Written by Joyce Smith, BS. High dose of Calcifediol, a main metabolite of the vitamin D endocrine system, significantly reduced the need for ICU treatment of patients hospitalized with COVID-19.

vitamin DMany published studies document an association between vitamin D and improved outcomes for acute respiratory disorders, such as Acute Respiratory Distress Syndrome (ARDS), a component of COVID-19 infections. Early on in our current pandemic, a study by Grant and colleagues 1 provided evidence of a relationship between vitamin D, immune function, and upper respiratory viral infections and that Vitamin D supplementation could reduce the risk of influenza, COVID-19 infections and deaths. As our country is in the grip of the COVID-19 pandemic, we desperately need public health measures to reduce the high infection risk and mortality. Past evidence has shown that vitamin D supplementation can minimize the risk of influenza during winter months when 25 hydroxyvitamin D (25[OH]D) levels are at their lowest 1. A more recent research 2 expounded on the hypothesizes that ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. (The vitamin D hormone 125(OH)2D activates the native or innate immune defense system, thus tapering down the acquired immune system and ARDS). Calcifediol, also known as 25-hydroxycholecalciferol, or 25(OH)D, is the main metabolite of the vitamin D endocrine system. This prehormone, produced in the liver by hydroxylation of vitamin D3, may be superior to native Vitamin D because of its more rapid intestinal absorption (almost 100%) and its ability to rapidly restore serum 25(OH)D levels by bypassing hydroxylation of vitamin D3 to 25(OH)D in the liver. Several randomized clinical trials using either oral vitamin D or oral calcifediol are ongoing with some having already provided their guidelines for vitamin D use in treating COVID-19. An August, 2020  follow-up pilot study to the recently published May 2020 work by the Castillo team, advocates the use of calcifediol as a promising therapeutic form of vitamin D for Covid-19 treatment.

This follow-up pilot study was a randomized open label, double-masked clinical trial 3, designed to evaluate the effect of calcifediol treatment on the Intensive Care Unit (ICU) admission and mortality rates of patients hospitalized for COVID-19. Seventy-five consecutive admissions of diagnosed Covid-19 patients (45 males, 31 females, average age 53 years) were randomized into a vitamin D treatment group (n=50) or a control group (n=26).  The control group received only standard care for COVID-19, consisting of a combination treatment of hydroxychloroquine and azithromycin and complemented with additional standard treatments as necessary while the Vitamin D group received, in addition to standard care, a .532 mg dose of oral calcifediol at admission, followed by .266 mg doses on days 3 and 7, and then once weekly until either discharged or admitted to the ICU.

The study found that the administration of Calcifediol at the early stages of COVID-19 infection significantly reduced the need for admission to the ICU, regardless of existing comorbidities. Of the 26 patients who received standard treatment only, 13 (50%) were not admitted to the ICU and were discharged; 13 patients were admitted to the ICU of which two died and the remaining 11 were discharged. However, of the 50 patients treated with calcifediol, only one was admitted to ICU, none died, and all were discharged without complications.

Although very small, this study validates the effectiveness of high dose Calcifediol in improving outcomes of COVID-19 and reducing the need for ICU admission. Additional trials of larger scope are needed to lend further credence to these findings.

Source: Castillo, Marta Entrenas, Luis Manuel Entrenas Costa, José Manuel Vaquero Barrios, Juan Francisco Alcalá Díaz, José López Miranda, Roger Bouillon, and José Manuel Quesada Gomez. “Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study.” The Journal of steroid biochemistry and molecular biology (2020): 105751.

© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Posted September 28, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Grant WB, Boucher BJ, Bhattoa HP, Lahore H. Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations. J Steroid Biochem Mol Biol. 2018;177:266-269.
  2. Quesada-Gomez J, Bouillon R. Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporosis International. 2018;29(8):1697-1711.
  3. Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, et al. “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”. J Steroid Biochem Mol Biol. 2020;203:105751.
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