December 4, 2019

Elderberry’s Anti-viral Activity: An Update

European elder (Sambucus nigra), also known as black elder and elderberry, is thought to be beneficial for the prevention and treatment of influenza and upper respiratory infections, though there is still debate as to which stage of infection it is most effective in and even what the exact mechanisms of action are that lend elderberry its anti-viral effects. American elder (Sambucus canadensis) is a fast-growing, deciduous North American shrub that can reach up to 12 feet with flowers and berries similar to S. nigra. Elder flower extracts are also used to treat the common cold and influenza. This review will confine discussion to European elder berries only.

A recent in vitro study published in the Journal of Functional Foods by Torabian et al1 investigated the mechanism of action of elderberry and its primary anthocyanin compound, cyanidin 3-glucoside, on the infectivity of the influenza virus. The study evaluated pasteurized, whole-elderberry extract at different concentrations, as well as the isolated bioactive compound cyanidin 3-glucoside at different concentrations. The primary outcome assessed was the effect of these extracts at different concentrations on influenza viral activity at different stages of infection.

While elderberry was shown to have inhibitory effect at all stages of influenza infection, it had a significantly stronger effect on the late-stage of infection than at early stage; smaller concentrations (higher dilutions) of elderberry had partial or no inhibitory effect during the early phase but those same concentrations had significant inhibitory effect during the late-phase of infection. Furthermore, the antiviral activity of elderberry on influenza was strongest when used in pre-treatment, during infection and post-infection, rather than when used solely during infection. The study confirmed that elderberry exerts its antiviral activity on influenza through a number of mechanisms of action, including suppressing the entry of the virus into cell, modulating the post-infectious phase, and preventing viral transmission to other cells. Elderberry also upregulates IL-6, IL-8 and TNF, suggesting an indirect effect on viral immune response in the body. Interestingly, elderberry was shown to have this effect but not its major bioactive compound, cyanidin 3-glucoside.

No human clinical trials have been published on the prevention of influenza with elderberry, however, black elderberry extract has previously been shown to inhibit human influenza A (H1N1) infection in vitro by binding to H1N1 virions, thereby blocking the ability of the viruses to infect host cells.2 The same study showed elderberry to be effective against 10 strains of influenza virus and compared its effectiveness favorably to the known anti-influenza activities of oseltamivir (Tamiflu) and amantadine.

The mechanistic study conducted by Torabian et al and summarized above was published nearly at the same time as the first meta-analysis of 4 randomized controlled trials on the effects of elderberry supplementation on acute upper respiratory symptoms.3 Three of the studies (Zakay-Rones 1995,4 2004;5 Tiralongo 20166) evaluated total duration of upper respiratory symptoms. Another study, Kong 2009,7 measured symptoms throughout a 48-hour intervention across 6 symptom scales. The meta-analysis included 89 participants in the elderberry group and 91 in the control group (total 180). Three of the studies evaluated the effects of elderberry treatment for either verified cases of influenza or cases with symptoms consistent with influenza infection. The other study evaluated the effects of elderberry on symptoms consistent with the common cold.

A large effect size (ES) was found, 1.717 (P<0.001), indicating elderberry substantially reduced duration of upper respiratory symptoms. Flu vaccination status was controlled for and found to not impact the overall effect of elderberry supplementation on upper respiratory symptoms. Elderberry appears to reduce symptoms caused by influenza virus (ES: 2.074) substantially more effectively than upper respiratory symptoms caused by the common cold (ES: 0.662), although the effect on cold symptoms is still within the standard for a medium effect.

The Tiralongo trial on elderberry’s effect on symptoms of the common cold in air travelers did not reach statistical significance, but the dose of 90—135 mg of anthocyanins daily was far lower than that used in the Zackay-Rones trials (1,900 mg daily).8 Kong’s trial used a 175 mg extract 4 times daily for 2 days. This reflects a wide variation in commercially available elderberry extracts.

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. Elderberry seems to be most effective when used before and throughout infection, though a higher concentration may be required in the early infective stages to achieve significant anti-viral activity.

*A note on safety: elderberries contain cyanogenic glycosides (i.e. sambunigrin) which are hydrolyzed to hydrogen cyanide in the gastrointestinal tract.9 Ingestion of uncooked products from elderberry species in the United States have resulted in poisoning and hospitalization.10 Smaller doses of these glycosides do not typically result in hospitalization, but can produce gastric complaints, such as nausea, vomiting, and diarrhea, particularly in children.11

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