Association Between Prehospital Vitamin D Status and Hospital‐Acquired Clostridium difficile Infections

Objective: To investigate whether preadmission 25‐hydroxyvitamin D (25(OH)D) levels are associated with the risk of hospital‐acquired Clostridium difficile infection (HACDI). Materials and Methods: Our retrospective cohort study focused on 568 adult patients from 2 Boston teaching hospitals between August 1993 and November 2006. All patients had 25(OH)D levels measured before hospitalization and were at risk for HACDI (defined as the presence of C difficile toxin A or B in stool samples obtained >48 hours after hospitalization). We performed multivariable regression analyses to test the association of prehospital 25(OH)D levels with HACDI while adjusting for clinically relevant covariates. Results: In these 568 patients, mean (SD) 25(OH)D level was 19 (12) ng/mL, and 11% of patients met criteria for incident HACDI. Following adjustment for age, sex, race (nonwhite vs white), patient type (medical vs surgical), and Deyo‐Charlson index, patients with 25(OH)D levels <10 ng/mL had higher odds of HACDI (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.01–8.34) compared with patients with 25(OH)D levels ≥30 ng/mL. When patients with HACDI were analyzed relative to a larger patient cohort without HACDI (n = 5047), those with 25(OH)D levels <10 ng/mL (OR, 4.96; 95% CI, 1.84–13.38) and 10–19.9 ng/mL (OR, 3.36; 95% CI, 1.28–8.85) had higher adjusted odds of HACDI compared with patients with 25(OH)D levels ≥30 ng/mL. Conclusions: In our cohort of adult patients, vitamin D status before hospital admission was inversely associated with the risk of developing HACDI. These data support the need for randomized, controlled trials to test the role of vitamin D supplementation to prevent HACDI.     

25‐Hydroxyvitamin D Concentrations and Clostridium difficile Infection: A Meta‐Analysis

Background: Well‐known risk factors for Clostridium difficile infection (CDI) are exposure to antibiotics and gastric acid suppressants. Recent studies have provided some evidence of an association between hypovitaminosis D and the risk of CDI. Therefore, this meta‐analysis aimed to pool all the existing evidence to investigate the association between 25‐hydroxyvitamin D (25[OH]D) and CDI. Methods: A systematic search was conducted in 3 databases (PubMed, Embase, and Web of Sciences) for epidemiological studies that examined the association between mean 25(OH)D concentrations and CDI as well as between 25(OH)D status and CDI severity or recurrence. 25(OH)D status was defined as “lower” or “higher” at a threshold concentration of <20 or ≥20 ng/mL, respectively. Pooled effect sizes were computed using the inverse variance heterogeneity model of meta‐analysis. Results: Eight publications (n = 4479 patients) were included in the meta‐analysis. The mean concentration of 25(OH)D in patients with CDI was 3.54 ng/mL (95% confidence interval [CI], 0.39–6.89 ng/mL) lower than in patients without CDI. Patients with lower 25(OH)D status had a higher odds (odds ratio [OR], 1.61; 95% CI, 1.02–2.53) of developing severe CDI compared with those with a higher 25(OH)D status. No significant association was found between 25(OH)D status and CDI recurrence. Conclusion: The results of this meta‐analysis suggest that lower mean concentrations of 25(OH)D were associated with CDI. A lower 25(OH)D status increased the odds of severe CDI but not of CDI recurrence.     

Association Between Serum 25(OH)D Level and Nonspecific Musculoskeletal Pain in Acute Rehabilitation Unit Patients

Objective: Nonspecific musculoskeletal pain can be difficult to manage in acute rehabilitation unit (ARU) patients. We investigated whether vitamin D status is a potential modifiable risk factor for nonspecific musculoskeletal pain in ARU patients. Materials and Methods: This cross‐sectional study focused on 414 adults from an inpatient ARU in Mission Viejo, California, between July 2011 and June 2012. On ARU admission, all patients had serum 25‐hydroxyvitamin D (25(OH)D) levels measured and were assessed for nonspecific musculoskeletal pain. We performed multivariable logistic regression to test the association of serum 25(OH)D level with nonspecific musculoskeletal pain while adjusting for clinically relevant covariates. Results: Among these 414 patients, mean (SD) 25(OH)D level was 29 (12) ng/mL, and 30% had nonspecific musculoskeletal pain. After adjustment for age, sex, race, body mass index, Functional Independence Measure score, Deyo‐Charlson Comorbidity Index, fractures, steroid use, history of osteoporosis/osteomalacia, and patient type (orthopedic, cardiac, neurological, spinal cord injury, or traumatic brain injury), serum 25(OH)D level was inversely associated with nonspecific musculoskeletal pain (odds ratio [OR] per 10 ng/mL, 0.67; 95% confidence interval [CI], 0.48–0.82). When 25(OH)D level was dichotomized, patients with levels <20 ng/mL had higher odds of nonspecific musculoskeletal pain (OR, 2.33; 95% CI, 1.23–4.17) compared with patients with levels ≥20 ng/mL. Conclusions: In adult patients, serum 25(OH)D level on admission to ARU was inversely associated with nonspecific musculoskeletal pain. These data support the need for randomized, controlled trials to test the role of vitamin D supplementation to improve nonspecific musculoskeletal pain in ARU patients.     

Prolonged Clostridium difficile Infection May Be Associated With Vitamin D Deficiency

Background: Clostridium difficile infection (CDI) is one of the leading causes of hospital‐acquired infections, creating a financial burden for the U.S. healthcare system. Reports suggest that vitamin D–deficient CDI patients incur higher healthcare‐associated expenses and longer lengths of stay compared to nondeficient counterparts. The objective here was to evaluate the relationship between vitamin D level and CDI recurrence. Materials and Methods: A retrospective chart review was conducted for 112 patients with vitamin D level drawn within 3 months of CDI diagnosis. Recurrence, severity of disease, 30‐day mortality, and course of CDI were assessed. Results: The vitamin D–deficient group included 56 patients, and the normal group included 56 patients. The mean age of vitamin D–deficient and –sufficient groups was 68 ± 15.7 and 71 ± 14.4 years, respectively. The mean 25(OH) D level in the deficient group was 11.7 ± 4.6 ng/mL, and it was 36.2 ± 16.2 ng/mL in the normal group. A longer course of diarrhea was apparent in the vitamin D–deficient group compared to the normal group: 6.1 days (95% confidence interval [CI], 4.9–7.2) vs 4.2 days (95% CI, 3.5–4.9; P = .01). Sepsis rate was 24% in vitamin D–deficient group and 13% in normal group (P = .03). There were no differences in CDI recurrence, length of stay, severity of illness, and mortality with respect to vitamin D status. Conclusion: There may be an association between course of diarrhea and increased rate of sepsis in vitamin D–deficient CDI patients.     

Association of Serum Vitamin D Concentration With Clinical Symptoms and Quality of Life in Patients With Irritable Bowel Syndrome

Objective: A high prevalence of vitamin D deficiency (VDD) in gastrointestinal (GI) disorders and the role of vitamin D in the function of the gut have been shown previously. Therefore, we aimed to evaluated the VDD and the possible association of the GI symptoms severity and quality of life (QoL) score with the serum levels of vitamin D in irritable bowel syndrome (IBS).

Methods: A total of 90 patients with IBS based on Rome III criteria enrolled in the study from the tertiary referral university hospital. In addition, 90 sex- and age-matched healthy controls (HCs) were recruited. To measure the serum levels of 25(OH)D₃, blood samples were taken from all the participants. Severity of clinical symptoms, IBS quality of life (IBS-QoL), and IBS symptom severity score (IBSSS) were assessed.

Results: In 66.7% of IBS patients, serum 25(OH)D₃ concentrations were <20?ng/mL. The mean serum 25(OH)D₃ of IBS patients was statistically (p?<?0.05) lower vs. HCs. When different subtypes were analyzed, the serum 25(OH)D₃ concentrations in diarrhea-predominant IBS were statistically (p?<?0.05) lower as compared to HCs. Furthermore, the lower serum concentrations of 25(OH)D₃ were associated (p?<?0.05) with higher severity of abdominal pain and distention, flatulence, overall GI symptoms, and IBSSS. However, a direct significant association was seen between IBS-QoL and serum 25(OH)D₃.

Conclusion: Results of this study showed a high prevalence of VDD in patients with IBS. In addition, VDD was associated with a higher severity of clinical symptoms and lower QoL in IBS.     

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.     

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.     

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.     

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.     

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 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.     

Assessing the Relationship between Vitamin D3 and Stratum Corneum Hydration for the Treatment of Xerotic Skin

Vitamin D₃ has been called the “sunshine” vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D₃ is linked to many health benefits, however serum levels of vitamin D₃ have been decreasing over the last few decades and the lower levels of vitamin D₃ may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D₃) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D₃ (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D₃.     

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.     

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.     

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 Metabolites and Clinical Outcome in Hospitalized COVID-19 Patients

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D₃, 25(OH)D₂, 24,25(OH)₂D₃, and 25,26(OH)₂D₃ were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19.     

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.     

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.     

Relationship of very low serum 25-hydroxyvitamin D<Subscript>3</Subscript> levels with long-term survival in a large cohort of colorectal cancer patients from Germany

To investigate the association of serum 25-hydroxyvitamin D (25(OH)D₃) with survival in a large prospective cohort study of colorectal cancer (CRC) patients. The study population consisted of 2,910 patients diagnosed with CRC between 2003 and 2010 who participated in the DACHS study, a multicenter study from Germany with comprehensive long-term follow-up. 25(OH)D₃ was determined in serum samples collected shortly after cancer diagnosis by High Performance Liquid Chromatography-Electro Spray Ionization-Mass Spectrometry. Analyses of survival outcomes were performed using Cox regression with comprehensive adjustment for relevant confounders. The majority (59%) of CRC patients were vitamin D deficient (serum 25(OH)D₃ levels <30 nmol/L). During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Compared to patients in the highest 25(OH)D₃ quintile (>45.20 nmol/L), those in the lowest 25(OH)D₃ quintile (<11.83 nmol/L) had a strongly increased mortality. Adjusted hazard ratios (95% Confidence Interval) were 1.78 (1.39–2.27), 1.65 (1.24–2.21), 1.32 (1.03–1.71) and 1.48 (1.18–1.85) for all-cause mortality, CRC-specific mortality, recurrence-free and disease-free survival, respectively. Subgroup analyses did not show any significant effect modification across strata defined by sex, age, stage, body mass index, or the late entry. Dose–response analyses showed a strong inverse relationship between serum 25(OH)D₃ levels and survival endpoints at 25(OH)D₃ levels <30 nmol/L, and no association with mortality at higher 25(OH)D₃ levels. Vitamin D deficiency is highly prevalent in CRC patients and a strong independent predictor of poor prognosis. The possibility of enhancing CRC prognosis by vitamin D supplementation, ideally combined with outdoor physical activity, should be evaluated by randomized controlled trials focusing on patients with vitamin D deficiency.     

Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease

Several lines of evidence point to a possible relationship between vitamin D and cardiovascular disease. Animal experiments and observational studies in humans suggest vitamin D to be arteriotoxic and an association of high intake of vitamin D with increased incidence of ischemic heart disease (IHD). The major source of vitamin D in adults is vitamin D synthesized in the skin through exposure to the sun. In tropical environment there is a possibility of high level of solar exposure and enhanced serum levels of vitamin D in the population. We explored the relation between serum level of 25-hydroxyvitamin D₃ and IHD in a case-control study involving 143 patients with either angiographic evidence of coronary artery disease or patients with acute myocardial infarction and 70 controls, all men in the age group of 45–65 years. Fasting blood samples were collected, serum separated and serum levels of 25-hydroxyvitamin D₃ was measured by protein binding radioligand assay. Serum levels of cholesterol, triglyceride, calcium, magnesium and inorganic phosphate were also determined. Prevalences of diabetes, hypertension and smoking history were noted. Statistical comparisons of variables between cases and controls were done using ²-tests. Multivariate logistic regression analysis was done to examine the association of IHD with serum levels of 25-hydroxyvitamin D₃ controlling for selected variables. Serum levels of 25-hydroxyvitamin D₃, calcium, inorganic phosphate, total cholesterol, low density lipoprotein and triglycerides were elevated in a higher proportion of patients, compared to controls. Serum levels of 25-OH-D₃ above 222.5 nmol/l (89 ng/ml) was observed in 59.4% of cases compared to 22.1% in controls (p < 0.001; unadjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 2.62–10.21). When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D₃ levels ( 222.5 nmol/l, 89 ng/ml) and IHD is 3.18 (95% CI: 1.31–7.73). Given the evidences for the arteriotoxicity of vitamin D, further investigations are warranted to probe whether the elevated serum levels of 25-hydroxyvitamin D₃ observed in patients with IHD in a tropical environment has any pathogenic significance.