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.