COVID-19 Lindsey Wells, ND on Melatonin, Quercetin, Vitamin C

We are so pleased to have Lindsey Wells, ND, join in our series of Q&As on COVID-19. Her focus will be on Vitamin C, Melatonin, and Quercetin.

Dr. Lindsey Wells is a naturopathic physician. Dr. Wells has focused her practice on consultative care for Autism Spectrum Disorder (ASD), PANS/PANDAS, Lyme and Co-Infections, other neurodevelopmental disorders, and various chronic illnesses. She uses therapies, including homeopathy, botanical medicine, nutraceuticals, nutrition, counseling, and water therapy. This model of care addresses the biochemical, nutritional, and energetic needs of each patient to improve overall health. For her complete bio and more information, please see her website.

Please Note: Coronavirus disease (COVID-19) is a new strain that was discovered in 2019 and has not been previously identified in humans. The WHO is closely monitoring and updating the information regularly. Recommendations regarding prevention and treatment will change and evolve as more data is processed. It is essential to communicate with your Primary Care Provider (PCP) directly regarding you and your family’s unique healthcare needs. WHO

Gabriella: Thank you for joining us again to talk about COVID-19. Today Dr. Wells is going to focus on Vitamin C, Quercetin, and Melatonin. But first, let’s do a review of COVID-19 symptoms.

Lindsey: 

Most Common Symptoms

• Fever
• Cough
• Shortness of Breath 

Other Symptoms

• Aches and Pains
• Sore Throat
• Fatigue
• GI Symptoms 
• Losing Sense of Smell OR overpowered with a sense of smell

Emergency Warning Signs to seek immediate medical attention:

• Trouble Breathing
• Persistent Pain or Pressure in the Chest
• New Confusion or Inability to Arouse
• Bluish Lips or Face

CDC Source

Gabriella: We hear a lot about Vitamin C for colds and flu, and now many people are talking about IV and oral Vitamin C for COVID-19. Can you please tell us a bit about this supplement and the literature that supports its use? Vitamin C is flying off the shelves too.

Lindsey: Vitamin C (Ascorbic Acid)

Function:

• Antioxidant
• Necessary for collagen 
• Improves absorption of iron 
• Supports the immune system 

Food High in Vitamin C:

• Oranges
• Grapefruit 
• Kiwis
• Broccoli 
• Strawberries
• Cantaloupe
• Potatoes
• Tomatoes 

Vitamin C Study 1:  

Title: Vitamin C supplementation and respiratory infections: a systematic review

Background/Results: This is a review of studies of military personnel, those living in dorms, marathon runners, and others in similar, close living situations. Five of the studies found that 45 to 91% of the subjects had a reduction in the symptoms of the common cold when supplemented with vitamin C. Three other studies showed 80-100% of the subjects had a reduction of pneumonia symptoms when supplemented with Vitamin C.

Source: Harri Hemilä, MD, PhD, Vitamin C Supplementation and Respiratory Infections: a Systematic Review, Military Medicine, Volume 169, Issue 11, November 2004, Pages 920–925, https://doi.org/10.7205/MILMED.169.11.920

Vitamin C Study 2:  

Title:  Vitamin C for preventing and treating pneumonia (Review)

Background/Results: This looked at patients with pneumonia. It assessed the therapeutic benefits of vitamin C based on a placebo-controlled study. Three of the studies found an 80% or higher reduction in pneumonia. One study done in elderly people showed reduced mortality, and improved symptoms in pneumonia in the Vitamin C treated group. One other study showed a decrease in the duration of pneumonia that was supplemented with vitamin C only two times.

Source: Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD005532. DOI: 10.1002/14651858.CD005532.pub3.

Vitamin C Study 3:  

Title: Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome.

Background/Results: This is a case study on a previously healthy 20 year old who contracted respiratory enterovirus that lead to acute lung injury, specifically progressing to Acute Respiratory Distress Syndrome (ARDS). ARDS is causing the most acute complications associated with coronavirus. This patient had mechanical respiration, but that failed, and they needed to add ECMO. Twelve hours after ECMO they administered High Dose IV Vitamin C. Soon after, they were able to disable the assisted breathing support and the patient recovered with no long term, negative impact. 

Conclusions: They suggested that IV Vitamin C be considered for viral-induced ARDS. So this is something we can definitely utilize and consider for COVID-19.

Source: Fowler Iii AA, Kim C, Lepler L, et al. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J Crit Care Med. 2017;6(1):85–90. Published 2017 Feb 4. doi:10.5492/wjccm.v6.i1.85

Statement by Dr. Paul Anderson on IVVC

This is not a study but a statement put out by Dr. Paul Anderson. He is a pioneer in the naturopathic medical field. The statement is regarding the use of IV Vitamin C for COVID-19. Essentially the executive summary stated, IV Vitamin C is a safe medical intervention and been shown to shorten hospital stays as well as ICU stays. It is an inexpensive treatment. It is simple to get compounded by the pharmacy and easy to administer by nursing staff. It has been used successfully for managing cytokine storms. The statement is all based on information that came from the Shanghai Expert Group. 

IVAA and COVID 19

• Shanghai Expert Group facilitated the addition of (IV Ascorbic Acid) IVAA to their therapeutic interventions in the hospital treatment of patients with COVID-19.
• Chinese facility patient load: 358 total COVID-19 patients as of March 17th, 2020. 
• Facility treated approximately 50 cases (of the 358) of moderate to severe COVID-19 infection with IVAA. 
• The IVAA dosing was moderate and affordable (detail below) and dose determined by clinical status. 
• All patients who received IVAA improved. 
• There was no mortality in the IVAA group. 
• There were no side effects reported from any patients in the IVAA group. 
• Average COVID-19 patients had a 30-day hospital stay, but COVID-19 patients that received IVAA had a hospital stay that was 3 to 5 days shorter than the non-IVAA treated patients.

Since many can’t access IV Vitamin C, here are some recommendations for Oral Vitamin C in adults. The recommendation is to spread out the dose during the day as Vitamin C is quickly metabolized in the body. 

Gabriella: What is the generally recommended dose for Oral Vitamin C?

Lindsey:

Oral Vitamin C Dosage –

For Prevention:

• Adults: 1000 mg THREE a day (total of 3000 mg) 

For Acute Use:

• Adults: 1000 mg FIVE or SIX times a day (total of 5000-6000 mg)

Source: http://www.orthomolecular.org/resources/omns/v16n14.shtml

I think a good preventative dose in children is about 500mg twice a day for a total of 1000mg. When you do increase the dose, there can be a laxative effect. So if there are looser stools, you may need to decrease the dose a little bit.  Vitamin C may also increase hyperactivity in some children. 

Gabriella: Let’s move onto Quercetin. What are some of the foods Quercetin is naturally found in?

Lindsey:

Quercetin

• A Polyphenol
• A Flavonoid 
• Antioxidant 
• Anti-viral
• Inhibitor of heat shock proteins which needed for viral assembly 
• Located in a way that disrupts the viral docking and penetration into the cell 
• Anti-inflammatory benefits
• Can be helpful with a cytokine storm
• Anti-histamine 
• Anti-aging
• Modulates DNA methylation and epigenetic expression

Found in the following foods

• Onions
• Blueberries
• Kale
• Cranberries
• Broccoli
• Green Tea
• Apples 

Quercetin Study 1:  

Title: Quercetin: A Promising Treatment for the Common Cold

Results/Discussion: This mouse model study gives an overview of Quercetin’s mechanisms of action, which offer therapeutic benefits for the common cold. It increases viral clearance by enhancing the mitochondrial anti-viral responses. We talk about cell danger response and how in some of the kids, their immune system is over heightened and how the mitochondria are part of that overall immune response. It also decreases the viral-induced expression of pro-inflammatory cytokines as well as inflammation in mice. This is of interest because, in COVID-19, we see pro-inflammatory cytokines but also damage to the lung. 

Source: Kinker, Brenton. (2014). Quercetin: A Promising Treatment for the Common Cold. Journal of Ancient Diseases & Preventive Remedies. 02. 10.4172/2329-8731.1000111.

Quercetin Study 2:  

Title: Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

Results/Discussion: This is another mouse model study. Although Influenza A is different than coronavirus, there are some similarities. So this shows Quercetin decreases susceptibility to Influenza A.

Quercetin exhibited anti-viral activity by interacting with glycoprotein, a blood protein, and inhibited the virus entering into cells. There was also an inhibitor effect of the Quercetin that was enhanced when the virus was pre-incubated with Quercetin. So this suggests that Quercetin effectively inhibited the viral infection when added during the virus entry stage. This shows it could be helpful to take it early on during symptom onset to help decrease that viral infection. 

Source: Wu W, Li R, Li X, et al. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses. 2015;8(1):6. Published 2015 Dec 25. doi:10.3390/v8010006

Quercetin Study 3:  

Title: Effect Of Quercetin Supplementation On Lung Antioxidants After Experimental Influenza Virus Infection

Background/Results: This mouse model study showed the Influenza virus decreased Endogenous lung antioxidants. So essentially, that means that when there was a virus, our natural antioxidants, specifically for the lungs, were decreased as a response. The antioxidants were catalase, reduced glutathione, vitamin E, and superoxide dismutase. Supplementation with the Quercetin increased the pulmonary concentration of the catalase, reduced glutathione and superoxide dismutase. So, therefore, Quercetin, in general, could be protective for the lungs in regards to the reactive oxygen species that are replaced during an influenza infection. 

Source: Pankaj Kumar, Madhu Khanna, Vikram Srivastava, Yogesh Kumar Tyagi, Hanumanthrao G. Raj & K. Ravi (2005) Effect Of Quercetin Supplementation On Lung Antioxidants After Experimental Influenza Virus Infection, Experimental Lung Research, 31:5, 449-459, DOI: 10.1080/019021490927088 

Gabriella: What brands of Quercetin do you like? Also, do you suggest a dose?

Lindsey: I like a few brands: Allergy Research, Designs for Health, or Pure Encapsulations.

The dose depends on a few things. Usually, I suggest between 300 and 600mg once per day in adults. For children, I am comfortable with 300mg once per day.

Gabriella: What are your thoughts about possible contra-indications of taking Quercetin and Azithromycin together, as mentioned by Dr. O’Hara during her talk with Dr. Bouboulis (insert link). 

Lindsey: There are no known interactions between Azithromycin and Quercetin. Therefore, you can take Quercetin with Azithromycin. However, you should contact your doctor for guidance on dosing.

Gabriella: No wonder it is getting a lot of attention as a nutrient to consider now due to its protectiveness against the lungs. Okay, tell us all about Melatonin. 

Lindsey:

Melatonin

• Hormone made by the pineal gland
• Helps to control sleep-wake cycles 
• We have low melatonin in the morning and increases throughout the day
• Antioxidant (at high levels)

There has been a lot of speculation about melatonin, COVID-19 and the reason why adults and the elderly tend to be more susceptible than children. Melatonin is being considered because your levels change based on your age. 

Melatonin Levels by Age

• In healthy people, melatonin levels decrease after 40 years old. This may contribute to the increased risk of death in patients with COVID 19 over 40 years old.
• Children may be protected as they have 10x more melatonin then a healthy adult.

 

Melatonin Study 1:  

Title: COVID-19: Melatonin as a potential adjuvant treatment.

Background/Results: Gave an overview of melatonin’s mechanism of action and the benefits against COVD-19. It is an antioxidant, anti-inflammatory as well as immuno-modulatory benefits. The specific immuno-modulatory benefits they are seeing is its action with an inflammasome (specifically inflammasome NLRP3) linked to lung infections and allergic airway inflammation. It also showed that melatonin had an impact on cytokine levels in humans, and supplementation significantly reduced tnfα and IL-6 levels, which are pro-inflammatory cytokines seen in COVID-19. 

Source: Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment [published online ahead of print, 2020 Mar 23]. Life Sci. 2020;250:117583. doi:10.1016/j.lfs.2020.117583

Melatonin Study 2:  

Title: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2

Background/Results: Looked at how patients with viral infections were more susceptible to immune-inflammatory injury due to oxidative stress and that in particular, the anti-oxidative benefits in melatonin could relieve the clinical symptoms as well as prolong the patient survival time. It showed that melatonin worked on several of the COVID-19 cellular targets, including the ACE2 receptor. 

Source: Zhou, Yadi & Hou, Yuan & Shen, Jiayu & Huang, Yin & Martin, William & Cheng, Feixiong. (2020). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discovery. 6. 14. 10.1038/s41421-020-0153-3.

Melatonin Study 3:  

Title: COVID-19 Infection During Pregnancy’s Third Trimester

Background/Results: It has been shown so far that even if a pregnant woman has tested positive for COVID-19, their babies were not testing positive after delivery. A possible explanation for that is the melatonin secretion in the third trimester is more than doubled compared to the first trimester. So women produce more melatonin later on in their pregnancy and that might provide a protective benefit for the newborn.

Source: Chen H et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020 Feb 12; [e-pub]. (https://doi.org/10.1016/S0140-6736(20)30360-3)

Melatonin Study 4:  

Title: Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production

Background/Results: This study demonstrated that increasing melatonin with melatonin receptor antagonist that there were protective effects from damaging effects of ventilator-induced lung injury 

Source: Wu, G., Peng, C., Liao, W. et al. Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production. Respir Res 21, 65 (2020). https://doi.org/10.1186/s12931-020-1325-2

Gabriella: How much melatonin would an adult take?

Lindsey: The research says to take 3mg once a day was sufficient in the evening, and the benefit is you get some help fall sleep. It doesn’t necessarily help people stay asleep as it has a short half-life of about 4 hours. You want to consider prolonged-release melatonin, so you don’t wake up in the middle of the night. With the non-prolonged release, some people can wake up after the short four-hour burst. It is one of the safest, well-researched supplements out there. For children, I usually don’t start at 3mg but start with 0.5-1mg. For children and adults, you would dose it 30-60 minutes before bedtime. You should try to avoid giving it during the day as it can interrupt the hormone cycle. You can work with your doctor on doses higher than these. I also probably would not give it to a patient who is also on a pharmaceutical sleeping aide. 

Gabriella: Some people have nightmares with melatonin. What do you suggest?

Lindsey: It does happen on occasion; I suggest taking the prolonged-release version and see if that helps. If the nightmares continue, there is nothing that you can really do to stop that besides stop using the melatonin.

Gabriella: Thank you, Dr. Wells. This provided us with clarity on this matter. We appreciate that you took time out of your busy day to speak with ASPIRE!

Dr. Lindsey wells and her colleagues at New England Center for Health are continuing to host a series of zoom calls on COVID-19. The schedule will be updated weekly.