Effects of vitamin D3 and calcium supplementation on serum levels of tocopherols, retinol, and specific vitamin D metabolites

γ-Tocopherol (γT) protects against DNA-damaging effects of nitrogen oxides, yet its physiologic regulation in vivo is unknown. Observational studies indicate inverse associations of 25[OH]-vitamin D with γT and leptin. To determine whether vitamin D(3) supplementation alters levels of lipid-soluble micronutrients, serum samples (N = 85 subjects) from a randomized, double-blind, placebo-controlled clinical trial of vitamin D(3) (800 IU) and calcium (2 g), alone and in combination, were analyzed for lipid micronutrients and specific vitamin D metabolites at baseline and after 6 mo of supplementation. Serum 25[OH]-vitamin D(3) levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas 25[OH]-vitamin D(2) levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the vitamin D(3) and vitamin D(3) plus calcium groups, respectively. At baseline, γT levels were inversely associated with 25[OH]D (r = -0.31, P = 0.004). With vitamin D(3) plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), whereas similar changes in γT (19% lower, P = 0.14) were observed. No significant effects were observed for D(3) supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D(3) ± calcium affects serum tocopherol and 25[OH]D(2) levels; however, studies using larger, more homogeneous populations are warranted.     

Vitamin D Status and Severity of Clostridium difficile Infections

Background: Clostridium difficile is the most common cause of nosocomial diarrhea, affecting up to 10% of hospitalized patients. Preliminary studies suggest an association between vitamin D status and C difficile infections (CDIs). Our goal was to investigate whether serum 25‐hydroxyvitamin D (25(OH)D) levels are associated with CDI severity. Methods: We prospectively enrolled patients diagnosed with CDI and divided them into 2 severity groups: group A (positive toxin A/B enzyme immunoassay only) and group B (positive toxin A/B enzyme immunoassay with abdominal computed tomography scan findings consistent with colitis). Serum 25(OH)D levels (25(OH)D₃, 25(OH)D₂, and total 25(OH)D) were measured on all patients after diagnosis of CDI. We performed multivariable logistic regression analyses to investigate the association between 25(OH)D levels and CDI severity, while adjusting for age, Deyo‐Charlson Comorbidity Index, recent hospitalization, and vitamin D supplementation. Results: One hundred patients were enrolled between July 2011 and February 2013. The mean (standard deviation) cohort age and Deyo‐Charlson Comorbidity Index were 62 (19) years and 4 (3), respectively; 54% of patients were male. Mean serum total 25(OH)D level was 22 (10) ng/mL. Mean 25(OH)D₃ level was significantly higher in group A (n = 71) than in group B (n = 29): 21 (1) vs 15 (2) ng/mL, respectively (P = .005). There was no observed difference in mean 25(OH)D₂ levels and total 25(OH)D levels between the 2 groups. Multivariable logistic regression analysis demonstrated an association between 25(OH)D₃ levels and CDI severity (adjusted odds ratio, 0.92; 95% confidence interval, 0.87–0.98). Conclusions: We found a significant inverse association between 25(OH)D₃ levels and CDI severity. Further studies are needed to determine whether vitamin D supplementation can improve outcomes in patients with CDI.     

Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients

Background: Hypovitaminosis D exists postburn. However, evidence‐based guidelines for vitamin D repletion are unknown. This investigation examined differences between D₂ and D₃ supplementation on outcome in children with burn injuries. Methods: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full‐thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7–18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D₂, D₃, or placebo was administered daily during hospitalization using a randomized, double‐blinded study design. Assay of total 25‐hydroxyvitamin D (D25), 1,25‐dihydroxyvitamin D (D1,25), 25‐hydroxyvitamin D₂ (25‐OH‐D₂), 25‐hydroxyvitamin D₃ (25‐OH‐D₃), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval. Results: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1‐year follow up for the placebo (75%), D₂ (56%), and D₃ (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation. Conclusions: The high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D₃ beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.     

Plasma 25-Hydroxyvitamin D Responses of Younger and Older Men to Three Weeks of Supplementation with 1800 IU/day of Vitamin D

Objective: The objective of this study was to compare changes in plasma 25-hydroxyvitamin D (25(OH)D) levels of younger and older men after three weeks of oral vitamin D supplementation.

Methods: Nine younger men (22 to 28 years) and nine older men (65 to 73 years) with self-reported vitamin D intakes below 200 IU/d were enrolled in February and randomized to 1800 IU/d of ergocalciferol (vitamin D₂, n=11) or to a control group (n=7) and followed for three weeks. Blood was collected at baseline, and after one, two and three weeks for measurement of plasma concentrations of total 25(OH)D, 25(OH)D₂ and 25(OH)D₃.

Results: In both the younger and older supplemented men, 25(OH)D₂ and total 25(OH)D concentrations increased significantly during the study, whereas values of these metabolites did not change in younger or older control subjects. No group showed significant changes in 25-hydroxyvitamin D₃. There was a significant interaction between age group and supplement group, suggesting that the effect of vitamin D₂ supplementation on changes in 25(OH)D₂ changes with age. The mean increase in 25(OH)D₂ was greater in the younger supplemented men than in the older supplemented men (37±9 nmol/L vs. 19.5 nmol/L, p=0.027), and this accounted for their significantly greater increase in total 25(OH)D.

Conclusion: These data are consistent with an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed vitamin D.     

Vitamin D2 vs. vitamin D3: They are not one and the same

Conflicting evidence has led to uncertainty as to whether vitamin D₂ and vitamin D₃ are equally efficacious in improving vitamin D status, despite historically being considered equipotent. A systematic review and meta‐analysis completed in 2012 indicated that D₃ was more effective at raising vitamin D levels {using total 25‐hydroxyvitamin D [25(OH)D] as a marker of status} but the meta‐analysis identified high levels of heterogeneity between studies and a lack of statistically powered sample sizes to provide a conclusive answer. Thus, to meet the need for robust data, our research team conducted the largest (to date) randomised, controlled trial comparing the two forms of vitamin D. The D₂–D₃ Study was conducted in 335 healthy South Asian (n = 90) and White European women (n = 245). The study was designed to compare the respective efficacy of vitamin D₂ with vitamin D₃ at raising total 25(OH)D when added to a juice or a biscuit, at a relatively low dose of 15 μg/day for 12 weeks. Overall, the results showed that those who consumed vitamin D₃ showed an average increase in vitamin D status of 74%–75%, whereas an average increase of 33%–34% in vitamin D status was found in those who consumed vitamin D₂. Therefore, this study emphatically shows that vitamin D₃ is more than twice as effective as vitamin D₂ at raising total 25(OH)D concentrations, when given in a low dose that is both physiologically relevant and in line with public health guidance.     

Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico

Abstract

This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana, Mexico and determined the effect of a single oral dose of 50?000?IU vitamin D₃ at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy. Healthy infants were randomized to receive vitamin D₃ or placebo at birth. At birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency (mean 25[OH]D level 18.9?ng/ml); 10% of mothers were vitamin D deficient and 61% were insufficient. Infants receiving vitamin D₃ had higher 25(OH)D levels at two months (N?=?29; 33.9 versus 24.2?ng/ml) and six months (N?=?21; 36.5 versus 27.4?ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months (14.9 versus 33.4?ng/ml). Vitamin D deficiency is common in infants and mothers in Tijuana, Mexico. A single dose of vitamin D₃ at birth was safe and significantly increased 25(OH)D levels during infancy.     

Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized,double-blind,placebo-controlled,clinical trial

PurposeTo estimate the effects of calcium or vitamin D supplementation or a combination of both on blood pressure and serum lipid and carotenoid levels.MethodsNinety-two colorectal adenoma patients were randomized in a pilot, double-blind, placebo-controlled clinical trial of supplemental vitamin D₃ 800 IU and elemental calcium 2.0 g (as calcium carbonate) alone or in combination in divided doses twice daily with meals over 6 months.ResultsRelative to placebo, mean serum triglycerides decreased 30% (P = .10) and 32% (P = .10) in the calcium and calcium plus vitamin D₃ treatment groups, respectively. When the two calcium intervention groups were pooled and compared with the pooled noncalcium groups, the estimated supplemental calcium treatment effects were statistically significant for triglycerides (P = .04). Similar but nonstatistically significant decreases (5%–7%) were observed for serum total cholesterol levels. Mean systolic blood pressure increased 6% (P = .08) in the calcium group; otherwise, there were no appreciable changes in systolic or diastolic blood pressures in any active treatment group. Mean serum total carotenoid levels decreased 14% (P = .07) in the calcium and 9% (P = .10) in the calcium plus vitamin D₃ groups.ConclusionsOur results suggest that supplemental calcium alone or combined with vitamin D₃ but not vitamin D₃ alone may reduce serum lipids and lipophilic micronutrients.     

A Randomized Clinical Trial of Vitamin D Supplementation in Healthy Adolescents

PurposeThe most safe and effective dose of vitamin D supplementation for healthy adolescents is currently unknown. The aim of this study was to compare the efficacy of 200 IU versus 1,000 IU of daily vitamin D₃ for supplementation in healthy adolescents with baseline vitamin D sufficiency.MethodsWe conducted a double-blind, randomized clinical trial. Fifty-six subjects, ages 11–19 years, with baseline vitamin D sufficiency received 1,000 IU or 200 IU of daily vitamin D₃ for 11 weeks. Compliance was assessed using MEMS6 Trackcaps and pill counts.ResultsFifty-three subjects completed the clinical trial. Subjects in the two treatment arms were similar in terms of age, race, gender, body mass index, and dietary calcium and vitamin D intake. Serum 25(OH)D level in the 200 IU treatment arm was 28.1 ± 6.2 ng/mL at baseline (mean ± SD) and 28.9 ± 7.0 ng/mL at follow-up. In the 1,000 IU treatment arm, 25(OH)D levels were 29.0 ± 7.3 and 30.1 ± 6.6 at baseline and follow-up, respectively. Mean change in 25(OH)D level did not differ significantly between treatment arms (p = .87), nor did mean change in parathyroid hormone, calcium, phosphate, bone turnover markers, fasting glucose, or fasting insulin.ConclusionsIn healthy adolescents with baseline vitamin D sufficiency, supplementation with vitamin D₃ doses of 200 and 1,000 IU for 11 weeks did not increase serum 25(OH)D levels, with no significant difference observed between treatment arms.     

Vitamin D nutritional status of women living on a solitary island in Japan: A population-based study

Objective: Serum 25-hydroxyvitamin D [25(OH)D] is a vitamin D metabolite and a good indicator of vitamin D nutritional status. Low 25(OH)D levels accelerate age-related bone loss in women. The aim of this study was to assess 25(OH)D levels using population-based samples from women in a community in Japan. Subjects and Methods: Of all 187 adult women living on a solitary island (Niigata, Japan), 150 (80.2%) were enrolled in a cross-sectional study in early June 1998. After excluding 6 subjects who were undergoing treatment for osteoporosis, 144 female subjects were analyzed. Serum 25(OH)D₂ and 25(OH)D₃ were determined by high-performance liquid chromatography. The sum of 25(OH)D₂ and 25(OH)D₃ was calculated, yielding 25(OH)D, for which a concentration of less than 30 nmol/L was defined as vitamin D insufficiency. Demographic data such as age, height, weight, and body mass index (BMI) were also recorded. Results: The average age of the subjects was 61.3 years (SD 12.8), ranging from 21 to 87. The average concentrations of 25(OH)D₂ and 25(OH)D₃ were 0.5 nmol/L (SD 3.2) and 64.6 nmol/L (SD 17.6), respectively. The number of subjects with 25(OH)D concentration less than 30 nmol/L was 4 of 149 (2.7%). Serum 25(OH)D concentrations were not significantly correlated with age (r=-0.065, p=0.44l) or BMI (r=0.086, p=0.310). Conclusion: The present population-based study confirms adequate levels of 25(OH)D and low prevalence of vitamin D insufficiency in Japanese women. Further research should be directed toward darifying which dietary factors determine vitamin D nutrition.     

Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis

Background: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D₂) or cholecalciferol (vitamin D₃), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. Methods: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to “Preferred Reporting Items for Systematic reviews and Meta-analysis” guidelines. Search terms were constructed on the basis of the “participants”, “intervention”, “control”, “outcome” and “study type” (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. Results: Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. Conclusions: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D₃) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.     

Effect of Vitamin D Supplementation on Depressive Symptoms in Patients With Knee Osteoarthritis

ObjectivesTo determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency.DesignA prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D₃ (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups.Setting and ParticipantsThis clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia.MeasuresThe primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27).ResultsOf 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: ?0.66, 95% confidence interval (CI): ?1.22 to ?0.11, P for difference = .02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: ?0.73, 95% CI: ?1.41 to ?0.05, P for difference = .04) over 24 months.Conclusions/ImplicationsThese findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA.     

Plasma 25-Hydroxyvitamin D3 Levels in Colorectal Cancer Patients and Associations with Physical Activity

Physical activity (PA) and vitamin D are thought to affect colorectal cancer prognosis. The present study investigates associations between 25(OH)D₃ and PA in prospectively followed colorectal cancer patients in the ColoCare study. At 6, 12, and 24 mo after surgery, patients donated a blood sample, wore an accelerometer for 10 consecutive days, and completed a PA questionnaire. Plasma 25-hydroxyvitamin D₃ (25(OH)D₃) levels were measured by high-performance liquid chromatography. We tested associations using partial correlations and multivariate linear regression analysis, adjusted for season, age, and body mass index. A total of 137 assessments of 25(OH)D₃ levels and PA were conducted (58 at 6 mo, 51 at 12 mo, and 28 at 24 mo). More than 60% of the patients were vitamin D-deficient (25(OH)D₃ ≤20 ng/ml), independent of study time point. At 6-mo follow-up, accelerometry-based vigorous and moderate-to-vigorous PAs were positively associated with 25(OH)D₃ levels (P = 0.04; P = 0.006,). PA together with season was a significant predictor of elevated 25(OH)D₃ levels. Our results suggest that the majority of colorectal cancer patients may suffer from vitamin D deficiency. Engaging in PA may be an effective approach to increase their 25(OH)D₃ levels.     

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women

The most representative indicator of vitamin D status in clinical practice is 25(OH)D₃, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D₃ concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)₂D₃/25(OH)D₃) and a higher R4 (24,25(OH)₂D₃/1,25(OH)₂D₃) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D₃/Vit D₃) and R3 (24,25(OH)₂D₃/25(OH)D₃), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.     

Vitamin D Deficiency in Patients With Neuromuscular Diseases With Chronic Respiratory Failure

Background: The prevalence and clinical implications of vitamin D deficiency have never been studied in patients with underlying neuromuscular diseases complicated with chronic respiratory failure. The aim of this study is to demonstrate the prevalence of vitamin D deficiency, its relationship with other bone markers, and mode of nutrition. Materials and Methods: Serum 25‐hydroxyvitamin D (25[OH]D) levels along with calcium, serum albumin, and phosphorus levels were obtained from 57 patients with chronic respiratory failure due to underlying neuromuscular diseases. These levels were obtained during their first visit to a chronic respiratory diseases clinic. Data with regard to nutrition, respiratory muscle function, and level of mobility were also obtained at the same time. Results: Seventy‐five percent of patients had serum 25(OH)D levels ≤30 ng/mL. There is a negative correlation between parathyroid hormone and 25(OH)D levels (P = .006) and corrected calcium levels (P = .066). Serum 25(OH)D levels varied with the mode of nutrition. Patients on enteral nutrition had the highest serum levels of 25(OH)D, whereas combined oral and tube feeds had the lowest 25(OH)D levels (P = .006). Conclusion: Low serum 25(OH)D levels are highly prevalent in patients with neuromuscular disease and chronic respiratory failure. The route of nutrition has an impact on these levels.     

Body Size and Serum 25 Hydroxy Vitamin D Response to Oral Supplements in Healthy Older Adults

Background: Vitamin D insufficiency is prevalent in the northeast United States. Since vitamin D insufficiency is readily amenable to supplementation, it is important to understand what factors are associated with serum 25 hydroxy vitamin D (25(OH)D) response to vitamin D supplementation.

Objective: In this study we examined the association of serum 25(OH)D response to vitamin D supplementation with body size in a population of elderly subjects.

Methods: 257 healthy, ambulatory men and women 65 years of age or older were randomly assigned to treatment with either 700 IU/day (17.5 μg/d) of supplemental vitamin D₃ and 500 mg/day (12.5 mmol/d) of supplemental calcium, or to placebo.

Results: In multivariate regression analyses, after adjusting for baseline 25(OH)D, season, and sex, we found change in 25(OH)D to be inversely associated with baseline BMI (p = 0.01) in subjects treated with supplements for one year. Change in 25(OH)D was also negatively associated with other baseline anthropometric measurements in these subjects.

Conclusion: Our study implies that body size should be taken into account when estimating the amount of vitamin D intake needed to raise 25(OH)D to the desired level.     

Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D₃, 25(OH)D₂, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D₂ and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D₃ was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D₂ or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D₂, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D₂ was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone.     

Vitamin D Metabolite Profile in Cholecalciferol- or Calcitriol-Supplemented Healthy and Mammary Gland Tumor-Bearing Mice

To analyze if the prometastatic activity of calcitriol (active vitamin D₃ metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D₃ diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D₃:24,25(OH)₂D₃ was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D₃:3-epi-25(OH)D₃ was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed.     

CYP24A1 and CYP27B1 Polymorphisms,Concentrations of Vitamin D Metabolites,and Odds of Colorectal Adenoma Recurrence

Development of colorectal adenoma and cancer are associated with low circulating 25-hydroxyvitamin D [25(OH)D] levels. However, less is known regarding colorectal neoplasia risk and variation in CYP27B1 or CYP24A1, genes encoding the enzymes responsible for the synthesis and catabolism of 1α,25-hydroxyvitamin D [1,25(OH)₂D]. This study examined associations between CYP27B1 and CYP24A1 polymorphisms, circulating 25(OH)D and 1,25(OH)₂D concentrations, and colorectal adenoma recurrence in a pooled sample from 2 clinical trials (n = 1,188). Nominal associations were observed between increasing copies of the T allele in CYP24A1 rs927650 and 25(OH)D concentrations (P = 0.02); as well as colorectal adenoma recurrence, with odds ratios (95% confidence intervals) of 1.30 (0.99–1.70) and 1.38 (1.01–1.89) for heterozygotes and minor allele homozygotes, respectively (P = 0.04). In addition, a statistically significant relationship between CYP24A1 rs35051736, a functional polymorphism, and odds for advanced colorectal adenoma recurrence was observed (P < 0.001). Further, nominally statistically significant interactions were observed between rs2296241 and 25(OH)D as well as rs2762939 and 1,25(OH)₂D (P_interaction = 0.10, respectively). Overall, CYP24A1 polymorphisms may influence the development of advanced lesions, and modify the effect of vitamin D metabolites on adenoma recurrence. Further study is necessary to characterize the differences between circulating vitamin D metabolite measurements compared to cellular level activity in relation to cancer risk.     

Ultra-Marathon-Induced Increase in Serum Levels of Vitamin D Metabolites: A Double-Blind Randomized Controlled Trial

Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon runs. Methods: A repeated-measures design was implemented, in which 27 amateur runners were assigned into two groups: those who received a single dose of vitamin D₃ (150,000 IU) 24 h before the start of the marathon (n = 13) and those (n = 14) who received a placebo. Blood samples were collected 24 h before, immediately after, and 24 h after the run. Results: In both groups of runners, serum 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ levels significantly increased by 83%, 63%, and 182% after the ultra-marathon, respectively. The increase was most pronounced in the vitamin D group. Body mass and fat mass significantly decreased after the run in both groups. Conclusions: Ultra-marathon induces the mobilization of vitamin D into the blood. Furthermore, the 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ increases imply that the exercise stimulates vitamin D metabolism.     

Fasting and Exercise Induce Changes in Serum Vitamin D Metabolites in Healthy Men

Background: Vitamin D plays pleiotropic roles in the body and hence, changes in its metabolism and distribution during starvation could play an important role in the adaptive response to famine. We aimed to identify the responses of some vitamin D metabolites to 8 d of fasting and exercise. Methods: A repeated-measures design was implemented, in which 14 male volunteers fasted for 8 d and performed an exercise test before and after fasting. Serum samples were collected on day 1 after night fasting and after 8 d of complete food restriction, before and 1 h and 3 h after exercise. Results: After 8 d of fasting, compared with baseline values, serum 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels significantly increased; those of 25(OH)D₃ and 1,25(OH)₂D₃ were unaffected; and those of 25(OH)D₂ decreased. Exercise on the first day of fasting induced an increase in serum 3-epi-25(OH)D₃ levels, while exercise performed after 8 d of fasting induced an increase in 25(OH)D₃, 24,25(OH)₂D₃, 25(OH)D₂, and 3-epi-25(OH)D₃ levels. Conclusion: Increases in 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels imply that fasting stimulates vitamin D metabolism. The effects of exercise on serum vitamin D metabolites, which are most pronounced after fasting and in subjects with serum 25(OH)D₃ above 25 ng/mL, support the notion that fasting and exercise augment vitamin D metabolism.