A critical evaluation of risk to reward ratio of quercetin supplementation for COVID‐19 and associated comorbid conditions

Abstract

The interim results of the large, multinational trials on coronavirus disease 2019 (COVID‐19) using a combination of antiviral drugs appear to have little to no effect on the 28‐day mortality or the in‐hospital course. Therefore, there is a still vivid interest in finding alternate re‐purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin's possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS‐CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID‐19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID‐19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS‐CoV‐2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID‐19.

High-dose Polyphenol-rich Nutrition Improves Lipid and Inflammation Profiles and Triggers Apoptotic Signaling in Healthy Elderly People (the ErdBEHR Study)

“…Quercetin is approved by the US Food and Drug Administration as GRAS (Generally Recognized As Safe) for use as an ingredient at levels up to 500 mg per serving (Barreca et al, 2021) (Pawar et al, 2022). In fact, with no reported side-effects, doses of 500 mg or 1000 mg were consumed daily over 12 weeks by ~600 adults (Knab et al, 2011), 1000 mg of quercetin daily were consumed over 6 weeks by ~20 healthy adults (athletes) (McAnulty et al, 2008), and doses from 250 mg to 5000 mg of quercetin daily over 4 weeks, by 30 chronic hepatitis C patients (Lu et al, 2016).…”

“…In fact, with no reported side-effects, doses of 500 mg or 1000 mg were consumed daily over 12 weeks by ~600 adults (Knab et al, 2011), 1000 mg of quercetin daily were consumed over 6 weeks by ~20 healthy adults (athletes) (McAnulty et al, 2008), and doses from 250 mg to 5000 mg of quercetin daily over 4 weeks, by 30 chronic hepatitis C patients (Lu et al, 2016). Moreover, quercetin (up to 600 mg daily) was suggested by some research groups to be a supplement of choice for COVID-19 and associated comorbid conditions (Pawar et al, 2022). Specific toxicity incidents related to anthocyanins are lacking, probably due to their very low bioavailability (Wallace & Giusti, 2015).…”

Introduction to Traditional Medicine and Their Role in Prevention and Treatment of Emerging and Re-Emerging Diseases

“…Since Quercetin is a safe and known natural product that has previously demonstrated antiviral capabilities including the novel SARS-CoV-2, it was evaluated in various clinical trials [ 170 ]. The results show, using Quercetin alone and in combination with other natural products (curcumin, zinc, vitamin C, etc.)…”

“… Various mechanisms via which quercetin neutralizes SARS-CoV-2 virus. Reproduced from reference [ 170 ] with permission. …”

In silico investigations of the multi‐targeted antiviral potential of small molecule phytochemicals of Nelumbo nucifera Gaertn. seed extracts against SARS‐CoV‐2 for therapeutics of COVID‐19

“…The climatic conditions of plant materials have a diversity of metabolites and keep phytocompounds as per stress conditions seen in aquatic and terrestrial plants. As a result of the diversity in plant metabolites, the area's local people show specific resistance against several ailments and disease conditions based on their food patterns and lifestyle (Pawar et al., 2022). The current investigation aimed to examine the multi‐targeted antiviral capability of Nelumbo nucifera seed extract phytochemicals against SARS‐CoV‐2 for COVID‐19 treatment.…”