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The objective of the present study was to evaluate the effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production. Cows entering their second or greater lactation (n = 158) were randomly assigned to a control group (CON) or one of 2 treatment groups receiving either 6 × 106 IU (6VitD) or 12 × 106 IU (12VitD) cholecalciferol intramuscularly on d 275 ± 1.2 (SD) of gestation. Concentrations of serum total Ca (tCa), phosphate, and Mg were determined on 1, 2, 3, 5, 7, and 10 d in milk (DIM). For a subsample of 30 cows entering the third lactation (n = 10/group), these samples were analyzed for cholecalciferol, 25-hydroxycholecalciferol (25-OHD 3), and 24,25-dihydroxycholecalciferol (24,25-[OH] 2 D 3). In these cows, we also determined 1,25-dihydroxycholecalciferol (1,25-[OH] 2 D 3), the biologically most active metabolite, on 1, 2, 3, and 5 DIM. Repeated measures ANOVA was performed to evaluate the effect of different dosages of cholecalciferol on blood minerals, vitamin D metabolites, and milk yield over the first 5 test days after calving. Binary outcomes such as retained placenta and metritis were analyzed using a chi-squared test. Although the 12VitD treatment increased tCa concentrations on 1, 2, and 3 DIM compared with CON, administration of 6VitD increased tCa concentrations only on 1 DIM. Compared with CON cows and 6VitD cows, 12VitD cows had greater serum phosphate concentration during the first 10 DIM. Furthermore, 6VitD cows had greater serum phosphate concentrations compared with CON cows. On the contrary, 12VitD cows had lower serum Mg concentrations during the first 10 DIM compared with CON and 6VitD cows. Cholecalciferol was increased by the treatment and decreased quickly until 10 DIM. In respect to 25-OHD 3 , the 6VitD treatment resulted in a 4.1-fold increase in comparison to the CON group, while a 6.5-fold increase was observed in 12VitD animals. The vitamin D metabolite 24,25-(OH) 2 D 3 increased linearly with 25-OHD 3 serum levels, resulting in the highest concentrations in the 12VitD group. An increase of 1,25-(OH) 2 D 3 until 3 DIM was observed in all cows. However, this rise was most pronounced in the CON group. The incidence of retained placenta was 1.9%, 11.5%, and 29.6%, and that of metritis was 11.5%, 15.4%, and 31.5% for CON, 6VitD, and 12VitD cows, respectively. Although none of the treated cows exerted clinical signs of hypocalcemia, one cow in CON incurred clinical hypocalcemia. Cows of the 12VitD group had a lower milk yield over the first 5 monthly test days compared with the control and 6VitD group (42.2 ± 0.5, 42.0, ± 0.5 and 40.7 ± 0.5 kg for control cows, 6VitD cows and 12VitD cows, respectively). Although no negative side effects were observed in 6VitD cows, we do not recommend the general application of 6 × 106 IU cholecalciferol before calving as positive effects on calcium homeostasis were marginal and restricted to the first DIM. The present findings confirm that the application of 12 × 106 IU cholecalciferol negatively affected milk production on this farm. [ABSTRACT FROM AUTHOR]

Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P = 0.02), hematuria (P = 0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P < 0.001) were significant. The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients. [ABSTRACT FROM AUTHOR]

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D--binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system. [ABSTRACT FROM AUTHOR]

Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels. [ABSTRACT FROM AUTHOR]

The relationship between Vitamin D (VD) and periodontitis in patients with metabolic syndrome (MetS) was unclear. This study was to investigate the relationship between VD and periodontitis in MetS patients. This cross-sectional study collected the data of 2165 MetS patients from the National Health and Nutrition Examination Survey (NHANES). The weighted univariate and multivariable Logistic regression models were applied to identify covariates and evaluate the association between 25-hydroxy vitamin D (25(OH)D) [25(OH)D] 2 + 25(OH)D 3 and periodontitis in patients. Odds ratio (OR) [95% confidence interval (CI)] was effect size. Subgroup analysis was performed in people with or without diabetes, dyslipidemia, hypertension, cardiovascular disease (CVD) and central obesity groups. In the unadjusted model, compared with patients with 25(OH)D 2 + 25(OH)D 3 < 50 nmol/L, those with 25(OH)D 2 + 25(OH)D 3 ≥ 50 nmol/L might be associated with decreased risk of periodontitis in MetS patients (OR = 0.70, 95% CI: 0.57–0.85). After adjusting for confounders including age, gender, race, education, poverty income ratio (PIR), smoking, diabetes, VD intake and supplement and number of missing teeth, 25(OH)D 2 + 25(OH)D 3 ≥ 50 nmol/L was correlated with reduced risk of periodontitis in MetS patients (OR = 0.76, 95% CI: 0.60–0.97). Subgroup analysis revealed that in patients with CVD (OR = 0.60, 95% CI: 0.37–0.98), dyslipidemia (OR = 0.75, 95% CI: 0.57–0.97), and patients with central obesity (OR = 0.73, 95% CI: 0.57–0.95), decreased risk of periodontitis was identified in 25(OH)D 2 + 25(OH)D 3 ≥ 50 nmol/L. VD was associated with the risk of periodontitis in patients with MetS, which suggest the importance of VD supplement in patients with MetS and provide a reference for the management of periodontitis in patients with MetS. [ABSTRACT FROM AUTHOR]

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• Melatonin, zinc and multivitamins were ones of the most recommended supplements for coronavirus disease 2019. • Melatonin only may be not enough to treat patients infected with Sars-Cov2, in a multicenter retrospective observational study involving 58 562 adult patients hospitalized for COVID-19, melatonin use (N = 272) at a mean daily dose of 2.6 mg was not associated with reduced mortality. • This is a multicenter prospective, randomized, double-blind, controlled trial to examine the efficacy and safety of the association. Melatonin, zinc, and multivitamins are among most recommended supplements in the fight against coronavirus disease 2019 (COVID-19). We aimed to examine the efficacy and safety of this association in the treatment of COVID-19 and COVID-like illnesses. We conducted a multicenter prospective, randomized, double-blind, controlled trial. Patients with no medical history consulting the emergency department for covid and covid-like illness and who were not hospitalized were included. Patients were assigned in a 1:1 ratio to the treatment or the placebo group. The primary outcome was studying the effectiveness of zinc multivitamin supplement and melatonin in the treatment of COVID and -like illnesses symptoms' according to the time from randomization to clinical improvement. The pre-specified secondary outcomes were date of disappearance of symptoms present on admission, appearance of an adverse effect due to the administration of the treatment, number of patients developing complications, requiring hospitalization, requiring respiratory support. One hundred sixty four patients were eligible for the study and were randomized to either the treatment group or the placebo group. Overall, 128 of the 164 patients had a PCR for SARS-CoV-2, yielding a positive PCR result in 49.1% of them. Regarding the disappearance of all initial presenting symptoms: on the 5th day of the follow-up, there was a significant difference between the two groups with a p value 0.04;On the 10th day, there was a significant difference too with p value of 0.038. There were no significant differences between the two groups in recovery during the 15th day of follow-up p>0.5. Finally, 100% of patients fully recovered in the treatment group vs 98.8% in the placebo group. No severe adverse events were reported throughout the trial. Our results showed that daily doses of Melatonin, zinc and vitamins did significantly reduce the duration of symptoms accelerating its disappearance among patients consulting with COVID-19 or COVID-19 like illness. [ABSTRACT FROM AUTHOR]

Background: Mushrooms are rich in fiber and vitamins B and vitamin D when exposed to UV light and are sometimes used as a meat substitute. A modeling study showed that adding a mushroom portion (84 g/d) to the diet of an American population caused a significant improvement in the intake of several nutrients. Objective: To study the association between habitual intake of mushrooms and nutrient intake and to assess the change in micronutrient intake with the modeled addition of 60 or 84 grams of UV-exposed mushrooms to the diet of the Dutch population, with a subanalysis on subjects with a low animal: plant protein ratio. Methods: A modeling study was conducted in 3121 Dutch persons aged 9-80 y, using cross-sectional data from the Dutch National Food Consumption Survey 2012-2016. Linear regression was used to explore the association between habitual intake of mushrooms and nutrients. Habitual intake and nutritional adequacy were calculated before and after the modeled addition of mushrooms. Results: A small association was observed between the habitual intake of mushrooms and the intake of copper, niacin, and vitamin B2 (beta ranging from 0.002 to 0.039). The modeled addition of UV-exposed mushrooms increased the intakes of plant protein (by 5-7%), fiber (4-6%), niacin (10-20%), vitamin D (176-388%), folate (11-17%), potassium (6-10%), and copper (29-48%). Nutritional adequacy also improved significantly. For subjects with a low animal:plant protein ratio, the added mushrooms increased the intakes of niacin (11-22%), potassium (6-11%), and vitamin D (190-445%). Conclusions: Consumption of mushrooms contributes to higher intakes of copper, niacin, and vitamin B2. Addition of UV-exposed mushrooms to the diet of the Dutch further improves nutrient intakes and, most notably, vitamin D, especially for people with low animal food consumption. [ABSTRACT FROM AUTHOR]

Vitamin D has been associated with an increased risk of tooth loss and the severity of periodontal diseases. This study aimed to evaluate the effect of vitamin D on the clinical, radiographic, and serum level changes of bone turnover biomarkers in ligature-induced periodontitis. A total of 28 rats were included in this study and divided into test groups: Vitamin D supplement (VS), Vitamin D deficient (VD), and control (CG). Ligature-induced periodontal tissue destruction was performed and kept for 21 days. Clinical attachment and radiographic changes were recorded, and serum samples were tested for Osteoprotegerin (OPG), Dickkopf-1 (DKK1), Sclerostin (SOST), and Fibroblast growth factor 23 (FGF23) on the initial and final day of the study. Groups that were made VD exhibited a more significant amount of clinical attachment loss (1.05 ± 0.50 mm) compared to the CG (0.83 ± 0.14 mm) and VS group (0.60 ± 0.13 mm), showing significant differences (p < 0.05). The radiographic alveolar bone loss amount was greater in the VD group compared to the other groups. For serum level assessment, the VD groups also exhibited a statistically significant reduction in the levels of OPG. They showed higher concentrations of DKK1, SOST, and FGF23 than other groups, with significant differences (p < 0.05). The results revealed that Vitamin D may play a role in the progression of periodontal disease. It was found to affect both clinical parameters and bone turnover biomarkers, suggesting its potential impact on the disease process. [ABSTRACT FROM AUTHOR]

Background: Milk is a key source of important nutrients including the nutrients of public health concern. However, most Americans do not meet current (dairy) United States Department of Agriculture (USDA) dietary guideline recommendations, and the intake has been declining. Objective: The aim of this study was to investigate milk and beverage intake trends and nutrient intakes from these products in United States children aged 6-18 y and to model the effect of isocaloric substitution of nondairy beverages with milk. Methods: Data from National Health and Nutrition Examination Survey (NHANES) 2001-2018 for children age 6-8 (N = 4696), 9-13 (N = 8117) and 14-18 y (N = 8514) were used with milk and other beverage intakes determined from the first 24-h in-person dietary recall. Nutrient intake was determined using the NHANES cycle-specific total nutrient intake files. Nutrient modeling was performed by isocaloric substitution with milk of all nondairy beverages consumed during lunch and dinner meals combined. Sample-weighted analyses were performed using SAS 9.4. Results: Between ages 6-8 and 14-18 y, daily intake of milk and flavored milk decreased by 10% and 62%, respectively, while daily intake of caloric beverages excluding milk increased by 96%. Daily intake from caloric beverages and milk combined decreased for fiber, protein, fat, saturated fat, calcium, magnesium, potassium, vitamin A, and vitamin D and increased for energy, carbohydrates, added sugars, and folate between ages 6-8 y and 14-18 y. Isocaloric substitution of all caloric nondairy beverages at meals with milk (using nutrient contribution of USDA milk, not further specified (NFS)) resulted in increases in protein, fat, saturated fat, calcium, magnesium, potassium, sodium, vitamin A, folate, vitamin B12, and vitamin D and decreases in carbohydrate, fiber, and added sugar. Conclusion: These findings provide additional evidence to support dietary recommendations for milk, and efforts should be made on behalf of leading health professionals and childhood meal programs to highlight milk as a beverage of choice in children and adolescents. [ABSTRACT FROM AUTHOR]

• We did a phase 3 randomized placebo-controlled trial of vitamin D to prevent tuberculosis (TB) infection in 1682 QuantiFERON-TB Plus-negative children in Cape Town, South Africa. • In total, 63.2% of participants had serum 25-hydroxyvitamin D (25[OH]D) concentrations <75 nmol/l at baseline. • The intervention was weekly oral administration of 10,000 IU vitamin D 3 for 3 years. • This was effective in elevating serum 25(OH)D concentrations in participants randomized to the intervention arm of the trial. • The intervention did not influence the risk of QuantiFERON-TB Plus conversion. To determine whether weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D 3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). Weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion. [ABSTRACT FROM AUTHOR]

Background: Campus food pantries are uniquely positioned to promote health equity with the foods they make accessible to food-insecure students. Objectives: This study assessed the implementation and effectiveness of a client-choice campus food pantry to understand its potential impact on nutrition security and to inform future implementation. Methods: This observational study was designed using the reach, effectiveness, adoption, implementation, and maintenance framework, leveraging administrative data collected from a client-choice campus food pantry at a large Midwest university from August 2020 to May 2022. Pantry staff tracked student usage and item inventory. Items were analyzed for specific nutrients using the Nutrition Data System for Research. The mean nutrients and servings per food group distributed per visit were calculated and compared with dietary recommendations (effectiveness). Characteristics of pantry operation and setup were detailed (adoption). The percentage of openings with adequate stock to meet distribution guidelines was determined (implementation). Descriptive statistics were calculated, and multiple linear regressions determined whether significant changes in nutrients and food were distributed based on distribution guidelines and stock available. Results: Effectiveness: Vitamin D, fruits, vegetables, and whole grains were below 3 d of the recommended intake for all students, and energy, fiber, potassium, vitamin A, and grains were low for male students. Adoption: The pantry was established through a collaboration with a pre-existing community food pantry and operates as a 501(c) and is managed by campus recreation staff. Implementation: The pantry supplied enough produce for 72% of openings to meet distribution guidelines and enough dairy for 63% of openings. Conclusions: The food and nutrients distributed in limited amounts are consistent with those underconsumed according to the Dietary Guidelines for Americans. More research is needed to understand how pantry implementation can best support nutrition security through the adequate distribution of key nutrients and food groups. [ABSTRACT FROM AUTHOR]

Vitamin D insufficiency/deficiency has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). This is associated with significantly increased morbidity and mortality leading to not only prolonged hospital and intensive care unit (ICU) stay, but increased risk of stroke, heart failure, dementia, and long-term atrial fibrillation. This analysis aims to evaluate the efficacy of vitamin D supplementation in preventing POAF in patients undergoing CABG. We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to June 2022 for randomized controlled trials (RCTs). The outcome of interest was the incidence of POAF. Secondarily, we analyzed the length of ICU stay, length of hospital stay, cardiac arrest, cardiac tamponade, and blood transfusion. Results were pooled using a random-effect model. Three RCTs consisting of 448 patients were included. Our results suggest that vitamin D significantly reduced the incidence of POAF (RR: 0.60; 95 % CI: 0.40, 0.90; p = 0.01; I2 = 8 %). It was also observed that vitamin D significantly reduced the duration of ICU stay (WMD: −1.639; 95 % CI: −1.857, −1.420; p < 0.00001). Furthermore, the length of hospital stay (WMD: −0.85; 95 % CI: −2.14, 0.43; p = 0.19; I2 = 87 %) was also reduced, however, the result was not significant. Our pooled analysis suggests that vitamin D prevents POAF. Future large-scale randomized trials are needed to confirm our results. [Display omitted] • Vitamin D deficiency is a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting. • Vitamin D supplementation reduces incidence of POAF and duration of intensive care unit stay. • Further large-scale trials are needed to yield powerful results. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is a challenging psychological disorder faced by 10–30% of mothers across the globe. In India, it occurs among 22% of mothers. Its aetiology and pathophysiology aren't fully understood as of today but multiple theories on the interplay of hormones, neurotransmitters, genetics, epigenetics, nutrients, socio-environmental factors, etc. exist. Nutrients are not only essential for the synthesis of neurotransmitters, but they may also indirectly influence genomic pathways that methylate DNA, and there is evidence for molecular associations between nutritional quality and psychological well-being. Increased behavioural disorders have been attributed to macro- and micronutrient deficiencies, and dietary supplementation has been effective in treating several neuropsychiatric illnesses. Nutritional deficiencies occur frequently in women, especially during pregnancy and breastfeeding. The aim of this study was to perform a comprehensive literature review of evidence-based research in order to identify, gather and summarize existing knowledge on PPD's aetiology, pathophysiology, and the role of nutrients in its prevention as well as management. The possible mechanisms of action of nutrients are also presented here. Study findings show that the risk of depression increases when omega-3 fatty acid levels are low. Both fish oil and folic acid supplements have been used to effectively treat depression. Antidepressant efficacy is lowered by folate insufficiency. Folate, vitamin B12, iron, etc. deficiencies are more prevalent in depressed people than in non-depressed people. Serum cholesterol levels and plasma tryptophan levels are found to be inversely correlated with PPD. Serum vitamin D levels were associated inversely with perinatal depression. These findings highlight the importance of adequate nutrition in the antepartum period. Given that nutritional therapies can be affordable, safe, simple to use, and are typically well-accepted by patients, more focus should be placed on dietary variables in PPD. [ABSTRACT FROM AUTHOR]

The level of vitamin D in pregnant women and the effect of vitamin D supplementation are lack in Taiwan. To investigate the vitamin D serum level and the effect of its supplementation on pregnancy. We included 1048 pregnant women who underwent prenatal exam with known serum 25-hydroxyvitamin D3 [25(OH)D3] levels and delivery at the Mackay Memorial Hospital, Taipei, Taiwan during 2015–2018. A daily dose 2000 IU of vitamin D was given, starting at 12–16 weeks of pregnancy, to reach the level of 20 ng/mL, and then a maintenance dose of 800 IU/day was given. The other 3654 women without vitamin D supplementation delivered in 2018 served as control group. Pregnancy outcomes were recorded for analysis. Over 80% of the 1048 pregnant women were vitamin D deficiency. There was an inverse correlation between serum vitamin D levels and maternal body mass index (p = 0.0366). We compared 375 women with serum vitamin D levels increased above 30 ng/mL after supplementation with control group. The rates of preterm birth, low birth weight, and postpartum hemorrhage between these 2 groups were 6.67% vs. 11.19% (p = 0.007), 6.40% vs. 10.0% (p = 0.025), and 1.33% vs. 3.20% (p = 0.04), respectively. Vitamin D deficiency is very prevalent in pregnant women, especially those with high BMI, in Taiwan. It can be corrected by adequate vitamin D supplementation, which may decrease the risk of pregnancy complications and bring benefits to the fetus. [ABSTRACT FROM AUTHOR]

Background: Food security and nutrient deficiencies are frequent issues for people living in northern remote regions of Canada. Objective: The objective of this study is to describe the nutrient intake of residents living in the Dene/Métis communities of the Dehcho and Sahtú regions of the Northwest Territories. Methods: A 24-h dietary recall survey was used to collect information from participants of a study completed in 9 communities during the winter seasons of January 2016 to March 2018. Intakes for food groups, vitamins, macroelements, and microelements were calculated. Nutrient intakes were compared with the available DRIs. Results: In total, there were 197 participants. On average, 37% of their energy was consumed from fat, and fruit/vegetable consumption was low (2.8 servings). Some vitamin levels (i.e., folate and vitamins A, B-6, C, and D) indicated a risk of nutritional deficiency for at least half of the participants. Of the nutrients examined, the nutrients least likely to meet the DRIs, according to the age/sex category of respondents were vitamin D (6%-20%), fiber (0%-11%), and calcium (4%-30%). Males tended to have a higher rate of nutrient adequacy above the DRIs. Importantly, 52% of the childbearing age female participants appeared deficient in folate, 48% deficient in zinc, 41% deficient in B12, and 22% deficient in iron, which might affect pregnancy and children's development. Conclusions: A focus on supporting a higher intake of nutrient-dense foods would benefit the health of these communities. Nutrition and health promotion programs should be implemented to improve public health efforts in the region. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency and anemia impact the health of women of reproductive age. Evidence suggests an inverse relationship between serum vitamin D (25-hydroxyvitamin D [25(OH)D]) and anemia/iron deficiency, but less is known about these associations in women of reproductive age, in particular in a setting with a combined burden of micronutrient deficiency, food insecurity, and obesity. Objective: We aimed to assess the associations between 25(OH)D and biomarkers of iron and anemia in a cohort of women of reproductive age from Soweto, South Africa. The prevalence of vitamin D deficiency was also assessed. Methods: In this cross-sectional substudy of the Healthy Life Trajectories Initiative (HeLTI) South Africa pilot trial, 25(OH)D, iron markers (ferritin and soluble transferrin receptor [sTFR]), and altitude-adjusted hemoglobin (Hb) were measured in 493 women aged 18 to 25 years. Associations between iron deficiency/anemia and vitamin D status were evaluated using multivariable logistic regression, adjusting for confounders including fat mass index (FMI). Structural equation modeling (SEM) was performed to evaluate direct and indirect pathways between 25(OH)D, iron and anemia markers, and covariates. Results: Of 493 participants, 136 (27.6%) had vitamin D insufficiency (25(OH)D ≥12-20 ng/mL), whereas 28 (5.6%) had vitamin D deficiency (<12 ng/mL). Anemia and iron deficiency were not significantly associated with vitamin D category (25(OH)D<20 ng/mL compared with ≥20 ng/mL) in multivariable logistic regression analyses. In SEM, log-transformed 25(OH)D was not significantly associated with Hb, ferritin, or sTFR, but it was significantly associated with season of data collection, hormonal contraceptive use, and FMI (total effects: B = 0.17, 95% CI: 0.104, 0.236, P < 0.001; B: 0.10, 95% CI: 0.041, 0.154, P < 0.001; B: -0.01, 95%CI: -0.016, -0.003, P = 0.003, respectively). Conclusion: No significant association between vitamin D (25(OH)D), anemia (Hb), and iron markers was found. The inverse relationship between FMI and vitamin D status emphasizes the overlap between adiposity and micronutrient deficiencies in young South African women, exacerbating their risk of disease development. [ABSTRACT FROM AUTHOR]

:Both periodontal disease and diabetes mellitus (DM) are long-term inflammatory disorders that are highly prevalent and have a significant health impact. Inflammaging, a state of pre-aging and hyperinflammatory state has been acknowledged for its role in DM patients to have heightened risk of periodontitis. Numerous evidences revealed that inflammaging contributed by cell senescence, acceleration of inflammation and oxidative stress participates in the destruction of periodontium in DM. Abilities of vitamin D in suppressing inflammation and oxidative stress have been revealed in a range of tissues, however in DM's gingival cells, the effect remain undefined. : Under the stimulation of advanced glycation end-products (AGEs), we assessed the cell proliferation in human gingival fibroblast (HGF), IL-6 and IL-8 secretions, cellular senescence expression and generation of reactive oxygen species (ROS) with or without vitamin D intervention. Following that, we examined the expression of Nrf2 and HO-1 to see if vitamin D was able to modulate the anti-oxidant signaling. A knockdown experiment was then conducted to proof the participation of Nrf2 on the secretion of pro-inflammatory IL-6 and IL-8. : Following the treatment of vitamin D, AGEs-elicited IL-6 and IL-8 production and cell senescence were dose-dependently repressed. Moreover, vitamin D attenuated AGEs-induced ROS in a dose-dependent pattern. Results from qRT-PCR demonstrated vitamin D reversed the suppression of Nrf2 and HO-1 induced by AGEs. Our findings revealed that the anti-inflammatory and anti-oxidant effect in vitamin D was mediated via the upregulation of Nrf2 expression. : These data showed that high levels of AGEs in the gingiva lead to inflammaging reflected by increased pro-inflammatory cytokines, cell senescence expression and oxidative stress. Vitamin D supplementation can reduce oxidative stress and inflammation via the upregulation of Nrf2 signaling and hence, may be a potential approach for treatment of diabetes-associated periodontitis. [ABSTRACT FROM AUTHOR]

Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = <0.001). Only 12% of elderly men had normal bone mineral density score. Serum testosterone, chronic obstructive pulmonary disease (COPD) and benign prostatic hypertrophy (BPH) were significantly associated with male osteoporosis with a p-value of 0.019, 0.016 and 0.010, respectively. Vitamin D levels, type 2 diabetes mellitus, hypertension and coronary artery disease did not show any significant association with male osteoporosis. Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures. [ABSTRACT FROM AUTHOR]

In spite of bone's healing capacity, critical-size bone defect regeneration and peri -implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration. Comprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened. Database search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro – 9/in vivo – 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route. Based on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration. [ABSTRACT FROM AUTHOR]

The objectives of the experiment were to determine the effects of supplementing 2 amounts of 25-hydroxyvitamin D 3 (calcidiol; CAL) compared with equal amounts of vitamin D 3 (cholecalciferol; CHOL) on serum concentrations, absorptions, and retentions of Ca, Mg, and P in periparturient dairy cows. One hundred seventy-seven (133 parous and 44 nulliparous) pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit for energy-corrected milk yield (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments. Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d gestation until parturition. The prepartum diet had a dietary cation-anion difference of −128 mEq/kg of dry matter. All cows were fed a common postpartum diet containing 46 μg of vitamin D 3 /kg of dry matter without further supplementation of treatments. Concentrations of vitamin D metabolites, Ca, Mg, and P in serum were measured pre- and postpartum, in addition to total-tract digestibility and urinary excretion of Ca, Mg, and P in the prepartum period. Feeding 3 mg compared with 1 mg of CAL increased serum 25-hydroxyvitamin D 3 (CAL1 = 94 vs. CAL3 = 173 ± 3 ng/mL). In comparison, the increment in serum 25-hydroxyvitamin D 3 from feeding 3 mg compared with 1 mg of CHOL was small (CHOL1 = 58 vs. CHOL3 = 64 ± 3 ng/mL). Feeding CAL increased prepartum concentration of P in serum compared with CHOL (CHOL = 1.87 vs. CAL = 2.01 ± 0.02 m M), regardless of the amount fed, but neither source nor amount affected prepartum Ca or Mg in serum. Feeding CAL increased serum Ca and P for the first 11 d postpartum compared with CHOL (CHOL = 2.12 vs. CAL = 2.16 ± 0.01 m M serum Ca; CHOL = 1.70 vs. CAL = 1.78 ± 0.02 m M serum P) but the amount of vitamin D did not affect postpartum concentrations of Ca, Mg, and P in serum. Feeding CAL increased prepartum apparent digestibility of Ca compared with CHOL (CHOL = 26.6 vs. CAL = 33.5 ± 2.8%) but treatments did not affect Ca retention prepartum. Neither source nor amount of vitamin D affected Mg and P apparent digestibility, but CAL decreased the concentration of P excreted in urine during the prepartum period (CHOL = 1.8 vs. CAL = 0.8 ± 0.3 g/d). Calcidiol tended to increase the amount of Ca secreted in colostrum (CHOL = 9.1 vs. CAL = 11.2 ± 0.9 g/d) and Ca excreted in urine postpartum (CHOL = 0.4 vs. CAL = 0.6 ± 0.1 g/d) compared with CHOL. Collectively, feeding CAL at 1 or 3 mg/d compared with CHOL in the last 24 d of gestation is an effective way to increase periparturient serum P concentration and postpartum serum Ca of dairy cows fed a prepartum diet with negative DCAD. [ABSTRACT FROM AUTHOR]

The objectives were to test the effects of dietary vitamin D 3 [cholecalciferol (CHOL)] compared with 25-hydroxyvitamin D 3 [calcidiol (CAL)] on vitamin D status and response to an endotoxin challenge. Forty-five Holstein bull calves (5 ± 2 d of age) were blocked into weekly cohorts, fed a basal diet that provided 0.25 µg/kg body weight (BW) CHOL, and assigned randomly to 1 of 5 treatments: control [(CON) no additional vitamin D], 1.5 µg/kg BW CHOL (CHOL1.5), 3 µg/kg BW CHOL (CHOL3), 1.5 µg/kg BW CAL (CAL1.5), or 3 µg/kg BW CAL (CAL3). Calves were fed milk replacer until weaning at 56 d of age and had ad libitum access to water and starter grain throughout the experiment. Treatments were added daily to the diet of milk replacer until weaning and starter grain after weaning. Measures of growth, dry matter intake, and serum concentrations of vitamin D, Ca, Mg, and P were collected from 0 to 91 d of the experiment. At 91 d of the experiment, calves received an intravenous injection of 0.1 µg/kg BW lipopolysaccharide (LPS). Clinical and physiological responses were measured from 0 to 72 h relative to LPS injection. Data were analyzed with mixed models that included fixed effects of treatment and time, and random effect of block. Orthogonal contrasts evaluated the effects of (1) source (CAL vs. CHOL), (2) dose (1.5 vs. 3.0 µg/kg BW), (3) interaction between source and dose, and (4) supplementation (CON vs. all other treatments) of vitamin D. From 21 to 91 d of the experiment, mean BW of supplemented calves was less compared with CON calves, but the effect was predominantly a result of the CHOL calves, which tended to weigh less than the CAL calves. Supplementing vitamin D increased concentrations of 25-hydroxyvitamin D in serum compared with CON, but the increment from increasing the dose from 1.5 to 3.0 µg/kg BW was greater for CAL compared with CHOL (CON = 18.9, CHOL = 24.7 and 29.6, CAL = 35.6 and 65.7 ± 3.2 ng/mL, respectively). Feeding CAL also increased serum Ca and P compared with CHOL. An interaction between source and dose of treatment was observed for rectal temperature and derivatives of reactive metabolites after LPS challenge because calves receiving CHOL3 and CAL1.5 had lower rectal temperatures and plasma derivatives of reactive metabolites compared with calves receiving CHOL1.5 and CAL3. Supplementing vitamin D increased plasma P concentrations post-LPS challenge compared with CON, but plasma concentrations of Ca, Mg, fatty acids, glucose, β-hydroxybutyrate, haptoglobin, tumor necrosis factor-α, and antioxidant potential did not differ among treatments post-LPS challenge. Last, supplementing vitamin D increased granulocytes as a percentage of blood leukocytes post-LPS challenge compared with CON. Supplementing CAL as a source of vitamin D to dairy calves was more effective at increasing serum 25-hydroxyvitamin D, Ca, and P concentrations compared with feeding CHOL. Supplemental source and dose of vitamin D also influenced responses to the LPS challenge. [ABSTRACT FROM AUTHOR]

The objectives of this experiment were to determine the effects of supplementing 25-hydroxyvitamin D 3 (calcidiol, CAL) compared with vitamin D 3 (cholecalciferol, CHOL) at 1 or 3 mg/d in late gestation on production outcomes of dairy cows. One hundred thirty-three parous and 44 nulliparous pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments (CAL1, CAL3, CHOL1, and CHOL3). Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d in gestation until parturition. The prepartum diet had a dietary cation-anion difference of −128 mEq/kg of dry matter. Production and disease were evaluated for the first 42 d in milk, and reproduction was evaluated to 300 d in milk. Incidence of postpartum diseases did not differ among treatments. Feeding CAL compared with CHOL increased yields of colostrum and colostrum fat, protein, and total solids, resulting in an increased amount of net energy for lactation secreted as colostrum (CHOL = 7.0 vs. CAL = 9.0 ± 0.7 Mcal). An interaction between source and amount was observed for milk yield: CAL3 increased milk yield compared with CHOL3 (CHOL3 = 34.1 vs. CAL3 = 38.7 ± 1.4 kg/d) but milk yield did not differ between CAL1 and CHOL1 (CHOL1 = 36.9 vs. CAL1 = 36.4 ± 1.4 kg/d). Concentrations of serum calcidiol on day of calving and average serum Ca from d 2 to 11 postpartum were positively associated with milk yield in the first 42 d in milk. Interactions between source and amount of vitamin D were also observed for pregnancy after first AI: the percentage of cows receiving CHOL1 and CAL3 that became pregnant was smaller than that of cows receiving CHOL3 and CAL1. However, pregnancy per AI and pregnancy by 300 d in milk did not differ among treatments. Overall, CAL3 increased milk yield compared with CHOL3, whereas in cows fed 1 mg/d (CAL1 and CHOL1), the source of vitamin D generally had no effect. The effect of CAL3 may be explained in part by serum CAL concentrations and postpartum serum Ca, which were associated with milk yield. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether 25(OH)D concentrations in children and female adults may be influenced by inflammation and thus require adjustment when estimating the population prevalence of vitamin D deficiency. Objectives: We examined correlations between inflammation biomarkers, CRP or alpha-1-acid glycoprotein (AGP), and serum 25(OH)D concentrations among preschool children (PSC; 6-59 mo) and nonpregnant females of reproductive age (FRA; 15-49 y). Methods: We analyzed cross-sectional data from 6 nationally representative nutrition surveys (Afghanistan, Cambodia, Pakistan, UK, USA, and Vietnam) conducted among PSC (n = 9880) and FRA (n = 14,749) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Rank correlations between CRP or AGP and 25(OH)D concentrations were examined while taking into account complex survey design effects. Results: Among both PSC and FRA, correlations between inflammation and vitamin D biomarkers were weak and inconsistent across surveys. For PSC, correlation coefficients between CRP and 25(OH)D concentrations ranged from -0.04 to 0.08, and correlations between AGP and 25(OH)D ranged from 0.01 to 0.05. Correlation coefficients between CRP and 25(OH)D for FRA ranged from -0.11 to 0.14, and correlations between AGP and 25(OH)D concentrations ranged from -0.05 to 0.01. Conclusions: Based on the weak and inconsistent correlations between CRP or AGP and 25(OH)D, there is no rationale to adjust for these inflammation biomarkers when estimating population prevalence of vitamin D deficiency in PSC or FRA. [ABSTRACT FROM AUTHOR]

Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss. A prospective community cohort study (enrollment 2010–2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates. Detroit, Michigan area. Self-identified African American or Black women aged 23–35 at enrollment without previous clinical diagnosis of fibroids. Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry. The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors. At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (<20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with <20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with <30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The >30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83). Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations >30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols. [ABSTRACT FROM AUTHOR]

Background: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear.Objectives: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L.Methods: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests.Results: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L.Conclusions: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www.clinicaltrials.gov/ct2/show/NCT02563015) as NCT02563015. [ABSTRACT FROM AUTHOR]

Objective: To assess the real-world effectiveness of vitamin D supplementation in patients with knee osteoarthritis (KOA) by replicating a randomized controlled trial (RCT) design in an observational study.Method: This study emulated a target trial using data from the Osteoarthritis Initiative (OAI). Eligible participants were ≥45 years, had symptomatic KOA and did not take vitamin D supplements in the past 30 days. A participant can enter the trial more than once. Participants were included in vitamin D group if they took ≥1,000 IU/day for ≥4 days/week in the past 30 days at the first follow-up visit after baseline. The control group did not use vitamin D in the past 30 days. Optimal propensity score matching at 1:1 ratio was performed. The primary outcome was change in knee pain 2 years after baseline measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included WOMAC physical function and quantitative joint space width (JSW). Standardized mean difference (SMD) was used to compare the findings with previous RCTs.Results: A total of 236 person-trials in the vitamin D group were pair-matched with a control. Compared to the control group, vitamin D supplementation did not reach significant changes in WOMAC pain (SMD = -0.04, 95%CI [-0.21, 0.13]), physical function and radiographic JSW over 2 years. The SMDs were consistent with the effect sizes reported in previous RCTs.Conclusion: Target trial emulation in the OAI cohort demonstrated findings close to published RCTs. This supports the future use of target trial emulation in evaluating other systemic therapies for KOA. [ABSTRACT FROM AUTHOR]

Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) 2 D 3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) 2 D 3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. In vitro , HaCaT cells were treated with 1,25(OH) 2 D 3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm2 then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. Compared with the HaCaT cells treated with 1,25(OH) 2 D 3 or TAK-242, the cells treated with both 1,25(OH) 2 D 3 and TAK-242 showed, 1) significantly lower production of ROS (P < 0.05); 2) significantly less apoptosis of HaCaT cells (P < 0.05); 3) significantly lower expression of NF- κ B, Caspase-8, Cyto-C, Caspase-3 (P < 0.05). The combination of 1,25(OH) 2 D 3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) 2 D 3 or TAK-242 alone. [ABSTRACT FROM AUTHOR]

Background The association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality among patients with metabolic dysfunction–associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) remains unclear. Objective The aim was to evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD. Methods The study included 4651 individuals with fatty liver disease (FLD; 3964 had MAFLD and 3968 had NAFLD) from NHANES III. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the HRs and 95% CIs, with adjustment of potential confounders. Results Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 y, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HRs and 95% CIs of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P -trend = 0.001) and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P -trend = 0.002). A nonlinear inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (P overall < 0.001; P nonlinear = 0.003) or NAFLD (P overall < 0.001; P nonlinear = 0.009), with a threshold effect at ∼50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 y (P -interaction = 0.001). Conclusions This study suggested a nonlinear inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at ∼50.0 nmol/L of serum 25(OH)D. [ABSTRACT FROM AUTHOR]

Background Vitamin D status has been found to be inversely associated with metabolic syndrome (MetS) in some studies. Vitamin D status varies by race and ethnicity, and the association of MetS with vitamin D status in US adults and by race and Hispanic origin has not been evaluated extensively. Objectives We aimed to examine the associations between vitamin D status and MetS overall, and across race and Hispanic origin groups, in a nationally representative sample of US adults who participated in the NHANES from 2007 to 2014. Methods The total sample included 8639 adults, ≥20 y of age. Serum vitamin D was measured using a standardized LC-tandem MS method and was categorized using data-driven tertiles. MetS was defined using measured waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were fitted [accounting for sociodemographic and lifestyle factors, dietary supplement use, and BMI (in kg/m2)] to examine the associations of serum vitamin D with MetS among adults overall, and by race and Hispanic origin. Results Serum vitamin D in the lowest tertile (≤56 nmol/L) was significantly associated with increased odds of MetS compared with the highest tertile (>77.9 nmol/L) (fully adjusted model OR: 1.85; 95% CI: 1.51, 2.27). Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic white (NHW) (OR: 2.24; 95% CI: 1.67, 3.01), non-Hispanic black (OR: 1.56; 95% CI: 1.06, 2.29), and Hispanic (OR: 1.48; 95% CI: 1.03, 2.14) adults. Conclusions Lower vitamin D status was significantly associated with MetS among US adults after adjusting for sociodemographic and lifestyle factors, dietary supplement use, and BMI. This finding was noted across all race and Hispanic origin groups, although the strength of the association varied, being strongest for NHW adults. [ABSTRACT FROM AUTHOR]

Background The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. Objectives We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. Methods This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. Results The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). Conclusions Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D. [ABSTRACT FROM AUTHOR]

Background Pregnancy induces bone mineral mobilization, which may be further compromised if diet and physical activity are suboptimal. Objectives We aimed to determine the effects of a Nutrition + Exercise intervention during pregnancy on maternal calciotropic and bone biomarker profiles throughout pregnancy and the postpartum. Methods In the Be Healthy in Pregnancy (BHIP) randomized controlled trial, 203 of 225 participants who consented to the bone health substudy were, randomly assigned at 12–17 weeks gestation to receive either usual care (control) or a structured and monitored Nutrition + Exercise plan (intervention) providing an individualized high dairy protein diet and a walking program throughout pregnancy. Maternal serum total procollagen type 1 N-terminal propeptide (P1NP; bone formation), C-terminal telopeptide of type I collagen (CTX; bone resorption), and insulin-like growth factor-1 (IGF-1) were measured by ELISA, and vitamin D metabolites by ultra-performance LC tandem MS at early and late pregnancy, 6 mo postpartum, and in cord blood. Results In 187 participants completing all measures, significantly higher intakes were observed in the intervention than in the control group for total protein (P  < 0.0001), protein intake from dairy foods (P  < 0.0001), and calcium (P  < 0.0001), whereas vitamin D intake was similar between treatment groups in both the second and third trimesters. The intervention group had significantly lower serum CTX at end of pregnancy (mean ± SD: 0.78 ± 0.31 ng/mL; n  = 91 compared with 0.89 ± 0.33 ng/mL; n  = 96, P  = 0.034) and in cord serum (0.58 ± 0.13 ng/mL; n  = 31 compared with 0.69 ± 0.18 ng/mL; n  = 22, P  < 0.025). Serum concentrations of P1NP rose significantly (P  < 0.02) from early pregnancy to 6 mo postpartum for the intervention group only. Serum 25-hydroxyvitamin D status was >50 nmol/L for 97% of all participants. Conclusions Higher maternal dietary protein and calcium intakes than usual care in concert with normal vitamin D status minimized bone resorption and maintained bone formation and may protect bone health during pregnancy. This trial was registered at clinicaltrials.gov as NCT01689961. [ABSTRACT FROM AUTHOR]

Cytokines regulate immune responses essential for maintaining immune homeostasis, as deregulated cytokine signaling can lead to detrimental outcomes, including inflammatory disorders. The antioxidants emerge as promising therapeutic agents because they mitigate oxidative stress and modulate inflammatory pathways. Antioxidants can potentially ameliorate inflammation-related disorders by counteracting excessive cytokine-mediated inflammatory responses. A comprehensive understanding of cytokine-mediated inflammatory pathways and the interplay with antioxidants is paramount for developing natural therapeutic agents targeting inflammation-related disorders and helping to improve clinical outcomes and enhance the quality of life for patients. Among these antioxidants, curcumin, vitamin C, vitamin D, propolis, allicin, and cinnamaldehyde have garnered attention for their anti-inflammatory properties and potential therapeutic benefits. This review highlights the interrelationship between cytokines-mediated disorders in various diseases and therapeutic approaches involving antioxidants. [Display omitted] • Cytokines, produced by immune cells, are pivotal players in many health conditions. • The imbalance of cytokines results in an excessive immune response. • Antioxidants provide therapeutic benefits in inflammatory conditions. • Antioxidants combined with radiotherapy can be an effective therapeutic option. [ABSTRACT FROM AUTHOR]

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management. [Display omitted] • Establishing a mouse model by controlling daily vitamin D3 intake since childhood. • Vitamin D influences striatal DNA methylations and gene expression dose-specifically. • Vitamin D regulates striatal signal-transduction at DNA methylation and mRNA levels. • Vitamin D has a synergistic effect on dopamine release with methylphenidate. [ABSTRACT FROM AUTHOR]

• There was no significant difference in the distribution frequency of the MTHFR C677T genotypes between the PCOS and the control group. • The serum homocysteine level in TT group of PCOS patients was significantly higher than that in CT and CC groups. • There was a significant negative correlation between vitamin D level and homocysteine level in PCOS patients. • Vitamin D concentration were an independent risk factor for hyperhomocysteinemia. To evaluate the correlation between serum vitamin D, homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism in women with polycystic ovary syndrome (PCOS). Study design We retrospectively compared the serum homocysteine and vitamin D levels and the MTHFR C677T polymorphism in 104 PCOS patients and 104 controls. Parameters related to PCOS were statistically analysed. Comparative analysis revealed that women with PCOS had significantly greater serum homocysteine levels (P = 0.002) and lower vitamin D concentrations (P = 0.040) than controls. The distribution frequency of the MTHFR C677T genotype did not significantly differ between the PCOS group and the control group. (P > 0.05). In the PCOS group, the serum level of homocysteine in the TT group was significantly greater than that in the CT (P = 0.003) and CC (P = 0.002) groups and the level of vitamin D in the TT group was significantly less than that in the CC (P < 0.001) and CT (P = 0.172) groups. The results were similar when the PCOS and control groups were divided according to whether they had insulin resistance. Vitamin D levels were significantly negatively correlated with homocysteine levels in all PCOS patients (r = −0.281, P = 0.004), similarly, vitamin D levels were negatively correlated with homocysteine levels in the CC, CT and TT of PCOS patients. According to multivariate analysis, vitamin D concentration was an independent risk factor for hyperhomocysteinaemia (adjusted OR 1.372, 95 % CI: 1.100–1.712). No significant differences were found in the distributions of MTHFR C677T genotypes between the PCOS and control groups but these genotypes affected the patients' serum homocysteine and vitamin D concentrations. Women with the TT genotype have significantly lower vitamin D levels and higher homocysteine levels than women with the CC and CT genotypes. However, because of the limitations of this investigation, large-sample, high-quality prospective studies are needed to further verify these results in the future. [ABSTRACT FROM AUTHOR]

Agricultural systems are under increasing pressure from declining environmental conditions, a growing population, and changes in consumer preferences, resulting in widespread malnutrition-related illnesses. Improving plant nutritional content through biotechnology techniques such as synthetic biology is a promising strategy to help combat hidden hunger caused by the lack of affordable and healthy foods in human diets. Production of compounds usually found in animal-rich diets, such as vitamin D or omega-3 fatty acids, has been recently demonstrated in planta. Here, we review recent biotechnological approaches to biofortifying plants with vitamins, minerals, and other metabolites, and summarise synthetic biology advances that offer the opportunity to build on these early biofortification efforts. [Display omitted] • Genetic modification of plants for nutritional benefits is now commonplace. • Vitamin accumulation by genetic modification has been widely explored. • Other key targets include reducing antinutrients and tuning macronutrient profiles. • Changing regulations may see more genetically modified plants approved for use. • Future studies need to address target bioaccessibility and real-world validation. [ABSTRACT FROM AUTHOR]

1,25(OH) 2 D 3 is a fat-soluble vitamin, involved in regulating Ca2+ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH) 2 D 3 blood level. In addition, 1,25(OH) 2 D 3 plays vital roles in Ca2+-P i and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH) 2 D 3 -deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. Several studies have revealed that cancer development in a background of 1,25(OH) 2 D 3 deficient obesity involves the VDR gene. Moreover, 1,25(OH) 2 D 3 is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH) 2 D 3 -based therapies without any side effects. [Display omitted] • Deficiencies of vitamin D and the VDR gene have been reported to be associated with obesity and obesity-related cancer. • VDR expression declines as the differentiation of adipose tissue progresses. • The adipogenesis suppressive effect of VDR may be due to its ability to cause competition between RXR and PPARγ. • Cancer can be cured with vitamin D supplementation. • Novel therapeutics may be developed along with the vitamin D supplement by targeting VDR, RXR, PPARγ, MARK and NF-kB signaling pathways. [ABSTRACT FROM AUTHOR]

Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum ( C. butyricum ) and 25-hydroxyvitamin D 3 (25-OH-D 3) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators' level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 109 CFU/kg (Cb), basal diet + C. butyricum at 109 CFU/kg and 25-OH-D 3 at 25 μg/kg (CbD), or basal diet + 25-OH-D 3 at 25 μg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut–brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers. [ABSTRACT FROM AUTHOR]

X-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (PHEX) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH) 2 D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia. Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions. Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few. In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy. Five Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH) 2 D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities. At entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH) 2 D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH) 2 D levels, and in TmP/GFR values (P < 0.05 - P < 0.0001). Serum ALP levels significantly declined (P < 0.05) to normal values. No changes of serum calcium and PTH levels (P NS) were found during burosumab. PROs significantly improved (P < 0.02 - P < 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH) 2 D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened with a significant reduction in quality of life. These consequences were not observed in the patient who continued burosumab treatment. Our data showed that conventional treatment improved only in part the signs and symptoms of XLH. Burosumab was well tolerated and was effective in improving phosphate metabolism, bone health, and PROs. All the benefits of burosumab were lost after its discontinuation. These results suggested that continuing burosumab is required to achieve and maintain the clinical benefits of the treatment during the transition to young adulthood in patients with XLH. [ABSTRACT FROM AUTHOR]

Background: Nonlinear association between serum 25-hydroxyvitamin D [25(OH)D] concentration and all-cause mortality has been widely reported for the general population, but this association has not been quantified for individuals with inflammatory bowel disease (IBD).Objectives: The aim was to explore the association between serum 25(OH)D and all-cause mortality in individuals with IBD.Methods: We identified 2690 females and 2532 males aged 40-69 y with diagnosed IBD at baseline in the UK Biobank. Serum 25(OH)D concentration was measured by direct competitive chemiluminescent immunoassay. The outcome was all-cause mortality, ascertained via the death registry. Cox proportional hazard regression was used to evaluate associations between serum 25(OH)D in quintiles and all-cause mortality among individuals with IBD [Crohn disease (CD; n = 1760) and ulcerative colitis (UC; n = 3462)]. Restricted cubic splines were used to investigate potential nonlinearity.Results: During the mean follow-up period of 11.9 y, 529 deaths (198 in CD and 331 in UC) were documented among 5222 individuals with IBD. Compared with the lowest quintile of serum 25(OH)D, HRs for the second to the highest quintiles were 0.82 (95% CI: 0.63, 1.06), 0.63 (95% CI: 0.47, 0.83), 0.64 (95% CI: 0.48, 0.85), and 0.74 (95% CI: 0.55, 0.99), respectively. Nonlinearity was detected in the dose-response association between serum 25(OH)D concentration and all-cause mortality (P-nonlinearity < 0.001), and 25(OH)D concentrations of 44-78 nmol/L were associated with a 50% lower risk of all-cause mortality (than 10 nmol/L). Subgroup analyses showed that the nonlinear association mostly applied to females (P-nonlinearity < 0.001 compared with 0.080 in males).Conclusions: We observed a nonlinear association, mostly applicable to females, between serum 25(OH)D concentrations and all-cause mortality among individuals with IBD. A 25(OH)D concentration range of 44-78 nmol/L can serve as a starting point for future research to confirm recommended 25(OH)D concentrations for individuals with IBD. [ABSTRACT FROM AUTHOR]

Background: The 2020-2025 Dietary Guidelines for Americans (2020 DGA) recommend 3 dietary patterns for Americans, including a Healthy Vegetarian Dietary Pattern (HVDP).Objectives: The objective of this study was to assess whether nutritionally adequate dairy-free and vegan adaptations to the HVDP can be modeled with foods already in the DGA.Methods: Using similar food pattern modeling procedures as the 2020 DGA, the nutrient composition of 2 alternative models-dairy-free and vegan-of the 1800-, 2000-, 2200-, and 2400-kcal/d HVDPs was assessed. The dairy food group was replaced with a dairy alternative group comprised of soy milk and soy yogurt fortified with calcium, vitamin A, and vitamin D. For the vegan model, eggs were replaced with equal proportions of vegetarian protein foods.Results: Dairy-free and vegan models required minimal changes to the HVDP. Cup-equivalents and/or ounce-equivalents of vegetables, fruits, grains, oils, and discretionary calories remained unchanged. Content of total fat, polyunsaturated fat, linoleic acid (18:2n-6), linolenic acid, iron, copper, vitamin D, riboflavin, vitamin B-12, and vitamin K increased in both models by ≥10% (all comparisons relative to the original HVDP). Choline increased ≥25% in the dairy-free models. Protein decreased 11% in both 1800-kcal/d models and 10% in both 2000-kcal/d models. Sodium, cholesterol, zinc, and phosphorus decreased across all energy levels in both models, and selenium decreased in the vegan model. Carbohydrate, fiber, saturated fat, EPA, DHA, calcium, magnesium, potassium, vitamin A, vitamin E, vitamin C, thiamin, folate, and vitamin B-6 changed ≤10%. Both models contained adequate nutrients to meet Dietary Reference Intakes (DRIs) for most age and sex groups for which 1800-, 2000-, 2200-, and 2400-kcal/d diets are appropriate. Zinc was the only nutrient below the DRI for males.Conclusions: The dairy-free and vegan HVDP models could help adults who do not consume dairy foods and/or other animal products to meet nutrition recommendations. [ABSTRACT FROM AUTHOR]

• Measuring liver stiffness by 2D SWE is a reliable addition to CFLD screening • Increased liver stiffness is associated with lower vitamin D levels • Increased liver stiffness is associated with lower FEV1% predicted • Increased liver stiffness is associated with abnormal glucose tolerance. Liver disease in Cystic Fibrosis (CFLD) is an early complication of CF. Evidence of CFLD is often subclinical and screening is recommended. Screening includes a biochemical work-up and an ultrasound investigation. Non-invasive methods measuring liver stiffness such as shear wave elastography could be beneficial. This study describes the use of 2D Shear Wave Elastography (2D SWE) in screening for CFLD in a clinical setting and explores its correlation to other indicators of CFLD. Furthermore, a relationship between liver stiffness and nutritional status, lung function and glucose tolerance was explored. A retrospective cohort study was performed at a pediatric CF center. Information was gathered from the patients' charts and the Swedish national CF registry. The patients included had been evaluated for the presence of CFLD by ultrasound and 2D SWE during 2018-2020. Demographic data as well as data concerning nutritional status, lung function and glucose tolerance were collected. Fifty-one subjects were included with a median age of 11 years. Four children who had biopsy confirmed liver cirrhosis had significantly increased liver stiffness. There was a statistically significant negative correlation between liver stiffness and vitamin D levels and FEV1% predicted respectively. Children with abnormal glucose tolerance had increased liver stiffness compared to their normal glucose tolerant counterparts. Measuring liver stiffness by 2D SWE is a reliable addition to CFLD screening with data comparable to the more conventional ultrasound investigation. Increased liver stiffness is associated with lower vitamin D levels, lower FEV1% predicted and abnormal glucose tolerance. [ABSTRACT FROM AUTHOR]

• Hypermagnesemia increases the risk of death 1.5-fold for patients with COVID-19. • Hyperphosphatemia increases the risk of death 2.4-fold for patients with COVID-19. • Decreased renal function does not seem to be a direct cause of those disturbances. Nonrespiratory manifestations of COVID-19 include endocrine disorders, among which are calcium-magnesium-phosphate homeostasis abnormalities, which seem to influence the disease severity and patient outcome. The aim of this study was to evaluate the prevalence and impact of calcium-magnesium-phosphate and vitamin D3 disorders on survival in patients hospitalized for COVID-19 depending on the severity of the disease and kidney function. The study was conducted between April 2020 and May 2021 at Central Clinical Hospital in Warsaw, Poland. A total of 146 patients who had tested concentration of at least one of the studied elements, estimated glomerular filtration ratio, creatinine levels, and blood saturation, and were diagnosed with COVID-19 disease were included in the analysis. We found that hypermagnesemia was common and associated with a 1.5-fold increased risk of death in the whole cohort. Hyperphosphatemia also increased the risk of death, exactly 2.4-fold. Furthermore, we found a statistically significant association between increased mortality in the whole cohort and hypovitaminosis D3 (P <0.05). Serum creatinine concentration and estimated glomerular filtration ratio significantly correlated with serum magnesium and phosphate levels. Hypermagnesemia, hyperphosphatemia, and hypovitaminosis D but not hypocalcemia influence the mortality of patients with COVID-19. These parameters should be monitored routinely in this group of patients, especially in those with decreased kidney function. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV.Objectives: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania.Methods: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression.Results: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05).Conclusions: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680. [ABSTRACT FROM AUTHOR]

• 25-hydroxy vitamin D levels reached the lowest point at two months of antituberculosis treatment. • Vitamin D may have a beneficial effect on the increase of CD4+ and CD8+ T cells. • Vitamin D had no effect on the time-to-sputum smear conversion. This study aimed to explore the effects of 25-hydroxy vitamin D (25[OH]D) on T lymphocyte subsets and sputum smear conversion during antituberculosis (TB) treatment. A total of 120 newly diagnosed patients with active pulmonary TB were collected and classified into vitamin D sufficiency group, vitamin D insufficiency group, and vitamin D deficiency group according to serum 25(OH)D levels. The clinical data and sputum smear conversion were collected and serum 25(OH)D and T lymphocyte subsets were also measured and compared. Our data showed that 25(OH)D levels reached the lowest point at two months of anti-TB treatment. Significant differences existed in the increase of CD4+ and CD8+ T cells on the basis of vitamin D levels. The vitamin D sufficiency group had a significantly higher increase of CD4+ T cells during six months of anti-TB treatment and CD8+ T cells after four months of anti-TB treatment than the other groups. Vitamin D had no effect on the time-to-sputum smear conversion (vitamin D sufficiency group: adjusted hazard ratio: 1.27, 95% confidence interval [CI]: 0.78–2.06); vitamin D insufficiency group: adjusted hazard ratio: 1.05, 95% CI: 0.63–1.75)]. Through null effects on sputum smear conversion, vitamin D may have a beneficial effect on the increase of CD4+ and CD8+ T cells during anti-TB treatment. [ABSTRACT FROM AUTHOR]

Evidence demonstrated that vitamin D insufficiency was involved in insulin resistance (IR) pathogenesis and associated with tuberculosis. However, the association of vitamin D and IR in patients with latent tuberculosis infection (LTBI) remains unclear. This study aims to evaluate the association between vitamin D and insulin resistance in US adults with LTBI. National Health and Nutrition Examination Survey (NHANES) participants ≥ 20 years during the years 2011–2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) or tuberculin skin testing (TST) were enrolled in present study. Participants with LTBI were divided into 2 groups: (1) vitamin D insufficiency group (n = 267), and (2) vitamin D sufficiency group (n = 437). Weighted analysis of all the population in the study showed that serum 25(OH)D inversely correlated with HOMA-IR (r = −0.14, P = 0.008). The vitamin D insufficiency group had higher fasting insulin (17.5 (1.38) vs. 15.29 (3.1), respectively, P = 0.0013) and HOMA-IR (5.0 (0.4) vs. 4.5 (1), respectively, P = 0.013) than the vitamin D sufficiency group. In adjusted analysis, vitamin D levels was independently associated with insulin resistance (adjusted OR [aOR] 2.74; 95% CI, 1.01–7.48, p = 0.0489). Taken together, our study suggested that serum 25(OH) D concentrations were inversely and independently associated with HOMA-IR in LTBI. [ABSTRACT FROM AUTHOR]

Background Higher vitamin D status has been suggested to have beneficial effects on the brain. Objectives To investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke. Methods We used prospective data from the UK Biobank (37–73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, center, and socioeconomic, lifestyle, sun behavior, and illness-related factors. Nonlinear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2399 and 3760 cases, respectively). Results Associations between 25(OH)D and total, gray matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P -nonlinear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10 nmol/L 25(OH)D; adjusted β: –6.1; 95% CI: –11.5, –7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25 nmol/L (compared with 50–75.9 nmol/L; adjusted HR: 1.79; 95% CI: 1.57, 2.04 and HR: 1.40; 95% CI: 1.26, 1.56, respectively). Nonlinear MR analyses confirmed the threshold effect of 25(OH)D on dementia, with the risk predicted to be 54% (95% CI: 1.21, 1.96) higher for participants at 25 nmol/L compared with 50 nmol/L. 25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses. Potential impact fraction suggests 17% (95% CI: 7.22, 30.58) of dementia could be prevented by increasing 25(OH)D to 50 nmol/L. Conclusions Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia but not on stroke risk. [ABSTRACT FROM AUTHOR]

Background Blood pressure in childhood tracks into later life. Vitamin D status in adults is associated with blood pressure, but the impact of vitamin D status in pregnancy and childhood on blood pressure still needs investigation. Objective We investigated whether fetal rather than current vitamin D status is associated with blood pressure in children. Methods In a prospective observational study within the population-based Odense Child Cohort (OCC), we examined serum 25-hydroxyvitamin D2+3 [s-25(OH)D] in early and late pregnancy, cord blood, and at 5 y age, and the associations with systolic and diastolic blood pressure (SBP/DBP) in the 5-y-old children (n = 1,677). Multiple regression models were adjusted for maternal country of origin, parity, smoking during pregnancy, 5-y height, and weight. Two-stage mixed effect modeling was performed, integrating all s-25(OH)D data from pregnancy and cord blood. Results The median (IQR) s-25(OH)D in early pregnancy, late pregnancy, the umbilical cord, and at 5 y was 65.5 (50.7–78.5), 78.5 (60.3– 95.8), 45.4 (31.1– 60.7), and 71.9 (54.6– 86.5) nmol/L, respectively. The mean ±SD 5-y SBP/DBP was 101.0/63.8 (7.1/5.9) mmHg. In adjusted analyses, a 10 nmol/L increase of s-25(OH)D in early pregnancy associated with a 0.3/0.2 mmHg lower SBP/DBP at 5 y (P < 0.05). Optimal s-25(OH)D (>75 nmol/L) in early pregnancy was associated with lower 5-y SBP and DBP, β (95% CI) −1.45 (−2.6, −0.3), and −0.97 (−1.9, −0.1), compared with reference s-25(OH)D (50-74.9 nmol/L). Two-stage analysis combining early pregnancy, late pregnancy, and cord s-25(OH)D data showed an inverse association with 5-y SBP and DBP for boys (P < 0.025) with significant sex-difference for DBP (Pinteraction = 0.004). No associations were found between s-25(OH)D and 5-y BP above the 90th percentile. Conclusion Early pregnancy s-25(OH)D concentrations, especially >75 nmol/L, were inversely associated with 5-y blood pressure in the offspring. A novel identified protective effect of optimal vitamin D levels in early pregnancy on offspring BP is suggested. [ABSTRACT FROM AUTHOR]