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.     

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.     

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 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.     

Pretreatment 25‐Hydroxyvitamin D Levels and Durability of Anti–Tumor Necrosis Factor–α Therapy in Inflammatory Bowel Diseases

Introduction: Emerging evidence supports an immunologic role for 25‐hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti–tumor necrosis factor (TNF)–α therapy in patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: All IBD patients who had plasma 25(OH)D level checked <3 months prior to initiating anti–TNF‐α therapy were included in this retrospective single‐center cohort study. Our main predictor variable was insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting for potential confounders was used to identify the independent effect of pretreatment vitamin D on biologic treatment cessation. Results: Our study included 101 IBD patients (74 CD; median disease duration 9 years). The median index 25(OH)D level was 27 ng/mL (interquartile range, 20–33 ng/mL). One‐third of the patients had prior exposure to anti–TNF‐α therapy. On multivariate analysis, patients with insufficient vitamin D demonstrated earlier cessation of anti–TNF‐α therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03–4.39; P = .04). This effect was significant in patients who stopped treatment for loss of response (HR, 3.49; 95% CI, 1.34–9.09) and stronger for CD (HR, 2.38; 95% CI, 0.95–5.99) than UC (P = NS). Conclusions: Our findings suggest that vitamin D levels may influence durability of anti–TNF‐α induction and maintenance therapy. Larger cohort studies and clinical trials of supplemental vitamin D use with disease activity as an end point may be warranted.     

Low 25-Hydroxyvitamin D Concentrations and Risk of Incident Cognitive Impairment in Black and White Older Adults: The Health ABC Study

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as <20?ng/mL, 20 to <30?ng/mL, or ≥30?ng/mL. Cognitive impairment was defined as a score >1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were <30?ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n?=?340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations <30?ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations <20?ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08–3.91), p?=?0.03) compared to participants with 25(OH)D concentrations ≥30?ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks.     

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients

Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.     

Comprehensive Safety Monitoring of 12‐Month Daily 7000‐IU Vitamin D3 Supplementation in Human Immunodeficiency Virus–Infected Children and Young Adults

Background: There is uncertainty whether long‐term daily dosing with vitamin D₃ (cholecalciferol) supplementation (vitD₃) above the 4000‐IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo‐controlled trial, we determined if supplementation with 7000‐IU/d vitD₃ for 12 months in human immunodeficiency virus (HIV)–Infected subjects was safe and/or associated with metabolic outcomes. Material and Methods: A total of 58 HIV‐infected subjects—aged 9–24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)—were recruited, randomized to 7000‐IU/d vitD₃ or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25‐hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study‐defined serious adverse events—that is, elevated serum calcium plus 25(OH)D >160 ng/mL—and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Results: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Conclusions: Safety of daily 7000‐IU vitD₃ supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High‐dose daily vitD₃ supplementation was efficacious in improving vitamin D status, and there were no safety events.     

Association of racial disparities in the prevalence of insulin resistance with racial disparities in vitamin D levels: National Health and Nutrition Examination Survey (2001-2006)

We tested the hypothesis that racial differences in vitamin D levels are associated with racial disparities in insulin resistance between blacks and whites. Among 3628 non-Hispanic black and white adults in the National Health and Nutrition Examination Survey from 2001 to 2006, we examined the association between race and insulin resistance using the homeostasis assessment model for insulin resistance. We conducted analyses with and without serum 25-hydroxyvitamin D (25[OH]D). We adjusted for age, sex, educational level, body mass index, waist circumference, physical activity, alcohol intake, smoking, estimated glomerular filtration rate, and urinary albumin/creatinine ratio. Blacks had a lower mean serum 25(OH)D level compared with whites (14.6 [0.3] ng/mL vs 25.6 [0.4] ng/mL, respectively; P < .0001). Blacks had a higher odds ratio (OR) for insulin resistance without controlling for serum 25(OH)D levels (OR, 1.67; 95% confidence interval, 1.26-2.20). The association was not significant (OR, 1.28; 95% confidence interval, 0.90-1.82) after accounting for serum 25(OH)D levels. The higher burden of insulin resistance in blacks compared with whites may be partially mediated by the disparity in serum 25(OH)D levels.     

Evaluation of the deficiency status of 25-hydroxyvitamin D and associated factors in Southwest China: A hospital-based retrospective cross-sectional analysis of a low-latitude,high-altitude,multiracial region

Vitamin D deficiency is widespread in different populations and regions worldwide and has become a global health issue. The vitamin D status of the population in the Yunnan Province of Southwest China has not been evaluated to date. Therefore, in this study, we evaluated the vitamin D status according to the serum concentrations of 25-hydroxyvitamin D (25(OH)D) in individuals of Yunnan Province, a low-latitude, high-altitude and multiracial region in China. The data on 25(OH)D concentrations from October 2012 to December 2017 were retrospectively collected and assessed using the laboratory information system from 52 950 hospital-based participants (age, 1 day–96 years; females, 73.74%). The serum concentration of 25(OH)D was evaluated using a chemiluminescent immunoassay. The analysis was stratified by sex, age, sampling season, testing year, minority, residential district, latitude, altitude and meteorological factors. Vitamin D status was classified as follows: severe deficiency: <10 ng/mL; deficiency: <20 ng/mL; insufficiency: <30 ng/mL; and sufficiency: ≥30 ng/mL. The results showed that vitamin D deficiency is highly prevalent in Yunnan Province in a hospital-based cohort, with a deficiency and severe deficiency rate of 65.1% and a sufficiency rate of 5.30%. Significantly lower vitamin D levels and sufficiency rates were observed in females than in males (20.13 ± 7.22 ng/mL vs. 17.56 ± 6.66 ng/mL and 8.20% vs. 4.20%; p < 0.01, respectively); in spring and winter (16.93 ± 6.24 ng/mL; 2.97% and 16.38 ± 6.43 ng/mL; 3.06%, respectively) than in summer and autumn (20.23 ± 7.14 ng/mL; 8.02% and 19.10 ± 6.97 ng/mL; 6.61% [p < 0.01], respectively); and in older individuals (0–6 years: 28.29 ± 13.13 ng/mL vs. >60 years: 14.88 ± 8.39 ng/mL; p < 0.01). Relatively higher vitamin D levels were observed in individuals of Yi, Zhuang, Hani, Dai, Miao and Lisu minorities and lower levels in individuals of Hui and Zang minorities compared with those of the Han nationality (p < 0.01). The mean sunlight duration, mean air temperature, maximum ultraviolet value and latitude were significantly correlated with vitamin D levels (r = −0.53, 0.60, 0.31, −0.68, respectively; p < 0.05). These results suggest that vitamin D status is influenced by sex, age, minority, latitude and some meteorological factors in areas with high and low altitudes. Hence, new public health policies, such as advice on sunshine exposure, food fortification and nutrition education, as well as the implementation of vitamin D supplementation programmes must be considered to alleviate vitamin D deficiency in Yunnan province, Southwest China.     

Association between Maternal Serum 25-Hydroxyvitamin D Concentrations and the Risk of Preterm Birth in Central Sudan: A Case–Control Study

There are few published studies on the association between vitamin D concentrations and preterm birth (PB) in sub-Saharan Africa. The current study aimed to assess the association between 25-hydroxyvitamin D (25[OH)] D) levels and PB. A matched case–control study (60 women in each arm) was conducted in Medani maternity hospital in central Sudan. The cases were women with spontaneous PB, and healthy women with term deliveries were the controls. The clinical/medical and obstetric history was gathered using a questionnaire. The enzyme-linked immunosorbent assay was used to measure the serum 25(OH)D levels. Women with PB had significantly lower median (interquartile range) 25(OH)D concentrations compared with the controls (18.4 (7.3) ng/mL vs. 20.2 (16.5) ng/mL, p = 0.001). Forty-two (70.0%) women with PB and 29 (48.3%) women in the control group had vitamin D deficiency (25(OH)D level ≤ 20 ng/mL). The results of the multivariable logistic regression showed that the 25(OH)D concentrations were negatively associated with PB (adjusted odds ratio (aOR) = 0.92, 95% confidence interval (CI) = 0.87–0.97). Vitamin D-deficient pregnant women were at a higher risk of PB (aOR = 2.69, 95% CI = 1.17–6.23). Low 25(OH)D concentrations were found at the time the variable was determined in women with spontaneous PB and were an independent risk factor for PB.     

Plasma 25‐Hydroxyvitamin D Levels at Initiation of Care and Duration of Mechanical Ventilation in Critically Ill Surgical Patients

Objective: Limited data exist regarding the relationship between plasma 25‐hydroxyvitamin D levels and duration of respiratory support. Our goal was to explore whether vitamin D status at the time of intensive care unit (ICU) admission is associated with duration of mechanical ventilation in critically ill surgical patients. Materials and Methods: We analyzed data from a prospective cohort study involving 210 critically ill surgical patients. To explore the relationship between admission plasma 25‐hydroxyvitamin D levels and duration of mechanical ventilation, we performed a Poisson regression while controlling for clinically relevant covariates. Only patients who required ≥48 hours of mechanical ventilation and survived ≥24 hours after discontinuation of respiratory support were included in the analytic cohort. Results: Ninety‐four patients met inclusion criteria. Mean (standard deviation) plasma 25‐hydroxyvitamin D level was 16 (7) ng/mL and median (interquartile range) duration of mechanical ventilation was 4 (2–7) days. Poisson regression analysis, adjusted for age, sex, race, body mass index, primary surgical service, Acute Physiology and Chronic Health Evaluation II score, and season of ICU admission, demonstrated an inverse association of plasma 25‐hydroxyvitamin D levels with duration of mechanical ventilation (incident rate ratio per 10 ng/mL, 0.66; 95% confidence interval, 0.54–0.82). Conclusions: In our cohort of critically ill surgical patients, plasma 25‐hydroxyvitamin D levels measured on ICU admission were inversely associated with the duration of respiratory support. Randomized controlled trials are needed to assess whether vitamin D supplementation can influence duration of mechanical ventilation in surgical ICU patients.     

Vitamin D Deficiency is Associated with Handgrip Strength,Nutritional Status and T2DM in Community-Dwelling Older Mexican Women: A Cross-Sectional Study

The aim of this study was to evaluate the association between handgrip strength, nutritional status and vitamin D deficiency in Mexican community-dwelling older women. A cross sectional study in women ≥ 60 years-old was performed. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured by a quantitative immunoassay technique. Handgrip strength was assessed using a dynamometer, while nutritional status was assessed through the Full Mini Nutritional Assessment (Full-MNA). A total of 116 women participated in the study, their mean age was 70.3 ± 5.8 years; 49.1% of the study group had plasma 25(OH)D levels lower than 40 nmol/L [16 ng/mL]. Meanwhile, 28.45% of participants had low handgrip strength (<16 kg), and 23.1% were identified at risk of malnutrition/malnourished according with Full-MNA score. Women with 25(OH)D deficiency (<40 nmol/L [16 ng/mL]) were more likely to have low handgrip strength (OR = 2.64, p = 0.025) compared with those with higher 25(OH)D values. Additionally, being malnourished or at risk of malnutrition (OR = 2.53, p = 0.045) or having type 2 diabetes mellitus (T2DM) (OR = 2.92, p = 0.044) was also associated with low 25(OH)D. The prevalence of low plasma 25(OH)D concentrations was high among Mexican active older women. Low handgrip strength, being at risk of malnutrition/malnourished, or diagnosed with T2DM was also associated with Vitamin D deficiency.     

The effect of body mass index on adequacy of serum 25-hydroxyvitamin D levels in US adults: the National Health and Nutrition Examination Survey 2001 to 2006

PurposeTo investigate the relationship between body mass index (BMI) and vitamin D adequacy among US adults.MethodsWe used data for US adults aged 18 years or older (n = 12,927) who participated in the 2001 to 2006 United States National Health and Nutrition Examination Survey. Log-binomial regression was used to estimate the strength of association between BMI categories and the prevalence of serum 25-hydroxyvitamin D [25(OH)D] greater than or equal to 20 ng/mL before and after controlling for selected characteristics. An interaction term between race or ethnicity and BMI categories was tested.ResultsAmong US adults, 67.2% had serum 25(OH)D greater than or equal to 20 ng/mL, a cut point suggested by the Office of Dietary Supplements for adequate bone and general health. Overweight and obese adults were 8% (95% confidence interval, 0.89–0.95) and 26% (95% confidence interval, 0.71–0.78), respectively, less likely to have serum 25(OH)D greater than or equal to 20 ng/mL than their normal weight counterparts after controlling for age, gender, race/ethnicity, nativity and marital status, as well as education and income. No heterogeneity of the association between BMI categories and the prevalence of 25(OH)D greater than or equal to 20 ng/mL was observed by race or ethnicity.ConclusionsThe low prevalence of 25(OH)D greater than equal to 20 ng/mL among overweight and obese adults in the US population underscores the need to comparatively assess vitamin D intakes across different BMIs.     

Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21–93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.     

Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study

Background: Older adults supplemented for 1 year with β‐hydroxy‐β‐methylbutyrate, arginine, and lysine (HMB/ARG/LYS) were previously shown to have significant gains in fat‐free mass (FFM) but not muscular strength. Objective: Recently, increasing levels of serum vitamin D have been associated with an increase in muscle function, particularly in the elderly. To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS, the authors performed post hoc analysis of strength based on the participants' vitamin D status. Methods: Elderly (age 76.0 ± 1.6 years) adults were recruited for a double‐blinded, controlled study and were randomly assigned to either an isonitrogenous control (n = 37) or HMB/ARG/LYS (n = 40) for the yearlong study. Participants were further segregated based on their vitamin D status of either <30 or ≥30 ng 25OH‐vitD₃/mL serum, and an analysis was performed on the 4 cohorts. Results: Regardless of vitamin D status, HMB/ARG/LYS resulted in significantly increased FFM (P < .02), but only in those with vitamin D status ≥30 ng 25OH‐vitD₃/mL was there a significant increase in strength with HMB/ARG/LYS (P < .01). Control‐supplemented participants, regardless of vitamin D status, and the HMB/ARG/LYS‐supplemented participants with vitamin D status <30 ng 25OH‐vitD₃ failed to show improvements in strength. Conclusions: The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status, but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and 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.     

Serum 25-hydroxyvitamin D Concentration Significantly Decreases in Patients with COVID-19 Pneumonia during the First 48 Hours after Hospital Admission

It is unclear how ongoing inflammation in Coronavirus Disease 2019 (COVID-19) affects 25-hydroxyvitamin D (25[OH]D) concentration. The objective of our study was to examine serum 25(OH)D levels during COVID-19 pneumonia. Patients were admitted between 1 November and 31 December 2021. Blood samples were taken on admission (day 0) and every 24 h for the subsequent four days (day 1–4). On admission, 59% of patients were 25(OH)D sufficient (>30 ng/mL), and 41% had 25(OH)D inadequacy (<30 ng/mL). A significant fall in mean 25(OH)D concentration from admission to day 2 (first 48 h) was observed (30.7 ng/mL vs. 26.4 ng/mL; p < 0.0001). No subsequent significant change in 25(OH)D concentration was observed between day 2 and 3 (26.4 ng/mL vs. 25.9 ng/mL; p = 0.230) and day 3 and day 4 (25.8 ng/mL vs. 25.9 ng/mL; p = 0.703). The absolute 25(OH)D change between hospital admission and day 4 was 16% (4.8 ng/mL; p < 0.0001). On day 4, the number of patients with 25(OH)D inadequacy increased by 18% (p = 0.018). Therefore, serum 25(OH)D concentration after hospital admission in acutely ill COVID-19 patients should be interpreted with caution. Whether low 25(OH)D in COVID-19 reflects tissue level vitamin D deficiency or represents only a laboratory phenomenon remains to be elucidated in further prospective trials of vitamin D supplementation.     

A comprehensive genetic and epidemiological association analysis of vitamin D with common diseases/traits in the UK Biobank

Vitamin D has been intensively studied for its association with human health, but the scope of such association and the causal role of vitamin D remain controversial. We aim to comprehensively investigate the links between vitamin D and human health through both epidemiological and Mendelian randomization (MR) analyses. We examined the epidemiological associations between serum 25‐hydroxyvitamin D (25(OH)D) concentration and 90 diseases/traits in 326,409 UK Biobank (UKBB) Europeans. The causal relations between 25(OH)D and 106 diseases/traits were investigated by performing MR analysis using genome‐wide significant 25(OH)D‐associated variants (N = 143) from the largest UKBB GWAS to date. In epidemiological analysis, we found 25(OH)D was associated with 45 diseases/traits across cardiovascular/metabolic diseases, psychiatric/neurological diseases, autoimmune/inflammatory diseases, cancer, musculoskeletal diseases, and quantitative traits. In MR‐analysis, we presented evidence suggesting potential causal role of 25(OH)D in increasing height (β = .064, 95% confidence interval [CI] = 0.019–0.11) and preventing the risk of ovarian cancer (odds ratio [OR] = 0.96, 95% CI = 0.93–0.99), multiple sclerosis (OR = 0.96, 95% CI = 0.94–0.98), leg fracture (OR = 0.60, 95% CI = 0.45–0.80) and femur fracture (OR = 0.53, 95% CI = 0.32–0.84). These findings confirmed associations of vitamin D with a broad spectrum of diseases/traits and supported the potential causal role of vitamin D in promoting health.     

Vitamin D status and hypertensive disorders in pregnancy

PurposeSeveral studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear.MethodsAmong women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4–36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%).ResultsWe did not detect an association between plasma 25(OH)D concentration (mean 58, standard deviation 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval, 0.77–1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval, 1.01–1.72) per each 25 nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest that this association was not because of reverse causation. Although the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension.ConclusionsThese data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy.