The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial.

BACKGROUND: Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients. METHODS: We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention. RESULTS: Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group. CONCLUSIONS: These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.

Comparative efficacies of vitamin D supplementation regimens in infants: a systematic review and network meta-analysis.

Vitamin D deficiency in infants is widely prevalent. Most paediatric professional associations recommend routine vitamin D prophylaxis for infants. However, the optimal dose and duration of supplementation are still debated. We aimed to compare the efficacy and safety of different vitamin D supplementation regimens in term and late preterm neonates. For this systematic review and network meta-analysis, we searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase. Randomised and quasi-randomised clinical trials that evaluated any enteral vitamin D supplementation regimen initiated within 6 weeks of life were included. Two researchers independently extracted data on study characteristics and outcomes and assessed quality of included studies. A network meta-analysis with a Bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. Primary outcomes were mean serum vitamin D concentrations and the proportion of infants with vitamin D insufficiency (VDI). We included twenty-nine trials that evaluated fourteen different regimens of vitamin D supplementation. While all dosage regimens of ≥400 IU/d increased the mean 25(OH)D levels compared with no treatment, supplementation of ≤250 IU/d and 1400 IU/week did not. The CoE varied from very low to high. Low CoE indicated that 1600 IU/d, compared with lower dosages, reduced the proportion of infants with VDI. However, our results indicated that any dosage of ≥800 IU/d increased the risk of hypervitaminosis D and hypercalcaemia. Data on major clinical outcomes were sparse. Vitamin D supplementation of 400-600 IU/d may be the most effective and safest in infants.

Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease.

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = - 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = - 0.399, P < 0.001).   Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts.   Trial registration: ClinicalTrials.gov , identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered. What is known: • Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients. • Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL). • Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD. What is new: • We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Immunomodulatory effect of vitamin D supplementation on Behçet's disease patients: effect on nitric oxide and Th17/Treg cytokines production.

INTRODUCTION: In the last decade, an immuno-modulatory effect of vitamin D supplementation have emerged as a potential therapeutic approach for some inflammatory and autoimmune diseases. As previously reported, vitamin D deficiency was strongly linked to several diseases as Behçet's disease (BD). BD is a chronic systemic inflammatory disorder with autoimmunity, genetic and environmental factors involvement. The aim of our current study is to set up a new therapeutic strategy in BD, combining conventional therapy and vitamin D supplementation. MATERIALS AND METHODS: Blood samples were collected from active and inactive BD patients and healthy controls (HC) to evaluate 25(OH) vitamin D levels using an electrochemiluminescence method. All deficient and insufficient vitamin D BD patients' were supplemented with vitamin D3 (CHOLECALCIFEROL, 200 000 UI/1 ml). In this context, NO, IL-17A and IL-10 levels were evaluated in patients and HC in vivo and ex vivo using Griess and ELISA methods respectively. RESULTS: Before supplementation, we noted with interest that BD patients had vitamin D deficiency, associated with elevated in vivo and ex vivo NO and IL-17A levels compared to HC. Conversely, low IL-10 levels were observed in the same BD patients in comparison to HC. Interestingly, restored vitamin D status in supplemented BD patients was related to the decreased NO levels. In the same way, the IL-10/IL-17A ratio was improved. CONCLUSIONS: Collectively, our data suggest that vitamin D supplementation in combination with conventional treatments has a beneficial effect and could constitute a good therapeutic candidate for alleviating inflammatory responses during Behçet disease.

Calcium and vitamin D supplements and burnout of anesthesiologists: National cross-sectional study from China.

OBJECTIVE: Job burnout among anesthesiologists has been consistently high. This study evaluated the association of calcium and vitamin D supplementation with burnout among Chinese anesthesiologists. METHOD: A cross-sectional online survey was conducted during April and May 2023. Burnout was evaluated using the Maslach Burnout Inventory, which assesses emotional exhaustion, depersonalization, and low personal accomplishment. Data on calcium and vitamin D supplementations were self-reported. Sociodemographic information and medical history were also assessed. Binary and ordinal logistic regression were used to evaluate the risk of burnout and burnout levels, respectively. The relative excess risk due to interaction and the attributable proportion due to interaction were examined to determine the synergistic effects of calcium and vitamin D supplementations on burnout risk. RESULTS: Among the 4222 invited anesthesiologists, 3766 submitted eligible questionnaires. Approximately 49.8% met the criteria for general burnout. Among anesthesiologists with burnout, 58.4% experienced emotional exhaustion, 35.8% depersonalization, and 61.2% low personal accomplishment. Anesthesiologists receiving calcium supplementation had a decreased risk of emotional exhaustion (OR = .83, 95% CI = .70-.99). Supplementation of vitamin D with or without calcium was not associated with overall burnout and any of its dimensions. No additive interaction of calcium and vitamin D on burnout was observed. CONCLUSIONS: Job burnout among anesthesiologists is of concern in China. Burnout is negatively associated with calcium supplementation but not with vitamin D. Further research is warranted to confirm the mechanism and causal relationship.

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

Vitamin D and Menopause.

Menopause is the transition period in female life cycle. Resultant hormonal changes lead to adverse health effects. Women may seek treatment due to significant impairment in quality of life. Vitamin D deficiency is a globally prevalent problem. Vitamin D deficiency in menopausal women may aggravate the adverse health risks associated with menopause. In this article, the authors discuss endocrinology and clinical features of menopause, Vitamin D and its links with menopause, and the potential role of Vitamin D supplementation to combat detrimental multi-organ system effects of menopause.

Vitamin D in blood serum and chronic pancreatitis.

Patients with chronic pancreatitis are at risk of developing malabsorption and malnutrition. Exocrine pancreatic insufficiency is accompanied by decreased serum micronutrient levels and low vitamin D levels are a frequent finding in up to 60-80% of patients. The aim of our prospective study was to investigate vitamin D in the blood serum of subjects with chronic pancreatitis with the possibility of influencing the reduced vitamin D levels with supplementation therapy. MATERIAL AND METHODOLOGY: Fifty patients with chronic pancreatitis and 20 subjects in the control group without gastrointestinal tract diseases, including pancreatic disease, were examined. The vitamin D level in blood serum was determined. The results were evaluated according to the age distribution of subjects with pancreatic disease and according to gender. Patients with low vitamin D levels were treated for 24 weeks with a dose of 1.500.000 IU of vitamin D3 per day, and then blood serum vitamin D levels were determined. RESULTS: In people with chronic pancreatitis, vitamin D levels were statistically significantly reduced compared to the control group. There was no statistically significant relationship of vitamin D with gender and age. Supplementation with vitamin D3 achieved an adjustment of vitamin D level to the level of the control group. CONCLUSION: Blood serum vitamin D levels are significantly reduced in people with chronic pancreatitis. Its correction by oral vitamin D supplementation was effective. Whether this adjustment of levels will be effective also in terms of e.g. beneficial effect on fibrogenesis will require further representative studies, because the limitation of the interpretation of the results of our study is the smaller number of subjects with chronic pancreatitis (Tab. 4, Ref. 29).

Impact of vitamin D supplementation on markers of bone turnover: Systematic review and meta-analysis of randomised controlled trials.

AIM: The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised controlled trials (RCTs) to examine the impact of vitamin D supplementation on BTMs. METHODS: To identify relevant RCTs, we searched the PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library and Embase databases for manuscripts published up to July 2022. The present study was conducted in agreement with the PRISMA guidelines. Weighed mean difference (WMD) and 95% confidence intervals (CI) were used to calculate the magnitude of the effect of the intervention. RESULTS: A total of 42 RCTs were included in the meta-analysis. The age of the participants enrolled in the RCTs ranged from 19.4 to 84 years. The pooled results depicted a decrease in deoxypyridinoline (DPD) concentrations (WMD: -1.58 nmol/mmol, 95% CI: -2.55, -.61, p = .001) following vitamin D supplementation. In addition, subgroup analyses demonstrated that vitamin D administration notably reduced procollagen type I N-terminal propeptide (PINP) levels in individuals aged >50 years and led to a pronounced decrease in alkaline phosphatase (ALP) values when the intervention lasted >12 weeks. No significant effect was observed on other BTMs, for example, collagen type 1 cross-linked C-telopeptide (CTX) and osteocalcin (OC) levels. CONCLUSION: Vitamin D administration decreases DPD, PINP and ALP levels, indicating a reduced bone turnover following the intervention. Other BTMs, for example, CTX or OC values, were not affected by vitamin D prescription. Vitamin D supplementation may exert a positive effect on some important BTMs.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.

Effects of vitamin D supplementation in obese and overweight children and adolescents: A systematic review and meta-analysis.

Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Vitamin D deficiency has in turn several consequences especially among children and adolescents. Therefore, a few supplementation strategies of vitamin D for pediatric subjects with an excessive body weight have been proposed, but their efficacy remains controversial. The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation in overweight and obese children and adolescents. Three databases (PubMed, Embase and Web of Science) were searched to collect trials on the effect of vitamin D supplementation in the pediatric overweight or obese population. Twenty-three studies were included in the systematic review. Results on modification of metabolic or cardiovascular outcomes were controversial. On the other hand, the meta-analysis showed a mean difference by 1.6 ng/ml in subjects supplemented with vitamin D as compared to placebo. In conclusion, vitamin D supplementation slightly increases 25(OH)D levels in pediatric subjects with overweight and obesity. However, the effects on metabolic and cardiovascular outcomes remain controversial. New efforts should be devoted to promoting effective interventions to improve the health of children and adolescents with overweight and obesity.

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

Effect of vitamin D supplementation on depression in older Australian adults.

OBJECTIVES: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. METHODS: We used data from the D-Health Trial (N = 21,315), a randomized double-blind placebo-controlled trial of monthly vitamin D3 for the prevention of all-cause mortality. Participants were Australians aged 60-84 years. Participants completed the Patient Health Questionnaire (PHQ-9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models. RESULTS: Analyses of PHQ-9 scores included 20,487 participants (mean age 69·3 years, 46% women); the mean difference (MD) in PHQ-9 score (vitamin D vs. placebo) was 0·02 (95% CI -0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ-9 score ≥10) (odds ratio 0·99; 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04; 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ-9 scores in those taking antidepressants at baseline (MD -0·25; 95% CI -0·49, -0·01; p-interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/L (HR 0·88; 95% CI 0·75, 1·02; p-interaction = 0·01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1·10; 95% CI 1·01, 1·20). CONCLUSION: Monthly supplementation with high-dose vitamin D3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. CLINICAL TRIAL REGISTRATION: The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.

Maternal vitamin D supplementation and treadmill exercise attenuated vitamin D deficiency-induced anxiety-and depressive-like behaviors in adult male offspring rats.

BACKGROUND: Vitamin D is a vital neuroactive steroid for brain development and function. Vitamin D deficiency is a worldwide health problem, particularly in children and women. Gestational or developmental vitamin D deficiency is associated with an increased risk of neurodevelopmental and neuropsychiatric disorders. This study examined the effect of maternal vitamin D dietary manipulations and treadmill exercise on anxiety-and depressive-related behaviors, pro-inflammatory cytokines, and prefrontal cortex (PFC) protein levels of brain-derived neurotrophic factor (BDNF) and vitamin D receptor (VDR) in adult male offspring born to vitamin D-deficient diet (VDD)-fed dams. METHODS AND RESULTS: Female rats were provided standard diet (SD) or VDD for six weeks and then were treated with SD (started a week before mating throughout gestation and lactation) and treadmill exercise (a week before mating until gestational day 20). Male offspring were separated on postnatal day (PND) 21 and fed SD chow until PND90. Our results demonstrated that maternal vitamin D deficiency increased anxiety and depression-related behaviors, increased levels of TNF-α and IL-1ß in serum, and decreased prefrontal protein expressions of BDNF and VDR in adult male offspring. However, maternal vitamin D supplementation and treadmill exercise reversed these changes alone or in combination. CONCLUSION: It seems that developmental vitamin D deficiency disrupts brain development and has a long-lasting effect on VDR and BDNF signaling in the rat brain resulting in neuropsychiatric disorders in offspring. Therefore, vitamin D supplementation and physical exercise are reasonable strategies to prevent these neurobehavioral impairments.

Efficacy of vitamin D supplementation on child and adolescent overweight/obesity: a systematic review and meta-analysis of randomized controlled trials.

The global prevalence of overweight and obesity in children and adolescents has been increasing. Child and adolescent overweight/obesity has been demonstrated to be partially associated with vitamin D deficiency. This systematic review and meta-analysis aims to assess the efficacy of vitamin D supplementation on child and adolescent overweight/obesity. PubMed, Embase, Cochrane Library, and Web of science were searched from inception to June 20th, 2022. Randomized controlled trials (RCTs) assessing the efficacy of vitamin D on child and adolescent overweight/obesity were included. The Cochrane bias risk assessment tool was used to assess the bias risk of included studies, and subgroup analysis was conducted based on different administration dosages. All data-analyses were performed using R 4.2.1. There were 1502 articles retrieved, and 10 eligible studies were finally included, with a total of 595 participants. Meta-analysis showed no differences in LDL, TC, TG, BMI, ALP, Ca, and PTH between vitamin-D (Vit-D) group and placebo, while Vit-D group resulted in improved HOMA-IR[WMD = - 0.348, 95%CI (- 0.477, - 0.219), p = 0.26]. Subgroup-analysis showed no significant difference in the increase of 25-(OH)-D between subgroups (p = 0.39), whereas the serum 25-(OH)-D level was increased under different Vit-D doses [WMD = 6.973, 95%CI (3.072, 10.873)]. High daily dose (≥ 4000 IU/d) of Vit-D might decrease CRP and increase HDL levels.   Conclusion: High dose of Vit-D supplementation (over 4000 IU/d) would reduce several cardiometabolic risk indicators and improve insulin resistance. More high-quality and large-scale RCTs are needed to provide more robust evidence. What is Known: • Vit-D deficiency is common in overweight/obesity (OW/OB) children and adolescents. • Previous randomized studies on the benefit of Vit-D supplementation to OW/OB children and adolescents are inconsistent. What is New: • This is the first meta-analysis conducted to assess the efficacy of Vit-D supplementation on child and adolescent OW/OB. • High dose of Vit-D supplementation is beneficial to cardiovascular metabolism, and improve insulin resistance on child and adolescent OW/OB.

Association between anaemia and vitamin D insufficiency among 6- to 12-month-old infants: implications for clinical practice.

BACKGROUND: Anaemia and vitamin D insufficiency (VDI) are among the most common nutritional problems. Anaemia screening is routinely performed; however, screening for VDI is not usually recommended. OBJECTIVES: To study the association between anaemia and VDI and identify the risk factors for VDI. METHODS: We conducted a cross-sectional study of 120 infants aged 6-12 months attending a well-child clinic at Songklanagarind Hospital between December 2020 and November 2021. Sociodemographic data and 24-h food records were also collected. Blood samples were obtained for complete blood count and 25-hydroxyvitamin D [25(OH)D] levels. Logistic regression analysis was used to determine risk factors for VDI. RESULTS: The mean 25(OH)D level was 22.2 ± 8.9 ng/mL in anaemic infants and 27.2 ± 9.6 ng/mL in non-anaemic infants (P value 0.01). The median (IQR) Hb level was 11.1 g/dL (10.3, 11.4) in the VDI group and 11.4 g/dL (11, 12.1) in the non-VDI group (P value 0.002). The proportion of breastfed infants was higher in infants with anaemia (80%) (P < 0.001) and VDI (85.3%) (P < 0.001). Sunlight exposure <15 min/day (odds ratio [OR] 3.84; 95% confidence interval [CI]: 1.23-12.00; P = 0.020) was a risk factor, and vitamin D intake (OR 0.37; 95% CI: 0.20-0.74; P = 0.004) was a protective factor for VDI. CONCLUSION: Infants with anaemia, short duration of sunlight exposure, breastfeeding, low vitamin D intake, and low iron intake were more likely to be vitamin D insufficient. However, after adjustment in the multivariate analyses, only sunlight exposure and vitamin D intake were significantly associated with vitamin D insufficiency.

Anaemia and vitamin D insufficiency (VDI) are the 2 most common global nutrition-related problems. Recently, data have been reported on the association between anaemia and VDI; however, no data exist for infants in Thailand. We assessed the vitamin D levels in infants attending a well-child clinic and investigated possible correlations with anaemia. We found that infants with anaemia, short duration of sunlight exposure, breastfeeding, low vitamin D intake, and low iron intake were more likely to be vitamin D insufficient. However, anaemia was not shown to be an independent risk factor for VDI. Risk factor and protective factor for VDI were short duration of sunlight exposure and adequate vitamin D intake, respectively. Vitamin D supplementation to infants has been recommended in many countries, yet, it has not been implemented in Thailand or other tropical countries. We suggest that VDI should be of concern in infants with anaemia or breastfeeding, particularly among those with inadequate sunlight exposure and low vitamin D intake. Implementing vitamin D supplementation should be considered for future practice.

Is vitamin D supplementation program in Iranian schools effective in reducing adolescent depressive symptoms? Cost effectiveness study.

PURPOSE: We aimed to assess the cost-effectiveness of the vitamin D supplementation program in Iranian adolescents reducing adolescent depressive Symptoms. METHODS: In the current cost-effectiveness analysis, the viewpoint of Iran's Ministry of Health was selected. The target population was 1,519,762 Iranian high school students (733,657 girls and 786,105 boys). The total costs of the vitamin D supplementations program were based on the reports of the Nutrition Improvement Office of Iran's Ministry of Health and were adjusted to 2018. The variable of Quality-Adjusted Life Years (QALYs) was considered a suitable variable for estimating the effectiveness of vitamin D supplementation. We chose one year as the time horizon. A decision tree model was constructed in TreeAge Pro. The results of the cost-effectiveness analysis were reported in term of the Incremental Cost-Effectiveness Ratio (ICER). RESULTS: The results of our study showed that the estimated cost per QALY gained of the vitamin D supplementation program is equal to 1528.6676 $, which indicates that vitamin D supplementation in adolescents(11-18Y) is a cost-effective and a dominant strategy in preventing depression through the cost-saving and QALYs increment compared to the no intervention. Sensitivity analysis showed that the possible variations in vitamin D supplement costs could not alter the results, and vitamin D supplementation may be a predominant and cost-effective strategy to prevent adulthood depression with a 100% probability. CONCLUSION: The national program of vitamin D supplementation among Iranian adolescents was a cost-efficient strategy reducing adolescent depressive Symptoms through the cost-saving and QALYs increment compared to the no intervention.