Abstract: nutrients Article The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency Dana A. Bader 1 , Anas Abed 2 , Beisan A. Mohammad 3 , Ahmad Aljaberi 4 , Ahmad Sundookah 5 , Maha Habash 6 , Ahmad R. Alsayed 1 , Mohammad Abusamak 7,8 , Sami Al-Shakhshir 6 and Mahmoud Abu-Samak 1, * 1 2 3 4 5 6 7 8 * Citation: Bader, D.A.; Abed, A.; Mohammad, B.A.; Aljaberi, A.; Sundookah, A.; Habash, M.; Alsayed, A.R.; Abusamak, M.; Al-Shakhshir, S.; Abu-Samak, M. The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency. Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 11931, Jordan Department of Pharmaceutical Sciences, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia Department of Pharmaceutical Sciences and Pharmaceutics, Applied Science Private University, Amman 11931, Jordan Department of Clinical Nutrition and Dietetics, Applied Science Private University, Amman 11931, Jordan Michael Sayegh, Faculty of Pharmacy, Aqaba University of Technology, Aqaba 77110, Jordan Department Surgery, School of Medicine, Al-Balqa Applied University, As-Salt 19117, Jordan Amman Eye Clinic, Amman 11931, Jordan Correspondence: m_abusamak@asu.edu.jo Abstract: This research aimed to evaluate the effects of high-dose cholecalciferol (VD3 ) supplements (50,000 IU/week) on selected circulating cytokines associated with cytokine storms in adults with vitamin D deficiency. This clinical trial, based in Jordan, included 50 participants receiving vitamin D3 supplements (50,000 IU/week) for 8 weeks; the exact number was assigned to the control group. Interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrotic factor-α (TNF-α), and leptin were measured in serum at baseline and 10 weeks (wash out: 2 weeks). Our results revealed that vitamin D3 supplementation significantly increased the serum levels of 25OHD, IL-6, IL-10, IL-1β, and leptin compared with baseline. In contrast, the serum level of TNF-α insignificantly increased in the group receiving vitamin D3 supplementation. Although the observations of this trial may refer to a potential negative effect of VD3 supplementation during cytokine storms, further trials are required to clarify the potential benefits of VD3 supplement during cytokine storms. Nutrients 2023, 15, 1188. https:// doi.org/10.3390/nu15051188 Academic Editor: Lucia Malaguarnera Keywords: vitamin D deficiency; vitamin D3 ; cytokine; storm; interleukin 6; interleukin 10; interleukin 1β; TNF-α Received: 6 February 2023 Revised: 23 February 2023 Accepted: 24 February 2023 Published: 27 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/