NSAIDs are COX1 and COX2 Inhibitors, while Antioxidants are COX2 Inhibitors

The mechanism involved in why NSAID medications like ibuprofen have been found to not help with treatment of COVID19 and may worsen the patient’s health instead has not been stated, however it likely involves COX1 and/or COX 2 inhibition.

NSAID medications (like ibuprofen and aspirin) or phytonutrients that act like NSAID medications (like wintergreen berries which contain methyl salicylate, chemically similar to aspirin, (3)) can be a cause of edema due to the COX 1 and COX2 inhibition effects of the drug. (1) The COVID19 virus is known to cause lung edema even in the early stages of the infection process before the symptoms are obvious. (2)

*Addition, an CDC/MedCram Update: Coronavirus Pandemic Update 40: Ibuprofen and COVID-19 (are NSAIDs safe?), trials of HIV medications, (7), includes the mechanism and controversy. Ibuprofen’s inhibition of COX2 would lead to a reduction in antibody production which wouldn’t help fight an infection, but it might also inhibit viral replication – net result, not sure whether to recommend using or not using it. Too large a dose might increase risk however. Aspirin has more activity than COX2 inhibition so it might be more of a risk for causing lung edema, especially if taken in large quantity. In the flu pandemic of 1918 a large increase in death rate occurred shortly after aspirin, a new medication at the time, was being recommended and in doses that are far larger than would be typically used now. (7)

(I was eating wintergreen berries in quantity,* 1/8-1/4 cup when I had problems with leg edema. They are botanically related to cranberries and are similar in tanginess and texture but taste like wintergreen/mint when raw. The wintergreen flavor isn’t retained after being cooked. *Don’t try this at home. 😉

Antioxidants can also be COX2 inhibitors (4) which can also be a cause of edema. Larger doses of a NSAID medication or phytonutrient would be more likely to cause fluid and sodium retention by the kidneys and lead to swelling due to edematous fluid build up in extracellular areas of the body. Non-selective NSAIDs inhibit both COX1 and COX2 and selective NSAIDs were developed that only inhibit the COX2 enzyme. (5)

We do need extra antioxidants during stress and infectious processes because the body is using them in greater quantities. We would also likely not be able to make as many of our own internally because our bodies would be dedicating more effort to making inflammatory cytokines to fight the infection. Too many inflammatory cytokines can become a problem though and providing extra antioxidants in the diet can help protect the body during conditions of infection such as a severe influenza. (6)

Dose makes the cure, dose makes the poison.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

Reference List

  1. J. Depew, Pomegranate extract update – has similar mechanism to NSAIDs, Aug 3, 2018, transcendingsqure.com, https://transcendingsquare.com/2018/08/03/pomegranate-extract-update-has-similar-mechanism-to-nsaids/
  2. The ASCO Post Staff, Pulmonary Pathology of Early COVID-19 Pneumonia Identified Retrospectively in Two Patients With Lung Cancer, ascopost.com, March 5, 2020 https://ascopost.com/news/march-2020/pulmonary-pathology-of-early-covid-19-pneumonia-identified-retrospectively-in-two-patients-with-lung-cancer/
  3. SpinSolve, Traditional Undergraduate Experiment: Synthesis of Aspirin. magritek.com, http://www.magritek.com/wp-content/uploads/2015/03/Lab-Manual-Synthesis-of-Aspirin-web.pdf
  4. Laube M, Kniess T, Pietzsch J. Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy-A Hypothesis-Driven Review. Antioxidants (Basel). 2016;5(2):14. Published 2016 Apr 19. doi:10.3390/antiox5020014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931535/
  5. Raymond C. Harris and Matthew D. Breyer, Update on Cyclooxygenase-2 Inhibitors. CJASN March 2006, 1 (2) 236-245; DOI: https://doi.org/10.2215/CJN.00890805 https://cjasn.asnjournals.org/content/1/2/236
  6. Liu Q, Zhou YH, Yang ZQ. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016;13(1):3–10. doi:10.1038/cmi.2015.74 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711683/
  7. Roger Seheult, MD, Coronavirus Pandemic Update 40: Ibuprofen and COVID-19 (are NSAIDs safe?), trials of HIV medications. CDC/MedCram.com https://youtu.be/dT6mHi_8V5E

Immune support against viral infection.

The concern about the Coronavirus outbreak is valid as the infection seems more dangerous than a winter flu season. People who smoke or have a chronic lung condition, or are elderly or have other chronic conditions, or who are obese, may be at increased risk of having a more severe case of Coronavirus.

*This blogpost is continued in a longer podcast / transcript, Fear and Immunity.

Symptoms can be non-noticeable or similar to a cold or mild flu. Digestive symptoms might occur in addition to lung symptoms, dry, non-productive cough, and chest pain, hot and cold feverish chills, and extreme tiredness. Smoking increases risk of lung symptoms developing into pneumonia. Recovery seems to take longer than for a cold or flu with some people needing hospital care for weeks with a ventilator for breathing. (World/national Coronavirus Statistics) Approximately 2-14 days from exposure to symptom onset, gradually developing symptoms with a cough and chest discomfort, fever, and shortness of breath/difficulty breathing being common symptoms. (Graphic by Robert Roy Britt)

Some people may be infectious without having developed symptoms yet, or at all possibly for the 20-29 year old age bracket based on South Korea’s more extensive testing of their population. (graphic-South Korea & Italy rates of COVID-19)

People seem to be most contagious before symptom onset and in the first week of illness. (link) Twenty days infectious is average and generally is reduced by the time coughing symptoms are over. Thirtyseven days infectious is the longest measured. (Zhou et al., 2020) Wearing a face mask while infectious might help protect others but is generally not recommended as necessary for people who are not sick. A Public Service video about reducing rate of infection by hand washing, staying home, focusing on not infecting others while we don’t know who might be contagious but not showing symptoms yet. (@thejuicemedia)

Contagion risk also seems worse than the flu or a cold as the virus can survive on surfaces longer than average, possibly a week or more. Respiratory droplets may be the usual route of infection however there also may be a risk of infection from an infected person’s bowel movement. Thorough hand washing with soap and plenty of water is more likely to disrupt the cell membrane of virus and remove them physically than depending on hand sanitizers which are designed for bacteria not virus.

Alcohol in the hand sanitizer may also be drying to the skin which also can increase risk of open sores which can allow infection to enter the body more easily. Moisturize with a hand lotion while the skin is still damp to seal in some of the water. Hand lotions don’t replace moisture, they add to an oily coating on the skin that helps prevent moisture loss.

Strengthening Immune Function – food and nutrients, rest, and water, cut down on sweets, increase positive thinking & stress coping habits.

*Nutrition is not a guarantee of not becoming infected with something but it can increase the likelihood of not becoming infected or not developing as severe symptoms, as seen in the Ebola outbreak (see embedded link) and with research on vitamin D and respiratory infection rate (see video link).

  • Sugar and high fructose corn syrup generally reduce immune health and may provide simple calories that support infectious microbes more than our own health. (Defeating the Coronavirus with Immunity & Hydrotherapy, Dr. Eddie Ramirez, Youtube)
  • Sleep helps the body recover and cope with healing or fighting infection.
  • Water is essential for the body to be able to have a thin protective layer of mucous in which white blood cells can more easily find and remove infected cells.
  • Positive feelings of hope and love are more likely to support health than fear and anxiety. Doris Day’s attitude in the song lyric may be more helpful, “Whatever will be, will be, que sera sera,” along with common sense health habits.
  • Vitamin C and/or zinc lozenges may be soothing for the throat and help immune function. Elderberry is also rich in antioxidants and may also be available in immune supporting lozenges.
An orange peeled so the white pith remains.
The orange zest layer of the orange peel can be trimmed to leave the white pith to be eaten with the sweet orange wedge. The white membrane is a source of nobiletin.
  • The white pithy membrane of an orange peel has beneficial phytonutrients and is also fairly mild like the inner peel of a pomegranate. Use a vegetable peeler or sharp knife to trim off just the outer layer of orange zest and then the sweetness of the orange sections will taste okay along with the white membrane.
    • The orange peel pith contains a phytonutrient, nobiletin, that may help with weigh loss too. (Orange Juice Molecule May ‘Drastically’ Reduce Obesity, Arterial Placque, slashgear.com)
    • Nobiletin is a chemical that promotes our circadian cycles and may be protective against metabolic syndrome. Genetic studies on animals suggest that differences in the CLOCK circadian protein can cause symptoms of metabolic syndrome – obesity, high blood lipids and blood sugar, low insulin levels, fatty liver, and respiratory uncoupling. (He, et al, 2016) Respiratory uncoupling changes the way mitochondria produce energy and if the changes continue for long may lead to worse dysfunction of the mitochondria which may lead to cancer (Seyfried, et al, 2014), or other chronic health problems. (Ruiz-Ramirez, et al., 2016) Research with nobiletin as a cancer treatment suggests that it stops cancer growth by deactivating cancerous genes. (plantmedicines.org)
    • Orange peel extract has also been studied for use against Coronavirus and it helped reduce replication of the virus. (Ulasli, et al., 2014)
    • Chen Pi, dried tangerine peel, is a traditional Chinese medicinal product sold as an anti-viral and digestive support. (alibaba.com/Chen Pi) Improving bioaccessibility of nobiletin with peanut protein nanoparticle encapsulation, for anti-cancer potential as a medication: (Ning, et al., 2019) Chen Pi is traditionally used as a digestive aid and for respiratory conditions that involve too much thick mucous. Chen Pi is thought to help thin the mucous and promote a more productive cough. (esgreen.com/Chen Pi)
  • Other immune supporting nutrients that may help against a Coronavirus infection include Nrf2 promoting sulfarophane and resveratrol. Elderberry is a good source of anthocyanins and other antioxidant phenols, blueberries and black beans would also be rich sources. Zinc and selenium are minerals with antioxidant function. (selenium sources) Having adequate Vitamin A and D is essential for immune function. NAC and lipoic acid are antioxidants. Nrf2 pathways increase our own internal production of antioxidants. (Other foods: Nrf2 Promoting Foods)
  • Both high dose vitamin C and zinc are listed as potential therapeutics for treatment of patients with COVID-19 and Chloroquine, the anti-malarial that was found helpful for treatment of the infection in China, is a zinc ionophore. (14) Zinc ionophores help with autophagy and apoptosis – the killing and engulfing of infected cells by white blood cells. (15)

Cytokine Storm Syndrome & Vitamin C Infusion, — webinar for medical professionals.

An over-reaction of the immune system called Cytokine Storm Syndrome or sepsis shock can be the cause of death from COVID-19 infection rather than the breathing problems and pneumonia symptoms. Some people may be more genetically at risk of having the inflammatory over-production of cytokines. (Cytokine Storm Syndrome/genetics) They are involved in killing infected cells but an excess can cause organ failure and lead to death. Intravenous Vitamin C Infusion can be safe and nontoxic for treating sepsis shock (Fowler 2014) and may improve survival rates (ScienceDaily) and is a strategy that was used in Wuhan, China for COVID-19 patients. (Video update by Dr. Cheng) (Clinical Trial/Peng) (Protocol used in China for Vitamin C Infusion IV treatment) A free webinar for medical professionals is being offered March 26 regarding Intravenous Vitamin C Infusion for COVID-19 treatment, see this for registration information. The webinar is now available as a video that can be viewed at any time, see the website: isom.ca. The Vitamin C Infusion technique is being used for COVID19 patients in a large hospital chain in New York, based on the improved survival rate seen in Shanghai China, (NYPost)

Patients from Wuhan with COVID-19 who were in the ICU had more cytokines, (“IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.”, (Huang, et al, 2020)), than patients who weren’t sick enough to be admitted to the ICU. Other possible guidance to check for cytokine storm besides the cytokine levels is C-Reactive Protein and serum ferritin levels. (Teachey 2016) The medication Anakinra may be treatment. (comment)

From a nutrition care perspective – the Nrf2 promoting foods also tend to inhibit the inflammatory NfKb pathway which leads to increased production of TNFalpha and other cytokines.

Chloroquine phosphate, 500 mg BID, was used as a treatment in China per a comment on a medical site. (Detailed document with specific recommendations, may be helpful medication as a preventive or treatment.) It is an anti-malarial drug. and the virus seems to be interfering with heme in red blood cells, a little similar to malaria taking over red blood cells. ( Dr’s summary; and his ref list) Artemisinin is an extract of the herb woodruff that is used to treat malaria. It is available as an herbal supplement. (nobelprizemedicine/pdf)

With a new strain of virus we are learning how to treat it and how it spreads and being brand new, no one has immunity against it. Being a coronavirus puts it in the same group as colds and flus which can mutate slightly and we can catch the illness more than once.

The COVID-19 may also be able to be infectious to people who already recovered. (LATimes) The cases of reinfection may also be the same infection in the patient seeming to get better and then relapsing again.

Prevention is safest. Wash hands and surfaces thoroughly and regularly. Soap, water, and scrubbing physically helps break down virus membranes and remove the virus from skin and other surfaces. Hand sanitizer is not more effective than thoroughly washing with soap and water. antibacterial ingredients are designed against bacteria, not virus.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

“Supplements thought to be useful in the prevention of coronavirus infection include NAC, elderberry, spirulina, beta-glucan, glucosamine, selenium, zinc, lipoic acid, sulforaphane, resveratrol, vitamin D, Bifidobacterium bifidum strain probiotics and sporebiotics. ”

– Dr. Joseph Mercola (Essential Nutrition to Protect Yourself from Coronavirus) *

Origins – not a bat in China, genetically traced to the US around Aug/Oct 2019.

*That link includes some speculation about origins of the current Coronavirus strain – supporting the immune system and reducing infection rate and severity of disease is necessary whether the strain was from bats in the wild or a lab or from a lab manipulation of a strain from bats – saving lives needs to be a goal now.

(statement from Robert Kennedy Jr) “He [Taiwan Virologist] demonstrated that only the US has all the five known strains of the virus (while Wuhan and most of China have only one, as do Taiwan and South Korea, Thailand and Vietnam, Singapore, and England, Belgium and Germany), constituting a thesis that the haplotypes in other nations may have originated in the US. Korea and Taiwan have a different haplotype of the virus than China, perhaps more infective but much less deadly, which would account for a death rate only 1/3 that of China. [*so infection rates from South Korea may not be represent the risk for all ares] Neither Iran nor Italy were included in the above tests, but both countries have now deciphered the locally prevalent genome and have declared them of different varieties from those in China, which means they did not originate in China but were of necessity introduced from another source. It is worth noting that the variety in Italy has approximately the same fatality rate as that of China, three times as great as other nations, while the haplotype in Iran appears to be the deadliest with a fatality rate of between 10% and 25%. (7) (8) (9)” (globalresearch.ca) (news stories). (transcript of a video) There seems to be at least two strains, more information is needed to understand the significance of that (abcnews.com).

Reference List – incomplete, see links within the blogpost also.

  1. Protocol used in China for Vitamin C Infusion treatment for COVID19 , translated from Chinese on Google Translate – https://docs.google.com/document/d/1f21o4uqO0QmrF8e1d8JKMhE6NU7k8im5bVKqwROreTc/edit?usp=sharing
  1. Vitamin C for the Treatment of Coronavirus (COVID-19), free webinar scheduled for March 19, 2019, International Society for Orthomolecular Medicine, https://isom.ca/vitamin-c-coronavirus/
  2. Wen-Bin Yu, Guang-Da Tang, Li Zhang, Richard T. Corlett. Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2) using whole genomic data. https://www.dropbox.com/s/se41lvl8esbr40l/202002.00033v2.pdf?dl=0 
  3. Xiaolu Tang, Changcheng Wu, Xiang Li, Yuhe Song, Xinmin Yao, Xinkai Wu, Yuange Duan, Hong Zhang, Yirong Wang, Zhaohui Qian, Jie Cui, Jian Lu, On the origin and continuing evolution of SARS-CoV-2, National Science Review, , nwaa036, https://doi.org/10.1093/nsr/nwaa036 https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463?searchresult=1
  4. Jon Cohen, Wuhan seafood market may not be source of novel virus spreading globally. ScienceMag.org,  Jan. 26, 2020, https://www.sciencemag.org/news/2020/01/wuhan-seafood-market-may-not-be-source-novel-virus-spreading-globally
  5. Other links until I complete this list are in the post Immune Support Against Viral Infection, https://transcendingsquare.com/2020/03/12/immune-support-against-viral-infection/
  6. The ASCO Post Staff, Pulmonary Pathology of Early COVID-19 Pneumonia Identified Retrospectively in Two Patients With Lung Cancer, ascopost.com, March 5, 2020 https://ascopost.com/news/march-2020/pulmonary-pathology-of-early-covid-19-pneumonia-identified-retrospectively-in-two-patients-with-lung-cancer/
  7. Chloroquine guidance for COVID19, as preventive or treatment of infection, https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub
  8. expert reaction to reports that the French Health Minister recommended use of paracetamol for fever from COVID-19 rather than ibuprofen or cortisone, March 16, 2020 https://www.sciencemediacentre.org/expert-reaction-to-reports-that-the-french-health-minister-recommended-use-of-paracetamol-for-fever-from-covid-19-rather-than-ibuprofen-or-cortisone/
  9. Fehr AR, Perlman S. Coronaviruses: an itoverview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23. doi:10.1007/978-1-4939-2438-7_1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369385/
  10. Roujian Lu, Xiang Zhao, Juan Li, et al.,  Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. January 29, 2020, https://doi.org/10.1016/S0140-6736(20)30251-8 https://www.cdc.gov/coronavirus/2019-ncov/downloads/genomic-characterization-of-2019-nCoV-Lancet-1-29-2020.pdf 
  11. Diagnostic detection of Wuhan coronavirus 2019 by real-time RTPCR. https://www.who.int/docs/default-source/coronaviruse/wuhan-virus-assay-v1991527e5122341d99287a1b17c111902.pdf 
  12.   http://www.aabb.org/advocacy/regulatorygovernment/Documents/Impact-of-2019-Novel-Coronavirus-on-Blood-Donation.pdf
  13. Sy Mukherjee, China’s high smoking rate may be exacerbating the coronavirus outbreak,  Feb. 19, 2020, Forbes.com, https://www.google.com/amp/s/fortune.com/2020/02/19/coronavirus-china-smoking-rate-men/amp/
  14. COVID-19 Science Report: Therapeutics, NUS Saw Swee Hock School of Public Health, March 12, 2020, https://sph.nus.edu.sg/wp-content/uploads/2020/03/COVID-19-Science-Report-Therapeutics-13-Mar.pdf
  15. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding W-Q (2014) Chloroquine Is a Zinc Ionophore. PLoS ONE 9(10): e109180. https://doi.org/10.1371/journal.pone.0109180 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180