COVID-19 Considerations: A Deeper Dive into Elderberry and Ibuprofen

Mar 23, 2020

Dear Friends,

Nothing brings us greater pleasure than providing support and education to confront the fear and uncertainty that we all face together in times like this. Our recommendations always take into account a combination of clinical research, a consensus of expert opinions from around the world, and of course, our very own experiences as we care for patients year after year. We also value all of your input and concerns, which is what truly makes these posts complete. As promised, we will delve into the current hot topics of Elderberry and Ibuprofen/NSAIDs as they relate to COVID-19 and any potential harm OR benefit each might impart on the infection.

First, we would like to impress on how beautifully complex we humans (and animals) are when it comes to our abilities to battle a raging infection. We have a huge arsenal of “weapons” at our disposal and we experience the consequences of that battle through “symptoms” (such as a fever as part of the increased immune response and a cough to keep the airway clear). Additionally, we have a system of checks and balances. Our internal weapon systems are smart in that as we mount an attack on an invader, we also know when to quit as to avoid collateral damage. Another concept involves synergism as many systems have to work together to maintain balance/homeostasis. This is how masterful and complex our immune system is when functioning properly. These concepts are why it can be so challenging to have all the answers and draw solid conclusions from headlines and reports we encounter on a daily or even hourly basis. 

ELDERBERRY

Black elderberry (Sambucus Nigra), as many practitioners and patients of integrative medicine practices are aware, is often valued for its potential antiviral properties.  Various studies have demonstrated that elderberry has a direct antiviral action AND may enhance our immune system by raising the levels of various pro-inflammatory cytokines, which improves our ability to fight an infection. It is this latter effect that has caused much controversy about its use as a supplement during the current COVID-19 outbreak. 

There are many cytokines that are released in response to an infection. Initially, many of these proinflammatory cytokines (PICs) are critical to mount an effective battle. Once these PICs reach a certain level, the body will “hit the brakes” by releasing anti-inflammatory cytokines and other related compounds in order to balance the response, thus preventing our healthy cells from being damaged by our own attack. The IL-6 cytokine, as well as other PICs, typically rise in response to a viral load. It is prudent to note that a cytokine storm can manifest in response to many viruses, including influenza, independent of ingesting any particular supplement. 

Although elderberry may increase IL-6 and other cytokines, it also inhibits the early stages of infection by blocking specific viral proteins responsible for attachment and entry of the virus into our cells, as well as viral replication once inside the cell. One would hope this effect may possibly offset the potential for a cytokine storm by mitigating a large enough release of IL-6. This is likely why we have not seen a “cytokine storm” in regard to treating various viruses with elderberry. 

That being said, concerns are not necessarily unfounded either! We found one study that suggests that the coronavirus associated with the previous SARS outbreak may trigger a higher IL-6 release than influenza does, and may also interfere with our ability to hit the brakes on IL-6. We do not know, however, if that effect is large enough to be clinically relevant. Additionally, one of the drugs being investigated to fight COVID-19 is designed to lower our IL-6 levels during an infection. 

In light of the above information as well as our extensive use of elderberry for many viral infections (including the coronaviruses that are responsible for about a quarter of common colds), we are recommending a balanced approach. While recognizing the critical role of IL-6 in mounting an adequate response to any pathogen, as well as the direct antiviral effects of elderberry, we suggest using this supplement for preventative purposes, contributing to a robust immune system during this outbreak. 

In an attempt to reduce the chances of a viral infection, in addition to our other immune supporting recommendations, at the first sign of viral symptoms (fever, cough, shortness of breath upon exertion, fatigue, body aches, or diarrhea, which early evidence suggests may also be a symptom of COVID-19), we continue to support the judicial use of black elderberry as a component of our complete protocol, along with other supplements, designed to keep the immune system strong and balanced. 

We acknowledge the concern of cytokine overstimulation exists; however, we feel that, based on elderberry’s antiviral effects and a long history of use within the practice of integrative medicine, the benefits of use outweigh the currently understood risks.   

IBUPROFEN/NSAIDs

Our philosophy is to not treat a fever, as it is part of the immune response of our body. We  are in favor of using fever/pain reducers if a person is suffering, such as being so uncomfortable that sleep and food/beverage intake is compromised. 

The concerns surrounding the use of NSAIDs and in particular, Ibuprofen, center around a study that suggested taking Ibuprofen might increase the number of  angiotensin converting enzyme 2 (ACE2) receptors. Due to the observation that COVID-19 attaches to the cells of the lungs via ACE2 receptors, some have hypothesized that taking certain drugs like ibuprofen may make one more vulnerable to infection or make the infection worse. 

It’s important to note that although this hypothesis is being examined further, and we will learn more over time, the current evidence for harm as it relates specifically to COVID-19 is not strong. This is a stance shared by the majority of world health bodies and many infectious disease physicians, rheumatologists, pulmonologists, toxicologists, and a virologist who was part of the team of researchers that discovered how this coronavirus binds to cells. Additionally, the World Health Organization (WHO) recently reversed their position on the matter after further research, stating they do not support a warning against the use of ibuprofen if needed at this time. According to many these experts, the few non-peer reviewed studies that demonstrated the possibility of ibuprofen raising ACE2 receptor levels in the lab does not necessarily mean this transfers to the clinical setting in humans (i.e., perhaps the increase of ACE2 receptors is small). Also, an increased ACE2 expression does not necessarily mean you will be any more susceptible to infection. 

This is not in any way to quash opinions of concern. Not at all. We agree that researchers should continue to study  this issue. Interestingly, there are past studies that have demonstrated the possibility that two other NSAIDs, naproxen and indomethacin, directly inhibit coronaviruses, including the strain responsible for the past SARS outbreak. This being said, we certainly recognize the general risks and benefits of NSAIDs. Well established risks include adverse effects on the GI tract, kidneys, and cardiovascular system. Additionally, as inflammation is a vital component of fighting an infection, one could reason that these drugs should be reserved for when fever and other symptoms are grossly impacting quality of life and the ability to function. On the other hand, ibuprofen has also reduced the morbidity in patients with lung disease by reducing the inflammation responsible for damaging the lungs.  

Confusing?

In medicine, like everything else, too much of a good thing can often lead to undesirable consequences. It’s really all about homeostasis.  

Based on the current available research and our experience, we do not believe the evidence for any UNIQUE association between ibuprofen and COVID-19 is strong enough to issue a stark warning against NSAID use at all cost. It is really a risk/benefit decision based on how debilitating the symptoms are, and one’s own personal medical history. 

As with other viruses, so the body can do the job it was designed to do, we recommend avoidance of any fever reducers and anti-inflammatory medications if functioning well enough. However, if fever or pain causes suffering despite using supplements per our protocol and perhaps a LUKEWARM bath (which is still at a cooler temp than your fever), options include the judicial use of ibuprofen at the lowest effective dose, and if you are still concerned about NSAIDs, then acetaminophen (with its own risks on the liver) can be considered. It should be noted, though, that acetaminophen can deplete levels of glutathione which is very important in helping reduce inflammation and oxidative stress to the cells

If one prefers to avoid ibuprofen and other NSAIDS, or cannot take these due to other medical conditions, we suggest taking Setria glutathione (250 mg twice a day for younger children, 500mg twice a day for older children and adults) with each dose of acetaminophen.

Friends, we hope this information is helpful and provides a certain sense of security and control. We wish everyone good health and peace of mind – we are all in this together!


REFERENCES:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/
  2. https://www.sciencedaily.com/releases/2019/04/190423133644.htm
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899428/
  4. https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.20556
  5. https://www.npr.org/sections/health-shots/2020/03/18/818026613/advice-from-france-to-avoid-ibuprofen-for-covid-19-leaves-experts-baffled
  6. https://www.medscape.com/viewarticle/926940
  7. https://apnews.com/f76c0a75f366efdb735d48714b2910cd
  8. https://www.intmedpress.com/servefile.cfm?suid=35d8dc5e-70f4-491f-acad-e35f99be9211
  9. https://www.bmj.com/content/368/bmj.m406/rr-9
  10. https://www.buzzfeednews.com/article/stephaniemlee/coronavirus-ibuprofen-who
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036659/
  12. https://www.ncbi.nlm.nih.gov/pubmed/3863757
  13. https://www.ncbi.nlm.nih.gov/pubmed/2915154
  14. https://www.fasebj.org/doi/abs/10.1096/fasebj.27.1_supplement.1107.4