Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc

Abstract

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.

Altered Vascular Endothelium-Dependent Responsiveness in Frail Elderly Patients Recovering from COVID-19 Pneumonia: Preliminary Evidence

“…This study could also open the discussion about possible treatments of this dysfunction: it is known that physical exercise can improve endothelial function [30,31], and rehabilitation attempts could lead to a beneficial improvement as well. Other treatments that could produce improvement are specific classes of dietary supplements [32] or drugs [33][34][35].…”

Zinc Deficiency, Plasma Fatty Acid Profile and Desaturase Activities in Hemodialysis Patients: Is Supplementation Necessary?

“…Zinc, as an antioxidant and antiinflammatory mediator, regulates the function of lymphocytes, making the body's immune system less susceptible to various infections (15)(16)(17). Recently, the protective role of zinc in vulnerable groups for COVID-19 such as hemodialysis patients has been mentioned (18).…”

A Narrative Review of the Safety of Anti-COVID-19 Nutraceuticals for Patients with Cancer

“…Vitamin D may decrease CRP, which has been implicated in the cytokine storm seen in severe cases of COVID-19 infection [ 18 ]. We identified an overwhelming majority of studies with results that point in favor of vitamin D use in patients with cancer, with positive effects seen in quality-of-life measures, mortality, recurrence, and pain indexes.…”

“…Vitamin C, similar to vitamin D, may contribute to a decrease in the pro-inflammatory cytokines, which are a hallmark of severe COVID-19 infection [ 18 ]. The evidence for vitamin C also strongly points in the direction of supplementation being safe, or perhaps even beneficial, for patients with cancer.…”

“…Another review by Lordan et al found an association between zinc deficiency and increased COVID-19 complications [ 17 ]. In vivo studies have also pointed to the role of nutraceuticals in the treatment and prevention of COVID-19, including a study by Corrao et al, which demonstrated an inverse relationship between C-reactive protein (CRP), a marker of systemic inflammation, and supplementation with vitamin C, vitamin D, and zinc [ 18 ]. Furthermore, there have been several theoretical papers discussing the potential mechanistic roles of nutraceuticals and how they might target the SARS-CoV-2 virus [ 19 , 20 , 21 ].…”