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Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial

Domazet Bugarin et al., Nutrients, doi:10.3390/nu15051234, NCT05384574

Feb 2023

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage.

The baseline mean age and median WHO scores for the treatment and control groups are both higher than the respective values reported for all patients combined, which is not possible.

The trial was registered after completion in May 2022.

Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 39% [26‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.

This is the 26th of 29 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000024.

This is the 107th of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 248 sextillion).

This study is excluded in the after exclusion results of meta analysis: very late stage study using cholecalciferol instead of calcifediol or calcitriol.

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risk of death, 21.0% lower, RR 0.79, p = 0.20, treatment 30 of 75 (40.0%), control 39 of 77 (50.6%), NNT 9.4, day 60.

risk of death, 12.5% lower, RR 0.87, p = 0.61, treatment 23 of 75 (30.7%), control 27 of 77 (35.1%), NNT 23, day 28.

risk of death, 28.9% lower, RR 0.71, p = 0.49, treatment 9 of 75 (12.0%), control 13 of 77 (16.9%), NNT 20, day 14.

WHO score, no change, RR 1.00, p = 0.70, treatment 75, control 77, day 28.

hospitalization time, 5.6% higher, relative time 1.06, p = 0.76, treatment 75, control 77.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Domazet Bugarin et al., 28 Feb 2023, Randomized Controlled Trial, Croatia, peer-reviewed, 9 authors, study period November 2021 - May 2022, dosage 10,000IU days 1-14, trial NCT05384574 (history). Contact: lenko.saric@gmail.com (corresponding author).

This Paper Vitamin D All

Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial

Josipa Domazet Bugarin, Svjetlana Dosenovic, Darko Ilic, Nikola Delic, Ivana Saric, Ivo Ugrina, Sanda Stojanovic Stipic, Bozidar Duplancic, Lenko Saric

Nutrients, doi:10.3390/nu15051234

COVID-19 symptoms vary from asymptomatic cases to moderate and severe illness with patients needing hospitalization and intensive care treatment. Vitamin D is associated with severity of viral infections and has an immune-modulatory effect in immune response. Observational studies showed a negative association of low vitamin D levels and COVID-19 severity and mortality outcomes. In this study, we aimed to determine whether daily supplementation of vitamin D during intensive care unit (ICU) stay in COVID-19 patients with severe illness affects clinically relevant outcomes. Patients with COVID-19 disease in need of respiratory support admitted to the ICU were eligible for inclusion. Patients with low vitamin D levels were randomized into one of two groups: the intervention group received daily supplementation of vitamin D and the control group did not receive vitamin D supplementation. In total, 155 patients were randomized: 78 into the intervention group and 77 into the control group. There was no statistically significant difference in number of days spent on respiratory support, although the trial was underpowered for the main outcome. There was no difference in any of the secondary outcomes analyzed between two groups. Our study suggests no benefit in vitamin D supplementation to patients with severe COVID-19 disease admitted to the ICU and in need of respiratory support in any of the analyzed outcomes.

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Late treatment
is less effective

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