Adequate Serum Levels Research Articles

Serum iron and transferrin saturation variation are circadian regulated and linked to the harmonic circadian oscillations of erythropoiesis and hepatic Tfrc expression in mice.

Serum iron has long been thought to exhibit diurnal variation and is subsequently considered an unreliable biomarker of systemic iron status. Circadian regulation (endogenous ~24-h periodic oscillation of a biologic function) governs many critical physiologic processes. It is unknown whether serum iron levels are regulated by circadian machinery; likewise, the circadian nature of key players of iron homeostasis is unstudied. Here we show that serum iron, transferrin saturation (TSAT), hepatic transferrin receptor (TFR1) gene (Tfrc) expression, and erythropoietic activity exhibit circadian rhythms. Daily oscillations of serum iron, TSAT, hepatic Tfrc expression, and erythropoietic activity are maintained in mice housed in constant darkness, where oscillation reflects an endogenous circadian period. Oscillations of serum iron, TSAT, hepatic Tfrc, and erythropoietic activity were ablated when circadian machinery was disrupted in Bmal1 knockout mice. Interestingly, we find that circadian oscillations of erythropoietic activity and hepatic Tfrc expression are maintained in opposing phase, likely allowing for optimized usage and storage of serum iron whilst maintaining adequate serum levels and TSAT. This study provides the first confirmatory evidence that serum iron is circadian regulated, discerns circadian rhythms of TSAT, a widely used clinical marker of iron status, and uncovers liver-specific circadian regulation of TFR1, a major player in cellular iron uptake.

Analysis of zinc and copper levels in very low birth weight infants using human milk additives: phase 1 trial findings

ObjectiveThe aim of this study was to assess whether the micronutrients zinc and copper, provided by human milk additives, are sufficient for very low birth weight preterm infants. MethodA phase 1 randomized double-blind controlled trial was conducted with very low birth weight preterm infants. This is a secondary analysis of copper and zinc. Sixty-six newborns were part of the initial sample, with forty participating and reaching the final stage of the study. Inclusion criteria were: gestational age less than 37 weeks, birth weight greater than or equal to 750 g and less than or equal to 1500 g, small or appropriate for gestational age, exclusively receiving human milk at a volume greater than or equal to 100 mL per kilogram per day, and hemodynamically stable. Participants were randomly assigned to two groups: intervention, Lioneo (received human milk with additive based on lyophilized human milk), n = 20, and control, HMCA (received human milk with commercial additive based on cow's milk protein), n = 20, and their serum levels of zinc and copper were measured on the first and twenty-first days. ResultsThere was a reduction in intragroup zinc serum levels from the first to the twenty-first day of the study (p < 0.01). There was no intergroup difference. No difference was found in serum copper levels. ConclusionHuman milk additives were not sufficient to maintain adequate zinc serum levels in very low birth weight newborns. It was not possible to affirm whether human milk additives were sufficient to maintain adequate serum copper levels in the studied sample. UTN: U1111–1220–0550.

A Systematic Review of the Relationship between Serum Vitamin D Levels and Caries in the Permanent Teeth of Children and Adolescents.

This systematic review critically evaluates the association between serum Vitamin D levels and dental caries incidence in the permanent teeth of children and adolescents. The search strategy comprised three databases (PubMed, Scopus, Embase), up to November 2023, targeting studies on the correlation between Vitamin D and dental caries in permanent dentition. The eligibility criteria focused on observational studies involving children and adolescents aged 12 to 19 years with permanent dentition. The screening process, guided by the PRISMA guidelines and the Newcastle-Ottawa Scale for quality assessment, resulted in the inclusion of eight studies conducted across various global regions from 2013 to 2023. The analysis revealed that Vitamin D insufficiency and deficiency were prevalent among the study populations, ranging from 17.3% to 69.4%. Specifically, children and adolescents with Vitamin D insufficiency (<50 nmol/L) were found to have significantly higher odds of developing caries, with odds ratios (ORs) ranging from 1.13 to 2.57. Conversely, two studies indicated a protective effect of higher Vitamin D levels, with an OR of 0.80 and 0.59, respectively, for caries among children and adolescents with serum levels ≥ 50 nmol/L, suggesting an inverse relationship between Vitamin D status and caries risk. The results indicate both the protective role of adequate serum levels of Vitamin D above 20 ng/mL and the increased risk associated with insufficient levels below this threshold. However, the variations in study quality, methodologies and geographic settings underscore the challenges in drawing universal conclusions. Despite these limitations, our review suggests that improving Vitamin D status could be a beneficial component of preventive strategies against dental caries in children and adolescents, warranting further research to clarify the clinical significance of our findings.

Select micronutrients for the preterm neonate.

If premature neonates are not provided with adequate nutrition, they will quickly become deficient because of increased requirements and a lack of nutrient stores to achieve adequate growth. The provision of many of the recommended micronutrients for pediatric and adult patients is challenging in premature neonates because of the limited data surrounding the true needs of premature neonates and the difficulty in assessing adequate serum levels of these nutrients in this patient population. Parenteral and enteral nutrition shortages further complicate providing adequate micronutrients to premature neonates. This review will discuss select micronutrients and their importance to the preterm neonate, with special emphasis on micronutrients with limited evidence and more challenging supplementation and repletion strategies.

Metabolic syndrome components and vitamin D availability relationship in late postmenopausal women

BACKGROUND: The global prevalence of vitamin D deficiency is currently a real threat due to association with major chronic non-communicable diseases. Abdominal obesity, hypertension, dyslipidemia, and hyperglycemia contribute significantly to cardiometabolic risk in late postmenopausal women.AIM: to assess the frequency of deficiency and insufficiency of 25(OH)D in late postmenopausal residents of Yekaterinburg; to establish associations of 25(OH)D serum concentration with components of metabolic syndrome and severity of menopausal symptoms.MATERIALS AND METHODS: During the period from October 2018 to March 2020 145 independently living late postmenopausal residents of Yekaterinburg were enrolled in a cross-sectional study. The following scope of data regarding each of the subjects was collected: complaints and anamnesis, anthropometry, diagnosis of metabolic syndrome, arterial hypertension and diabetes mellitus, assessment of 25 (OH)D level by the ECLIA method, LDL-C, HDL-C levels, serum TG by the enzymatic colorimetric method, as well as the evaluation of the modified menopausal index.RESULTS: Adequate serum level of 25(OH)D was detected in 20.6% patients, insufficiency and deficiency were found in 33.1 and 46.2% cases, respectively. In patients with vitamin D deficiency and insufficiency, the most frequent metabolic syndrome components were arterial hypertension (p=0.02; OR 3.5; CI 1.2–10.6) and abdominal obesity (p=0.03; OR 2.8; CI 1.1–7.2). Vitamin D deficient subjects had significantly lower serum HDL and increased TG levels (p=0.04), compared to the adequately provided 25(OH)D patients. Vitamin D levels were not associated with the severity of menopausal symptoms in late postmenopausal women. Regular daily intake of 400–2000 IU of colecalciferol contributed to higher serum 25(OH)D level.CONCLUSION: a high prevalence of vitamin D deficiency among postmenopausal women of Yekaterinburg was detected. Diagnosis and correction of vitamin D levels are necessary for timely reduction of cardiometabolic risk, primarily due to the potential pleiotropic effects of D-hormone on the renin-angiotensin-aldosterone system, carbohydrate and lipid metabolism.

Brain changes in neuroimaging of adult patients with vitamin D deficiency: systematic review protocol

IntroductionBrain abnormalities detected through neuroimaging are described in patients with vitamin D deficiency, however, it is still not clear which cerebral alterations are more frequent and characteristic in this population....

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Influence and Role of Vitamin D on Dental Implants

Dental implants are one of the methods for replacing missing teeth and their use has become an important part of dentistry. Dental implants have many advantages over traditional fixed partial dentures, including a high success rate of over 97% for 10 years among certain others. Vitamin D is involved in the calcium and phosphate metabolism of bone tissue in the body and in the maxillofacial region. This information can help dentists reduce the risk of complications after different types of surgery, like dental implant surgery and bone grafting. Due to its involvement in bone metabolic processes and regulation of the immune system, vitamin D is currently of particular interest to dentists performing implant procedures. It is believed that the correct concentration of this prohormone is positively correlated with the process of osseointegration. Numerous studies show that vitamin D is potentially important for the process of postoperative tissue repair, as well as the integration of the implant with bone tissue and bone homeostasis around the implant after it is loaded with a prosthetic crown. Furthermore, adequate serum levels of vitamin D may improve peri-implant bone healing. To date, only a few studies have investigated the possible association between serum vitamin D levels and early dental implant failure hence further clinical research is need of time to provide evidence -based results for the role of vitamin D in dental implants. The purpose of this research is to review the available information about influence and role of vitamin D on dental implants.

Vitamin A and D deficiencies in the prognosis of respiratory tract infections: A systematic review with perspectives for COVID-19 and a critical analysis on supplementation

Considering the rapid spread of COVID-19, the scientific community has been looking for ways to recognize factors that may interfere with the outcome of viral infection. Despite the lack of studies with the new coronavirus, it is known that adequate serum levels of micronutrients are essential for the organic response to infectious diseases. Thus, we aim to review the effects of vitamin A, D, iron, zinc, or folate deficiency on the prognosis of patients with respiratory infections with manifestations similar to COVID-19 and discuss about supplementation of the nutrients analyzed in this review. The search was conducted in the databases PubMed, Lilacs, and SciELO, including observational studies published between 2010-2020, with results for individuals with respiratory tract infections with manifestations similar to COVID-19. Six articles met the inclusion criteria, all of which were related to deficiencies of vitamins A and D. In general, vitamin A deficiency was associated with cough, fever, and greater total respiratory resistance. Regarding vitamin D, the lack of this nutrient led to higher rates of ICU admission, the need for mechanical ventilation, and mortality. Evidence linking specific relationships between nutritional deficiencies and COVID-19 remain lacking due to the small number of studies and heterogeneities in population subgroups. In conclusion, deficiencies of vitamins A and D seem to negatively affect the prognosis of respiratory tract infections. Supplementation of these nutrients for prevention or treatment of patients diagnosed with COVID-19 should respect serum levels, nutritional status and housing conditions (e.g.,endemic location) of individuals.

Vitamin D Assessment in Patients with Multisystem Inflammatory Syndrome and SARS-CoV-2 Infection

Objective - To assess 25(OH)D status in children with Multisystem Inflammatory Syndrome (MIS-C) associated with SARSCoV-2 infection, and the association between serum levels of 25(OH)D and inflammatory marker values.Patients and methods - This retrospective study was conducted at the Clinic for Children’s Diseases, University Clinical Center, Tuzla in the period from November 2020 to November 2021.Results - The study included 23 children with MIS-C with a median age of 6.9 years, and 22 children with acute SARS-CoV-2 infection, with a median age of 1.1 years. Both groups of children had low serum levels of 25(OH)D in the range of deficiency; median levels of 25(OH)D in MIS-C children were lower (median 44.60 nmol/L) than in children with acute SARS-CoV-2 infection - median 52.45 nmol/L. There was no statistically significant difference in 25(OH) D levels between the two groups of children included in the study (P=0.33). The same number of children in both groups had adequate serum levels of 25(OH)D. The children in both groups had elevated markers of inflammation, but we did not find a significant correlation between the values of 25(OH)D and the inflammatory marker values.Conclusion - Deficiency of 25(OH) D could be one of the precipitating factors that lead to the development of both MIS-C - related SARS-CoV-2 and more severe forms of acute infection. 25(OH)D enriched food, as well as supplementation with 25(OH)D, should be considered a long-term strategy in all high-risk children and adolescents.

Vitamin D Immune-Mediated Responses and SARS-CoV-2 Infection: Clinical Implications in COVID-19

Active vitamin D is a true steroid hormone with pleiotropic biological effects that go beyond the classical concept of bone metabolism regulation. In fact, adequate serum levels of 25-hydroxyvitamin D (&gt;40 ng/mL) are required to support several biological functions, including the control of innate and adaptive immunity in course of infectious, inflammatory and autoimmune diseases. SARS-CoV-2 is responsible for the COVID-19 pandemic and deficient/insufficient serum levels of 25-hydroxyvitamin D are reported in very large cohorts of patients. Of note, vitamin D is involved in different pathophysiological processes, such as expression of SARS-CoV-2 receptor (ACE2), activation of innate (neutrophils with their extracellular traps, monocytes/macrophages, dendritic cells, natural killer cells) and adaptive (T and B lymphocytes) immune cells and clinical manifestations, such as coagulation/thrombotic disorders and acute respiratory distress syndrome. Randomized clinical trials regarding vitamin D supplementation in COVID-19 patients have shown favorable effects on the control of inflammation markers, arterial oxygen saturation/inspired fraction of oxygen ratio, admission to hospital intensive care units and mortality. A target of serum 25-hydroxyvitamin D &gt; 50 ng/mL has been identified as protective for the course of COVID-19, potentially playing an ancillary role in the treatment of the disease.

Association between Serum 25-hydroxyvitamin D Levels and Incidences of Infection in Long-Term Care

Insufficient serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with increased respiratory tract infections, influenza, and other infectious diseases. As the world deals with the COVID-19 pandemic, the interest of adequate serum levels to reduce the risk of infection has surfaced. This study determined if the number of infections per year are associated with serum 25(OH)D concentrations in long-term care (LTC). Participants (≥ 65 years) in a cross-sectional study were recruited across five LTC communities in Texas. Medical records were used to collect a one-year medical history using double-blind protocols. Blood draws were collected to measure serum 25(OH)D concentrations. Medical records were used to classify infections based upon documentation of signs and symptoms of infection concurrent with either a physician’s note or antibiotic/antiviral medication prescription. Race, BMI, sex, age, and liver and renal disease diagnoses were used as confounders. Of the 177 participants (89% Caucasian, 63% female, mean age 83 years) 69% had ≥1 infection over year and 55% had insufficient serum 25(OH)D concentrations <30 mg/mL (mean 32.6 ng/mL). Linear regression did not show a significant association between serum 25(OH)D concentrations and number of infections (β 0.003; 95% CI -0.014, 0.018; p=0.760). Additionally, insufficient serum concentration did not increase the odds of having an infection (OR 1.02; 95% CI 0.05, -19.34; p=0.987). This study did not show a significant association between infection rates and serum 25(OH)D concentrations. However, further research is needed to determine if vitamin D supplementation could be an effective therapeutic intervention to reduce infection rates, including COVID-19.

Association between lower serum vitamin D (25-hydroxy-cholecalciferol) concentrations and cognitive impairment in older adults: data from a populational-based cohort study in a middle-income country.

To investigate the association between serum vitamin D (25-hydroxy-cholecalciferol) (25(OH)D) concentrations and cognitive impairment in older adults living in Southern Brazil. Cross-sectional analysis using data from the second follow-up wave of the populational-based EpiFloripa Aging Cohort Study was collected in 2013-2014. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE). Blood samples were collected to measure serum vitamin D concentrations using a chemiluminescent microparticle immunoassay. Vitamin D concentrations were distributed in quartiles (Q1: 4·0-20·7 ng/ml; Q2: 20·8-26·6 ng/ml; Q3: 26·7-32·0 ng/ml and Q4: 32·1-60·1 ng/ml), and its association with cognitive impairment was tested by crude and adjusted logistic regression (sociodemographic, behavioural and health aspects) using Q4 as a reference group. 200 men and 371 women aged 60 years or older participated in this study. The prevalence of probable cognitive impairment was 21·7 %. Those without cognitive impairment had a higher mean of vitamin D serum concentrations (26·8 v. 24·6, P = 0·014). In the crude analysis, only individuals in Q2 of vitamin D presented an increased risk for probable cognitive impairment compared with Q4 (highest quartile) (OR 2·65, 95 % CI 1·46, 4·81), remaining significant in the adjusted analysis (OR 6·04, 95 % CI 2·78, 13·13). While Q1 (lowest quartile) was not associated in the crude analysis, but when adjusted, an increased risk of cognitive impairment was observed. The lowest quartile of vitamin D was directly associated with probable cognitive impairment in older adults in Southern Brazil. More studies are needed to investigate whether maintaining adequate serum levels may represent a significant factor in preventing age-related neurological disorders as well as to verify the need for new cutoff points for this age group.

Vitamin D serum levels and non-melanoma skin cancer risk.

BackgroundSkin cancer is one of the common malignancies. There is sufficient evidence that sunlight (ultraviolet radiation) contributes to the development of skin cancer, but there is also evidence that relates adequate serum levels of vitamin D produced on the skin by the action of ultraviolet radiation with the decreased risk of various types of cancers, including skin cancer. The aim of this study was to investigate the association of vitamin D serum levels among patients with non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) and controls.MethodsA prospective observational case-control study was conducted in a sample of 84 subjects in Extremadura (Spain). Forty-one patients with histologically diagnosed basal cell carcinomas and squamous cell carcinomas and 43 healthy controls were randomly chosen to assess whether vitamin D (25(OH)D3) serum level, age and sex were related to non-melanoma skin cancer and to determine the possible risk of this type of skin cancer for these variables.ResultsWhen analysing serum vitamin D levels, we ensured that all our subjects, both cases and controls, had normal or low serum vitamin D levels, even though the samples were taken during months with the highest solar irradiance in our region. It is striking in our results that there was a higher percentage of subjects with deficits of vitamin D who did not have skin cancer (66%) than patients with deficits with these types of skin cancers (34%). When adjusting the model for age and sex, vitamin D values above 18 ng/ml increased the risk of suffering from non-melanoma skin cancer by nearly 7-fold (aOR: 6.94, 95% CI [1.55–31.11], p = 0.01).ConclusionsDespite the controversial data obtained in the literature, our results suggest that lower levels of vitamin D may be related to a reduced incidence of non-melanoma skin cancer.

VITAMINA D Y DIABETES MELLITUS. PARTE 1

Introduction: diabetes mellitus (DM) has become a major global public health problem. Vitamin D (VD) deficiency, on the other hand, has pandemic characteristics and its consequences go beyond its known effect on bone metabolism. The discovery of vitamin receptors in various tissues has led to increased interest in non-skeletal functions, many of which are related to the prevention and progression of DM. 25(OH) D is the main circulating form and is the most appropriate and most widely used marker for assessing the nutritional status of VD, since it reflects both endogenous production and intake of the vitamin. Objectives: as a Working Group we proposed to make a review of the topic VD and Diabetes. In this first part we analyzed the VD: metabolic aspects, food intake and controversies about the definition of adequate serum levels. Materials and methods: a bibliographic search was carried out using the PubMed, MEDLINE, Cochrane, Research Gate search engines. The search criteria were "vitamin D", "vitamin D and diabetes", "vitamin D functions, metabolism, sources" "vitamin D toxicity". Complete articles related to the topic were selected. The vitamin D content of foods was obtained from the Souci Fachmann Kraut and USDA food composition data bases. Conclusions: considering the scarce distribution of VD in natural foods, the low consumption of source foods in the Argentine population and the current recommendations to limit sun exposure due to skin cancer, it is necessary to have fortified foods for massive consumption, in addition to milk. Nutritional supplements offer a safe option to supplement the diet as long as serum levels are monitored. There is no consensus on reference levels for considering an individual deficient, although most authors agree on the need to maintain serum levels above 30 ng/ml.

750. Isavuconazole Cerebrospinal Fluid Concentration in Refractory Coccidioidal Meningitis - A Three-Patient Case Series

BackgroundCoccidioidal meningitis (CM) causes life-threatening infection with limited treatment options. Small series have reported variable treatment success with isavuconazole. An absence of published data exists on cerebrospinal fluid (CSF) penetration of this agent.MethodsPaired serum and CSF levels were measured on three patients with refractory CM treated on salvage isavuconazole therapy.Results11 CSF levels were sent on 3 patients; 7 from ventricular sources (Ommaya reservoir or external ventricular drain) and 4 from lumbar punctures at 6-44 days after treatment initiation, 2-24.6 hours after oral or intravenous dose. All levels sent from ventricular sources were undetectable < 25µg/mL despite adequate paired serum levels (mean 2.45 µg/mL, range 1.25-6.38 µg/mL; n = 7 levels). Mean lumbar CSF levels were 1.00 µg/mL (range 0.45-1.72 µg/mL; n = 4 levels) with adequate serum levels (mean 3.57 µg/mL, range 1.78-5.63 µg/mL; n = 4 levels).Table 1. Isavuconazole serum and cerebrospinal fluid concentration measurements ConclusionIsavuconazole was detected in lumbar, but not ventricular CSF in three patients treated for CM.Disclosures All Authors: No reported disclosures

The curious fate of bone following bariatric surgery: bone effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in mice.

Bone loss and increased fracture risk following bariatric surgery has been reported. We investigated whether the two most commonly performed surgeries, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), lead to bone loss. In addition, we examined whether fortification of the diet with calcium citrate prevents bone loss. We used mouse models for SG and RYGB and compared bone loss with a group of sham mice with similar weight loss. All groups were switched at the time of surgery to a low-fat diet (LFD). We also examined whether fortification of the diet with calcium citrate and vitamin D was able to prevent bone loss. At 2 weeks we observed no major bone effects. However, at 8 weeks, both trabecular and cortical bone were lost to the same extent after SG and RYGB, despite increased calcium absorption and adequate serum levels of calcium, vitamin D, and parathyroid hormone (PTH). Diet fortification with calcium citrate and vitamin D was able to partially prevent bone loss. Both SG and RYGB lead to excess bone loss, despite intestinal adaptations to increase calcium absorption. Fortifying the diet with calcium citrate and vitamin D partly prevented the observed bone loss. This finding emphasizes the importance of nutritional support strategies after bariatric surgery, but also affirms that the exact mechanisms leading to bone loss after bariatric surgery remain elusive and thus warrant further research.

Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism – A pilot study

Background & ObjectivePatients with mild hypothyroidismoften are depressed and have impaired quality of life despite serumfree-T4 and T3 within reference values.Therefore, we investigated whether their symptoms weredependenton the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). MethodsTwenty-five newly diagnosed, untreatedhypothyroid subjects and as many age-and sex-matched healthy controls were investigated. Blood and CSF sampling wasperformedin the morningafter an overnight fast.Quality of life (QoL) was assessed byaLikert scale. In the hypothyroid subjects, theMADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaireswere related toserum and CSFlevels offree- T4 and T3 as well as the ratiosbetween them in CSF and in serum. ResultsSelf-reported health was considerably lower in hypothyroid subjects.MADRS was considerably higher than the normal range for healthy individuals.Low CSF/serum free-T4ratio was correlated with an increased depressed state according to MADRS(p < 0.01),andin addition,CSF/serum free-T4 ratiocorrelated positively withthe self-reported general healthLikert scale (p < 0.05).Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. ConclusionsLowCSF/serumratio offree-T4was correlated withimpairedgeneral health and mood, in contrast to serum measurements not showing any correlations. Thesefindings mightpartlyexplain whysomepatients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4.However, the findings need to be confirmed in further and larger studies.

Vitamin D Treatment Is Associated with Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study

Background: The 2019 novel coronavirus disease (Covid-19) worldwide pandemic has posed the most substantial and severe public health issue for several generations, and therapeutic options for it have not yet been optimised. Vitamin D has been proposed in the pharmacological management of Covid-19 by various sources. This study aimed to determine whether Covid-19 disease outcomes were affected by vitamin D status, and to elucidate any predictors of Covid-19 outcomes.Methods: Patients hospitalised with Covid-19 were opportunistically recruited from three different UK hospitals and their data were collected. Logistic regression was used to determine any relationships between vitamin D status and various predictors, including mortality and ventilation, and to determine any relationships between mortality, ventilation, and various predictors.Findings: Vitamin D status was not associated with any outcomes of Covid-19 investigated, following adjustment for age and sex. However, treatment with vitamin D was significantly associated with a reduced risk of death, following adjustment for age and sex (ORadj 0·48, 95% CI 0·32 – 0·70, p = 1·79x10-4). This relationship remained significant when also adjusted for baseline vitamin D levels (ORadj 0·47, 95% CI 0·33 – 0·70, p = 1·27x10-4).Interpretation: Treatment with vitamin D, regardless of baseline serum vitamin D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with Covid-19. Further work on large population studies needs to be carried out to determine adequate serum levels of vitamin D, as well as multi-dose clinical trials of vitamin D treatment to assess maximum efficacy.Trial Registration: The study was also registered on Clinicaltrials.gov (reference number NCT04386044), prior to commencement.Funding: None.Declaration of Interests: The authors have no conflicts of interest.Ethics Approval Statement: Ethical approval was granted by the Health and Care Research Wales Research Ethics Committee (IRAS number 285337).

Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.