A narrative review focusing on randomized clinical trials of vitamin D supplementation for COVID-19 disease
Front. Nutr. 11:1461485. doi: 10.3389/fnut.2024.1461485
Limi Huang1*, Zhiwei Song2, Chaosheng Lu1, Shenwen Wang3, Changsheng Guo4, Xin-He Lai1,5* and Zhenfeng Zhao6*
Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China, Department of Infection Diseases, Xianju County People's Hospital, Taizhou, Zhejiang, China, 3School of Information Engineering, Hebei GEO University, Shijiazhuang, Hebei, China, 4Shaoxing BWK Biotechnology Co., Ltd., Zhuji City High-Tech Entrepreneurship Center, Shaoxing, Zhejiang, China, 5Shenzhen Boya Gene Technology Co., Ltd., Shenzhen, China, 6Hebei Huiji Technology Co., Ltd., Shijiazhuang, Hebei, China
Current evidence is inconsistent on whether vitamin D supplementation can prevent COVID-19 infection or improve its clinical outcomes. To better understand and look into the issue, we went through the background knowledge of COVID-19 and vitamin D, searched in Pubmed [by using key words in the title containing “randomized clinical trial", “COVID-19", and “vitamin D (25-hydroxyvitamin D, or cholecalciferol, or calcidiol, or calcifediol) supplementation"] for publications of studies on vitamin D/supplementation in COVID-19 patients, especially those about the randomized clinical trials (RCTs). After reviewing these papers, we did a short background review of vitamin D and the pathophysiology of COVID-19, summarized the key features of the 25 RCTs in text and tabulated in a table of some of the features, commented, compared and discussed the differences between RCTs (for example, change the serum 25-hydroxyvitamin D concentration from nmol/L to ng/mL, making the comparison easier). The take-home question of the review is that serum 25-hydroxyvitamin D concentration is an important indicator of the supplementation effect of vitamin D correction but may not be reliable in predicting the supplementation effect on the clinical outcomes of COVID-19.
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Conclusion (from PDF)
Together, the general conclusion from these studies is that VD insufficiency/deficiency is highly related to COVID-19 infection, its severity and mortality, but data of the effect on clinical benefit from VD supplementation is conflicting, further RCT study is surely needed.
One key but puzzling observation after carefully reviewing these 25 RCTs is that the endline serum 25D concentration, although a good indicator of the VD supplementation effect on correcting VD insufficiency/deficiency, it is not reliable to predict that VD sufficiency after supplementation is a guarantee of clinical improvement of COVID-19. There are 7 RCTs reviewed above that had endline serum 25D concentration at or above the optimal level (#: 2, 5, 9, 15, 16, 18, 22; the exact ng/mL values in Table 1; optimal level > 30 ng/mL) but only three reached its trial outcome (RCTs, #2, 5, 9) and the other four failed, despite having the VD deficit of the patients corrected. By contrast, the supplementation in three RCTs (#3, 4, 6) failed to correct the VD insufficiency/deficiency but succeeded in improving the clinical outcome(s). Apparently, the scientific community need to work out a (set of) biomarker(s) that can be used as a correlate of the effect of VD supplementation on protection (prophylactic), treatment (therapeutic) or both.
Although it is a long way to go, there are already some pioneering work that has been done. Among others, calprotectin (70, 71), endocan (72), growth differentiation factor 15 (GDF15) (73), inflammatory cytokines (IL1 and IL6) (74), miRNAs (75), neopterin (76), soluble suppressor of tumorigenicity 2 (sST2) (77), and T cell immunoglobulin and mucin domain containing protein 3 (Tim) (78) have been reviewed having the potential as biomarkers for COVID-19 severity.
Comment by VitaminDWiki
In order for the body to fight COVID the Vitamin D level must be high BEFORE COVID has gotten out of control in the body.
Similarly, a fire truck cannot put out a major fire once it has gotten out of control.
- RCTs that do NOT use a loading dose within a few days of infection (not just entering the hospital) will likely fail.
- The Vitamin D level needed to fight COVID appears to be 125 nmol (50 ng), not just the 75 nmol (30 ng) needed to fight bone problems.