Elderberry and Cytokine Storms
We’re all seeing this question and concern making the rounds. There has been a suggestion circulating that we take a look at the widespread use of Elderberry for use in anti-viral formulas as a panacea. I've decided to break down some leading clinical herbalists' thoughts and perspectives on the relationship between Elder (Sambucus nigra) and its influence on the body's natural cytokine response to infection - I've pulled together literature and thoughts from herbalists Jim McDonald, Stephan Buhner, Paul Bergner, Guido Masé, and 7Song.
It is important to remember that it seems no clinical herbalist has yet worked directly with COVID-19 to have definitive information for the particular behavior of Elder with this virus. This should also assumed to be the case with all herbal treatments and this virus -- we just don't have the luxury of experience to give definitive answers as to what will work best.
However, many of you have used elderberry in the past for viral infections and it might be on your radar. Here is a break down of what exactly elder does do in the body and some background to cytokine storms.
What is a Cytokine Storm?
When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. Cytokines activate those cells, stimulating them to produce more cytokines. If this natural response spirals out of control, cytokines can attack healthy organs and cells, resulting in a cytokine storm. (For a more indepth discussion of immune system response head over to this article by herbalist and clinician Donald Yance).
The cytokine storm is a phenomenon when an excessive immune response may occur in late stages of severe illness, typically occurring in conditions of a critical care unit. Cytokine storms were a feature of H5N1 influenza, aka Bird Flu, (1997) and SARS (2003) corona virus and elevated levels of two of these cytokines (IL-6 and IL-8) were identified in some folks with severe cases. It was speculated that the 1918 Spanish Flu's severity in young adults was due to an excessive cytokine response.
Some of this is proving also to be the case with advanced COVID-19 infections.
Paul Bergner reminds us that in 2009, during the H1N1 flu, the question arose among herbalists about whether the herb Echinacea should be used for this flu, or if it presented a problem of stimulating a cytokine storm.
The question of how to deal properly with the cytokine cascade led to a variety of adjustments to critically ill patients, from increased use of corticosteroids to attempts to eliminate inflammatory responses altogether. These treatment modalities unfortunately did not prove to be successful. Fortunately, according to Bergner (2020), "today's understanding of the cytokine storm is more nuanced, that it is not a simple on-off, inflammatory switch, but a complex orchestrated response of many cytokines. While some induce pathologies related to inflammation, others are not pathological but positive."
Non-inflammatory portions of the cytokine storm process actually facilitate viral clearance, promote the repair of damaged tissues, and regulate the severity of the inflammatory cytokines (Guo, 2017). This may explain why corticosteroids, resulted in death in all the N5N1 patients they were given to (Bergner, 2020). The beneficial and regulatory cytokines were suppressed, along with the inflammatory and anti-viral ones.
Elderberry's Mechanism of Action on Inflammatory Response:
Elderberry extract can increase certain pro-inflammatory cytokines -- the same ones involved in cytokine storms, yes, but also the same cytokines that exist for normal infection response (they are the same). So far, there is conflicting, theoretical evidence that elderberry (Sambucus species) may increase cytokine release in some cases (Masé).
In fact, both Echinacea and Sambucus have shown the ability to stimulate immuno-regulatory cytokines, with a net non-inflammatory effect (Bergner, 2020). Barak and colleagues (2002) found that elderberry extracts enhanced both inflammatory and anti-inflammatory cytokines in human cells in lab experiments.
In Barak's study, published in 2001 in the European Cytokine Network Journal, which was a double-blind, placebo-controlled, randomized study of elderberry extract, it was shown to reduce the duration of flu symptoms to 3-4 days. There was no mention of a cytokine storm, but within the study there was reference to the enhancement of pro-inflammatory cytokines after taking elderberry extract leading to the quick, effective recovery and specifically, antibody production.
The study never warned against using elderberry, nor did the researchers express concerns of elderberry causing a cytokine storm.
According to herbalist Jim McDonald, there is likely to be benefit and unlikely to be harm when elderberry is used in the context of a larger protocol, appropriate to the person, and their specific needs in the moment. In this view, this may mean NOT using it in *some* folks with auto-immune conditions and/or when there is already plenty of pro-inflammatory cytokine activity, as in active, feverish infection.
McDonald goes on to say, "To my knowledge and that of other herbalists responding to this same concern, there's no evidence clinically or via research that elderberry has ever caused a cytokine storm, which is an uncontrolled inflammatory response which damages tissue--here we mean lung tissue." In the clinical practice that he participated in during H1N1 (where cytokine storms were also an issue), huge amounts of the population self-treated at the time with elderberry, but his and other herbal practitioners did not identify a relationship between use of elder and a worsening of flu symptoms. Rather, in his anecdotal experience, he heard numerous feedback of those who reported back that elderberry helped their recovery times or helped to maintain health.
Similarly, NY herbalist 7Song advocates for the use of elder due to its antiviral activity, noting that the Ithaca Free Clinic is still just beginning to treat actual cases of COVID-19 - but, based on previous experience with viral infections, this recommendation still stands and he is still using it. Herbalist Stephan Buhner only advocates the use of elder in conjunction with other herbs within a whole herbal protocol due to its immunomodulating abilities - and he prefers the use of elder leaf versus berry or flower, which all exhibit different phytoactions within the body.
When to Use Elder and When to Switch Out:
While it is believed that for most individuals elderberry is safe before infection, it may be that it should be avoided if symptoms develop during outbreaks of novel infections – just to be on the safe side. Elderberry may also not be safe for individuals with autoimmune conditions (though some folks with these conditions do just fine using elderberry, according to McDonald).
Elderberry contains immune-active lectins in the berry. These ramp up immune function and may limit viral incursion into cells, theoretically impacting likelihood of first infection, according to herbalist Guido Masé. In his recommendations, taking elderberry ONCE SYMPTOMS ARE PRESENT will not likely be as effective as some of the other measures discussed, and in folks with immune dysregulation or with severe symptoms, might (theoretically) be contraindicated. The likelihood that a hospitalized patient will be taking elderberry is low.
If a fever (a sign of more pro-inflammatory cytokines) were to become present, Jim McDonald suggests the stop of elderberry and move towards more appropriate herbs to address fever management -- not suppression -- like yarrow, elder flower, and peppermint. "The point is that I would use elderberry when it’s appropriate and most effective and then shift to other herbs when they are more indicated. Not because I’m worried that elderberry will cause harm, but because other herbs will likely work better at different stages of illness."
Licorice and Baikal skullcap can be strong anti-inflammatories. If you’d like to play it ultra-safe, you can avoid elderberry altogether and use some other immune-supportive herbs, such as licorice (Glycyrrhiza glabra) root (not for individuals with high blood pressure or for long-term use), astragalus (Astragalus membranaceus) root, turkey tail (Trametes versicolor) mushroom, and/or reishi (Ganoderma spp.) mushroom.
I have to reiterate that the best course of action is always to rely on the medical system for severe cases and check in with your healthcare provider if you suspect that you have COVID-19, as per the CDC. While there are no exact answers to how to best treat this virus or maintain optimum health while you are social distancing so you don't contract it, we must use the best information we have and our experience to share what we learn as we proceed through this together. Please don’t suggest folks choose herbs over any recommended medical treatment or that taking herbs means folks can be less careful with exposure of themselves or others.
Barak V, Birkenfeld S, Halperin T, Kalickman I. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Isr Med Assoc J. 2002 Nov;4(11 Suppl):919-22.
Bergner, Paul. (2020). Herbal Medicines and Cytokine Storm in respiratory infection. Link: here
Guo XJ, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 2017 Jul;39(5):541-550.
Kimberly Jean, BSN, MA
Herbalist and Educator, Perfect Supplements
Kimberly holds a Bachelor's of Science in Nursing and a Master's of Arts in Education Research and Administration. She currently sits on the Editorial Review Board for the Journal of the American Herbalists Guild. Kimberly has studied directly under Alexis Durham lead herbalist at Herb Pharm, Sajah Popham of Organic Unity spagyrics, Pearl Sites and Tyler Wauters of Hawthorn Institute, amongst many others. Kim, in recent years, started and directed several large scale commercial herbal apothecaries for community retailers on both the West and East coast, with close working knowledge of over 300+ botanicals.
As always, the information in this section is intended for educational purposes only and is not a substitute for the advice of a qualified healthcare professional. Herbs can have interactions with medications and other natural products. If you consider taking an herb, I encourage you to read up on it before you begin consuming it, its extract, or essential oil.In addition if you are pregnant or nursing, you have to be very careful as to which herbs you can safely take. As an herbalist, I am sharing this information as a starting point, if you do decide to take action, please consult with a qualified healthcare professional who is familiar with your unique and specific situation.