Quercetin in Early Covid

Results of a randomized clinical trial

Reference

Di Pierro F, Kham A, Iqtadar S, et al. Quercetin as a possible complementary agent for early-stage Covid-19: concluding results of a randomized clinical trial. Front Pharmacol. 2023;13:1096853.

Study Objective

To assess possible therapeutic effects of quercetin in outpatients with early-stage, mild-to-moderate symptoms of Covid-19

Key Takeaway

In this study, patients taking quercetin during early-stage Covid cleared the virus and experienced symptom resolution significantly earlier than those in a control group.

Design

Open-label, randomized, controlled clinical trial

Participants

There were 108 participants who started the trial and were randomly assigned in a 1:1 ratio to a treatment or control group. There were 4 participants per group who dropped out, leaving a total of 50 participants per group (50% female in the control group; 54% female in the quercetin group). A significant difference between the groups was that the treatment group had a mean age of 41.1 years and the control group had a mean age of 54.1 years.

Inclusion criteria included being 18 years or older, positive RT-PCR (reverse transcription–polymerase chain reaction) test results, and mild-moderate Covid-19 symptoms defined as: fever, dyspnea, dry cough, sore throat, myalgia, and/or weakness. In addition, participants had to have an O2 stat over 93% and be appropriate candidates for outpatient care.

Exclusion criteria included allergy to quercetin, chronic kidney disease, pregnancy, severe hypotension, moderate-to-severe thrombocytopenia, and being on an immune stimulant prior to time of enrollment.

Comorbidities and symptom profile between groups were well-matched. This trial took place in Lahore, Pakistan. The paper made no mention of racial identity. Notably, none of the participants were vaccinated.

Intervention

By Caitlin O’Connor, ND

Participants received 500 mg quercetin phytosome 3 times daily for 1 week and 2 times daily for week 2 as an add-on to standardized care. The control group received only standardized care; no placebo was used.

Study Parameters Assessed

This study measured SARS-CoV-2 infection by RT-PCR testing and symptom prevalence and severity as clinically assessed by outpatient physicians. Additionally, investigators assessed laboratory levels of C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), ferritin, and complete blood count (CBC).

Primary Outcome

The primary outcomes assessed in this study were the time needed to achieve a negative SARS-CoV-2 RT-PCR test and improvement in acute symptoms at the 1- and 2-week mark as assessed by an outpatient physician. Secondary outcomes included laboratory changes over the same period.

Key Findings

The quercetin treatment group had significantly more participants test negative for the SARS-CoV-2 virus at 1 week compared to the control group (68% vs 24%, P=0.0004). Interestingly, by week 2 nearly all participants, regardless of group, had cleared the virus (98% in treatment group and 94% in control).

Clinical resolution of acute symptoms also occurred more quickly in the treatment group (52%) vs the control (24%; P=0.0031). Again, both groups seemed to fare equally well at the 2-week mark, with “most of patients” being free of symptoms—although the article did not show this specific dataset.

Transparency

The quercetin phytosome used in this trial was donated by 2 companies (PharmExtracta and Indena) that distribute the quercetin phytosome; 4 of the 13 authors are on the boards of said companies.

PRACTICE IMPLICATIONS & LIMITATIONS

As we are learning to coexist with SARS-CoV-2, any information on how to mitigate the impact and improve patient outcomes is welcome. The most compelling component of this study from a clinical standpoint was the accessibility of the intervention: The quercetin phytosome was dosed at 500 mg 3 times a day for the first week and 500 mg 2 times a day for the subsequent week. Additionally, participants tolerated the intervention well, with no adverse effects reported.

However, the study has some significant limitations. The first is the significant age difference between the treatment group (mean age 41.1 years) and the control group (mean age 54.1 years). With age being one of the main risk factors for acute complications from SARS-CoV-2 infection, it is hard to know if we can attribute the benefits seen in the treatment group to quercetin or just younger age. The small sample size is also a drawback—although one that is common in the evaluation of complementary treatments. Additionally, we can only hypothesize how these findings may translate into a vaccinated population.

Despite these limitations, the outcomes at 1 week are impressive; certainly many of our patients would love to clear the virus more quickly and, thus, decrease the timeframe in which they could possibly infect others. Moreover, many patients would be quite thrilled with any intervention that reduces their acute symptomatic phase. With these 2 things in mind, I think many clinicians might be willing to offer this safe, relatively inexpensive, and possibly beneficial intervention.

Another compelling finding was the similarity between the 2 groups after 2 weeks. At this point, nearly all patients had cleared the virus and were asymptomatic. Put another way, while the phytosomal quercetin seemed to speed recovery, both groups eventually recovered by the end of 2 weeks. This rapid recovery may have been in part due to the mean age of both groups, their outpatient status, and (possibly) their lack of comorbidities (though the article did not clearly define these).

Fortunately, most people who contract Covid will recover. The odds greatly increase with lower age and lack of complicating health factors. The statistics vary around what percentage of these patients go on to develop symptoms of long Covid, and certainly we could use more clarity about the definition and prevalence of this syndrome. It would be interesting to note if the quercetin intervention affected the development of long Covid symptoms, though the small sample size would likely preclude any statistically significant data.

Nevertheless, phytosomal quercetin may be an accessible and safe option to offer patients looking to shorten their symptomatic Covid, even though clearance is the most likely natural course of the infection.

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Long Covid Prevention and Recovery

A discussion with 3 veteran integrative medical practitioners

Nearly 1 in 5 adults who have had Covid currently experience symptoms of “long Covid,” according to the US government’s Household Pulse Survey.1 Long Covid is defined as symptoms lasting 3 months or more after first contracting SARS-CoV-2. Natural Medicine Journal Editor-in-Chief Tina Kaczor, ND, FABNO, recently discussed prevention of long Covid with 3 colleagues, each of whom has been practicing as a clinician for at least 25 years.

Kaczor posed 4 important questions to these experts:

1. What do you think the cause of long Covid is, and how is it related to other chronic fatigue syndromes?

2. What do you do across the board for your patients for acute Covid and long Covid?

3. Are there any certain labs that you use?

4. And do you consider long Covid curable, or is it something people have to manage for the rest of their lives?

The experts who weighed in are:

· Edythe Vickers, ND, LAc, a naturopathic physician and licensed acupuncturist with expertise in seamlessly combining Chinese medicine and naturopathic medicine to create personalized treatments for each patient. Vickers is the clinical director of An Hao Natural Health Care Clinic, a division of the Institute for Traditional Medicine (ITM), a nonprofit organization dedicated to keeping traditional medicine relevant in the modern setting. She practices in Portland, Oregon.

· Virender Sodhi, MD (Ayurveda), ND, has been practicing since 1988. He is founder and current CEO of Ayush Herbs, offering high-quality Ayurvedic herbal products and supplements worldwide. He practices at his clinic in Bellevue, Washington, which is fittingly called the Ayurvedic and Naturopathic Medical Clinic.

· Jacob Teitelbaum, MD, is a medical doctor who is board certified in internal medicine and is known for his work in chronic fatigue syndrome, fibromyalgia, sleep, and pain. He has authored numerous books, including the best-selling From Fatigued to Fantastic, which is now in its fourth edition. He has also developed the popular free smartphone app CuresA-Z. Teitelbaum currently resides in Kona, Hawaii.

What follows is a condensed and edited version of the discussion. The full episode, which includes specific approaches, supplements, and treatments, is available on the Natural Medicine Journal Podcast.

Kaczor: Let’s begin with Dr Teitelbaum. Dr Teitelbaum, what do you think is the cause of long Covid, and how is it related to other chronic fatigue syndromes?

Teitelbaum: Long Covid is simply one more form of postviral chronic fatigue syndrome (CFS) and fibromyalgia. Fibromyalgia and CFS reflect an energy crisis, where the hypothalamus in the brain, which controls various functions, malfunctions due to a drop in energy production in the body. This can be triggered by various infections, as many viruses trigger the lowering of energy production and this can lead to malfunctioning of the hypothalamus, which uses an inordinate amount of energy itself. The body’s energy production slows down to starve out infections, but sometimes it gets stuck in this process, resulting in insufficient energy production in muscles and other long-lasting symptoms. Our research shows that it is possible to restore the proper functioning of the hypothalamus, with 91% of people recovering and experiencing a 90% increase in their quality of life.

Kaczor: Thank you, Dr Teitelbaum. Dr Sodhi, what are your thoughts on the matter?

Sodhi: I believe there are similarities between long Covid and other chronic fatigue syndromes. From an Ayurvedic perspective, imbalances in the body can lead to a toxic load. These imbalances can arise from various factors, including mental and emotional aspects. When the body is overwhelmed by toxins, it becomes more susceptible to infections. The imbalances affect different systems in the body, leading to a range of symptoms, and precisely which symptoms arise depends on the person’s constitution. Restoring balance through addressing mental, emotional, physical, and nutritional factors is crucial to bringing the person back into a state of balance.

Kaczor: That’s intriguing, Dr Sodhi. Dr Vickers, could you share your perspective?

Vickers: From a naturopathic medicine viewpoint, long Covid can result from immune dysfunction or residual inflammation. In Chinese medicine, it is seen as a wind invasion that transforms into internal heat and pathogenic responses. These toxins accumulate between the heart and diaphragm, causing deficiencies in different organs based on the individual’s weaknesses. The symptoms manifest depending on the affected areas, such as the lungs, digestive system, or musculoskeletal system. Long Covid shares similarities with other chronic conditions like chronic fatigue syndrome, chronic Lyme, and chronic viral infections. The underlying constitution of the patient, external forces, and nutrient deficiencies all play a significant role in understanding and addressing these conditions.

Kaczor: So, Dr Vickers, would it be fair to say that external forces, including pathogens, emotions, and stressors, can affect individuals based on their vulnerabilities?

Vickers: Indeed, external forces such as pathogens, emotions, and stressors can impact individuals differently based on their vulnerabilities and constitutions. A subset of individuals may be more susceptible to long Covid based on their constitutional weaknesses. For example, individuals with more of a “Metal” constitution may experience symptoms related to the respiratory system, such as asthma in childhood or develop pneumonia more easily. It is also possible that the large intestine manifests symptoms, in which case symptoms like chronic diarrhea or colitis can appear. The vulnerability of an individual to long Covid depends on their unique constitutional makeup and how it interacts with the effects of the virus. It’s important to consider these individual factors when managing and treating long Covid.

Kaczor: As Dr Vickers mentioned, the constitution of the patient from a Chinese medicine perspective can dictate not only the pathology direction but also the vulnerability of the patient. Dr Sodhi, could you explain this further from an Ayurvedic perspective?

Sodhi: Certainly. In Ayurveda, we recognize different constitutional types (or doshas) known as Vata, Pitta, and Kapha. Each type has its own characteristics and tendencies. For example, individuals with a Vata type are always moving and can experience anxiety and fear easily. Pitta individuals are energetic and driven, they are go-getters but may also struggle with anger and frustration. Kapha individuals tend to be slower and can lack movement or motivation, they can be stuck in their ideas, and they are more prone to laziness and weight gain. When there is imbalance in the doshas, health problems can occur. By understanding one’s constitution and making lifestyle and dietary adjustments accordingly, we can promote balance and prevent issues from arising.

Kaczor: Thank you, Dr Sodhi. It seems that both Chinese medicine and Ayurveda emphasize the importance of considering individual constitution and imbalances when addressing health conditions. This holistic approach provides valuable insights into managing long Covid and other chronic conditions.

Kaczor: What do you do across the board for your patients for acute Covid and to prevent long Covid?

Sodhi: For both acute and long Covid, I recommend simple and free remedies. Rest is crucial, along with maintaining a healthy diet and staying hydrated. Breathing exercises and cleansing programs can also support the body’s natural healing processes.

Vickers: In Chinese medicine, we treat the specific symptoms caused by Covid. For acute cases, we focus on clearing toxic heat, and once that’s resolved, we introduce tonic herbs to prevent long Covid. I use a combination of acupuncture, herbs, nutraceuticals, and specific antiviral formulas.

Teitelbaum: Rest is vital during acute Covid. To prevent long Covid, I recommend taking a multivitamin high in zinc, and a mix of elderberries. Metformin can be beneficial in the early stages to improve energy production and overcome insulin resistance.

Kaczor: Is resuming normal life too quickly a risk factor for developing long Covid?

Vickers: Yes, it is. People should avoid rushing back into their daily routines too soon after feeling better. Adequate rest and avoiding excessive physical exertion for at least 2 weeks after the symptoms have resolved comepletley can help prevent the evolution into long Covid.

Sodhi: I absolutely agree. People who lead highly active or stressful lives are more prone to developing long Covid. It’s essential to prioritize rest and make necessary lifestyle changes.

Kaczor: Dr Teitelbaum, how do you approach chronic fatigue in patients who previously had Covid?

Teitelbaum: I recommend the SHINE protocol, which focuses on restoring energy production. This involves optimizing Sleep, addressing Hormonal deficiencies, treating Infections, and providing Nutritional support. Exercise should also be incorporated to prevent deconditioning.

Kaczor: What treatments do you suggest for long Covid?

Teitelbaum: For the fatigue, body aches, and brain fog associated with long Covid, I recommend the SHINE protocol. Additionally, curcumin supplements can help reduce inflammation, and specific formulas like Cura Pro can target organ damage. Nutritional support, including B vitamins, magnesium, and ribose, along with exercise, are crucial for recovery.

Vickers: I utilize various treatments such as antiviral herbs, like Istatis and others, low-dose naltrexone for brain fog and inflammation, and acupuncture to address long Covid symptoms. Specific herbs like Boswellia can help with lung inflammation. There are many more herbal combinations that are individualized based on the patient’s symptoms and constitution.

Sodhi: I focus on lifestyle changes, including a healthy diet, breathing exercises, and cleansing programs. Supplements like vitamin C, magnesium chloride, and herbal formulations such as curcumin can also be beneficial.

Kaczor: How do you address specific organ damage caused by Covid?

Teitelbaum: For heart and lung damage, I recommend using supplements like coenzyme Q10, magnesium, and a recipe of specific nutrients for heart failure. Curcumin and glutathione supplements can help reduce inflammation and oxidative stress.

Vickers: I use organ-specific treatments such as hawthorne for lung inflammation and formulas like Isatis 6 for antiviral support. Acupuncture can also be beneficial for heart and lung conditions.

Sodhi: Specific organ damage requires targeted approaches. For lung inflammation, boswellia can be effective, and for heart conditions, I recommend supplements like magnesium and coenzyme Q10. Always, the balancing of the doshas is part of the treatment.

Kaczor: What advice do you have for patients recovering from Covid to prevent relapse?

Teitelbaum: It’s essential for patients to prioritize activities that bring them joy and avoid falling back into the habits that may have contributed to their initial illness. They should focus on optimizing energy levels, addressing any underlying conditions, and avoiding overexertion. Following a balanced and healthy lifestyle is key to preventing relapse.

Vickers: I echo Dr Teitelbaum’s advice. Patients should use their recovery as an opportunity to reassess their priorities and engage in activities that nourish their spirits. It’s crucial to avoid returning to a lifestyle that contributed to their illness in the first place.

Sodhi: I completely agree. Patients need to recognize the importance of self-care and make conscious choices to maintain a balanced and healthy lifestyle. Prioritizing rest, nourishing their bodies with healthy food, and managing stress are essential for preventing relapse.

Kaczor: Are there any certain labs that you use?

Teitelbaum: To diagnose long Covid, CFS, and fibromyalgia, bloodwork is not necessary. Normal ranges in blood tests don’t indicate if a person is fine or not. I rely on symptoms to