CI, 1.23-3.32, respectively) and lymphoid malignancies (HR, 2.07; 95% CI, 1.79-2.40 and HR, 1.91; 95% CI, 1.61-2.25, respectively), as well as outcomes for several lymphoma subtypes individually. Furthermore, a lower pretransplant vitamin D level was associated with poorer OS in autologous and allogeneic HSCT (HR, 1.65; 95% CI, 1.04-2.61 and HR, 1.50; 95% CI, 1.03-2.18, respectively). Despite the relatively small number of studies evaluated, these data suggest the importance of vitamin D status in outcomes of hematological malignancies (PROSPERO registration number: CRD42020205821).

Abstract. Both vitamin D insufficiency and deficiency are now well-documented worldwide in relation to human health, and this has raised interest in vitamin D research. The aim of this article is therefore to review the literature on sources of vitamin D. It can be endogenously synthesised under ultraviolet B radiation in the skin, or ingested through dietary supplements and dietary sources, which include food of animal and plant origin, as well as fortified foods. Vitamin D is mainly found in two forms, D3 (cholecalciferol) and D2 (ergocalciferol). In addition to the D3 and D2 forms of vitamin D, 25-hydroxy vitamin D also contributes significantly to dietary vitamin D intake. It is found in many animal-derived products. Fortified food can contain D3 or D2 forms or vitamin D metabolite 25-hydroxy vitamin D. Not many foods are a rich source (> 4 μg/100 g) of vitamin D (D represents D3 and/or D2), e.g., many but not all fish (5–25 μg/100 g), mushrooms (21.1–58.7 μg/100 g), Reindeer lichen (87 μg/100 g) and fish liver oils (250 μg/100 g). Other dietary sources are cheese, beef liver and eggs (1.3–2.9 μg/100 g), dark chocolate (4 μg/100 g), as well as fortified foods (milk, yoghurt, fat spreads, orange juice, breakfast grains, plant-based beverages). Since an adequate intake of vitamin D (15 μg/day set by the European Food Safety Authority) is hard to achieve through diet alone, dietary supplements of vitamin D are usually recommended. This review summarizes current knowledge about different sources of vitamin D for humans.

Background Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. Objective Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. Design Cross-sectional. Setting All 288 MVMs on the market in the United States in the National Institutes of Health’s Dietary Supplement Label Database in 2018 labeled for children 1 to Main outcome measures Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. Statistical analyses Number of products and percent DV per day provided by each micronutrient in each product. Results The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children’s diets. Conclusions A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p

Context The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (± calcium) for fracture prevention has led to contradictory guidelines. Objective This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. Methods We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. Results Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). Conclusion Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.

Vitamin D is an important cornerstone in the immunologic cascade of many skin infections, systemic infections with cutaneous presentation, and other infectious dermatologic diseases where infections could be a culprit. Vitamin D supplementation is proposed as a protection against their occurrence and exacerbation, especially with the emergence of several viral pandemics in recent years. Vitamin D plays a key role in the maintenance of a balanced immunologic profile which could be reflected by a lowered incidence and morbidity of infections. Vitamin D screening and supplementation in patients with deficiencies or insufficiencies should be a part of the dermatologic approach to patients with these diseases.

Urticaria is a distressing dermatologic condition for many. Although the wheals of urticaria are characteristically evanescent, lasting less than 24 hours, patients tend to have recurrent episodes. Hives that last less than 6 weeks are considered acute urticaria. Acute urticaria does not routinely require supplementary work-up because the history often identifies a convincing, inciting allergen. Chronic urticaria is defined as episodes that occur for longer than 6 weeks, and there is often not an easily identifiable trigger. For both acute and chronic urticaria, patients frequently report food as a precipitating cause. For acute urticaria, the foods that are associated with true allergies, such as nuts and shellfish, are the most frequent offenders. The relationship between diet and chronic urticaria is not as firmly defined. Many patients unnecessarily restrict their diets, so it becomes the role of dermatologists to help patients identify if there is a reproducible link between their symptoms and their dietary exposures. The literature suggests that diets free from pseudoallergens and histamine-releasing foods may attenuate urticaria. Supplements such as fats, vitamin D, iron, and flavonoids have also been studied and may diminish symptoms.

Nonmelanoma skin cancer (NMSC), the most widely diagnosed cancer in the United States (US), is rising in incidence despite public health and educational campaigns that highlight the importance of sun avoidance. It is therefore important to establish other modifiable risk factors that may be contributing to this increase. There is a growing body of evidence in the literature suggesting certain nutrients may have protective and/or harmful effects on NMSC. We review the current literature on nutrition and its effect on NMSC with a focus on dietary fat, vitamin A, nicotinamide, folate, vitamin C, vitamin D, vitamin E, polyphenols, and selenium.

Abstract. Critically ill patients in intensive care units (ICUs) are exposed to various risk factors for vitamin D deficiency. Vitamin D deficiency in extended-stay patients may result in decreased muscle mass and increased fat tissue, which may impair rehabilitation and recovery. Our study aimed to evaluate the degree of serum vitamin D deficiency in critically ill surgical patients and its association with clinical outcomes. Clinical data from 186 adult male (n = 121; 65.1%) and female (n = 65; 34.9%) patients hospitalized in surgical ICUs at Ajou University Hospital from April 2015 to September 2016 were retrospectively analyzed. All adult surgical patients between the age of 18 and 88 years were enrolled. The mean serum 25-hydroxyvitamin D (25[OH]D) level of all patients was 17.8 ng/mL. A total of 120 patients (64.5%) with serum 25(OH)D levels

The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.

Glioma is the most prevalent primary brain tumor in adults among which glioblastoma is the most malignant and lethal subtype. Its common resistance to conventional chemotherapeutics calls for the development of alternative or concomitant treatment. Taking advantage of its endocrine function as a neurosteroid, vitamin D has become a target of interest to be used in conjunction with different chemotherapies. In this article, we review the mechanisms through which vitamin D and its analogs induce anti-tumor activity in glioblastoma, and the practical issues relevant to their potential application based on in vitro and in vivo studies. Vitamin D has largely been reported to promote cell cycle arrest and induce cell death to suppress tumor growth in glioblastoma. Glioblastoma cells treated with vitamin D have also shown reduced migratory and invasive phenotypes, and reduced stemness. It is worth noting that vitamin D analogs are able to produce similar inhibitory actions without causing adverse effects such as hypercalcemia in vivo. Upregulation of vitamin D receptors by vitamin D and its analogs may also play a role in enhancing its anti-tumor activity. Based on current findings and taking into consideration its potential cancer-protective effects, the clinical application of vitamin D in glioblastoma treatment and prevention will be discussed. With some study findings subject to controversy, further investigation is warranted to elucidate the mechanism of action of vitamin D and to evaluate relevant issues regarding its treatment efficacy and potential clinical application. Vitamin D has recently emerged as a neurosteroid and a regulator of various physiological functions. It has been widely reported to promote tumor-suppressive effects, however this proposal remains controversial. This article reviews the anti-tumoral mechanisms of vitamin D in glioblastoma, current evidence of its therapeutic application as a supplement to standard chemotherapy, and its potential applications for cancer prevention; it endeavors to offer insight into new means of overcoming chemoresistance and improving glioma patient survival.

BACKGROUND Vitamin D deficiency in the perioperative surgical period is associated with inferior surgical outcomes. There are no established preoperative supplementation regimens in the orthopedic literature. The purpose of this study is to compare the efficacy between 2 different supplementation regimens of vitamin D prior to total knee arthroplasty. METHODS We conducted a retrospective analysis of 174 patients identified as vitamin D deficient (25(OH)D < 30 ng/mL) who received one of 2 vitamin D supplementation protocols: (1) daily supplementation with D3 on a sliding scale from 1000 to 6000 IU or (2) a loading dose of 50,000 IU D3 weekly for 4 weeks then 2000 IU/d. Serum vitamin D levels were measured at 3 months and 1 month preoperatively. RESULTS Mean patient age was 65.5(±8.6) years, and 54.6% were female. Deficiency was corrected in 73.3% of patients in the loading dose group and 42.4% of patients in the daily, low-dose group [χ2 (1, N = 174) = 16.53, P < .001]. Patients in the loading dose group also achieved a greater average correction in vitamin D levels. CONCLUSION This is the first study to compare preoperative vitamin D supplementation protocols. A loading dose regimen of 50,000 IU weekly for 4 weeks followed by a maintenance dose of 2000 IU/d more effectively corrects vitamin D deficiency compared to a low-dose, daily regimen among total knee arthroplasty patients. We recommend this regimen for deficiency correction in patients who have been screened to be deficient in vitamin D preoperatively.

Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function. Free and total vitamin D concentrations were measured in all patients. Multiple linear regression analysis considering patient age, sex, body mass index, height, smoking and drinking situation, the use of antihypertensive drugs, cholecalciferol treatment, C-reactive protein and estimated glomerular filtration rate as confounding factors were conducted to compare the association of free and total vitamin D with systolic and diastolic blood pressure (SBP and DBP). Multiple linear regression analysis revealed that neither SBP nor DBP was correlated with total vitamin D (SBP, 95% CI -0.405 ~ 0.159, p = 0.390; DBP, 95% CI -0.131 ~ 0.142, p = 0.933) (Table 2). However, the concentration of free vitamin D was independently associated with SBP (95% CI -2.691 ~ -0.210; p = 0.022) (Table 3), but not with DBP (95% CI -0.934 ~ 0.285; p = 0.293). In conclusion, free - but not total - vitamin D serum concentrations in patients with diabetes and impaired kidney function are inversely correlated with SBP. This study suggests that free vitamin D measurements might be more clinically relevant - as compared to measurements of total vitamin D - to adjust vitamin D therapy in diabetic patients with impaired kidney function.

Background Vitamin D plays a critical role in skeletal development and maintenance, thus sufficiency is an important goal for public health programs. Given the absence of foods fortified in vitamin D in Armenia, we hypothesized that vitamin D insufficiency would be widespread. Methods We conducted a random modified cluster model survey of vitamin D status of women in the country. We measured 25-hydroxyvitamin D [25(OH)D] by liquid chromatography mass spectrometry in dried blood spot samples and utilized a questionnaire to assess lifestyle factors. Results In summer, we sampled 1206 participants from 40 communities in Armenia. Mean 25-OH D level among women aged 18–24 was 20 ± 8 ng/mL; aged 25–64 was 21 ± 7 ng/mL; and >65 was 18 ± 8 ng/mL. The country-wide mean of the entire female population was 20 ± 8 ng/mL. A majority (>54%) had 25-OH D levels p values 0.004, 0.0002, and 0.03 respectively) as did pre- vs. postmenopausal women (p = 0.01), pregnant vs. nonpregnant women (p = p = 0.004). Conclusion In Armenia, there is a high prevalence of vitamin D insufficiency. This information provides data that can be used to inform public health directives to address this pervasive threat to optimal health.

Introduction: Vitamin D deficiency is highly prevalent during pregnancy and in premature infants. This study was done to investigate the maternal and infantile levels of vitamin D in preterm infants. Methods: Using available sampling during 2018-2020, the maternal and umbilical cord serum levels of vitamin D were measured in 294 premature infants in Ghaem Hospital, Mashhad, Iran. A researcher- made questionnaire consisting of neonatal demographic and clinical characteristics was used as the data collection tool. Both maternal and placental vitamin D levels were categorized into four classes: severe deficiency (vitamin D30.1ng ml). Results: Vitamin D deficiency was seen in 89% of premature infants (46.6% severe, 30.6% moderate, and 11.9% mild). Serum levels of vitamin D were 18.28±13.94 ng/ml and 14.10±9.70 ng/ml in mothers and infants, respectively. The infants below and above 32 weeks exhibited vitamin D values of 10.97±6.31 ng/ml and 18.05±11.64 ng/ml, respectively. The difference in vitamin D levels between boys (12.59±8.40 ng/ml) and girls (16.05±11.45 ng/ml) was found to be significant (P=0.009). Moderate and severe vitamin D deficiency was more common at earlier pregnancy ages (P=0.001). Conclusion: Vitamin D deficiency is more common and severe in preterm infants and their mothers. Controlling vitamin D levels during pregnancy, especially in women at risk of preterm labor and preterm infants, may help reduce prematurity problems.

Background: Low blood status in several nutritional compounds, including long-chain omega-3 fatty acids (LC n-3 PUFA), carotenoids, and vitamin D, have been associated with a higher risk to develop dementia. Nutritional deficiencies may potentiate each other regarding dementia risk; yet the association of multiple nutritional deficiencies with dementia has been little explored. Objective: To develop an index of micronutritional biological status (MNBS) for the screening of multi-micronutritional deficiencies associated with the risk of dementia in a prospective population-based cohort of older persons. Methods: We included participants from the Bordeaux Three-City study, who were free of dementia at baseline, had blood measurements of LC n-3 PUFA, carotenoids, and 25(OH)D, and who were followed for up to 18 years for dementia. We used penalized splines in Cox models to model dose-response relationships of each nutritional component with the risk of dementia and construct a risk index. Results: 629 participants with an average age of 73.1 years were included in the study. Each increase of 1 SD of the MNBS index was associated with a 46%higher risk of dementia (HR = 1.46, 95%CI 1.23; 1.73). Participants with highest index ([mean+1SD; max]) had a 4-fold increased risk of dementia compared with participants with a low index ([min; mean-1SD]) (HR = 4.17, 95%CI 2.30; 7.57). Conclusion: This index of assessment of micronutritional biological status is a practical tool that may help identify populations with inadequate nutritional status, screen eligible individuals for nutritional prevention in primary care, or for supplementation in preventive trials of dementia.

Infancy is a period of rapid bone growth and mineral accretion; nonetheless, reference data remain scarce for this age group. The purpose of this report is to generate reference data for bone mass in breastfed vitamin D replete infants and investigate patterns of bone mineral accretion and sex differences. This is a secondary analysis from a double-blinded randomized controlled trial (NCT00381914). Healthy term breastfed (exclusively or mixed) infants were randomized to different doses of oral vitamin D supplementation (400-1600 IU/d) and followed prospectively from 1 to 12 mo. Plasma 25-hydroxyvitamin D (LC-MS/MS), bone mineral content (BMC; whole body (WB) and lumbar spine (LS)) and bone mineral density (BMD; LS) were measured at 1, 3, 6, 9, and 12 mo by dual-energy x-ray absorptiometry (Hologic Discovery 4500A) with no effect of supplementation on bone outcomes. For the purpose of this analysis, 63 infants with adequate plasma 25-hydroxyvitamin D ≥ 50 nmol/L at baseline, were included. Differences over time and between sexes were tested using mixed model repeated measures ANOVA. Infants (31 males, 32 females) were 39.5 ± 1.1 wk gestational age at birth and appropriate for gestational age. WB BMC, LS BMC, and LS BMD increased by 143.2%, 116.8%, and 31.1% respectively across infancy. WB BMC was higher (4.2% - 9.4%; p = 0.03) in males than in females across the study. After adjusting WB BMC for weight, length or head BMC, sex differences were not evident. LS BMC and LS BMD did not vary by sex. LS BMD growth charts for both sexes combined, were generated using LMS chartmaker. WB BMC more than doubles during the first year of life confirming the importance of skeletal growth and the need for age-specific reference data in infancy. Sex differences in BMC, if any, are mostly driven by differences in body size.

Purpose: To quantitatively evaluate the retinal structural parameters of pediatric patients who were determined to be deficient in vitamin D. Design: Prospective, cross-sectional study. Methods: Retinal structural parameters, including the peripapillary retinal nerve fiber layer (RNFL), central macula, retinal layer, and choroidal thicknesses, central retinal artery equivalent (CRAE), and central retinal vein equivalent (CRVE), in pediatric subjects with vitamin D deficiency (group 1) and those without (group 2) were compared. Results: Group 1 comprised 70 individuals, while group 2 comprised 80 individuals. The mean peripapillary RNFL (except for the nasal superior sector [P = .037]), central macula, and retinal layer thicknesses were also determined to be similar in both groups (P > .05 for both groups). The mean choroidal thickness was lower in the subfoveal (P = .006) and nasal 3000-µm–diameter areas (P = .004) in group 1. The mean CRAE was determined to be lower (P = .031) and the CRVE was higher in group 1 (P = .005); it was determined that there was a significant correlation between the vitamin D level and both the CRAE (r = 0.447, P < .001) and CRVE (r = −0.320, P = .013). Conclusion: Choroidal thinning, a decrease in the CRAE, and increase in the CRVE were structural changes that occurred in the pediatric subjects who had vitamin D deficiency. The alterations in these parameters became more prominent in pediatric subjects who were determined to have lower vitamin D levels.

Made available in DSpace on 2022-05-01T09:47:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 This study aimed to evaluate the immunomodulatory effect of vitamin D (VD) on the NLRP1 and NLRP3 inflammasomes in placental explants from preeclamptic (PE) and normotensive (NT) pregnant women. Placental explants from eight PE and eight NT pregnant women were cultured with or without hydrogen peroxide (H2O2), VD or H2O2 + VD. Gene and protein expression of NLRP1, NLRP3, HMGB1, caspase-1, IL-1β, TNF-α and IL-18 were determined by qPCR and Western blotting/ELISA. Compared to NT pregnant women, the endogenous gene expression of NLRP1, NLRP3, HMGB1, IL-1β, TNF-α and IL-18 was significantly higher in explants from PE and became decreased after VD treatment. Similarly, VD decreased the protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE. Placental explants from NT cultured with H2O2 showed increased gene and protein expression of NLRP1, NLRP3, caspase-1, IL-1β, TNF-α and HMGB1, while H2O2 was also able to increase TNF-α and caspase-1 gene expression in PE. Treatment with H2O2 + VD decreased gene/protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE and NT explants with H2O2. NLRP1 and NLRP3 are upregulated in the PE. VD may play an immunomodulatory role in the placental inflammation and downregulates oxidative stress induced in vitro by H2O2. Botucatu Medical School Sao Paulo State University (Unesp) Institute of Biosciences Sao Paulo State University (Unesp) Botucatu Medical School Sao Paulo State University (Unesp) Institute of Biosciences Sao Paulo State University (Unesp)

Mechanisms linking ingested pollutants to increased incidence of allergy are poorly understood. We report that mice exposed to low doses of cadmium develop higher IgE responses following oral allergen sensitization and more severe allergic symptoms upon allergen challenge. The environmentally relevant doses of this pollutant also induced oxidative/inflammatory responses in the gut of SPF, but not germ-free mice. Interestingly, the increased IgE responses correlated with stimulation of the vitamin D3-metabolizing enzymes CYP27B1 and CYP24A1 in the gut and increased luminal levels of oxidized vitamin D3 metabolites that are not ligands of the vitamin D receptor. Inhibition of CYP27B1 and CYP24A1 via oral administration of pharmacological inhibitors reduced IgE responses induced in mice orally exposed to cadmium. Our findings identify local alteration of vitamin D signaling as a new mechanism for induction of IgE responses by environmental pollutants. They also identify vitamin D3-metabolizing enzymes as therapeutic targets for the treatment of allergy.

Objective To examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults. Methods This study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, 74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels. Results During a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group. Conclusion Higher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.

Compared with adult athletes, rather little is known about supplementation behavior in adolescent athletes. This study’s aim was to determine elite adolescent athletes’ supplement use and sources of information relating thereto. A total of 430 (87%) of 496 questioned athletes returned the anonymized questionnaire. Thereof, 84% consumed at least one weekly supplement and 97% indicated some supplement intake during the previous 4 weeks. On average, 13.3 supplement servings were consumed per week. The 25th, 50th, and 75th percentile was 4.5, 10.5, and 20.0 servings per week, with a maximum of 67. The most prevalent supplements in use were multimineral products (41% of all athletes), multivitamins (34%), Vitamin C (34%), and Vitamin D (33%). Male athletes consumed significantly more Vitamin C and D, sports drinks, protein powder, and recovery products compared with female athletes; whereas, women consumed more iron supplements. The three most important motives for supplement use were recovery support (40%), health maintenance (39%), and performance enhancement (30%). The most frequent answers to the question “who recommended that you use supplements” were family/friends (36%), a physician (27%), and a trainer/coach (25%). The main three information sources about the supplements in use were the persons who recommended the supplementation (56%), the internet (25%), and information provided by supplement suppliers (11%). A positive doping attitude was associated with the consumption of performance enhancing supplements (p = .017). In conclusion, this study among elite adolescent Swiss athletes indicates a widespread and large-scale use of dietary supplements, which was associated with a low level of information quality.

Problem The association between serum 25-Hydroxyvitamin D (25-OHD) level and asthma occurrence in children was controversial. Eligibility criteria The Pubmed, Ovid Medline, Embase, Cochrane Library were systematically searched up to April 13th 2020. All the study measured the serum 25-OHD level in children, or classified the children based on the 25-OHD level into severe vitamin D deficiency, insufficient deficiency and comparing the prevalence of asthma in childhood were included in our study. Sample A total of 35 studies were included in our meta-analysis. Among them, 24 studies were included for analyzing the association between 25-OHD level and asthma, and 12 studies evaluated the treatment effect of vitamin D. Results The children with asthma (5711 participants) had significant lower 25-OHD level than children without asthma (21,561 participants) (21.7 ng/ml versus 26.5 ng/ml, SMD = −1.36, 95% = −2.40--0.32, P = 0.010). Besides, the children with asthma treated with vitamin D supplement had a significantly lower recurrence rate than the placebo group (18.4% versus 35.9%, RR = 0.35, 95%CI = 0.35–0.79, P = 0.002). Conclusions Children with asthma had a lower 25-OHD level than healthy children. Vitamin D supplement could decrease the asthma recurrence rate in the follow-up years. Implications This study implies that lower 25-OHD may cause asthma in childhood.

Objective Free concentrations of highly protein bound hormones, such as cortisol and thyroxine, are unchanged in critical illness despite substantial decreases in total concentration. Total 25-hydroxyvitamin D (25(OH)D) concentration is decreased in critical illness, but the free concentration of 25(OH)D has had less attention. The aim of this study was to compare total and calculated free 25(OH)D concentrations in critically ill patients with healthy controls. Design Case control study. Methods 38 patients with critical illness were compared with 68 healthy controls. 25(OH)D was measured by liquid chromatography tandem mass spectrometry (LCMS/MS) and vitamin D binding protein (VDBP) by direct sandwich enzyme-linked immunosorbent assay (ELISA). Total and calculated free 25(OH)D concentrations were compared using unpaired T-tests. Results Total 25(OH)D concentrations were significantly lower in critically ill patients than controls (37 (95% CI 31 - 43) vs 57 (53 - 60) nmol/L). Calculated free concentrations of 25(OH)D were not lower in critically ill patients than healthy controls (26 (22 - 29) vs 19 (18 - 20) pmol/L). Conclusions Calculated free 25(OH)D concentrations are not decreased in critical illness. Measuring total 25(OH)D concentrations in patients with critical illness potentially underestimates vitamin D and overestimates the number of patients who are deficient in vitamin D. This article is protected by copyright. All rights reserved.

Background: The currently available bone turnover markers are mostly derived from osteoblasts or osteoclasts. Protein markers derived from osteocytes, the most abundant bone cells that can regulate bone turnover activities by other cells, are less explored. Objective: This study aimed to compare the circulating markers of osteocytes and calcium homeostasis between Malaysian postmenopausal women with and without osteoporosis. Method: Postmenopausal women with (n=20) or without osteoporosis (n=20) as determined by dual- energy X-ray absorptiometry were randomly drawn from a bone health cohort. Their fasting blood was collected and assayed by a multiplex immunoassay panel. Results: The results showed that osteoprotegerin and sclerostin levels were significantly lower among postmenopausal women with osteoporosis than the normal control. No significant differences in other markers were observed between the two groups. Sclerostin level correlated positively with spine Bone Mineral Density (BMD), while 25-hydroxyvitamin D correlated negatively with hip BMD in the control group. No significant correlation was observed between other markers with spine or hip BMD. Conclusion: These data provide an insight into the possible roles of osteocyte markers, especially osteoprotegerin and sclerostin, in classifying subjects with osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is a complex and multifactorial condition.

Human kidney organoids possess early glomerular and tubular function. However, little is known about their hormone producing ability. In this report, we show that kidney organoids take up and metabolize inactive 25(OH) vitamin D (25(OH)D3). Uptake of 25(OH)D3 led to a significant upregulation of vitamin D metabolizing CYP24A1 mRNA levels, indicating that kidney organoids possess a feedback mechanism to control active vitamin D (1,25(OH)2D3) levels. They therefore resemble the kidney in its regulation of vitamin D and illustrate the presence of the kidney endocrine system in organoids. These findings underscore the value of kidney organoids for research into the hormonal function of the kidney.

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Background: In Covid-19 infection, leukopenia, inflammation, and elevated liver enzymes are found in most patients. Also, vitamin D deficiency attenuates the immune system and predisposes a person to being more susceptible to infection. In this context, we aimed to evaluate vitamin D, electrolytes, complete blood count, liver enzymes, urea, creatinine, albumin, CRP and ESR levels in patients with Covid-19. Methods: We conducted a cross-sectional study on 118 patients with Covid-19 who were hospitalized from 2020/2/19 to 2020/4/3 in ICU. Serum levels of electrolytes, liver enzymes, blood factors, urea, creatinine, CRP and ESR, as well as anthropometric parameters and serum vitamin D concentration, were measured. Results: A total of 118 patients (80 male and 38 female) were enrolled in the study (65.05±15.75 years). Only 5.08% of patients had no risk factors and 55.9% had ≥ 2 risk factors. Diabetes (44.1%) and obesity (23.7%) were more common among patients. Laboratory findings showed that 80.50% of patients had hyponatremia, but other electrolytes including K, Mg, Ca and P were normal in the majority of participants as well as CBC, Cr, Urea, Alb, ALT and ALKP. The AST concentration increased in most patients (66.94%). All patients had high levels of inflammatory factors such as CRP and ESR. The mean of 25-hydroxy-vitamin D levels in participants (25.95 ± 14.56 ng/mL) was lower than its levels in the general population. However, it was not statistically significant (P= 0.88). A significant negative correlation was found between vitamin D and ALT (P= 0.02, -0.21) as well as vitamin D and CRP (P= 0.05, -0.17). Conclusion: Due to the regulatory role of vitamin D in the immune system and low levels of vitamin D in Covid-19 infected patients, the evaluation of vitamin D levels and prescribed supplements, if necessary, is suggested.

Objectives: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). Methods: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. Results: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P Conclusions: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.

OBJECTIVES Eating disorders (EDs) are severe psychiatric conditions characterized by malnutrition, dysfunctional behaviors, and hypovitaminosis D. In various psychiatric conditions, including EDs, preliminary evidence has correlated impulsivity to a low level of 25-hydroxyvitamin D [25(OH)D]. This study aims to reinforce this evidence by examining different facets, both behavioral and psychological, of the impulsivity construct in patients with ED. METHODS A sample of 119 women was evaluated with a validated questionnaire and computerized neuropsychological tasks: the UPPS-P impulsive behavior scale, a go/no-go task, and the Balloon Analogue Risk Task (BART). A clinical evaluation for EDs and blood sample collection were also performed to assess specific psychopathology and determine the serum level of 25(OH)D. RESULTS Significant correlations were found between serum levels of 25(OH)D and BART scores (p = 0.012) and lack of perseverance (p = 0.034). Moreover, regression analyses showed that higher BART scores may be explained by hypovitaminosis D and higher levels of lack of perseverance in patients with EDs. CONCLUSIONS The specific aspect of impulsivity linked to goal strategy and behaviors may be explained in patients with EDs by hypovitaminosis D. A possible connection to the brain inflammatory system is also discussed, along with possible directions for future research.

OBJECTIVES To determine vitamin D supplementation frequency among children aged 1 to 24 months, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. METHODS This cross-sectional study was conducted using a questionnaire administered to the mothers via face-to-face interview of 560 children aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. RESULTS A total of 351 children were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among exclusively formula-fed children (p

Purpose There is an ongoing debate whether vegetarian (VG) and especially vegan (VN) diets are nutritionally adequate in early childhood. Hence, the Vegetarian and Vegan Children Study (VeChi Diet Study) aimed to assess the food and nutrient intake of VG and VN infants. Methods The study examined the diets of 1–3-year-old VG, VN, and omnivorous (OM) children (n = 430). Dietary intake was assessed via a 3-day weighed dietary record and compared between groups using ANCOVA. Lifestyle data were collected using a questionnaire. Here, the results of micronutrient and fatty acid intakes are presented. Results Most nutrient intakes (with and without supplements) differed significantly between VN children and the two other groups, with a more favourable overall micronutrient intake in VN, followed by VG children, [e.g., the highest intake of vitamin E (8.3 mg/d vs. VG 7.4 mg/d and OM 5.1 mg/d), vitamin B1 (569 µg/d vs. VG 513 µg/d and OM 481 µg/d), folate (143 µg/d vs. VG 116 µg/d and OM 108 µg/d), magnesium (241 mg/d vs. VG 188 mg/d and OM 164 mg/d), and iron (8.9 mg/d vs. VG 7.3 mg/d and OM 6.0 mg/d)] as well as fat quality [highest intake of polyunsaturated fatty acids (8.7 E% vs. VG 6.9 E% and OM 4.5 E%) and lowest intake of saturated fatty acids (9.1 E% vs. VG 11.9 E% and OM 14.0 E%)]. In contrast, OM children had the highest intake of vitamin B2 (639 µg/d vs. VG 461 µg/d and VN 429 µg/d), calcium (445 mg/d vs. VG 399 mg/d and VN 320 mg/d), iodine (47 µg/d vs. VG 33 µg/d and VN 31 µg/d), and DHA (35.4 mg/d vs. VG 16.6 mg/d and VN 18.4 mg/d). Without supplementation, OM children had the highest average vitamin B12 intake (1.5 µg/d vs. VG 0.6 µg/d and VN 0.2 µg/d), whereas VN children had the highest average vitamin B12 intake with supplementation (73.8 µg/d vs. VG 1.3 µg/d and OM 1.7 µg/d). Without supplementation, none of the groups’ median intakes met the harmonised Average Requirement (h-AR) for vitamin D and iodine. Moreover, VG and VN children did not achieve h-ARs for vitamin B2, vitamin B12, and iron—if a low absorption of iron is anticipated; VN children also did not do so for calcium. Conclusion In early childhood, VN and VG diets can provide most micronutrients in desirable amounts and a preferable fat quality compared to an OM diet. Special focus should be paid to (potentially) critical nutrients, particularly vitamin D, iodine, and DHA for all children regardless of diet, as well as vitamin B2, vitamin B12, calcium, and iron for VG and VN children. Trail registration This study was registered with the German Clinical Trials Register (DRKS00010982) on (September 2, 2016).

Background: Vitamin D deficiency was associated with an increased risk of coronavirus disease 2019 (COVID-19) infection. Vitamin D deficient mothers are more likely to have infants with vitamin D deficiency, affecting their immunity and protection against infection. This study aimed at comparing the concentrations of vitamin D3 and T cell-related cytokines in milk between mothers with confirmed COVID-19 polymerase chain reaction (PCR) test, mothers with viral infections suggestive of COVID-19, and mothers without infection. Materials and Methods: Concentrations of vitamin D3 and T cell-related cytokines in milk samples were determined by ELISA from 10 mothers who had a positive COVID-19 PCR test, 10 mothers with viral symptoms suggestive of COVID-19, and 20 mothers without infection. Results: Vitamin D3 concentration in human milk was higher in women without infection than in women with viral symptoms or COVID-19 PCR. Interleukin-2 level in milk was higher in the no-infection group than the COVID-19 PCR group but it did not differ with the viral symptoms group. Vitamin D3 did not correlate with any cytokines in human milk. Prenatal vitamin intake did not affect the vitamin D3 in human milk. The percentage of milk from mothers with

Vitamin D insufficiency has been suggested as a risk factor for several metabolic disorders. The objective of the study was to investigate the association between serum 25 hydroxyvitamin D [25(OH)D] and metabolic health markers of Brazilian individuals with normal-weight, overweight or obesity. We hypothesized that serum 25(OH)D would be inversely associated with glycemic, lipid and inflammatory markers indicative of metabolic abnormality. Data of 511 individuals (33-79 years), recruited from a longitudinal investigation (Pró-Saúde Study), were analyzed cross-sectionally. Anthropometric, biochemical, body composition, socio-demographic and lifestyle data were collected. Based on body mass index (BMI; normal weight, overweight, obesity) and metabolic health (metabolically healthy (MH) and metabolically unhealthy (MU)) categories, the participants were classified into 6 phenotypes. Individuals having zero components of the metabolic syndrome were considered as "MH". MH obesity was frequent in 2.0% of the participants and 56.0% exhibited vitamin D insufficiency (20 ng/mL). In the subgroups of the same BMI category, there were no significant differences in 25(OH)D concentrations between individuals classified as MH and MU. After adjustments (including %body fat and BMI), an inverse association was observed between 25(OH)D and visceral adipose tissue (B = -6.46, 95% confidence interval, CI: -12.87, -0.04), leptin (B = -0.09, 95% confidence interval, CI: -0.14, -0.03), insulin (B = -0.21, 95%CI: -0.34, -0.07), HOMA-IR (B = -0.06, 95%CI: -0.10, -0.02), triglycerides (B = -2.44, 95%CI: -3.66, -1.22), and TNF-α (B = -0.12, 95%CI: -0.24, -0.005) only in MU individuals. Our results indicate that the association of 25(OH)D concentrations with a favorable biochemical profile (glycemic, lipidic and inflammatory) seems to depend on the individual's overall metabolic health, suggesting more benefits from higher serum vitamin D in MU individuals, regardless of their adiposity.

Background: Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. Objectives: To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. Methods: In a 2 × 2-factorial trial, 200 healthy, 6-to 8-year-old, Danish, children with light skin (55°N) were randomized to 20 μg/d vitamin D3 or placebo and to substitute 260 g/d dairy with HP (10 g protein/100 g) or NP (3.5 g protein/100 g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. Results: In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased by 7.2 ± 14.1 nmol/L and decreased by 32.3 ± 17.5 nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4 ± 2.4 energy percentage (E%), which increased to 18.3 ± 3.4 E% with HP. There were no vitamin D-yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. Conclusions: Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20 μg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732.

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: transient receptor potential vanilloid 5/6 , sodium/calcium exchanger 1, plasma membrane calcium ATPase 1, calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm–oocyte binding. In humans, seminal calcium concentration between 5 and 10 mM was associated with a higher fraction of motile and morphologically normal sperm cells, and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.

Background: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations. Methods: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of participants. We calculated cumulative average predicted vitamin D score at every cycle by averaging scores from cycles up to and including that cycle. Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence according to predicted score quartiles. Results: Over follow-up, 488 incident colorectal cancers occurred. Compared with women in the highest quartile of predicted vitamin D score, those in the lowest had an estimated 41% (HR = 1.41; 95% CI, 1.05–1.90) higher colorectal cancer risk. Comparable HRs were 1.44 (95% CI, 1.02–2.01) for colon and 1.34 (95% CI, 0.70–2.56) for rectal cancer. Conclusions: Low vitamin D status may lead to elevated colorectal cancer risk in African American women. Impact: Our findings, taken together with established evidence that vitamin D levels are generally lower in African Americans than other U.S. groups, suggest that low vitamin D status may contribute to the disproportionately high colorectal cancer incidence among African Americans.

Patients who have undergone kidney transplantation (KTx) (KTxps) are a distinctive population characterized by the persistence of some metabolic anomalies present during end-stage renal disease. Mineral metabolism (MM) parameters are frequently altered after KTx. These alterations involve calcium, phosphorus, vitamin D, and parathormone (PTH) disarrangements. At present, there is little consensus about the correct monitoring and management of PTH disorders in KTxps. This article presents the prevalence and epidemiologic and clinical impact of post-KTx hyper-PTH. The principal biochemical and instrumental investigations and the therapeutic options for these conditions are also reported.