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No, Elderberry will not kill you!

The latest unsubstantiated rumor circulating the internet involves a claim that elderberry is unsafe when taken during the coronavirus.  The alleged danger is that elderberry may activate cytokines in the immune system.  According to the authors of the letter, since there have been reports of a “cytokine storm” in some Covid19 patients – elderberry, therefore, must not be consumed.  
SUMMARY:  The primary issue is that the authors have conflated two very different physiological processes.  Cytokine activation DOES NOT EQUAL a cytokine storm.  To even have to say that, makes my head want to explode!  A healthy increase in immune activity is needed to prevent viruses from overtaking the body. If you stop the body from being overwhelmed, you don’t need to worry about experiencing widespread infection and the possibility of a “cytokine storm”. That’s why everyone is in search of a magic anti-viral drug.  Stop the virus from replicating excessively, allow the immune system to contain and eliminate it, and everyone lives happily ever after. If you are currently on your way to the hospital, do not take it.  There, now everyone can be happy.  

This disinformation campaign, straight from the “anti-natural” playbook, is a baseless scare tactic that may cause many people to make a poorly informed decision.  There is only one way to reveal the truth of any issue and that’s to take a look at what the scientific literature actually reports.  I will provide referenced data for each point so that an individual can draw their own conclusions.  
Claim #1:   Elderberry needs to be avoided because it may activate cytokines in the body.  
The implication is that this must be harmful because cytokines are involved in what is described as a “cytokine storm”.  A “cytokine storm” is an unregulated/unbalanced immune process that may occur at the end stages of sepsis in some patients.  Although you are being led to believe that this is just an “inflammatory” problem, it is equally an issue with not enough anti-inflammatory and regulatory cytokines being produced.  Again, this phenomenon is not unique to Covid19.
Truth:  The response to elderberry is actually variable.  It possesses immune-stimulating, anti-inflammatory, and antioxidant properties.  It seems to actually work by bringing a balanced mix of effects to the body.  There have been NO published studies ever that link the use of elderberry to the induction of a cytokine storm. Here are the facts as we know them:
1. A study that looked at cells incubated with elderberry did increase the production of inflammatory cytokines in human monocytes. (1)   Is this bad news?  The authors of this study didn’t seem to think so.  
They stated, “We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases.” 
How could the authors come to such a conclusion?  Although we have been led to believe that all inflammation is to be feared, controlled inflammatory reactions to a virus actually improve immunity against viruses. This is part of the body’s first line of defense (2) In fact, it is critical for eliminating viral infection. (3) A healthy immune system seems to manage a healthy balance between inflammatory and anti-inflammatory chemicals.  
2. A study that looked at obese mice found that elderberry exerted a different effect. In this study, serum concentrations of tumor necrosis factor-alpha decreased. This is one of the major cytokines involved in the inflammatory response that was shown to go down. (6)
The authors concluded, “These results suggest that BEE(Black Elderberry Extract) may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum
TAG, inflammatory markers and insulin resistance”
3. Sambucus nigra (elderberry) and Aronia melanocarpa extracts were investigated for their effects on immune system disorders within diabetes mellitus. (7)  This was another animal model.
The paper found, “Natural polyphenols extracted from S. nigra and A. melanocarpa modulate specific and non-specific immune defenses in insulin-deficiency diabetes and reduce the inflammatory status and self-sustained pancreatic insulitis.”
4. Sambucus nigra and effect on UVB induced photoaging and inflammatory response in human skin keratinocytes(8)
Conclusion: “These results indicated that EB(elderberry) has the potential to ameliorate UVB-induced skin photoaging and inflammation.”
Verdict:  The claim that elderberry should be avoided by everyone because it may activate immune defenses is currently without a shred of published evidence to support this supposition.  The data that we presented shows that elderberry may activate the immune system in a healthy way and provide additional anti-inflammatory and antioxidant benefits.  All of these actions are needed by a healthy immune system.  Furthermore, you can search day and night (I have) and you will not find one published or even anecdotal claim that demonstrates elderberry induced a “cytokine storm” in a human being.  
The most important point, that has been missed, involves some common sense.  If someone is very ill, getting sicker, and/or facing severe immune dysregulation they need to go to the hospital!  I would make a reasonable presumption that no physician is going to be pumping elderberry into their IV during this time.  We can all agree that this scenario would not be the right time to rely on elderberry.  
Claim #2Elderberry will provide no benefit.  
Truth: That’s a pretty bold statement considering we have centuries of positive historical data, human clinical data with influenza viruses and colds, and an in vitro study with a coronavirus.  I am sure that everyone realizes that currently there are no interventions (medical or natural) that have been subjected to randomized controlled trials.  This is a new virus.  Additionally, I know of no funding that the government has put aside to investigate the potential of natural remedies.  As such, here is the data that we currently possess:
1. In vitro, an extract of Sambucus nigra inhibited the replication of infectious bronchitis virus, which is a coronavirus that infects the respiratory tract of chickens. (5) The authors made an important point,
“…and Sambucus nigra fruit were tested for anti-IBV activity since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses.”
2. A 2019 study used an extract of Sambucus FormosanaNakaiagainst human coronavirus NL63. (16)  The researchers believed that the caffeic acid in this species of Sambucus was responsible for the ability of this extract to block viral attachment and inhibit replication.  Sambucus nigra is also a source of caffeic acid(17)
Conclusion: “Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC50 = 8.1 μM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.”
3. Elderberry has been shown to inhibit the replication of influenza virus types A and B in vitro.(9)  
4. Another study used an elderberry extract alone and found similar results. (10)
Conclusion: “Rubini elderberry liquid extract is active against human pathogenic bacteria as well as influenza viruses. The activities shown suggest that additional and alternative approaches to combat infections might be provided by this natural product”
5. An extract of Sambucus nigra decreased the activity of human influenza virus H1N1 in vitro. The extract compared favorably to standard antiviral drugs(11)
Conclusion: “The H1N1 inhibition activities of the elderberry flavonoids compare favorably to the known anti-influenza activities of Oseltamivir (Tamiflu; 0.32 microM) and Amantadine (27 microM).”
6. Two clinical trials demonstrated that treatment with Sambucol decreased the duration of illness in patients with influenza(12,13)  
In the first of the two studies cited above:
• “Symptoms were relieved 4 days earlier in the treatment group”
• “use of rescue medication was significantly less in those receiving elderberry extract”
             In the second of the studies cites above:
• “ A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM(Sambucol/Elderberry)-treated group within 2 days”
7. A meta-analysis of randomized controlled trial was undertaken to identify any effect that elderberry may have on upper respiratory infection(14)
Conclusion” Supplementation with elderberry was found to substantially reduce upper respiratory symptoms. The quantitative synthesis of the effects yielded a large mean effect size. These findings present an alternative to antibiotic misuse for upper respiratory symptoms due to viral infections, and a potentially safer alternative to prescription drugs for routine cases of the common cold and influenza”
8. Elderberry reduced cold duration and symptoms in travelers (15).
Conclusion:” These data suggest a significant reduction of cold duration and severity in air travelers.”
Verdict:  The research tells us the following about elderberry:
• It may block viral entry into cells
• It may interfere with viral replication
• It may stimulate the immune system
• It may have an anti-inflammatory effect
• It may act as an antioxidant in the body
Claim #2 put forth by the authors of the letter is without substantiation.  Everyone must make decisions about what is best for their own health.  Decisions are best made based on actual evidence rather than unsubstantiated rumor. Good luck and Good health!!
(1) Eur Cytokine Netw. 2001 Apr-Jun;12(2):290-6.
(2) Microbiol Mol Biol Rev. 2001 Mar; 65(1): 131–150
(3) Immunol Rev. 2009 January ; 227(1): 75–86. 
(4) VIROLOGICA SINICA 2016, 31 (1): 12–23
(5) Chenet al. BMC Veterinary Research2014,10:24
(6) Br J Nutr. 2015 Oct 28;114(8):1123-31.
(7) Pharm Biol. 2015 Apr;53(4):533-9. doi: 10.3109/13880209.2014.931441. Epub 2014 Oct 20.
(8) Cytotechnology. 2019 Oct;71(5):1003-1017. doi: 10.1007/s10616-019-00342-1. Epub 2019 Sep 11.
(9) Mumcuoglu M, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus and beneficial effect of Sambucol in the treatment of naturally occurring influenza B ina double blind preliminary study. 6th Int Cong Infect Dis 1994(Apr 26-30):392
(10) Krawitz C, Mraheil MA, Stein M, et al. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med 2011;11:16.
(11) Roschek B jr, Finc RC, McMichael MD, et al. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 2009;70:1255-1261
(12) Zakay-Rones Z, Thom E, Wollan T. WadsteinJ. Randomized study of the efficacy and safetyof oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res 2004;32:132-140
(13) Zakay-Rones Z, Varsano N, Zlotnike M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med 1995;1:361-369.
(14) Complement Ther Med. 2019 Feb;42:361-365. doi: 10.1016/j.ctim.2018.12.004. Epub 2018 Dec 18.
(15) Nutrients. 2016 Mar 24;8(4):182. doi: 10.3390/nu8040182.
(16) Virus Res. 2019 Nov;273:197767. doi: 10.1016/j.virusres.2019.197767. Epub 2019 Sep 24.
(17) Plant Foods Hum Nutr. 2017 Mar;72(1):82-87. doi: 10.1007/s11130-016-0594-x
  Elisa Song M.D. David Brady M.D.

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