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High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients - a randomized, double-blind clinical trial

Sistanizad et al., European Journal of Integrative Medicine, doi:10.1016/j.eujim.2020.101271
Dec 2020  
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Mortality 64% Improvement Relative Risk Vitamin D  Sistanizad et al.  ICU PATIENTS  RCT Is very late treatment with vitamin D beneficial for COVID-19? RCT 30 patients in Iran Lower mortality with vitamin D (p=0.0039) c19early.org Sistanizad et al., European J. Integra.., Dec 2020 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 110 treatments. c19early.org
RCT of 30 ventilated ICU patients showing lower mortality with vitamin D treatment, RR 0.36, p = 0.004. Authors do not indicate why the patients were hospitalized or if any of the patients were COVID-19 patients. 300,000 IU intramuscular vitamin D was used.
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: 69% [47‑82%] lower risk vs. 39% [27‑49%] 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.
Bolus treatment is less effective. Pharmacokinetics and the potential side effects of high bolus doses suggest that ongoing treatment spread over time is more appropriate. Research has confirmed that lower dose regular treatment with vitamin D is more effective than intermittent high-dose bolus treatment for various conditions, including rickets and acute respiratory infections1,2. The biological mechanisms supporting these findings involve the induction of enzymes such as 24-hydroxylase and fibroblast growth factor 23 (FGF23) by high-dose bolus treatments. These enzymes play roles in inactivating vitamin D, which can paradoxically reduce levels of activated vitamin D and suppress its activation for extended periods post-dosage. Evidence indicates that 24-hydroxylase activity may remain elevated for several weeks following a bolus dose, leading to reduced levels of the activated form of vitamin D. Additionally, FGF23 levels can increase for at least three months after a large bolus dose, which also contributes to the suppression of vitamin D activation1.
risk of death, 63.5% lower, RR 0.36, p = 0.004, treatment 5 of 16 (31.2%), control 12 of 14 (85.7%), NNT 1.8.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Sistanizad et al., 26 Dec 2020, Randomized Controlled Trial, Iran, peer-reviewed, 8 authors, dosage 300,000IU single dose, intramuscular.
This PaperVitamin DAll
High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients - A randomized, double-blind clinical trial
Mohammad Sistanizad, Mehran Kouchek, Mirmohammad Miri, Sara Salarian, Seyedpouzhia Shojaei, Fatemeh Moeini Vasegh, Hossein Seifi Kafshgari, Roja Qobadighadikolaei
European Journal of Integrative Medicine, doi:10.1016/j.eujim.2020.101271
Introduction: Mechanical ventilation can increase the rate of free radicals in the systemic circulation due to its effect on the inflammatory system. Previous research has suggested that vitamin D has antioxidant properties. This study aimed to evaluate the effect of vitamin D on total Antioxidant Capacity (TAC) and its relationship with ICU patients' outcomes . Methods: In this prospective randomized clinical trial, 36 ventilated ICU patients were randomly allocated to receive either a single intramuscular vitamin D 300,000 IU or its placebo. Serum Vitamin D and TAC were measured before and on day 7 after the intervention. Clinical Pulmonary Infection Score (CPIS) and sequential organ failure assessment (SOFA) scores were measured daily for seven days and on days 14 and 28. Results: Thirty patients completed the study. The results show that injection of vitamin D leads to a significant increase in the mean changes of vitamin D level on the seventh day of the study ( + 3.5 ± 1.3 vs -0.4 ± 0.2 P = 0.00) and TAC levels (3.2 ± 3.9 vs -2.0 ± 2.6 P = 0.00. ICU length of stay was 18.3 ± 8.4 and 25.4 ± 6.6 days in the intervention and placebo arms of the study. Twelve patients in the placebo group and 5 in the vitamin D group died within the 28 day study period. The duration of mechanical ventilation was 15.7 ± 9.3 vs. 22.6 ± 9.1 days in vitamin D and placebo arms, respectively. Conclusion: : Administration of vitamin D may increase TAC levels and decrease the length of stay and duration of mechanical ventilation in ICU patients.
Author contributions MS: study design, data collection, data analysis, conducting the study, and drafting the manuscript. MK: study design, conducting the study, and supervised the study. MMM, SPS, and SS: study design and conducting the study. FMV: data collection, statistical analysis. HSK: statistical analysis and reviewing the paper. RQG: reviewing the paper, writing the final approval, and data analysis. Declaration of Competing Interest The authors declared that there is no conflict of interest. Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.eujim.2020.101271 .
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Late treatment
is less effective
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