Relationship between Vitamin D3 Deficiency, Metabolic Syndrome and VDR, GC, and CYP2R1 Gene Polymorphisms.

The presence of vitamin D3 deficiency associated with the presence of metabolic syndrome (MS) has important public health effects. This study aims to investigate the relationship between vitamin D3 deficiency, MS and vitamin D3 receptor (VDR), GC Vitamin D binding protein (GC), and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene polymorphisms, and genes whose encoded proteins are responsible for vitamin D3 metabolism and transport. A total of 58 participants were included in this study (age 39 ± 12 years) and were selected over a 12-month period. They were divided into four groups, depending on the presence of polymorphisms in VDR, GC, and CYP2R1 genes and their weight status. At baseline, in months 3, 6, and 12, biochemical parameters including 25(OH)D3, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and homeostatic model assessment (HOMA index), the insulin resistance indicator were measured. Our results show that all subjects in the polymorphism group supplemented with vitamin D3 reached an optimal level of vitamin D3 associated with high concentrations of 25(OH)D3. Weight loss was most significant in patients in the POW group (overweight patients).

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

An 8-Week Vitamin D3-Fortified Fruit Drink Supplementation Increases Serum Ferritin Concentration: A Randomized Controlled Trial in Malaysian Women With Low Iron Stores.

BACKGROUND: There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. OBJECTIVE: The aim of this study was to determine the effect of vitamin D3-fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 µg/L [to convert µg/L ferritin to ng/mL, multiply by 1]). DESIGN: An 8-week double-blind randomized controlled trial was conducted. SUBJECTS/SETTING: A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. INTERVENTION: Subjects were randomly assigned to receive either vitamin D3-fortified fruit drink or a placebo. MAIN OUTCOME MEASURES: Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. STATISTICAL ANALYSES: A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. RESULTS: Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3-fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ -1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] µg/L vs Δ -0.3 [3.4] µg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. CONCLUSIONS: Our study found that daily vitamin D3-fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

Vitamin D3 resolved human and experimental asthma via B lymphocyte-induced maturation protein 1 in T cells and innate lymphoid cells.

Background: Vitamin D3 (VitD3) is known to have immunomodulatory functions, and VitD3 deficiency is associated with more severe asthma. Objective: We aimed to assess the immunoregulatory effects of VitD3 food supplementation on asthma manifestation, with particular focus on T cells and type 2 innate lymphoid cells. Methods: Preschool children and adult asthmatic cohorts were analyzed in the context of VitD3 supplementation and serum levels. In a murine model of ovalbumin-induced asthma, effects of diet VitD3 sufficiency and deficiency on T cells and type 2 innate lymphoid cells immune mechanisms were investigated. Results: We found less severe and better-controlled asthma phenotypes along with reduced need for steroid medication in preschool children and asthmatic adults with VitD3 supplementation. VitD3 serum levels correlated with B lymphocyte-induced maturation protein 1 (Blimp-1) expression in blood peripheral mononuclear cells. VitD3-supplement-fed mice showed decreased asthmatic traits, with a decrease in IgE serum levels, reduced airway mucus, and increased IL-10 production by lung cells. Furthermore, we discovered an upregulation of effector T cells and Blimp-1+ lung tissue-resident memory T cells as well as induction of anti-inflammatory Blimp-1+ lung innate lymphoid cells producing IL-10. Conclusion: Supplementing VitD3 resulted in amelioration of clinical asthma manifestations in human studies as well as in experimental allergic asthma, indicating that VitD3 shifts proinflammatory immune responses to anti-inflammatory immune responses via upregulating Blimp-1 in lung innate lymphoid cells and tissue-resident memory cells.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Background: Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. Objective: We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. Methods: In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. Results: In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Conclusion: Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. Clinical trial registration: clinicaltrials.gov, identifier: NCT05706259.

Effect of physical training on parathyroid hormone and bone turnover marker profile in relation to vitamin D supplementation in soccer players.

The aim of the study was to assess the impact of vitamin D supplementation and regular physical activity on 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone turnover marker concentrations in healthy male athletes. Twenty-five youth soccer players were divided into groups: non-supplemented (GN) and supplemented (GS) with a vitamin D dose of 20 000 IU twice a week for 8 weeks. The study was conducted during an 8-week preseason period, from mid-January to mid-March. At baseline (T1) and at the end of this period (T2), the serum concentrations of 25(OH)D, (PTH), osteocalcin (OC) and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTx) were measured. At T2, 25(OH)D increased by 70% in GS (p = 0.004) and by 6% in GN (p > 0.05). Significant differences between GS and GN groups were observed throughout the study in the group-by-time interaction and changes of 25(OH)D (p = 0.002; η 2 p = 0.36) and OC (p = 0.008; η 2 p = 0.26). Increased OC (ES = 0.74; moderate) and ß-CTx (ES = 1.31, large) in GN athletes who had an optimal baseline vitamin D level (GO) were observed. In GN, at T2, ß-CTx positively correlated with PTH and OC (p = 0.007 and p = 0.002). In GS, ß-CTx positively correlated with OC at both time points (T1, p = 0.027 and T2, p = 0.037). A negative correlation between 25(OH)D and PTH was observed at T2 (p = 0.018). The obtained results suggest that the 20 000 IU vitamin D3 dose applied twice a week for 8 weeks is effective for vitamin D compensation and sufficient to maintain the correct PTH concentration, as revealed by changes in the bone marker concentrations. In conclusion, the results suggest that the applied vitamin D supplementation dose in athletes leads to intensive bone remodelling and has protective effects on bone under intensive physical effort.

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

Effect of Vitamin D3 Supplementation on Interleukin 6 and C-Reactive Protein Profile in Athletes.

Vitamin D3 has a preventive, anti-inflammatory effect. However, there are still few studies linking the effects of athlete training to vitamin D3 supplementation and the immune response. The study evaluated the impact of vitamin D3 supplementation on interleukin 6 (IL-6) release during physical exercise in relation to C-reactive protein (CRP) levels in healthy male athletes. Twenty-five soccer players were divided into two groups-with (GS) and without (GN) vitamin D3 supplementation in a dose of 20,000 IU twice a week for 8 wk (about 6,000 IU/d). At the baseline (T1) and at the end (T2) of the training cycle serum concentrations of 25-hydroxyvitamin D [25(OH)D], IL-6 and CRP were measured. In the GS group, we observed a significant increase in 25(OH)D concentration (p=0.004), and non-significantly increased levels (p>0.05) of IL-6 and CRP. At the baseline, CRP in the supplemented athletes who had suboptimal vitamin D3 concentration in T1 (GSO) was significantly higher than in those with an optimal baseline vitamin D3 level (GO) (p=0.028). However, in GO in T2, a non-significant trend of negative correlation (p=0.055) between 25(OH)D concentration and IL-6 level was found. In the total study group (TG), a statistically significant (p=0.021) negative correlation in T1 was observed between 25(OH)D and CRP. However, our results do not support the immune-modulatory effect of vitamin D3 supplementation in a dose of 6,000 IU/d in athletes, in relation to IL-6 production and its subsequent stimulatory effect on CRP releasing.

A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.

Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.

The interactive effect of vitamin D3 supplementation and vitamin D receptor polymorphisms on weight and body composition in overweight women with hypovitaminosis D: a randomized, double-blind, placebo-controlled clinical trial.

Different responses to vitamin D supplementation may be due to genes involved in vitamin D metabolism, including the vitamin D receptor (VDR) gene. The present study aimed to determine the interactive effect of vitamin D supplementation and VDR polymorphisms, including FokI (rs2228570) and BsmI (1544410) on weight and body composition in overweight women with hypovitaminosis D. This study comprised two phases: a double-blind, randomized and a before-after clinical trial. In the first phase, 50 healthy overweight women aged 20-45 years with hypovitaminosis D were randomly categorized into intervention and control groups and were given 50 000 IU/w vitamin D3 or placebo for 12 weeks. In the second phase, 75 women received 50 000 IU/w of vitamin D3 for 12 weeks. All variables were measured at baseline and after 12 weeks. Circulating 25(OH)D was measured using an ELISA kit. Anthropometric indices were calculated according to standard protocol (WHO-TRH-854). Body composition was determined using the body impedance analysis method. The VDR polymorphisms were detected using the PCR sequence. Supplementation resulted in a significant increase in the level of 25(OH)D in the intervention group but did not affect the anthropometric profile of the subjects. When considering FokI genotypes, carriers of the FF genotype had higher fat mass reduction than carriers of Ff + ff genotypes.

Effect of Vitamin D Supplementation on CD4 Count in HIV-Infected Children and Adolescents in North India: A Non-Randomized Comparative Study.

BACKGROUND: HIV infection is still a serious public health issue globally. Suboptimal vitamin D status is highly prevalent in HIV-infected children and adolescents throughout the world. OBJECTIVES: To evaluate the outcome of vitamin D supplementation on CD4 count in HIV-infected children and adolescents with suboptimal vitamin D status. METHODS: Vitamin D level of HIV-infected children and adolescents were measured at enrolment. Suboptimal vitamin D level was defined as 25(OH)D < 30 ng/ml. Vitamin D insufficiency and deficiency were defined as 21-29 and <20 ng/ml, respectively. Children with suboptimal vitamin D levels were supplemented with vitamin D. RESULTS: This was a single-centre, non-randomized comparative study enrolling 50 eligible participants. There were 20 patients who were vitamin D sufficient, 7 were vitamin D insufficient and 23 were found to be vitamin D deficient at enrolment. However, after supplementation, the status of sufficient remained same and 7 insufficient become sufficient, whereas in 23 deficient, 18 (78.3%) become sufficient and 5 (21.7%) become insufficient and this change was found statistically significant among the groups (χ2 = 6.52, p = 0.038). There was a significant improvement of CD4 count from baseline to 4 months in deficient group on vitamin D supplementation (p value < 0.001; 1.2-fold rise). No significant change was seen in vitamin D insufficient (p value = 0.791) and sufficient groups (p value = 0.168). CONCLUSION: Vitamin D should be supplemented in HIV-infected children on ART with low CD4 counts.

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial.

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53-74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4-13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12-45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

The Impact of Vitamin D3 Supplementation to Topiramate Therapy on Pediatric Migraine Prophylaxis.

Background:There is still a need for more studies to evaluate the role of vitamin D3 in pediatric migraine prophylaxis. Objectives: We aimed to evaluate the effects and safety of vitamin D3 supplementation to topiramate on pediatric migraine. Methods: A double-blinded prospective clinical trial was conducted on 5- to 14-year-old children with migraine. They were randomly assigned in a 1:1 ratio into 2 groups, one with vitamin D3 supplementation (the supplementation group) and the other without vitamin D supplementation (the placebo group). The supplementation group received topiramate plus one 5000-IU dose of vitamin D3 daily for 4 months. The placebo group received topiramate with a placebo capsule without any effective substances. The primary outcomes were a monthly frequency of headache attacks, a good response to intervention, and reduction in migraine severity, duration, and disability before and after treatment. Fifty-six children completed the trial. Vitamin D3 supplementation to topiramate was more effective than the placebo group in the reduction of monthly frequency (6231.31 vs 9792.24 times, P = .01) and disability score for migraines (17 566.43 vs 25 187.65, P = .04). A good response was observed in 76.13% of patients in the vitamin D3 supplementation group and 53.5% of patients in the placebo group, and vitamin D3 supplementation was significantly more effective than placebo (P = .01). Side effects were observed in 13.3% and 20% of the intervention group and placebo groups, respectively, P = .5. Conclusion: Vitamin D3 supplementation in pediatric migraine prophylaxis could be a well-tolerated, safe, and effective strategy.

Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,000, 10,000, 40,000 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were downregulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.

The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease.

In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.

The Effect of Vitamin D3 Supplementation on Physical Capacity among Active College-Aged Males.

Vitamin D3 supplementation can affect strength and power; however, the effect on both aerobic and anaerobic performance remains unclear. Here, we investigate the effects of eight weeks of a high dose of vitamin D3 supplementation and its impact on circulating 25-hydroxyvitamin D (25-OH-D3) concentrations and selected indicators of physical capacity. Subjects (n = 28, age 21.1 ± 1.6) were divided into two groups: supplemented (SUP), which was given 6000 IU of vitamin D3 daily for eight weeks; and placebo group (PLA). Serum 25-OH-D3 concentrations were determined in pre- and post-intervention. Aerobic (VO2max test) and anaerobic (Wingate Anaerobic Test) capacity were determined before and after the supplementation. The mean baseline concentration of 25-OH-D3 was recognized as deficient (20 ng/mL) and significantly increased over time in the supplemented group (p < 0.01, η2 = 0.86), whilst it remained unchanged in the placebo group. Moreover, the supplementation caused a significant improvement in maximal aerobic (p < 0.05, η2 = 0.27) and anaerobic power (p < 0.01, η2 = 0.51) whereas no changes were observed in PLA group. The VO2max differences were also significant in the supplemented group (p < 0.05). In summary, the changes in aerobic and anaerobic capacity observed in this study were associated with a serum concentration of 25-OH-D3. Our data imply that vitamin D3 supplementation with a dose of 6000 IU daily for eight weeks is sufficient to improve physical capacity and vitamin D3 status.

Effect of genetic factors on the response to vitamin D3 supplementation in the VIDARIS randomized controlled trial.

OBJECTIVES: Supplementation provides the best means of improving vitamin D status; however, individual responses vary partly owing to genetics. The aim of this study was to determine whether 28 single nucleotide polymorphisms (SNPs) in six key vitamin D pathway genes (GC, DHCR7, CYP2 R1, CYP24 A1, CYP27 B1, VDR) were associated with differences in response to supplementation. METHODS: Participants (N = 313; n = 160 vitamin D, n = 153 placebo) were part of VIDARIS (Vitamin D and Acute Respiratory Infections Study), a double-blind, randomized controlled trial involving oral monthly supplementation of either vitamin D3 (200 000 IU each for the first 2 mo, thereafter 100 000 IU monthly) or placebo for 18 mo. Circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline and 2, 6, 12, and 18 mo, and vitamin D binding protein (Gc-globulin) and calculated free 25(OH)D concentrations at baseline and 2 mo were obtained. Multiple regression was used to model associations between genetic variants and 25(OH)D, Gc-globulin, and free 25(OH)D concentrations. RESULTS: SNPs within GC, CYP2 R1, and CYP27 B1 were associated with 25(OH)D concentrations following supplementation. However, only two GC gene SNPs (rs2282679, rs1155563) were significant after adjustment for multiple testing. This effect disappeared after more than 2 mo of supplementation. None of the SNPs were significantly associated with Gc-globulin concentrations; however, there was a significant interaction with one SNP in DHCR7 (rs12785878), which was associated with reduced free 25(OH)D concentrations in the supplemented arm. CONCLUSION: Only variants of GC were associated with 25(OH)D concentrations after supplementation. This effect was modest and disappeared after >2 mo of supplementation, suggesting it may be time/dose-dependent and saturable.

Effects of Maternal Vitamin D3 Supplementation on Offspring Epigenetic Clock of Gestational Age at Birth: A Post-hoc Analysis of a Randomized Controlled Trial.

Vitamin D could be beneficial for healthy ageing in humans. We previously found that vitamin D supplementation may slow down epigenetic ageing in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that maternal vitamin D supplementation would slow down the epigenetic gestational age acceleration (GAA) in newborn babies. Ninety-two pregnant women (aged 29.6 ± 4.8 y; 21% African Americans, 28% Hispanics) were randomized to receive 4000 IU/day vitamin D3 or placebo, plus prenatal vitamins containing 400 IU vitamin D3 during pregnancy in a randomized controlled trial (RCT). Cord blood genome-wide methylation analysis was performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age was calculated based on two calculations developed by Knight and Bohlin. DNA methylation gestational ages calculated by Knight's clock and Bohlin' clock were highly correlated with the gestational age in the placebo group (correlation coefficients = 0.88, p s< 0.001, respectively). GAA was associated with higher birth weight (p = 0.039). In the entire cohort, vitamin D3 supplementation was not associated with GAA (p > 0.05). However, vitamin D3 supplementation decreased GAA by both Knight's clock (ß = -0.89, p = 0.047) and Bohlin's clock (ß = -0.71, p = 0.005) in the African American participants. Maternal vitamin D3 supplementation may slow down the epigenetic gestational ageing process in African American neonates. Long-term follow-up studies are warranted to determine the role of epigenetic age acceleration in the growth and development of offspring.

Obesity and efficacy of vitamin D3 supplementation in healthy black adults.

PURPOSE: Results from recent clinical trials suggest that vitamin D efficacy against cancer may be influenced by body mass index. As suppression of parathyroid hormone (PTH) is one indicator of vitamin D efficacy, we examined to what extent doses of vitamin D3 supplementation suppress PTH levels in individuals with and without obesity. METHODS: A total of 328 healthy African Americans were randomized into the following four groups and treated for 3 months: placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 supplementation. RESULTS: Among the participants, 250 individuals with PTH measurements were included in the analysis. Obese individuals (n = 141) experienced a steep reduction of 3-month PTH from placebo to 1,000 IU/day of vitamin D3 supplementation, but no further reduction at 2,000 or 4,000 IU/day. For non-obese individuals (n = 109), the reduction of 3-month PTH was approximately linear for increasing vitamin D3 doses. At supplementation of 2,000 to 4,000 IU/day, 3-month 25(OH)vitamin D levels were high in both non-obese and obese individuals, but the 3-month PTH levels remained about 10 pg/mL higher in individuals with obesity. CONCLUSION: Our findings suggest that excess adiposity confers resistance to vitamin D efficacy in suppressing PTH levels, even when given at high doses.

The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study.

BACKGROUND/AIM: To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D3 Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. RESULTS: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). CONCLUSION: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D3 supplementation.