Higher dietary vitamin D intake is associated with better survival among older women: Results from the French EPIDOS cohort.

Background: Hypovitaminosis D, a condition highly common among older adults, is associated with 35-percent increased all-cause mortality. In contrast, vitamin D supplementation prevents all-cause mortality. The possible role of the dietary intake of vitamin D on mortality remains yet unknown. Objectives: The objective of this prospective study was to determine all-cause mortality risk according to baseline dietary vitamin D intake among older adults while accounting for potential confounders including dietary calcium intake. Methods: Vitamin D and calcium dietary intakes were estimated at baseline from a self-administered food frequency questionnaire among 3,066 community-dwelling older women aged ≥75 years, recruited in the French EPIDOS cohort between 1992 and 1994, and for whom information about vital status was available in 2010. Dietary vitamin D and calcium intakes were defined as low if <400 IU/day or <1,200 mg/day, respectively. Results: The mean ± SD age of the whole cohort was 80.1 ± 3.6 years at baseline. The median survival time from baseline for participants with low dietary vitamin D intake was 11.5 years [95% confidence interval (CI): 11.0-11.9] vs. 12.2 years (95% CI: 11.7-12.9) for those consuming more than 400 IU/day (p = 0.003). Among those with calcium dietary intake <1,200 mg/day, a vitamin D consumption of 400 IU/day and over had a significant positive effect on all-cause mortality (RR: 0.86, p < 0.05). However, no association was retrieved between dietary vitamin D intake and all-cause mortality among participants with dietary calcium intake ≥1,200 mg/day. Conclusion: Higher dietary vitamin D intake was associated with better survival in the study cohort, specifically among those consuming <1,200 mg/day of dietary calcium.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial.

BACKGROUND: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. METHODS: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. DISCUSSION: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Body position and motor imagery strategy effects on imagining gait in healthy adults: Results from a cross-sectional study.

BACKGROUND: Assessment of changes in higher levels of gait control with aging is important to better understand age-related gait instability, with the perspective to improve the screening of individuals at risk for falls. The comparison between actual Timed Up and Go test (aTUG) and its imagined version (iTUG) is a simple clinical way to assess age-related changes in gait control. The modulations of iTUG performances by body positions and motor imagery (MI) strategies with normal aging have not been evaluated yet. This study aims 1) to compare the aTUG time with the iTUG time under different body positions (i.e., sitting, standing or supine) in healthy young and middle age, and older adults, and 2) to examine the associations of body positions and MI strategies (i.e., egocentric versus allocentric) with the time needed to complete the iTUG and the delta TUG time (i.e., relative difference between aTUG and iTUG) while taking into consideration clinical characteristics of participants. METHODS: A total of 60 healthy individuals (30 young and middle age participants 26.6±7.4 years, and 30 old participants 75.0±4.4 years) were recruited in this cross-sectional study. The iTUG was performed while sitting, standing and in supine position. Times of the aTUG, the iTUG under the three body positions, the TUG delta time and the strategies of MI (i.e., ego representation, defined as representation of the location of objects in space relative to the body axes of the self, versus allocentric representation defined as encoding information about body movement with respect to other object, the location of body being defined relative to the location of other objects) were used as outcomes. Age, sex, height, weight, number of drugs taken daily, level of physical activity and prevalence of closed eyes while performing iTUG were recorded. RESULTS: The aTUG time is significantly greater than iTUG while sitting and standing (P<0.001), except when older participants are standing. A significant difference is reported between iTUG while sitting or standing and iTUG while supine (P≤0.002), higher time being reported in supine position. The multiple linear regressions confirm that the supine position is associated with significant increased iTUG (P≤0.04) and decreased TUG delta time (P≤0.010), regardless of the adjustment. Older participants use the allocentric MI while imagining TUG more frequently than young and middle age participants, regardless of body positions (P≤0.001). Allocentric MI strategy is associated with a significant decrease in iTUG (P = 0.037) only while adjusting for age. A significant increase of iTUG time is associated with age (P≤0.026). CONCLUSIONS: Supine position while imagining TUG represents a more accurate position of actual performance of TUG. Age has a limited effect on iTUG performance but is associated with a change in MI from ego to allocentric representation that decreases the iTUG performances, and thus increases the discrepancy with aTUG.