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.     

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.     

Vitamin D Metabolite Ratio in Pregnant Women with Low Blood Vitamin D Concentrations Is Associated with Neonatal Anthropometric Data

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)₂D₃ to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D₃ to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D₂, 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.     

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.     

Bariatric Surgery Induced Changes in Blood Cholesterol Are Modulated by Vitamin D Status

The effect of metabolically active bariatric surgery treatment on lipid metabolism is inconclusive. The authors of this study presume that initial vitamin D status may play a regulating role in influencing the beneficial post-effects of bariatric surgery, especially the lipid profile. The biochemical data obtained from 24 patients who had undergone laparoscopic one-anastomosis gastric bypass (OAGB) at baseline, 3 months before the surgery, at the time of surgery, and 6 months later, demonstrate that vitamin D status influenced the postoperative lipid profile. The baseline established the partition line which divided patients into two groups according to the stated calcidiol initial concentration level of 32 ng/mL. The data shows that OAGB induces a decrease in TG and hsCRP while increasing HDL. Conversely, in patients whose 25(OH)D₃ was below 32 ng/mL TC significantly increased while those above this concentration remained in the normal physiological range. The changes induced by OAGB in TG, glucose, and hsCRP were similar in both groups. Unexpectedly, the surgery did not affect vitamin D metabolites. In conclusion, the results of the study suggest that a higher concentration of serum 25(OH)D₃ may enhance the protective effects of OAGB.     

Differences in the Concentration of Vitamin D Metabolites in Plasma Due to the Low-Carbohydrate-High-Fat Diet and the Eastern European Diet—A Pilot Study

Vitamin D deficiency is a global problem with many health consequences, and it is currently recommended to supplement vitamin D. Change of diet should also be considered to ensure adequate vitamin D in the human body. The aim of this study was to assess the concentration of vitamin D metabolites in two different groups: one group on the low-carbohydrate-high-fat (LCHF) diet and the other group on the Eastern European (EE) diet. In the first stage, 817 participants declaring traditional EE diet or LCHF diet were investigated. Nutrition (self-reported 3-day estimated food record) and basic anthropometric parameters were assessed. After extra screening, 67 participants on the EE diet and 41 on the LCHF diet were qualified for the second stage. Plasma 25-hydroxycholecalciferol (25(OH)D₃) and (25(OH)D₂) concentration was measured by the validated HPLC—MS/MS method. Plasma 25(OH)D₃ concentration was significantly higher in the group on the LCHF diet (34.9 ± 15.9 ng/mL) than in the group on the EE diet (22.6 ± 12.1 ng/mL). No statistical differences were observed in plasma 25(OH)D₂ concentration between the study groups (p > 0.05). Women had a higher plasma 25(OH)D₂ concentration than men regardless of diet type. The LCHF diet had a positive influence on plasma vitamin D concentration. However, long-term use of the LCHF diet remains contentious due to the high risk of cardiovascular disease. This study confirmed that the type of diet influences the concentration of vitamin D metabolites in the plasma.     

Association of Dietary Vitamin D Intake,Serum 25(OH)D3, 25(OH)D2 with Cognitive Performance in the Elderly

Background: As life expectancy increases, cognitive performance decline in the elderly has become one of the major global challenges. We aimed to evaluate the association of dietary vitamin D (VD), serum 25-hydroxyvitamin D3 (25(OH)D₃), 25-hydroxyvitamin D2 (25(OH)D₂), and total 25-hydroxyvitamin (25(OH)D) concentration with cognitive performance in older Americans. Methods: The data from the National Health and Nutrition Examination Survey (NHANES), 2011–2014 was used. The cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). A binary logistic regression model was applied to evaluate the association between VD and cognitive performance, and restricted cubic spline model was adopted to evaluate the dose–response relationship. Results: While comparing to the lowest dietary VD intake group, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest dietary VD intake group were 0.51 (0.36–0.72) for the Animal Fluency test score and 0.45 (0.31–0.66) for DSST score, respectively; and those of serum total 25(OH)D and 25(OH)D₃ concentration were 0.68 (0.47–0.97) and 0.62 (0.44–0.86) for DSST score. L-shaped relationships were identified for dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration with cognition performance. The associations between dietary VD intake, serum total 25(OH)D and cognitive performance were non-significant when stratified by gender. Conclusions: The study indicates that dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration were positively associated with cognitive performance. Further studies are needed to clarify the possible effects of dietary VD intake and serum 25(OH)D₂, 25(OH)D₃ on cognitive performance.     

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.     

Nordic Walking Rather Than High Intensity Interval Training Reduced Myostatin Concentration More Effectively in Elderly Subjects and the Range of This Drop Was Modified by Metabolites of Vitamin D

The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training that can be performed independently. In this study, we examined the effects of Nordic walking (NW) and high intensity interval training (HIIT) with regard to the impact of the metabolite vitamin D. We assigned 32 overweight adults (age = 61 ± 12 years) to one of two training groups: NW = 18 and HIIT = 14. Body composition assessment and blood sample collection were conducted before starting the training programs and a day after their completion. NW training induced a significant decrease in myostatin (p = 0.05) concentration; however, the range was dependent on the baseline concentrations of vitamin D metabolites. This drop was accompanied by a significant negative correlation with the decorin concentration. Unexpectedly, NW caused a decrement in both forms of osteocalcin: undercarboxylated (Glu-OC) and carboxylated-type (Gla-OC). The scope of Glu-OC changes was dependent on a baseline concentration of 25(OH)D₂ (r = −0.60, p = 0.01). In contrast, the HIIT protocol did not induce any changes. Overall results revealed that NW diminished the myostatin concentration and that this effect is more pronounced among adults with a sufficient concentration of vitamin D metabolites.     

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)₂D₃ and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.     

Determination of vitamin D3 and 25-hydroxyvitamin D3 in foodstuffs by HPLC UV-DAD and LC–MS/MS

In order to generate new data for vitamin D content for the Canadian Nutrient File, a method for the quantification of vitamin D₃ and 25(OH)D₃ in foodstuffs has been modified and improved. Vitamin D₃ was quantified using reverse phase liquid chromatography (LC) with UV-diode array detector (UV-DAD), while 25(OH)D₃ was measured by triple quadrupole mass spectrometry (APCI MS/MS). Quantification was by internal standards (IS) using vitamin D₂ and 25(OH)D₂. A Certified Reference Material (CRM-421 containing vitamin D₃) and a control sample (internally generated reference material of ground pork containing both vitamin D₃ and 25(OH)D₃) were used as validation and quality control tools. Limit of detection for both compounds was 0.04 μg/100 g. Accuracy for vitamin D in the CRM-421 was 99% (0.142 mg/kg for a target of 0.143, n = 10). Recovery of vitamin D₃ in ground pork was 97% (88% absolute recovery). For 25(OH)D₃, a recovery of 94% (73% absolute recovery) was obtained. Using this method, data for vitamin D₃ and 25(OH)D₃ content in a variety of foods (pork, beef, eggs, poultry, fish, and dinners) have been generated.     

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.     

The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D₃ (25(OH)D₃), 25-hydroxyvitamin D₂ (25(OH)D₂) and Epi-25-hydroxyvitamin D₃ (Epi-25(OH)D₃)), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12–25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen’s Kappa test. Serum total 25(OH)D ranged from 33.8–169.8 nmol/L and plasma ranged from 28.6–211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D₃ (7.38 nmol/L; 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D₃ (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.     

Dietary vitamin D intake is not associated with 25-hydroxyvitamin D3 or parathyroid hormone in elderly subjects,whereas the calcium-to-phosphate ratio affects parathyroid hormone

This cross-sectional study investigates whether serum 25-hydroxyvitamin D₃ [25(OH)D₃] and intact parathyroid hormone (iPTH) are affected by vitamin D, calcium, or phosphate intake in 140 independently living elderly subjects from Germany (99 women and 41 men; age, 66-96 years). We hypothesized that habitual dietary intakes of vitamin D, calcium, and phosphate are not associated with 25(OH)D₃ or iPTH and that body mass index confounds these associations. Serum 25(OH)D₃ and iPTH were measured by an electrochemiluminescence immunoassay. Dietary intake was determined using a 3-day estimated dietary record. The median dietary intake levels of vitamin D, calcium, and phosphate were 3 μg/d, 999 mg/d, and 1250 mg/d, respectively. Multiple regression analyses confirmed that dietary vitamin D and calcium did not affect 25(OH)D₃ or iPTH; however, supplemental intakes of vitamin D and calcium were associated with 25(OH)D₃ after adjustment for age, sex, body composition, sun exposure, physical activity, and smoking. In addition, phosphate intake and the calcium-to-phosphate ratio were associated with iPTH after multiple adjustments. In a subgroup analysis, calcium and vitamin D supplements, as well as phosphate intake, were associated with 25(OH)D₃ and/or iPTH in normal-weight subjects only. Our results indicate that habitual dietary vitamin D and calcium intakes have no independent effects on 25(OH)D₃ or iPTH in elderly subjects without vitamin D deficiency, whereas phosphate intake and the calcium-to-phosphate ratio affect iPTH. However, vitamin D and calcium supplements may increase 25(OH)D₃ and decrease iPTH, even during the summer, but the impact of supplements may depend on body mass index.     

Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D₃, 25(OH)D₂, 1,25(OH)₂D₃, 3-epi-25(OH)D₃ and 24,25(OH)₂D₃), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D₃ levels (p > 0.05) and higher 25(OH)D₃/24,25(OH)₂D₃ ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D₃/24,25(OH)₂D₃ ratio (r = 0.36, p < 0.05). The increase in 25(OH)D₃ after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D₃/24,25(OH)₂D₃ ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.     

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)₂D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)₂D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites.     

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.     

Food fortification and biofortification as potential strategies for prevention of vitamin D deficiency

Hypovitaminosis D (vitamin D deficiency) is widespread throughout the world. The cutaneous production of vitamin D through sunlight can be limited by several factors (e.g. skin pigmentation, sunscreen usage and, increasingly, indoor lifestyle). Thus, diet has become an important strategy to increase vitamin D intake and status {blood 25‐hydroxyvitamin D [25(OH)D]}. However, there are a limited number of foods that naturally contain vitamin D, and concentrations can vary significantly between and within species. The need for vitamin D‐fortified foods (including via direct fortification and biofortification) to support the adequacy of vitamin D status is a corollary of several limitations to synthesise vitamin D from sunlight. Ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) can be found in some mushrooms and animal‐derived foods, respectively. Evidence has shown vitamin D₃ is more effective than vitamin D₂ at raising 25(OH)D blood concentrations. The vitamin D metabolite, 25(OH)D_3, is present in animal‐derived foods (e.g. meat, eggs and fish), and several intervention trials have shown 25(OH)D₃ to be more effective at raising blood 25(OH)D concentrations than vitamin D₃. In addition, 25(OH)D₃ supplements may prove to be preferable to vitamin D₃ for patients with certain clinical conditions. However, there is limited evidence on the effects of 25(OH)D₃‐fortified foods on human vitamin D status and health, both in the general population and patients with certain conditions, and long‐term randomised controlled trials are needed in this area.     

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.