Vitamin D (Mood)

BACKGROUND: The possible anti-Mullerian hormone (AMH)-reduction impact of vitamin D supplementation has been assessed in a number of interventional investigations. The outcomes are still incongruous, however. This research sought to thoroughly examine the effects of vitamin D supplementation on AMH in order to have a better understanding of them. METHODS: Using standard keywords, the Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched to find all controlled trials examining the levels of AMH after vitamin D treatment. For the best result estimate, random-effects model analysis produced 95% confidence intervals and a pooled weighted mean difference. RESULTS: This article includes sixteen research with a total of 484 participants. Vitamin D supplementation did not significantly affect AMH levels in single-arm (pooled WMD of -0.22 ng/ml; 95% CI -0.68 to 0.23; P = 0.333) or randomized clinical trial (pooled WMD of -0.07 ng/ml; 95% CI -1.01 to 0.87; P = 0.887) studies, according to pooled results from the random-effects model. Vitamin D during the intervention < 8 weeks and in individuals with low baseline levels of vitamin D serum induces a higher drop in AMH levels, according to the findings of subgroup analysis. CONCLUSIONS: Despite the inconclusive and conflicting evidence on the relationship between vitamin D supplementation and AMH levels in women, it is evident that vitamin D may play a role in mitigating the negative impact of AMH on follicular development and granulosa cell differentiation. CLINICAL TRIAL NUMBER: Not applicable. © 2025. The Author(s).

The health implications of lacto-ovo-vegetarian and vegan diets in childhood remain debated. This meta-analysis compares lacto-ovo-vegetarian and vegan diets with omnivorous diets across a wide spectrum of nutrients and health outcomes among children <18 years worldwide without chronic disease. Searches in MEDLINE, Embase, Scopus, and Web of Science up to March 2025 identified 59 studies including 48,626 participants (7,280 lacto-ovo-vegetarians, 1289 vegans, and 40,059 omnivores). Lacto-ovo-vegetarian children consumed less energy, protein, fat, vitamin B12, vitamin D, and zinc, but more fiber, iron, folate, vitamin C, and magnesium. Vegans showed similar patterns, with particularly low calcium intake. Growth and body composition indicated a leaner phenotype: lacto-ovo-vegetarians had lower height, weight, BMI z-scores, fat mass, and bone mineral content, while vegans had shorter stature and lower BMI z-scores. Biomarkers showed lower ferritin and 25(OH)D in lacto-ovo-vegetarians, and lower hemoglobin and ferritin in vegans. Although group averages for most nutrients and biomarkers remained within pediatric reference ranges, increased odds of iron deficiency and anemia were observed in lacto-ovo-vegetarians, and vitamin B12 deficiency in vegans. Both groups showed lower total and LDL cholesterol. These findings underscore the need for careful dietary planning and supplementation in lacto-ovo-vegetarian and vegan children.

BACKGROUND: Vitamin D have been proposed as a supplement to improve cardiometabolic risk factors in obese/overweight children and adolescents. However, findings evidence remains inconsistent. This meta-analysis aimed to assess the effects of vitamin D supplementation on cardiometabolic risk factors in obese/overweight children and adolescents. METHODS: A systematic review of PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar up to April 2025 was searched. This study aimed to evaluate the effect of vitamin D supplementation on cardiometabolic factors including anthropometric indices, glycemic state and lipid profile. Data were pooled using a random-effects model to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Nine studies with 440 participants were included. The meta-analysis revealed that vitamin D supplementation no significantly improved BMI, BMI-Z, FBS, insulin, HOMA-IR, QUICKI, TG, TC, and LDL-C. However, it was accompanied with a significant reduction in HDL-C level. Subgroup-analysis showed that vitamin D2 showed a greater reduction in HOMA-IR compared to vitamin D3, though the effect was statistically significant (WMD = -0.51, 95% CI: -1.00 to -0.03; p = 0.038). CONCLUSIONS: The current meta-analysis revealed vitamin D supplementation has no favorable effect on cardiometabolic risk factors. More high-quality and large-scale trials are needed to provide more robust evidence. © 2025. The Author(s).

BACKGROUND: Immunomodulation and respiratory health have a critical role in the offspring well-being. Maternal status of vitamin D during pregnancy seems to have immunomodulatory and respiratory protective effects in children. However, evidence regarding respiratory and allergy-related outcomes remains conflicting. Therefore, this study aimed to synthesize the available data in this regard to provide a firm direction. METHODS: Comprehensive searches were made in the databases of PubMed, Scopus, the Web of Science, and the Cochrane Library until August 2025. We included randomized controlled trials (RCTs) to evaluate the effects of maternal intake of vitamin D during pregnancy on outcomes in children with respiratory and allergy conditions. Also, the quality of evidence was evaluated using GRADE method and the Cochrane risk-of-bias tool was used to evaluate study quality. RESULTS: Seven RCTs were included. Prenatal supplementation of vitamin D did not affect respiratory outcomes in the children who followed: RTI (RR: 1.04; 95% CI: 0.99, 1.09; P = 0.122, I2 = 0.0%), asthma (RR: 0.94; 95% CI: 0.67, 1.31; P = 0.701, I2 = 64.9%), and wheezing (RR: 0.82; 95% CI: 0.62, 1.09; P = 0.176, I2 = 0.0%). Similarly, vitamin D supplementation in pregnant women was associated with non-significant effects on eczema (RR: 0.95; 95% CI: 0.83, 1.10; P = 0.524, I2 = 0.0%), allergic condition (RR: 0.95; 95% CI: 0.85, 1.06; P = 0.324, I2 = 0.0%), and immunoglobulin E (IgE) (RR: 0.94; 95% CI: 0.73, 1.21; P = 0.639, I2 = 52.6%) in children. CONCLUSION: Overall, the vitamin D supplementation during pregnancy has no significant effect on respiratory and allergy-related outcomes in children. © 2025. The Author(s).

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG), contributing to increased morbidity, prolonged hospitalization, and elevated healthcare costs. Emerging evidence suggests that vitamin D (Vit. D), via its anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system (RAAS), may have a cardioprotective role. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy of preoperative Vit. D supplementation in reducing the incidence of POAF among CABG patients, with a focus on populations with Vit. D deficiency and insufficiency. METHODS: Our study was conducted in accordance with the PRISMA 2020 Guidelines. The electronic databases PubMed, Cochrane Library and Google Scholar were searched from 2014 to 2024. Randomized controlled trials and retrospective observational studies involving adult subjects, evaluating Vit. D deficient and/or insufficient patients who have undergone CABG and received Vit. D supplementation in addition to standard care, compared to patients receiving standard care alone or with placebo, and reporting incidence of new-onset POAF were included. Statistical analysis was performed using RevMan v5.4 software, utilizing a random effects model with heterogeneity assessed using the I2 statistic. RESULTS: A total of four randomized controlled trials were included in our study, evaluating a sample size of 694 (Vitamin D group- 342, Control group- 352; mean age- 61.8 years, 42.6% females). Our meta-analysis revealed that preoperative Vit. D supplementation significantly reduced the incidence of POAF in post-CABG patients with sub-optimal Vit. D levels (RR = 0.55, 95% CI: 0.40-0.76, p = 0.0003, I2 = 1%). However, no significant effect was noted in the Vit. D insufficient population. Supplementation did not significantly affect length of hospital stay (MD = -0.62, 95% CI: -0.74-0.50, p = 0.28) or duration of intubation (MD = 0.00, 95% CI: -0.26-0.26, p = 0.99). CONCLUSION: Preoperative Vit. D supplementation appears beneficial in reducing POAF risk in deficient CABG patients, but not in insufficient populations. These findings sup

Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that can greatly affect quality of life in middle-aged and elderly individuals. Nutritional supplements are increasingly used for KOA due to their low risk, but direct comparative evidence on their efficacy and safety remains scarce. This study aimed to systematically compare the effectiveness and safety of seven common nutritional supplements for KOA. Methods: A systematic review and network meta-analysis were conducted following PRISMA guidelines. Embase, PubMed, and the Cochrane Library were searched through December 2024 for randomized controlled trials (RCTs) evaluating use of eggshell membrane, vitamin D, Boswellia, curcumin, ginger, krill oil, or collagen, versus placebo, in adults with KOA. Primary outcomes included changes in scores for WOMAC pain, stiffness and function, and pain visual analog scale (VAS). Adverse events were also assessed. Bayesian network meta-analyses estimated ranking probabilities for each intervention. Results: In total, 39 RCTs (42 studies; 4599 patients) were included. Compared with placebo, Boswellia showed significant improvements in WOMAC pain (mean difference [MD] = 10.58, 95% CI: 6.45 to 14.78, p < 0.05), stiffness (MD = 9.47, 95% CI: 6.39 254 to 12.74, p < 0.05), function (MD = 14.00, 95% CI: 7.74 to 20.21, p < 0.05), and VAS pain (MD = 17.26, 95% CI: 8.06 to 26.52, p < 0.05). Curcumin, collagen, ginger, and krill oil also demonstrated benefits in some outcomes. No supplement was associated with increased adverse events compared to placebo. Bayesian rankings indicated Boswellia had the highest probability of being most effective for pain and stiffness, with krill oil and curcumin showing potential for function improvement. Conclusions: Nutritional supplements, particularly Boswellia, appear to be effective and well-tolerated for improving KOA symptoms and function. These results suggest that certain supplements may be useful as part of non-pharmacological KOA management. However, further large-scale, well-designed randomized controlled trials (RCTs) are needed to confirm these findings, particularly those that include more standardized dosages

OBJECTIVE: This study aims to investigate the effects of vitamin D3 supplementation on androgen levels and semen parameters in infertile men. METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Cochrane Library, Scopus and Embase, to identify studies investigating the effects of vitamin D3 supplementation on androgen levels and semen parameters in infertile males. Data pertaining to changes in testosterone, sex hormone-binding globulin (SHBG), total sperm count and percentage of motile sperm before and after intervention were extracted and analysed. RESULTS: Six studies, involving 945 subjects, were included in the quantitative analysis. With regard to testosterone levels, vitamin D3 supplementation was found to increase testosterone, although this change was not statistically significant (standard mean difference (SMD) = 0.07, 95% confidence interval (CI): -0.11, 0.25). Similarly, an increase in SHBG levels was observed after vitamin D3 supplementation, but the change was not statistically significant (SMD = 0.42, 95% CI: -0.38, 1.22). By contrast, an increase in total sperm count was observed (SMD = 1.04, 95% CI: 0.11, 2.19). Additionally, vitamin D3 supplementation significantly increased the percentage of motile sperm (SMD = 0.82, 95% CI: 0.00, 1.64). CONCLUSIONS: In infertile men, vitamin D3 supplementation does not significantly affect androgen levels. Nevertheless, it may contribute to improvements in total sperm count and the percentage of motile sperm, potentially enhancing reproductive function. © 2025 The Author(s).

BACKGROUND: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs. METHODS: Updated systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Subgroup analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, dosing regimen, or age. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov between May 1, 2020 (end-date of search of our previous meta-analysis) and April 30, 2024. No language restrictions were imposed. Double-blind RCTs supplementing vitamin D for any duration, with placebo or lower-dose vitamin D control, were eligible if approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. The study was registered with PROSPERO (no. CRD42024527191). FINDINGS: We identified six new RCTs (19 337 participants). Data were obtained for 16 085 (83·2%) participants in three new RCTs and combined with data from 48 488 participants in 43 RCTs identified in our previous meta-analysis. For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88-1·00], p=0·057; 40 studies; 61 589 participants; I2=26·4%). Pre-specified subgroup analysis did not reveal evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0·96 [95% CI 0·90-1·04]; 38 studies; I2=0·0%).

BACKGROUND: Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity. OBJECTIVE: We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases. METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis. RESULTS: 18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions. CONCLUSION: We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.

PURPOSE: The aim of the present systematic review was to corroborate existing evidence on how serum25(OH)D levels affect obstructive sleep apnea syndrome (OSAS) severity in the absence of comorbidities. METHODS: From inception to May 2024, PubMed, Scopus, and Embase electronic databases were systematically screened to identify randomized controlled trials (RCTs), quasi-RCTs, prospective, and retrospective studies. A strict search protocol was applied following the application of PROSPERO, under the registration number CRD42023468744. The formulated question based on PICO process was: "how do serum25(OH)D levels affect the severity of OSAS or result in enhanced sleep function?". Collected results were finally reviewed for meta-analysis and quality assessment according to the ROBINS-I tool. RESULTS: Data from 24 studies were pooled and divided into 15 case-control studies and 9 cross-sectional studies. All studies involved a total of 2640 OSAS subjects and 933 healthy subjects. All studies underwent qualitative analysis whereas only 20 were collected for meta-analysis. Mild OSAS showed 25(OH)D levels non-statistically significant (P = 0.12) than the healthy patients whereas moderate OSAS (P = 0.004) and severe OSAS (P < 0.001) differed significantly from control groups. Meta-regression suggested that OSAS severity correlated inversely to the deficiency of 25(OH)D serum levels. Qualitative assessment and Egger's test revealed an elevated risk of bias but low presence of publication bias, respectively. CONCLUSION: Serum levels of 25(OH)D were observed to be inversely proportional to OSAS severity in patients without coexisting morbidities. 25(OH)D levels in mild OSAS patients were not significantly different from non-OSAS patients, suggesting vitamin supplementation to improve potential sleep disorders. © 2024. The Author(s).

BACKGROUND: Initial studies suggest vitamin D (VD) supplementation may aid in treating major depressive disorder, but rigorous randomised controlled trials are needed. TRIAL DESIGN: DepFuD trial was a six-month, double-blinded, parallel-group, randomised controlled superiority design trial with a 1:1 allocation ratio. Outpatients with mild to severe depression episode, aged 18-65 years, were included. METHODS: The primary aim was to compare the effects of low-dose versus high-dose VD as adjunctive to participants' existing depression treatments, hypothesising that the high-dose group would show greater symptom reduction over six months. Participants were randomised to receive either 100 μg (4000 IU) or 10 μg (400 IU) of VD (cholecalciferol) daily for six months. The primary outcome was measured by between-group differential change over six months in the Montgomery-Åsberg Depression Rating Scale (MADRS) score (range: 0-60). Data was collected in Finland between November 2015 and December 2020. RESULTS: A total of 281 participants were randomised: 142 in the low-dose and 139 in the high-dose group. At baseline, 46% of the participants in low-dose and 42% in high-dose group had VD deficiency (<50 nmol/l). Primary outcome data were available for 234 participants (116 in low-dose and 118 in high-dose). The standardised adjusted MADRS mean difference was small and non-significant (Cohen's d = -0.09; 95% CI -0.32 to 0.14). CONCLUSIONS: The six-month trial demonstrated no superior effect of the higher VD supplementation compared to the lower VD supplementation on depressive symptoms. REGISTRATION: ClinicalTrials.gov: NCT02521012. DepFuD was supported by Finnish State Research Funding (VTR).

Vitamin D plays a key role in immune modulation, cell proliferation, and hormone regulation. Dysregulated testosterone may contribute to breast cancer progression. We investigated whether long-term vitamin D supplementation affects serum testosterone levels in breast cancer survivors. Complete data at baseline, 12, and 24 months were derived from 253 women with early-stage breast cancer participating in the DEDiCa trial and randomized to receive either a high-dose vitamin D to maintain serum 25(OH)D at 60 ng/mL (group A) or a standard dose to maintain serum levels at 30 ng/mL (group B). Serum 25(OH)D levels significantly increased in both groups (p < 0.001). No significant changes in testosterone concentrations were observed between treatment groups over the 24 month treatment period (A: 0.125 to 0.140 ng/mL; B: 0.162 to 0.193 ng/mL; p = 0.682). Baseline serum testosterone levels emerged as the most significant predictor of testosterone trajectories, possibly modulated by hormone-suppressive therapy. These results are reassuring that vitamin D supplementation did not adversely affect testosterone levels in this population of breast cancer survivors and may partially concur with a healthy lifestyle to equilibrate testosterone levels.

BACKGROUND: Prediabetes is a public health concern, and its prevalence is growing around the world. Providing an effective strategy to prevent prediabetes progression and, consequently, type-2 diabetes mellitus (T2DM) could be useful for global health. The present study aimed to investigate the impact of vitamin D supplementation on metabolic factors, serum omentin-1 levels, and anthropometric indices in women with prediabetes. METHODS: This randomized controlled trial (RCT) study was carried out on women with prediabetes aged 18-65 years. The women were allocated to the intervention (n = 48) or placebo (n = 48) groups to receive vitamin D (50000 IU) or a placebo every two weeks for 12 weeks, respectively. Fasting blood samples, anthropometric measurements, and information about the dietary intake and physical activity of the participants were collected at the beginning and after the intervention. Data analyses were done using IBM SPSS Statistics software. RESULTS: Vitamin D intervention significantly enhanced 25-hydroxyvitamin D (MD (CI 95%): 11.610 ng/ml (8.264, 14.956)), insulin (MD (CI 95%): 0.413 µIU/mL (0.321, 0.505)), Homeostatic Model Assessment of Insulin Resistance (MD (CI 95%): 0.411 (0.319, 0.502)), and Homeostatic Model Assessment of Insulin Resistance-β cell function (MD (CI 95%): 29.505% (22.114, 36.986)) levels compared to the placebo at the end of trial (all, p < 0.05). Moreover, a significant reduction in QUICKI was observed after the intervention (MD (CI 95%): -0.062 (-0.076, -0.048)). Changes in fasting blood sugar (FBS), lipid profiles, omentin-1 levels, and anthropometric indices were not significant between the groups after the intervention. CONCLUSION: The findings revealed that vitamin D administration improved insulin secretion but failed to affect FBS, lipid profiles, anthropometric indices, and body composition in women with prediabetes. Due to inconsistent results, more well-designed RCTs are required to clarify the effects of vitamin D supplementation on these patients. © 2025. The Author(s).

BACKGROUND: Infants born to pregnant women living with HIV (WLHIV) are at greater risk for morbidity and mortality and may also have poorer developmental outcomes as compared with infants who are not exposed to HIV. Nutrition interventions in pregnancy may affect developmental outcomes. OBJECTIVES: This study evaluated the effect of maternal vitamin D supplementation on infant development outcomes. DESIGN: We conducted a secondary analysis of a randomised, triple-blind, placebo-controlled trial of maternal vitamin D supplementation from June 2015 to October 2019. SETTING: Antenatal care clinics in Dar es Salaam, Tanzania. PARTICIPANTS: Pregnant WLHIV and their offspring. INTERVENTIONS: Daily 3000 IU vitamin D3 or placebo supplements taken during pregnancy and lactation. OUTCOME MEASURES: Infants were assessed for cognitive, language and motor development at 1 year of age with the Caregiver Reported Early Development Instruments (CREDI). RESULTS: A total of 2167 infants were eligible, and 1312 of them completed CREDI assessments at 1 year of age. Vitamin D supplementation had no effect on overall CREDI z-scores (standardised mean difference (SMD) 0.03, 95% CI -0.09, 0.15, p value 0.66). There was also no evidence of a difference between vitamin D and placebo groups in language (SMD 0.06, 95% CI -0.08, 0.21, p value 0.40), motor (SMD 0.02, 95% CI -0.09, 0.14, p value 0.69) or cognitive domain z-scores (SMD 0.05, 95% CI -0.08, 0.17, p 0.48). CONCLUSIONS: Maternal vitamin D supplementation during pregnancy and lactation did not affect infant development outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02305927. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

BACKGROUND AND AIMS: Vitamins K2 and D3 may improve cardiovascular health by modulating inflammation and vascular calcification. Inflammation contributes to atherosclerosis and can be assessed through imaging and systemic biomarkers. This study investigated whether vitamin K2 and D3 supplementation reduces inflammation in epicardial adipose tissue (EAT), including pericoronary adipose tissue (PCAT), and systemic inflammation in elderly men at cardiovascular risk. METHODS: In the Aortic Valve DECalcification (AVADEC) trial, 388 men aged 65-74 received daily vitamin K2 (720 μg) and D3 (25 μg) or placebo for 24 months. EAT inflammation was assessed using non-contrast CT [EAT volume and attenuation] and contrast-enhanced CT [PCAT attenuation]. Systemic inflammation was evaluated via hs-CRP, IL-6, TNF-α, Fetuin-A, and osteopontin (OPN). Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), the inactive form of MGP, served as a proxy for vitamin K2 status. RESULTS: After 24 months, EAT volume increased in the placebo group (Δ5.66 cm3,95% CI 1.35; 9.98) and non-significantly in the vitamin group (Δ3.44 cm3, 95% CI -0.44; 7.33), with an intergroup difference of -2.22 cm3 (95% CI -8.01; 3.57). EAT attenuation declined similarly (intergroup difference: 0.32 HU, 95% CI -0.23; 0.87). PCAT attenuation remained unchanged. No significant changes were seen in systemic markers, though OPN increased modestly in the vitamin group (Δ25.72 pg/mL, 95% CI 2.40; 49.05). dp-ucMGP decreased significantly with supplementation (intergroup difference: 255.31 pmol/L, 95% CI -289.56; -221.05). CONCLUSIONS: Despite reduction in dp-ucMGP, high-dose vitamin K2 and D3 supplementation did not affect EAT, PCAT or systemic inflammation over 24 months. Alternative strategies may be needed to target inflammatory pathways in cardiovascular disease prevention.

BACKGROUND: Previous studies have shown that individuals with high body mass index typically require high doses of vitamin D supplementation to correct vitamin D deficiency. However, it is unclear which specific body composition is the determining factor affecting the bioavailability of vitamin D after supplementation. The aim of this study was to determine which body components affect the bioavailability of vitamin D. METHODS: In order to ensure the compliance of the study subjects and avoid the impact of sunlight on vitamin D3 levels, the subjects received multiple intramuscular (i.m.) injections of vitamin D2 until their serum levels of 25-hydroxyvitamin D [25(OH)D] were above 30 ng/mL. All subjects received two i.m. injections of 600,000 IU vitamin D2, and dose adjustments were made every 6 weeks based on whether serum 25(OH)D levels were sufficient. The levels of serum 25(OH)D2 and 25(OH)D3 were determined by liquid chromatography tandem mass spectrometry. The body composition was measured using dual-energy X-ray absorptiometry and corrected using body fat mass index (FMI). Based on the 100% difference in 25(OH)D levels before and after vitamin D supplementation, the sample size was calculated, and 20 subjects would provide over 95% of the power to show the difference. RESULTS: After two dose adjustment, the serum 25(OH)D levels of all subjects were above 30 ng/mL. The subjects were divided into ≤ 1,200,000 IU vitamin D2 (n=10) and ≥ 2,400,000 IU vitamin D2 (n=15) based on the i.m. dose of vitamin D2. The results showed that compared with subjects receiving ≤ 1,200,000 IU vitamin D2, subjects receiving ≥ 2,400,000 IU of vitamin D2 had a higher total body fat mass index (FMI), particularly with higher trunk fat content and high visceral adipose tissue mass. However, the dosage of vitamin D2 supplementation was not related to BMI and lean mass content. CONCLUSION: The body fat content, especially trunk fat content, is the main body component that affects the bioavailability of vitamin D in healthy adults. Healthy adults with high trunk fat content have low bioavailability of vitamin D and require relatively high dose of vitamin D to achieve sufficient levels.

BACKGROUND: Angiogenesis is essential for placental growth and development. Improper placental vascular development can reduce blood flow to the fetus and increase the risk of adverse pregnancy and birth outcomes. The objectives of this study were to examine the effect of prenatal vitamin D supplementation on placental angiogenic factors and terminal villi, and associations between angiogenic factors, terminal villi and birth outcomes. METHODS: This is a secondary analysis using data and specimens from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (n = 1298). Participants were enrolled at 17-24 weeks gestation and randomized to receive (IU/week): placebo, 4200, 16,800 or 28,000 vitamin D3 supplement until birth. Newborns and placentas were measured at birth. We examined a subset of randomly selected placentas (n = 80). Tissue sections were evaluated for vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) using immunofluorescence. We measured intensity and percent area of expression for angiogenic factors, and total number and surface area of terminal villi. Vitamin D treatment effect was estimated using ANOVA. Regression models were used to assess associations of markers of placental angiogenesis with birth outcomes. Interactions by infant sex were examined. RESULTS: The overall mean (SD) percent area of expression was 17.0 (4.0) for VEGF-A and 15.0 (1.9) for PlGF. The mean (SD) number of terminal villi was 39 (15) per 12 in2, and surface area was 0.096 (0.040) in2. Vitamin D treatment groups were similar to placebo for all outcomes. No associations were observed between angiogenic factors or terminal villi placental and birth outcomes. CONCLUSIONS: Vitamin D supplementation starting from mid-pregnancy until birth did not affect expression of two key angiogenic factors or terminal villi in the placenta. Placental angiogenic factors or terminal villi did not have an association with birth outcomes. These results do not support a role of maternal vitamin D starting mid-pregnancy in impacting placental development. © 2025. The Author(s).

BACKGROUND: Previous evidence suggests that vitamin D may help with neurodegeneration in multiple sclerosis (MS). Considering this, the study aims to investigate whether higher-dose vitamin D supplementation in individuals with MS can lead to reduced atrophy, as measured by optical coherence tomography (OCT) and MRI structural outcomes. This objective builds upon the established notion of thalamic and brainstem atrophy as reliable markers of disease progression and the potential association between adequate vitamin D levels and improved visual outcomes in MS patients. OBJECTIVE: To assess the impact of vitamin D as a neuroprotective intervention on visual and imaging biomarkers. METHOD: Participants enrolled in the EVIDIMS trial underwent an assessment to investigate the impact of high and low-dose vitamin D supplementation at 12 and 18 months using a nonparametric multiple contrast test procedure (MCTP). The primary outcomes included four MRI-radiological measures: change in the mean upper cervical cord area (MUCCA) and hippocampal, thalamic and brainstem volumes, and the visual system outcomes included assessment of the peripapillary retinal nerve fiber layer (pRNFL) thickness and macular combined ganglion cell and inner plexiform layer (GCIPL), and inner nuclear layer (INL). RESULTS: MCTPs indicated that there were no statistically significant differences in the volumes of the thalamus, hippocampus, and brainstem, as well as in MUCCA, between the low and high-dose supplementation groups. Moreover, MTCPs only revealed a different thinning pattern in the INL at 18 months between the low versus high-dose treatment arm attributable to patients who suffered optic neuritis (NO), with no significant differences in neither pRNFL nor GCIPL. CONCLUSION: Vitamin D supplementation did not affect MS imaging parameters. However, future studies should thoroughly evaluate patient histories of attacks and endogenous vitamin D levels before inclusion in dose-related investigations.

Inulin-type fructans did not significantly improve serum levels of calcium, magnesium, vitamin D, or bone turnover markers in people with type 2 diabetes (T2D). However, interactions between gut microbiota and bone health were suggested, indicating the need for further research in this population. BACKGROUND: Evidence suggests that a healthy gut microbiome benefits bone health, especially in immunocompromised populations like the elderly and people with T2D. OBJECTIVE: We investigated the effect of prebiotics (inulin-type fructans) on serum concentrations of calcium, magnesium, 25(OH) vitamin D, and the bone turnover markers N-terminal propeptide of type 1 collagen (P1NP), and C-terminal telopeptide of type 1 collagen (CTX-1) in people with T2D. DESIGN: Participants (29) were treated for 6 weeks with 16 g inulin-type fructans and 16 g control supplement (maltodextrin) in randomised and double-blind crossover design, with a 4-week washout between treatments. RESULTS: Compared to the control, inulin-type fructans did not significantly affect serum concentrations (mean ± SEM) of calcium (0.05 ± 0.02 mmol/L vs. 0.02 ± 0.03 mmol/L, p = 0.324), magnesium (0.02 ± 0.01 mmol/L vs. 0.00 ± 0.01 mmol/L, p = 0.352), 25(OH) vitamin D (-3.60 ± 1.94 nmol/L vs. -2.00 ± 1.97 nmol/L, P = 0.564), P1NP (0.81 ± 0.95 ug/L vs. -0.89 ± 0.97 ug/L, p = 0.210), or CTX-1 (-0.01 ± 0.01 ug/L vs. 0.00 ± 0.01 ug/L, p = 0.438). However, post hoc analyses of correlations between changes support that cross-talk between the human host and gut microbiota may influence bone health in this population. CONCLUSION: This study does not support that inulin-type fructans may improve serum levels of calcium, magnesium, or 25(OH) vitamin D, nor that they affect bone turnover markers in people with T2D over 6 weeks. Interactions between microbiota and bone health in this population warrants further investigations. The trial is registered at clinicaltrials.gov (NCT02569684). © 2025. The Author(s).

BACKGROUND: Adverse pregnancy outcomes (APOs) affect ∼20% of pregnancies and pose significant health risks for mothers and fetuses. Identifying risk factors is crucial for developing prevention strategies. OBJECTIVES: This study examined the association between vitamin D status, measured by 25-hydroxyvitamin D (25(OH)D) concentrations, and APO risk, and whether this association varies by pregnancy timing and body mass index (BMI) (kg/m2). METHODS: In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial, we used multivariable logistic regression models to examine the association between 25(OH)D concentrations in early (10-18 wk) and late (32-38 wk) pregnancy, and development of a composite APO outcome, including pre-eclampsia, gestational hypertension, gestational diabetes, intrauterine growth restriction, and preterm birth. RESULTS: Among 816 participants in the intention-to-treat analysis, 283 composite APO events occurred. Vitamin D supplementation did not significantly reduce APO risk. Participants who developed APOs had lower baseline 25(OH)D concentrations than those who did not (mean ± SD: 21.72 ± 10.04 vs. 23.47 ± 10.29 ng/mL; mean difference ± SE: 1.75 ± 0.78; P = 0.026). A significant interaction was observed between baseline 25(OH)D and BMI (interaction term, odds ratio [OR]: 1.04; 95% confidence interval [95% CI]: 1.00, 1.08; P = 0.041). Among participants with BMI < 25 (reference group), each unit increase in baseline 25(OH)D (ng/mL) was associated with 4% lower odds of developing an APO (OR: 0.96; 95% CI: 0.93, 0.99; P = 0.013), whereas no association was observed among participants with BMI ≥ 25 kg/m2 (OR: 1.00; 95% CI: 0.98, 1.02; P = 0.83). Third-trimester 25(OH)D concentrations did not differ between participants with and without APOs. CONCLUSIONS: Although vitamin D supplementation did not reduce APO risk, higher early pregnancy 25(OH)D concentrations were associated with lower odds of APOs in participants with BMI < 25. These findings highlight the potential importance of higher early pregnancy 25(OH)D concentrations, particularly among those with normal BMI, in reducing APO risk. TRIAL REGISTRATION: This study is an ancil

Vitamin D deficiency frequently occurs in older people, especially in individuals with comorbidity and polypharmacotherapy. In this group, low vitamin D plasma concentration is related to osteoporosis, osteomalacia, sarcopenia and myalgia. Vitamin D levels in humans is an effect of the joint interaction of all vitamin D metabolic pathways. Therefore, all factors interfering with individual metabolic stages may affect 25-hydroxyvitamin D plasma concentration. The known factors affecting vitamin D metabolism interfere with cytochrome CYP3A4 activity. There is another group of factors that impairs intestinal vitamin D absorption. The phenomenon of drugs and vitamin D interactions is observed first and foremost in patients with comorbidity. This is a typical situation, where the absence of "hard evidence" is not synonymous with the possible lack of adverse effects. Osteoporosis and sarcopenia (generalized and progressive decrease of skeletal muscle mass and strength) are some of the musculoskeletal consequences of hypovitaminosis D. These consequences are related to an increased risk of adverse outcomes, including bone fractures, physical disabilities, and a lower quality of life. This can lead not only to an increased risk of falls and fractures but is also one of the main causes of frailty syndrome in the aging population. Generally, Vitamin D plasma concentration is significantly lower in subjects with osteoporosis and muscle deterioration. In some observational and uncontrolled treatment studies, vitamin D supplementation resulted in a reduction of proximal myopathy and muscle pain. The most conclusive results were found in subjects with severe vitamin D deficiency and in patients avoiding large doses of vitamin D. However, the role of vitamin D in muscle pathologies is not clear and research has provided conflicting results. This is plausibly due to the heterogeneity of the subjects, vitamin D doses and environmental factors. This report presents data on some problems with vitamin D deficiency in the elderly population and the management of vitamin D deficiency D in successful or unsuccessful aging.

Loop diuretics (LD) may affect bone health by inhibiting renal calcium reuptake. However, whether vitamin D status and dietary calcium intake modify the association between LD and bone outcome is unclear. Therefore, this study aimed to evaluate whether vitamin D level or calcium intake modify the association between LD and various indices of bone health including bone mineral density (BMD) and Trabecular Bone Score (TBS). From The Rotterdam Study, a prospective population-based cohort study, we used data from 6990 participants aged > 45 year with a DXA scan (2002-2008), 6908 participants with femoral neck (FN)-BMD, 6677 participants with lumbar spine (LS)-BMD and 6476 participants with LS-TBS measurements. Use of LD was available from pharmacy dispensing records. Vitamin D (25(OH)D) level was measured in serum, and dietary calcium intake was measured with a validated food frequency questionnaire. Almost eight percent of the participants used LD. The association between LD (past-users compared to never-users) and LS-TBS was significantly different by 25(OH)D concentrations (P for interaction = 0.04). A significantly lower LS-TBS among LD past-users was observed for 25(OH)D ≥ 50 nmol/l compared to ≤ 20 and 20-50 nmol/l (β = - 0.036, 95% CI - 0.060; - 0.013 vs. β = - 0.012, 95% CI - 0.036; 0.013 and β = - 0.031, 95% CI - 0.096; 0.034, respectively). However, no other significant effect modification by 25(OH)D and dietary calcium intake was found in the associations between LD use and bone health outcomes (P-interaction > 0.13). This study suggests that the association between LD use and indices of bone health is not consistently modified by vitamin D or dietary calcium intake.

Network coupled cells, such as astrocytes, regulate their cellular homeostasis via Ca2+ signals spread between the cells through gap junctions. Intracellular Ca2+ release is controlled by different signaling pathways that can be stimulated by ATP, glutamate and serotonin (5-HT). Based on our findings, all these pathways are influenced by inflammatory agents and must be restored to fully recover the Ca2+ signaling network. An ultralow concentration of the local anesthetic agent bupivacaine reduced 5-HT-evoked intracellular Ca2+ release, and an ultralow concentration of the phosphodiesterase-5 inhibitor sildenafil in combination with vitamin D3 reduced ATP-evoked intracellular Ca2+ release. Combinations of these three substances downregulated 5-HT-, glutamate- and ATP-evoked intracellular Ca2+ release to a more normal Ca2+ signaling state. Furthermore, inflammatory Toll-like receptor 4 expression decreased with a combination of these three substances. Substance P receptor neurokinin (NK)-1 expression was reduced by ultralow concentrations of bupivacaine. Here, bupivacaine and sildenafil (at extremely low concentrations) combined with vitamin D3 have potential anti-inflammatory properties. According to the present study, drug combinations at the right concentrations, especially extremely low concentrations of bupivacaine and sildenafil, affect different cellular biochemical mechanisms and represent a potential solution for downregulating inflammatory parameters, thereby restoring cells or networks to normal physiological homeostasis.

BACKGROUND: Although modulation of the vitamin D receptor (VDR) and endothelin-A receptor (ETAR) has previously been reported to offer renoprotection against cisplatin-induced nephrotoxicity, the possible interaction between the ET-1 and vitamin D pathways remains obscure. Therefore, the present study addressed the possible interaction between these signalling pathways using BQ-123 (a selective ETAR blocker) and alfacalcidol (a vitamin D3 analogue) separately or in combination. METHODS: Male Sprague-Dawley rats were divided into the following groups: control (DMSO orally), cisplatin (single dose of 6 mg/kg ip; nephrotoxicity model), cisplatin + BQ-123 (1 mg/kg BQ-123 ip 1 h before and 1 day after cisplatin), cisplatin + alfacalcidol (50 ng/kg alfacalcidol orally 5 days before and 14 days after cisplatin), and cisplatin + BQ-123+alfacalcidol. Nephrotoxicity was evaluated 96 h and 14 days following cisplatin administration. RESULTS: Both BQ-123 and alfacalcidol counteracted cisplatin-induced nephrotoxic changes. Specifically, they reduced serum creatinine and urea levels; renal tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), and phosphorylated nuclear factor-kappa B (pNF-κB) content; and caspase-3 activity. They downregulated ET-1 and ETAR expression and ameliorated cisplatin-induced acute tubular necrosis. In addition, the treatments have increased VDR and endothelin-B receptor (ETBR) expression; however, BQ-123 did not affect ETBR. The effect of the combination regimen surpassed that of each drug alone. CONCLUSION: These findings highlight the potential cross-talk between vitamin D and ET-1 pathways and pave the way for future preclinical/clinical studies to explore further mechanisms involved in this cross-talk.

Erratum in JAMA. 2017 Nov 21;318(19):1937. doi: 10.1001/jama.2017.16959. IMPORTANCE: Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. OBJECTIVE: To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. EXPOSURE: Administration of 10 mg/d of biotin supplementation for 7 days. MAIN OUTCOMES AND MEASURES: Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. RESULTS: Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. CONCLUSIONS AND RELEVANCE: In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassay

To further investigate the interaction between vitamin D system and estrogen-mimetic compounds in the human vasculature we studied the effect of the "less- calcemic" analog of 1,25(OH)2D3 (1,25D); JK 1624F2-2 (JKF) in the presence of selective estrogen modulator femarelle (F), the phytoestrogen daidzein (D) and estradiol-17b (E2) on 3[H] thymidine incorporation (DNA synthesis) and creatine kinase specific activity (CK) in human umbilical artery vascular smooth muscle cells (VSMC). F, D and E2, stimulated DNA synthesis at low concentrations, and inhibited it at high concentrations. All estrogen-related compounds increased CK dose- dependently. Daily treatment with JKF (1nM for 3days) resulted in decreased DNA synthesis, increased CK and up- regulation of the stimulation of DNA synthesis by low estrogen-related hormones whereas D- and E2- mediated inhibition of cell proliferation was abolished by JKF. In contrast, inhibition of cell proliferation by F could not be blocked by JKF. JKF also up-regulated the stimulatory effects on CK by F, E2 and D. VSMC expressed Estrogen Receptor (ER)a and ERb mRNA at a relative ratio of 2.7:1.0, respectively. JKF pretreatment increased ERa (∼50%) and decreased ERb (∼25%) expression. E2 did not affect ERs whereas both D and F up-regulated ERb (∼100%) and ERa (∼50%). Additionally, JKF increased the intracellular competitive binding of F (from ∼70 to ∼310%), of D (from ∼60 to ∼250%) and of E2 from (from∼70 to ∼320%). F reciprocally modulated the vitamin D system by up-regulating VDR- and 25 hydroxyy vitamin D 1-a hydroxylase (1OHase) mRNA expression (∼120%). F also stimulated 1OHase activity as indicated by an increase in the production of 1, 25D (∼250%). A similar increase was elicited by D (∼90%) but not by E2. In conclusion, F has unique effects on human VSMC in that it can sustain inhibition of cell growth even in the presence of the vitamin D analog JKF. That JKF increases ER expression and F increased the endogenous production of 1, 25D and VDR expression offer new opportunities to modulate VSMC growth. Whether or not these mutual effects of F and JKF can be exploited to promote vascular health, particularly in estrogen-deficie

Adjunctive vitamin D treatment for pulmonary tuberculosis enhances resolution of inflammation but has modest effects on bacterial clearance. Sodium 4-phenylbutyrate (PBA) is in clinical use for a range of conditions and has been shown to synergise with vitamin D metabolites to upregulate cathelicidin antimicrobial peptide (CAMP) expression. We investigated whether clinically attainable plasma concentrations of PBA (0.4-4 mM) directly affect Mycobacterium tuberculosis (Mtb) growth and human macrophage and PBMC response to infection. We also tested the ability of PBA to enhance the immunomodulatory actions of the vitamin D metabolite 25(OH)D3 during infection and synergistically inhibit intracellular Mtb growth. PBA inhibited Mtb growth in broth with an MIC99 of 1 mM, which was reduced to 0.25 mM by lowering pH. During human macrophage infection, PBA treatment restricted Mtb uptake, phagocytic receptor expression and intracellular growth in a dose-dependent manner. PBA independently regulated CCL chemokine secretion and induced expression of the antimicrobial LTF (lactoferrin), the anti-inflammatory PROC (protein C) and multiple genes within the NLRP3 inflammasome pathway. PBA co-treatment with 25(OH)D3 synergistically modulated expression of numerous vitamin D-response genes, including CAMP, CYP24A1, CXCL10 and IL-37. This synergistic effect was dependent on MAPK signalling, while the effect of PBA on LTF, PROC and NLRP3 was MAPK-independent. During PBA and 25(OH)D3 co-treatment of human macrophages, in the absence of exogenous proteinase 3 (PR3) to activate cathelicidin, Mtb growth restriction was dominated by the effect of PBA, while the addition of PR3 enhanced growth restriction by 25(OH)D3 and PBA co-treatment. This suggests that PBA augments vitamin D-mediated cathelicidin-dependent Mtb growth restriction by human macrophages and independently induces antimicrobial and anti-inflammatory action. Therefore through both host-directed and bacterial-directed mechanisms PBA and vitamin D may prove an effective combinatorial adjunct therapy for tuberculosis to both resolve immunopathology and enhance bacterial clearance.

BACKGROUND: Vitamin D is hypothesized to have some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid (ICS). OBJECTIVE: To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers (ICS or ICS plus long-acting β-agonist) on airway functions. METHODS: A randomized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period. Data on age, sex, body mass index, stage of asthma, serum total IgE, history of allergic rhinitis, atopic dermatitis, food allergy, and urticaria were collected. Spirometric parameters (forced expiratory volume in 1 second [FEV1] and ratio of FEV1 to forced vital capacity) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention. Patients were divided in 2 groups randomly. Both groups received asthma controllers (budesonide or budesonide plus formoterol) according to their stage, but the intervention group received vitamin D supplementation (100,000-U bolus intramuscularly plus 50,000 U orally weekly) in addition to asthma controllers. RESULTS: FEV1 improved significantly in both groups after 8 weeks, but no significant difference was found between the 2 groups at baseline (P = .20) or after 8 weeks (P = .99); however, a significant improvement was seen in the intervention group in the last 16 weeks, and FEV1 was significantly better in the intervention group than the other group after 24 weeks (P < .001). CONCLUSION: Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks. TRIAL REGISTRATION: irct.ir Identifier: IRCT201302079608N1.

110. Nutr Hosp. 2014;29 Suppl 2:47-56. [Effect of pharmacologic treatment of the nutritional status of neurologic patients]. [Article in Spanish] Piñeiro Corrales G, Vázquez López C, Álvarez Payero M. Clinical manifestations accompanying neurological diseases are diverse and affect multiple organs. Nutritional status of patients with certain neurological diseases such as stroke, Alzheimer's disease, Parkinson's disease, Epilepsy and Multiple Sclerosis can be altered because of symptoms associated with disease course, including certain micronutrient deficiency (folic acid, zinc, vitamin B6 and B12, vitamin D, vitamin E and vitamin C), changes in energy expenditure, intake decreased, gastrointestinal disorders and dysfunction of the bone mass. Also, we have to take in account other factors as: advanced age, multiple co morbidities, polypharmacy, the use of herbal products, social habits, diet and pharmacological treatments effect. An assessment of the factors related to neurological treatment that cause alterations in metabolic and nutritional status was performed: side effects of anti-Parkinson drugs, antiepileptic drugs, and multiple sclerosis drugs; drug-nutrient interactions; and nutrient-drug interactions.

OBJECTIVE: 1,25(OH)2 vitamin D3 can affect immune cells. However, the mechanism responsible for the favorable effects of 1(OH) vitamin D3, which becomes 1,25(OH)2 vitamin D3 in the liver, is not clear. The aim of this study is to analyze the immunological response of 1(OH) vitamin D3 supplementation in CH-C patients. DESIGN: Forty-two CH-C patients were treated with 1(OH) vitamin D3/Peg-IFNα/RBV. Forty-two case-matched controls were treated with Peg-IFNα/RBV. The expression of Interferon-stimulated genes (ISGs)-mRNA in the liver biopsy samples and JFH-1 replicating Huh-7 cells were quantified by real-time PCR. Ten kinds of cytokines in the plasma were quantified during treatment by using a suspension beads array. A trans-well co-culture system with peripheral blood mononuclear cells (PBMCs) and Huh-7 cells was used to analyze the effect of 1(OH) vitamin D3. The activities of the Th1 response were compared between subjects treated with 1(OH) vitamin D3/Peg-IFN/RBV and those treated with Peg-IFN/RBV therapy alone. RESULTS: 1(OH) vitamin D3/Peg-IFN/RBV treatment could induce rapid viral reduction, especially in IL28B T/T polymorphism. Several kinds of cytokines including IP-10 were significantly decreased after 4 weeks of 1(OH) vitamin D3 treatment (p<0.05). Th1 responses in the subjects treated with 1(OH) vitamin D3/Peg-IFN/RBV were significantly higher than those treated with Peg-IFN/RBV at 12 weeks after Peg-IFN/RBV therapy (p<0.05). The expression of ISGs in the patient's liver biopsy samples was significantly lower than in those treated without 1(OH) vitamin D3 (p<0.05). CONCLUSION: 1(OH) vitamin D3 could improve the sensitivity of Peg-IFN/RBV therapy on HCV-infected hepatocytes by reducing the IP-10 production from PBMCs and ISGs expression in the liver.