Myth? Will Elderberry Induce a Cytokine Storm?
Elderberry is one of the most used, and most trusted immune support botanicals in the integrative
medicine repertoire. Lately there has been a lot of discussion within online clinician forums on whether
elderberry could or would induce a cytokine storm if used during an infection where that is the risk.
Please read below the facts and opinion from a very respected physician.
Cytokine Release Syndrome (CRS) and it’s extreme form, cytokine storm, can occur in advanced infection
states like Acute Respiratory Distress Syndrome (ARDS), sepsis, or with specific immunologic medications.
It is relatively rare, very serious, and is an ICU-level intervention required if it occurs. This is a
serious condition, and if a patient is experiencing cytokine storm or ARDS, herbal medicine is not the goto.
Emergency medicine is. So, I’d like to frame this conversation very much in the space of academic
discussion, and in the space where we are talking about elderberry use in the healthy population for
immune supportive purposes. Not as a treatment for severe disease or even mild disease!
Pro- and anti-inflammatory cytokines are a big part of the pathology of CRS and of ARDS. Studies looking
in the bronchoalveolar lavage (BAL) of patients with ARDS have shown elevation in cytokines like
TNF-alpha, IL-1 beta, IL-6, and IL-8 levels, with a more rapid rise and more persistent elevation in non-survivors
compared to survivors.
The study I have seen cited over and over again to back up a claim that elderberry could trigger a cytokine
storm is a study published in European Cytokine Networks in 2001 by Barak, et al. This study was
done in monocytes collected from 12 healthy human donors. This study showed that there was an
increase in IL-1 beta, TNF-alpha, IL-6, and IL-8 after exposure of the monocytes to a commercially available
elderberry extract, with a particularly noted increase in TNF-alpha release by the monocytes. The
study concluded that elderberry extract could “activate the healthy immune system by increasing inflammatory
cytokine production.”
Let’s put this into perspective- running in a marathon has been shown to increase IL-6 about 100-fold,
and another study in PLOS One on the dynamics of cytokine storm (in a drug-induced model in healthy
adults) measured (or estimated, when levels exceeded measurable limits) many cytokine levels (including
inflammatory cytokines men-tioned like IL-6, etc) to be up 4,000-5,000 fold in a cytokine storm.
1 https://www.ncbi.nlm.nih.gov/pubmed/7587434
2 https://www.ncbi.nlm.nih.gov/pubmed/11399518
3 https://www.ncbi.nlm.nih.gov/pubmed/12455180
4 https://www.ncbi.nlm.nih.gov/pubmed/11579746
5 https://journals.plos.org/plosone/article?id=10.13...
Myth? Will Elderberry Induce a Cytokine Storm?
So, weaving these studies into a story that “elderberry could cause cytokine storm” is a far leap, in my
opinion. There is no evidence to suggest that the small elevation in cytokine release by monocytes after
high-dose elderberry exposure is enough to trigger a cytokine storm in a human.
In addition, remember that IL-6 and other cytokines are not produced only by monoctyes, but by a range
of cells- T-cells, B-cells, monocytes, fibroblasts, osteoclasts, keratinocytes, skeletal muscle cells, and many
others. You cannot extract data from monoctyes and apply it to the whole human, or to the local cellular
environment in the lungs. There is just not enough data to support this.
Sambucus nigra has also been studied in humans with influenza, an infection with a known risk of cytokine
storm and ARDS, and there are no studies reporting an increased risk of respiratory distress, cytokine
storm, or ARDS. (To be clear, we make no claims about Sambucus to prevent or treat influenza or any
other condition, we cite these for safety purposes only). Here are a few examples:
1) A 2004 study in Norway followed 60 patients (aged 18-54) suffering from influenza-like symptoms
for 48 hours or less. They were given 15 mL of elderberry extract 5 times daily or placebo for 5
days. Among reported outcomes, the patient use of respiratory rescue medication was reduced,
suggesting fewer respiratory complications in the elderberry group.
2) A 2019 meta-analysis of Sambucus supplementation for upper respiratory symptoms (including
influenza) reported no increase in respiratory risk or side effects and determined elderberry to be
safe in this population.
Again, these studies do not report an increased risk of respiratory complications and continue to represent
elderberry as a safe therapeutic.
It is my conclusion that a risk of elderberry extract triggering a cytokine storm is implausible, and that
elderberry still appears to be one of the safest botanicals we have in our toolkit.*
*These statements have not been evaluated by the Food and Drug Administration. This is not
intended to diagnose, treat or cure any disease.
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