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From ... in Biology —

Attacks the Flu, Commonly Found in Onion Skins

STORY AT-A-GLANCE This article was previously published September 9, 2019, and has been updated with new information.

Attacks the Flu, Commonly Found in Onion Skins

Your immune system is your first-line defense against bacterial and viral infections, so the most effective way to prevent infectious illness is maintaining robust immune function. Your diet and other lifestyle factors are foundational for this, but certain supplements can also be helpful.

One such supplement is quercetin,1 an antioxidant fiavonol found naturally in apples, plums, red grapes, green tea, elder fiower and onions, just to name a few. Quercetin is one of those compounds with a wide range of benefits, making it useful for a variety of different conditions. That said, it's perhaps most known for its strong antioxidant and antiviral activity. Elderfiower extract, which is rich in quercetin, is also a traditional tonic used to boost immunity. In supplement form, quercetin has been used to ameliorate obesity, Type 2 diabetes, circulatory dysfunction, chronic infiammation, hay fever and mood disorders. Several studies have also highlighted quercetin's ability to prevent and treat the common cold and infiuenza. In fact, its antiviral capacity appears to be the primary focus of many studies looking at quercetin's benefits. But there are also other, less known uses for this supplement, including blood pressure control and tumor regression.

Quercetin May Lower Blood Pressure

For example, there's evidence to suggest quercetin benefits the heart, and can help lower blood pressure in patients with Stage 1 high blood pressure. As noted in one 2007 study:

"Epidemiological studies report that quercetin … is associated with reduced riskof coronary heart disease and stroke … Men and women with prehypertensionand stage 1 hypertension were enrolled in a randomized, double-blind, placebo-controlled, crossover study to test the eficacy of 730 mg quercetin/d for 28d[ays] vs. placebo.Blood pressure at enrollment was … 148 +/- 2/96 +/- 1 in stage 1 hypertensivesubjects … [R]eductions in systolic (-7 +/- 2 mm Hg), diastolic (-5 +/- 2 mm Hg),and mean arterial pressures (-5 +/- 2 mm Hg) were observed in stage 1hypertensive patients after quercetin treatment … These data are the first to our
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knowledge to show that quercetin supplementation reduces blood pressure inhypertensive subjects."

Quercetin May Regress Tumors

Another study, published in Scientific Reports in 2016, found quercetin has the ability to trigger tumor regression by interacting with your DNA and activating the mitochondrial pathway of apoptosis, which is the programmed cell death of damaged cells. As noted in the abstract of this study:

"… quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner… Besides leukemic cells, quercetin also induced cytotoxicity in breast cancercells, however, its effect on normal cells was limited or none.Further, quercetin caused S phase arrest during cell cycle progression in testedcancer cells … Importantly, administration of quercetin lead to ~5 fold increasein the life span in tumor bearing mice compared to that of untreated controls.Further, we found that quercetin interacts with DNA directly, and could be one ofthe mechanisms for inducing apoptosis in both cancer cell lines and tumortissues by activating the intrinsic pathway. Thus, our data suggests thatquercetin can be further explored for its potential to be used in cancertherapeutics and combination therapy."

How Quercetin Combats Infiammation and Boosts Immunity

As mentioned, quercetin is most known for boosting immunity and combating infiammation. As noted in a 2016 study in the journal Nutrients, mechanisms of action include (but is not limited to) the inhibition of: • Lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF- α ) production in macrophages (TNF- α is a cytokine involved in systemic infiammation, secreted by

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activated macrophages, a type of immune cell that digests foreign substances, microbes and other harmful or damaged components) • LPS-induced mRNA levels of TNF- α and interleukin (IL)-1 α in glial cells, which results in "diminished apoptotic neuronal cell death" • The production of infiammation-producing enzymes • Calcium infiux into the cell, which in turn inhibits: ◦ Pro-infiammatory cytokine release ◦ Histamine and serotonin release from intestinal mast cells release According to this paper, quercetin also stabilizes mast cells, has cytoprotective activity in the gastrointestinal tract, and "a direct regulatory effect on basic functional properties of immune cells," which allows it to inhibit "a huge panoply of molecular targets in the micromolar concentration range, either by down-regulating or suppressing many infiammatory pathways and functions." The following figure from the journal Nutrients shows the many possible pathways by which quercetin inhibits infiammation and boosts immune function. Table 1 in this study also summarizes the primary effects of quercetin on infiammation and immune function depending on the specific cell line used in the investigation.

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Demonstrated Health Benefits of Quercetin

In animal models, quercetin has been shown to: Ameliorate the infiammatory response induced by carrageenan, a common food additive Reduce the production of TNF- α in visceral adipose tissue (intra-abdominal fat that raises your risk of health complications such as Type 2 diabetes and heart disease) Reduce clinical signs of arthritis Improve recovery of motor function after spinal cord injury (according to this paper, "Intraperitoneal doses of 5-100 micromoles quercetin/kg body weight resulted in half or more of the animals walking … This ability to promote recovery from spinal cord injury appears to be highly dependent on the dose and frequency of dosing" In human studies, quercetin has been shown to: Reduce total sick days and symptom severity associated with upper-respiratory tract infection (URTI) in physically fit individuals over the age of 40 (dosage: 500 or 1000 mg/day for 12 weeks) Significantly reduce risk of illness, infiammation and oxidative stress after intense exercise Augment innate immune function in exercise-stressed athletes Reduce viral illness and boost mental performance after extreme physical stress that might otherwise undermine your immune function (in one study, 45% in the placebo group got sick with a cold or infiuenza after a strenuous three-day exercise routine, compared to just 5% in the treatment group, which received 1,000 milligrams quercetin combined with vitamin C and niacin to improve absorption) Protect against abroad spectrum of pathogens, including rhinoviruses, adenoviruses and coronaviruses

Quercetin Is a Potent Antiviral Remedy

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Indeed, several studies have confirmed quercetin's effectiveness against a range of viral infections. Below, I list some of them. In summary, quercetin's powerful antiviral effects can be attributed to three main mechanisms of action: 1. Inhibiting the virus' ability to infect cells 2. Inhibiting replication of already infected cells 3. Reducing infected cells' resistance to treatment with antiviral medication A 1985 study found quercetin inhibits infectivity and replication of herpes simplex virus type 1, polio-virus type 1, parainfiuenza virus type 3 and respiratory syncytial virus. A 2010 animal study found quercetin inhibits infiuenza A and B viruses. Two other important discoveries were made: 1. The viruses were unable to develop resistance to quercetin 2. When used concomitant with antiviral drugs (amantadine or oseltamivir), the effect was significantly amplified — and it prevented drug-resistance from developing A 2004 animal study investigating quercetin's effect on infiuenza used a strain of the H3N2 virus. According to the authors: "In the mice, instillation of infiuenza virus A/Udorn/317/72(H3N2) intranasally resulted in a significant decrease in the pulmonary concentrations of catalase, reduced glutathione and superoxide dismutase … These effects were observed on the 5th day after viral instillation. Oral supplementation with quercetin simultaneous with viral instillation produced significant increases in the pulmonary concentrations of catalase, reduced glutathione and superoxide dismutase …

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It is concluded that during infiuenza virus infection, there is 'oxidative stress.' Because quercetin restored the concentrations of many antioxidants, it is proposed that it may be useful as a drug in protecting the lung from the deleterious effects of oxygen derived free radicals released during infiuenza virus infection." In 2014, researchers noted that quercetin appears to be "a promising treatment for the common cold" caused by the rhinovirus, adding that "Quercetin has been shown to reduce viral internalization and replication in vitro, and viral load, lung infiammation and airways hyper-responsiveness in vivo." By attenuating oxidative damage, it also lowers your risk of secondary bacterial infections, which is actually the primary cause of infiuenza-related deaths. Importantly, quercetin increases mitochondrial biogenesis in skeletal muscle, which suggests part of its antiviral effects are due to enhanced mitochondrial antiviral signaling. According to the authors: "… [I]n vitro studies have demonstrated that quercetin acts as a potent antiviral agent by inhibiting viral replication of several respiratory viruses, including infiuenza virus, parainfiuenza virus, respiratory syncytial virus, adenovirus and rhinovirus. Although the quercetin's antiviral mechanisms are not well understood, a number of possibilities have been proposed and is summarized in Figure 1."

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Research published in 2015 found quercetin inhibited hepatitis B virus replication in human liver cells, protecting cells from infection and limiting the spread of infection in already infected samples. What's more, when combined with antiviral drugs (lamivudine, entecavir or adefovir), the antiviral effect was greatly enhanced. According to the authors, "The results indicate that quercetin inhibited HBV [hepatitis B virus] antigen secretion and genome replication in human hepatoma cell lines, which suggests that quercetin may be a potentially effective anti-HBV agent." Other studies show quercetin can inhibit hepatitis C infection as well. A 2016 animal study found quercetin inhibited mouse hepatitis virus and the dengue virus.

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Another 2016 study found quercetin offered protection against infiuenza A virus H1N1 by modulating protein expression. More specifically, the regulation of heat shock proteins, fibronectin 1 and prohibitin was instrumental in reducing viral replication. A third study published in 2016 found quercetin inhibited a wide spectrum of infiuenza strains, including H1N1, H3N2 and H5N1. According to the authors, "This study indicates that quercetin showing inhibitory activity in the early stage of infiuenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of [infiuenza A viruses] infections."

Quercetin Is a Far Safer Alternative to Antiviral Drugs

Considering the powerful antiviral effects of quercetin, it would be sensible to make use of it first, before resorting to antiviral drugs such as Tamifiu. Not only has Tamifiu been shown to shorten the duration of fiu symptoms by less than 17 hours, it also does not reduce viral transmission and does not lower your risk of complications from the fiu, such as pneumonia. Scientists have also warned that the risks of Tamifiu far outweigh the benefits. These risks include convulsions, brain infections, psychosis and other neuropsychiatric problems, including mood swings, suicidal feelings, auditory hallucinations, memory deterioration and insomnia. The drug is particularly risky for children, and more than half of all children taking Tamifiu suffer side effects from the drug. Considering its risks, and its limited effectiveness, quercetin appears to be a far safer and more effective alternative. Studies have repeatedly found quercetin to be nontoxic, with no adverse side effects.

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