Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Efficiency of the Vitamin D Status Diagnosticator amongst Geriatric Patients with COVID-19.

The vitamin D status diagnosticator (VDSD), a 16-item tool, effectively identifies hypovitaminosis D in healthy older adults and can assist in determining the need for blood tests in this population. Assessing vitamin D levels is particularly crucial in the context of COVID-19. This study aimed to evaluate the VDSD's effectiveness in pinpointing hypovitaminosis D in older adults affected by COVID-19. The research involved 102 unsupplemented geriatric inpatients consecutively admitted to the acute geriatric division of Angers University Hospital, France, with an average age of 85.0 ± 5.9 years (47.1% women). The physician-administered VDSD was conducted simultaneously with the measurement of serum 25-hydroxyvitamin D (25(OH)D). Hypovitaminosis D was defined as a serum 25(OH)D concentration of ≤75 nmol/L for vitamin D insufficiency and ≤50 nmol/L for vitamin D deficiency. Results revealed that 87 participants (85.3%) had vitamin D insufficiency and 63 (61.8%) had vitamin D deficiency. The VDSD accurately identified vitamin D deficiency with an area under the curve (AUC) of 0.81 and an odds ratio (OR) of 40. However, its accuracy in identifying vitamin D insufficiency was lower (AUC = 0.57). In conclusion, the 16-item VDSD, a concise questionnaire, effectively identifies vitamin D deficiency in geriatric patients with COVID-19. This tool can be valuable in guiding the decision to administer vitamin D supplementation during the early stages of COVID-19.

A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health.

Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world's population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death.

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1.

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

Upregulation of Irisin and Vitamin D-Binding Protein Concentrations by Increasing Maternal 25-Hydrovitamin D Concentrations in Combination with Specific Genotypes of Vitamin D-Binding Protein Polymorphisms.

Dyshomeostasis of vitamin D-binding protein (VDBP) has been implicated in the pathogenesis of various pregnancy complications, including preeclampsia, preterm birth, gestational diabetes, and adverse metabolic profiles in the offspring. VDBP polymorphisms have been consistently reported to contribute to this intriguing interplay. Until recently, the effects of VDBP polymorphism heterogeneity on maternal and neonatal adipomyokine profiles have not been investigated, specifically after incorporating the different maternal and neonatal 25-hydroxyvitamin D concentration cut-offs at birth. We aimed to investigate the potential effects of maternal and neonatal VDBP polymorphisms on adiponectin, irisin, and VDBP concentrations at birth, according to different cut-offs of vitamin D status, in maternal-neonatal dyads recruited from the sunny region of Northern Greece. We obtained blood samples from 66 mother-child pairs at birth. Results indicated that (i) Neonatal serum biomarkers were not affected by any included neonatal VDBP polymorphism according to different cut-offs of neonatal vitamin D status at birth, (ii) neonatal VDBP concentration was elevated in neonates with maternal rs7041 GG genotype, (iii) maternal 25(OH)D at ≤75 nmol/L resulted in increased concentrations of maternal VBDP and irisin concentrations in women with CC genotype for rs2298850 and rs4588,whereas this effect was also evident for this cut-off for neonatal VDBP concentrations at birth for GC genotype for rs 7041, and (iv) no significant effect of neonatal VDBP polymorphisms was observed on neonatal VDBP, adiponectin, or irisin levels when stratified according to maternal 25(OH)D cut-offs. In conclusion, these findings confirm that among women with the combination of CC genotype for rs2298850 and rs4588, a specific high cut-off of maternal 25(OH)D results in increasing maternal VBDP concentrations, hence providing a mechanistic rationale for aiming for specific cut-offs of vitamin D after supplementation during pregnancy, in daily clinical practice.

Vitamin D and cognition in older adults: international consensus guidelines.

Hypovitaminosis D, a common condition in older adults, is associated with brain changes and dementia. Given the fast growing contribution of literature in this research field, clear guidance is needed for clinicians and researchers. International experts met at the invitational summit on "Vitamin D and cognition in older adults" in Boston, MA, July 2013. Based upon literature and expert opinion, the task force focused on key questions on the role of vitamin D in Alzheimer disease and related disorders. Each question was discussed and voted using a Delphi-like approach. Experts reached agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults, may alter the clinical presentation as a consequence of related comorbidities, but should not be used thus far as a diagnostic or prognostic biomarker of Alzheimer disease due to lack of specificity and insufficient evidence. Hypovitaminosis D should be screened in this population because of its high prevalence and supplemented, if necessary, but this advice was not specific to cognition. The task force agreed on 5 overarching principles related to vitamin D and cognition in older adults.

A new mechanism for amyloid-ß induction of iNOS: vitamin D-VDR pathway disruption.

The inflammatory process in Alzheimer's disease (AD) has been suggested to include oxidative and nitrosative damage caused by elevated levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Here, we investigated iNOS expression in cortical neurons following amyloid-ß (Aß) treatment, vitamin D treatment, Aß combined with vitamin D treatment, and vitamin D signaling disruption via silencing of nuclear (vitamin D receptor-VDR) or membrane vitamin D (1,25-MARRS) receptors. We observed that Aß induced iNOS expression. Vitamin D prevented Aß-induced cytotoxicity and iNOS upregulation in cortical neurons. Our silencing experiments suggest that vitamin D regulates iNOS via VDR, not 1,25-MARRS, in cortical neurons. Consequently, VDR absence induces iNOS expression in either the absence or presence of Aß. While our previous work demonstrates that Aß pathology includes VDR suppression, our present work demonstrates that Aß induces iNOS and that this effect is mediated via disruption of the vitamin D-VDR pathway. These data suggest the existence of crosstalk between Aß pathology and VDR. Thus, vitamin D supplementation should be considered a candidate in both the treatment and prevention of AD.