Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial

Patients with newly resected stage II melanoma (n = 104) were randomized to receive adjuvant vitamin D3 (100,000 IU every 50 days) or placebo for 3 years to investigate vitamin D3 protective effects on developing a recurrent disease. Median age at diagnosis was 50 years, and 43% of the patients were female. Median serum 25-hydroxy vitamin D (25OHD) level at baseline was 18 ng/mL, interquartile range (IQ) was 13–24 ng/mL, and 80% of the patients had insufficient vitamin D levels. We observed pronounced increases in 25OHD levels after 4 months in the active arm (median 32.9 ng/mL; IQ range 25.9–38.4) against placebo (median 19.05 ng/mL; IQ range 13.0–25.9), constantly rising during treatment. Remarkably, patients with low Breslow score (<3 mm) had a double increase in 25OHD levels from baseline, whereas patients with Breslow score ≥3 mm had a significantly lower increase over time. After 12 months, subjects with low 25OHD levels and Breslow score ≥3 mm had shorter disease-free survival (p = 0.02) compared to those with Breslow score <3 mm and/or high levels of 25OHD. Adjusting for age and treatment arm, the hazard ratio for relapse was 4.81 (95% CI: 1.44–16.09, p = 0.011). Despite the evidence of a role of 25OHD in melanoma prognosis, larger trials with vitamin D supplementation involving subjects with melanoma are needed.     

Comparison of Vitamin D and 25-Hydroxyvitamin D Concentrations in Human Breast Milk between 1989 and 2016–2017

Background: Breast milk is considered the optimal source of nutrition during infancy. Although the vitamin D concentration in human breast milk is generally considered poor for infants, vitamin D in breast milk is an important source for exclusively breastfed infants. Increases in vitamin D insufficiency and deficiency in lactating mothers may reduce vitamin D concentrations in breast milk. This study aimed to compare vitamin D and 25-hydroxyvitamin D (25OHD) concentrations in breast milk collected in 1989 and 2016–2017 and simultaneously analyze them with liquid chromatography-tandem mass spectrometry (LC-MS/MS); the association between the lifestyle of recent lactating mothers (2016–2017) and vitamin D status in human breast milk was also evaluated. Method: Lactating mothers were recruited from three regions of Japan in 1989 (n = 72) and 2016–2017 (n = 90), and milk from 3–4 months was collected in summer and winter. The samples were strictly sealed and stored at −80℃ until measurement. Breast milk vitamin D and 25OHD concentrations were analyzed by LC-MS/MS. Vitamin D intake, sun exposure, and sunscreen use of the lactating mothers in 2016–2017 were assessed. Results: Both vitamin D and 25OHD concentrations in breast milk were higher in the summer regardless of the survey year. Significantly lower vitamin D and 25OHD concentrations were observed in 2016–2017 compared with 1989 in summer, but no survey year difference was observed in winter. The stepwise multiple regression analyses identified season, daily outdoor activity, and suntan in the last 12 months as independent factors associated with vitamin D₃ concentrations. Conclusion: The results suggest that low vitamin D status in recent lactating mothers may have decreased vitamin D and 25OHD concentrations in breast milk compared with the 1980s. These results are helpful for developing public health strategies to improve vitamin D status in lactating mothers and infants.     

Fat-Soluble Vitamin Supplementation Using Liposomes,Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19–28), body mass index of 20.6 kg/m² [18.4–22.0], and forced expiratory volume in 1 s of 65% (44–84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR −44.3–86.1) vs. −38.8 ng/mL (−71.2–6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0–17.0) vs. +3.0 ng/mL (−4.0–7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33–6.52) vs. −0.34 µg/mL (−1.71–2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).     

The Usefulness of Serum Vitamin D Levels in the Assessment of IBD Activity and Response to Biologics

The main role of vitamin D is calcium homeostasis and bone metabolism, although its activity as an immuno-modulator and its anti-inflammatory effect is well-known. Low blood vitamin D levels are common among patients with inflammatory bowel disease (IBD). Whether low vitamin D levels could affect the disease activity or it is an effect of a worse condition of the disease is still unclear. This study aimed to investigate the role of blood vitamin D levels to identify the clinical, endoscopic, and histological activity in a cohort of patients with ulcerative colitis (UC) or Crohn’s disease (CD) on therapy with biological drugs. In this retrospective cohort study, 50 IBD patients (24 UC and 26 CD) that underwent colonoscopy from January 2017 to January 2020 with a concomitant serological evaluation of vitamin D were included. Patients with clinical, endoscopic, and histological activity and those who lost their clinical response to the biological drug had lower vitamin D levels compared to patients in remission or patients that did not change therapeutic regimens. A receiver operating characteristic (ROC) analysis and Youden’s Index were performed to assess the optimal vitamin D levels to identify patients with the active disease. The ROC analysis showed an area under the curve (AUC) of 0.709 (p = 0.005; confidence interval (CI): 0.564–0.829), 0.769 (p < 0.001; CI: 0.628–0.876), and 0.810 (p < 0.001; CI: 0.670–0.910) for the clinical, endoscopic, and histological outcomes, respectively. The optimal vitamin D cut-off was ≤25 ng/mL. The vitamin D level is an additional useful tool in the evaluation of IBD patients with good accuracy to predict their endoscopic and histological activity and clinical response to biologics.     

Vitamin D Status and Acute Respiratory Infection: Cross Sectional Results from the United States National Health and Nutrition Examination Survey, 2001–2006

Vitamin D is a promising, though under-explored, potential modifiable risk factor for acute respiratory infections (ARIs). We sought to investigate the association of vitamin D status with ARI in a large, nationally-representative sample of non-institutionalized individuals from the United States. We analyzed 14,108 individuals over 16 years of age in the National Health and Nutrition Survey (NHANES) 2001–2006 in this cross-sectional study. We used locally weighted scatterplot smoothing (LOWESS) to depict the relationship between increasing 25-hydroxyvitamin D (25OHD) levels and ARI. We then performed a multivariable regression analysis to investigate the association of 25OHD levels with ARI, while adjusting for known confounders. The median serum 25OHD level was 21 (IQR 15–27) ng/mL. Overall, 4.8% (95% CI: 4.5–5.2) of participants reported an ARI within 30 days before their participation in the national survey. LOWESS analysis revealed a near-linear relationship between vitamin D status and the cumulative frequency of ARI up to 25OHD levels around 30 ng/mL. After adjusting for season, demographic factors, and clinical data, 25OHD levels <30 ng/mL were associated with 58% higher odds of ARI (OR 1.58; 95% CI: 1.07–2.33) compared to levels ≥30 ng/mL. Among the 14,108 participants in NHANES 2001–2006, 25OHD levels were inversely associated with ARI. Carefully designed, randomized, controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of ARI.     

Low Serum Vitamin D in COVID-19 Patients Is Not Related to Inflammatory Markers and Patients’ Outcomes—A Single-Center Experience and a Brief Review of the Literature

The aim of the study was to evaluate the vitamin D status in hospitalized COVID-19 patients and the correlation with C reactive protein (CRP), ferritin, fibrinogen, and peripheral blood leukocytes, as well as inflammatory derived indices. A prospective study was performed on 203 COVID-19 hospitalized patients, classified by disease severity. Blood was collected after admission, and inflammatory biomarkers and vitamin D status were assessed using routine laboratory procedures. No significant correlation was found between vitamin D serum levels and disease severity stratified by different age groups. However, the highest vitamin D levels were found in patients with mild disease: median 29.39 (IQR 12.12–44.02) ng/mL, while for moderate and severe forms the serum levels were significantly lower: median 15.10 (IQR 9.56–24.11) ng/mL for moderate, and 18.86 (IQR 12.50–27.88) ng/mL for severe; p = 0.009. Patients with no comorbidities showed a significantly higher level of vitamin D median 24.72 (IQR 16.05–31.52) ng/mL compared to subjects with at least one comorbidity: median 16.02 (IQR 9.81–25.22) ng/mL, p = 0.004. We did not find an association between vitamin D levels and inflammatory biomarkers except for significantly lower vitamin D levels in moderate and severe COVID-19 compared to mild disease forms.     

Optimal Serum 25(OH)D Level and Vitamin D Intake in Young Korean Women

Vitamin D status is essential for preventing bone disease. Young Korean women have the highest vitamin D deficiency prevalence compared with other demographic groups. This study aimed to establish the optimal vitamin D intake level for maintaining an adequate serum 25-hydroxyvitamin D (25[OH]D) level by season in young Korean women (mean age: 23.1 years). Each participant (wintertime, n = 101; summertime, n = 117) completed a lifestyle survey, dietary record, bone mineral density, and biochemical tests. Seasonal factors impacting 25(OH)D were identified, vitamin D intake for sufficient 25(OH)D levels was calculated, and the relationship between 25(OH)D and intact parathyroid hormone (iPTH) was analyzed. During summertime, 25(OH)D levels were higher than in wintertime (17.9 vs. 15.0 ng/mL). A 1 µg/1000 kcal increase in vitamin D intake increased 25(OH)D levels by 0.170 ng/mL in wintertime and 0.149 ng/mL in summertime. iPTH levels reached a theoretical plateau corresponding to an 18.4 ng/mL 25(OH)D level. The vitamin D intake threshold for maintaining 25(OH)D levels at ≥20 and ≥18.4 ng/mL was ≥10.97 μg/day. For a sufficient level of 25(OH)D in young Korean women, increasing summertime UV irradiation time and increasing vitamin D supplements and vitamin D-containing foods throughout the year is beneficial.     

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800–1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.     

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.     

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case–Control Study

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.     

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.     

Lower Blood Vitamin D Levels Are Associated with Depressive Symptoms in a Population of Older Adults in Kuwait: A Cross-Sectional Study

Low serum vitamin D has been associated with an increased risk of neuropsychiatry disorders. This study aimed to examine the association between vitamin D deficiency and depression in adults aged 65 years and older. This cross-sectional study was conducted in seven primary healthcare centers across Kuwait (November 2020 to June 2021). The participants (n = 237) had their serum vitamin D 25-(OH)-D concentrations (analyzed by LC-MS) classified as sufficient, ≥75 nmol/L (30 ng/mL); insufficient, 50–75 nmol/L (20–30 ng/mL); or deficient, <50 nmol/L (20 ng/mL). Depressive symptoms were evaluated using the 15-Item Geriatric Depression Scale (15-item GDS). The mean serum 25-OH-D levels (nmol/L) in volunteers with normal, mild, moderate, and severe depression were 100.0 ± 31.7, 71.2 ± 38.6, 58.6 ± 30.1 and 49.0 ± 6.93, respectively (p < 0.001). The participants in the vitamin D sufficiency group were significantly less likely to exhibit depressive symptoms (88.2%) than patients with mild (36%) and moderate (21%) depression (p < 0.001). Ordinal logistic regression showed that vitamin D deficiency (OR = 19.7, 95% CI 5.60, 74.86, p < 0.001) and insufficiency (OR = 6.40, 95% CI 2.20, 19.91, p < 0.001) were associated with higher odds of having depressive symptoms. A low serum vitamin D level is a significant predictor of symptoms of depression among older individuals.     

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.     

Vitamin D Nutritional Status of Chinese Pregnant Women,Comparing the Chinese National Nutrition Surveillance (CNHS) 2015–2017 with CNHS 2010–2012

Optimal vitamin D (vitD) status is beneficial for both pregnant women and their newborns. The aim of this study was to evaluate the vitamin D status of Chinese pregnant women in the latest China Nutrition and Health Surveillance (CNHS) 2015–2017, analyze the risk factors of vitamin D deficiency (VDD), and compare them with those in CNHS 2010–2012. Serum 25 hydroxyvitamin D (25(OH)D) was measured by ELISA method. City type, district, latitude, location, age, vitamin D supplements intake, education, marital status, annual family income, etc., were recorded. The median 25(OH)D concentration was 13.02 (10.17–17.01) ng/mL in 2015–2017, and 15.48 (11.89–20.09) ng/mL in 2010–2012. The vitamin D sufficient rate was only 12.57% in 2015–2017, comparing to 25.17% in 2010–2012. The risk factors of vitamin D inadequacy (25(OH)D < 20 ng/mL) in 2015–2017 were not exactly consistent with that in 2010–2012. The risk factors included season of spring (p < 0.0001) and winter (p < 0.001), subtropical (p < 0.001), median (p < 0.0001) and warm temperate zones (p < 0.0001), the western (p = 0.027) and the central areas (p = 0.041), while vitD supplements intake (p = 0.021) was a protective factor in pregnant women. In conclusion, vitD inadequacy is very common among Chinese pregnant women. We encourage pregnant women to take more effective sunlight and proper vitD supplements, especially for those from the subtropical, warm and medium temperate zones, the western and the central, and in the seasons of spring and winter.     

Prevalence and Impact of Vitamin D Deficiency in Critically Ill Cancer Patients Admitted to the Intensive Care Unit

Vitamin D deficiency is frequent in cancer patients and a risk factor for morbidity and mortality during critical illness. This single-center retrospective study analyzed 25-hydroxyvitamin D levels in critically ill cancer patients (n = 178; hematologic, n = 108; solid, n = 70) enrolled in a prospective ICU registry. The primary analysis was the prevalence of vitamin D deficiency (<20 ng/mL) and the severe deficiency (≤12 ng/mL). Secondary analyses included risk factors for vitamin D deficiency and its impact on ICU, hospital, and 1-year mortality. The prevalence of vitamin D deficiency and severe deficiency was 74% (95% CI: 67–80%) and 54% (95% CI: 47–61%). Younger age, relapsed/refractory disease, and a higher sepsis-related organ failure assessment (SOFA) score were independent risk factors for vitamin D deficiency (p < 0.05). After adjusting for relapsed/refractory disease, infection, the SOFA score, and the early need for life-supporting interventions, severe vitamin D deficiency was an independent predictor of hospital mortality (OR: 2.21, 95% CI: 1.03–4.72, p = 0.04) and 1-year mortality (OR: 3.40, 95% CI: 1.50–7.71, p < 0.01), but not of ICU mortality. Conclusion: Vitamin D deficiency is common in critically ill cancer patients requiring ICU admission, but its impact on short-term mortality in this group is uncertain. The observed association of severe vitamin D deficiency with the post-ICU outcome warrants clinical consideration and further study.     

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.     

Vitamin D Status in Pediatric and Young Adult Cystic Fibrosis Patients. Are the New Recommendations Effective?

Introduction: In recent years, guidelines for vitamin D supplementation have been updated and prophylactic recommended doses have been increased in patients with cystic fibrosis (CF). Objective: To evaluate safety and efficacy of these new recommendations. Results: Two cohorts of pancreatic insufficient CF patients were compared before (cohort 1: 179 patients) and after (cohort 2: 71 patients) American CF Foundation and European CF Society recommendations were published. Cohort 2 patients received higher Vitamin D doses: 1509 (1306–1711 95% CI) vs 1084 (983–1184 95% CI) IU/Day (p < 0.001), had higher 25 OH vitamin D levels: 30.6 (27.9–33.26 95% CI) vs. 27.4 (25.9–28.8 95% CI) ng/mL (p = 0.028), and had a lower prevalence of insufficient vitamin D levels (<30 ng/mL): 48% vs 65% (p = 0.011). Adjusted by confounding factors, patients in cohort 1 had a higher risk of vitamin D insufficiency: OR 2.23 (1.09–4.57 95% CI) (p = 0.028). Conclusion: After the implementation of new guidelines, CF patients received higher doses of vitamin D and a risk of vitamin D insufficiency decreased. Despite this, almost a third of CF patients still do not reach sufficient serum calcidiol levels.     

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.     

Temporal Association of Reduced Serum Vitamin D with COVID-19 Infection: Two Single-Institution Case–Control Studies

(1) Background: Vitamin D supplementation has been proposed for the prevention and treatment of COVID-19, but it is not clear if reduced serum vitamin D predisposes individuals to COVID-19 and/or is a secondary consequence of infection. This study assessed the temporal association between serum vitamin D and COVID-19 with two single-institution case–control studies through the University of California San Diego (UCSD) Health System. (2) Methods: This study included patients who tested positive for COVID-19 from 1 January to 30 September 2020 with serum 25-hydroxy-vitamin D (25(OH)D) measured within 180 days of diagnosis. Patients were separated based on whether 25(OH)D was measured before (n = 107 cases, 214 controls) or after (n = 203 cases, 406 controls) COVID-19 diagnosis. COVID-19 infection status was the outcome variable in the pre-diagnosis study, whereas serum 25(OH)D level was the outcome variable in the post-diagnosis study. (3) Results: Serum 25(OH)D levels were not associated with the odds of subsequent COVID-19 infection (OR 1.0, 95% CI: 1.0 to 1.0, p = 0.98). However, COVID-19-positive individuals had serum 25(OH)D measurements that were 2.7 ng/mL lower than the controls (95% CI: −5.2 to −0.2, p = 0.03). (4) Conclusions: In our study population, serum 25(OH)D levels were not associated with the risk of acquiring COVID-19 infection but were reduced in subjects after COVID-19 infection. These results support the possibility that reduced serum 25(OH)D is a consequence and not a cause of COVID-19 infection.