Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial

Abstract

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53–74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4–13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12–45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay

“…We observed a significant increase in the mean serum 25(OH)D 3 level in the intervention group compared to the control group, which resulted in a significant higher mean level at discharge in the intervention group and significantly more patients had serum 25(OH)D 3 levels ≥50 nmol/L in the intervention group. At the same time, there was no clinically relevant increase in calcium or phosphate in the intervention group, which is in line with previous results [24,[40][41][42]. This indicates that a single bolus of high dose vitamin D 3 in addition to daily low dose maintenance therapy is effective to elevate serum 25(OH)D 3 levels quickly.…”

High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials

“…Of the 15 articles, we excluded 10 for various reasons, including being sub‐studies or analyses of previous studies, withdrawn by the journal (Lakkireddy et al., 2021 ), study protocols, or not meeting our high‐dose definition (Caballero‐Garcia et al., 2021 ; Entrenas Castillo et al., 2020 ; Karonova, Chernikova, et al., 2022 ; Maghbooli et al., 2021 ). Finally, the search strategy leaves us with five RCTs involving 834 patients for our meta‐analysis (Annweiler et al., 2022 ; Cervero et al., 2022 ; Mariani et al., 2022 ; Murai et al., 2021 ; Rastogi et al., 2022 ). The flow of the study is depicted in Figure 1 , and Table 1 presents the baseline characteristics of the eligible trials.…”

Vitamin D, acute respiratory infections, and Covid-19: the curse of small-size randomised trials. A critical review with meta-analysis of randomised trials

“…After full article reading, nine articles [16,28,[31][32][33][34][35][36][37] were selected for review and 14 articles were excluded. Reasons for exclusion were: high vs. low dose VDS [38][39][40], no specific numbers of patients who were admitted in ICU [14,15,30,[41][42][43][44][45], failure of randomization [29], and not a randomised trial [46,47]. Characteristics of the nine selected randomised trials are summarized in Table 1.…”