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Standardized Elderberry Syrup Shortens the Severity and Duration of Influenza in Adults

HerbalGram. 2004;63:16-17 © American Botanical Council

by Donald J. Brown, N.D.

Reviewed: Zakay-Rones Z, Thom E, Wollan T, et al. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J International Med Res. 2004;32:132–140.

Summary: In a randomized, double-blind, placebo controlled trial, 60 male and female patients (18-54 years old; mean 30 years old) were recruited from four primary care sites in Norway to study the efficacy of a standardized elderberry syrup for the treatment of influenza. Patients were screened for participation between December and February, when influenza infection is most prevalent. All volunteers selected for the study had a fever ?38.00C (100.40F) and at least one respiratory influenza symptom. Influenza type A virus was isolated from 54 patients and influenza type B from 6 patients. Patients were randomized to receive either a standardized black elder (Sambucus nigra L., Caprifoliaceae) berry syrup preparation (containing 38% elderberry extract plus small amounts of raspberry extract, glucose, citric acid, and honey; Sambucol®, Razei Bar, Jerusalem, Israel) or a placebo syrup (same as above but with no elderberry). Patients were instructed to take 15 ml of elderberry or placebo 4 times per day. Study medication was started within 48 hours (mean 27.2 hours) of the onset of the influenza-like symptoms and continued for 5 days. Patients were also allowed to take a “rescue medication” (oral paracetamol and/or a dose-metered nasal spray [Otrivin®, Novartis, Basel, Switzerland]) if necessary during the study. The primary study outcomes included visual analogue scores (VAS) for aches and pains, frequency of coughing, quality of sleep, mucus discharge in the respiratory tract, and nasal congestion. The VAS used a 10-point rating scale with 0 = no improvement and 10 = pronounced improvement. A self-evaluation score measuring overall personal well-being was also completed. Patients scored their symptoms on diary cards at baseline, four times a day during treatment, and twice daily for 5 days after the treatment had finished. Baseline VAS scores did not differ significantly between the elderberry and placebo groups. There was a significant difference (p < 0.001) between the two groups in the development of mean VAS scores. By days 3-4 of treatment, most of the VAS scores in the elderberry group were close to 10 (pronounced improvement), while the placebo group reached this level after 7-8 days. A significant difference (p < 0.001) in the global evaluation scores for the two groups was noted after a mean of 3.1 ± 1.3 days, while a similar score was obtained after 7.1 ± 2.5 days in the placebo group. Mean VAS scores for aches and pains, quality of sleep, mucus discharge in the respiratory tract, and nasal congestion were all greater than 9.0 by day 4 in the elderberry group and were ? 1.0 in the placebo group. The mean VAS score for aches and pains was 10.0 at day 5 in the elderberry group and at day 8 in the placebo group. Taking rescue medication was significantly less (p < 0.001) in the elderberry group (7 used paracetamol and 5 the nasal spray) versus the placebo group (26 and 21, respectively). Patients from both groups were fully recovered after 8 days. None of the patients reported any adverse events during the study.
Comments/Opinions: Sponsored by the makers of Sambucol, this trial demonstrates the safety and efficacy of the standardized elderberry syrup for the treatment of influenza A in otherwise healthy adults. A previous Israeli trial with both adults and children showed similar efficacy in the treatment of influenza B/Panama.1 In that trial, 27 subjects were randomized to receive Sambucol for 3 days at the onset of flu symptoms. Adults were instructed to take 4 tablespoons per day and children (under 12 years; the youngest was 5 years old) 2 tablespoons per day. A significant improvement of symptoms, including fever, was seen in 93.3% of the elderberry group within 2 days, compared to 91.7% of the placebo group not showing improvement until day 6 (p <0.001). Complete resolution (“cure”) was achieved within 2 to 3 days in approximately 90% of the elderberry group and within 6 days in the placebo group (p < 0.001).

While the active constituents in this extract have not been clearly disclosed, it is thought that anthocyanins such as cyanidin 3-glucoside and cyanidin 3-sambuboside may be the key constituents in the extract.2 Both are detectable in the plasma after oral ingestion of the extract.3 Possible mechanisms of action suggested for the extract include immunomodulatory actions as well as possible inhibition of viral adhesion to cell receptors. One ex vivo study found that incubation of human monocytes with Sambucol increased cytokine production—most notably tumor necrosis factor alpha (TNF-a) but also various interleukins (IL-1?, IL-6, IL-8).4 An in vitro study found Sambucol inhibited the replication of common human and animal influenza A and B strains as well as prevention of viral adhesion to cell receptors.1

Practice Implications: The results of this clinical trial support the use of a standardized elderberry syrup extract for the treatment of symptoms associated with influenza in otherwise healthy adults. Although based on small clinical trials, the data suggests a 50% reduction in both the severity and duration of symptoms in persons (adults and children) using the extract for 3 to 5 days. Based on the cost effectiveness of elderberry extract, future trials should focus on its potential value in preventing influenza and also its safety and efficacy in high risk populations such as immunocompromised patients, young children and infants, as well as the elderly.


1. Zakay-Rones Z, Varsano N, Zlotnik 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(4):361-–369.

2. Abuja PM, Murkovic M, Pfannhauser W. Antioxidant and prooxidant activities of elderberry (Sambucus nigra) extract in low density lipoprotein oxidation. J Agric Food Chem. 1998;46:4091–4096.

3. Cao G, Prior RL. Anthocyanins are detected in human plasma after oral administration of an elderberry extract. Clin Chem. 1999;45(4):574–576.

4. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001;12(2):290–296.

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Israel's elderberry remedy Sambucol provides solution to U.S. flu vaccine shortage
By David Brinn   October 31, 2004

Americans are nervously bracing for the expected flu vaccine shortage as health experts predict people will begin feeling the effects of the flu by next month. But as the hundreds of thousands of Americans who use Israel's elderberry extract Sambucol will tell you, vaccines aren't the only answer to the flu's debilitating symptoms.

Nicknamed 'nature's flu fighter', Sambucol, which is produced by Jerusalem company Razei Bar, has been clinically proven to eliminate flu symptoms within one to two days. A standardized extract, the 100% natural Sambucol contains a potent antiviral compound, AntiVirin as well as a high amount of three flavonoids, naturally occurring plant antioxidants.

Developed by world renowned Israeli virologist Dr. Madeleine Mumcuoglu, SAMBUCOL is derived from the black elder tree, Sambucus nigra L. Beginning in the 1970s, Mumcuoglu began research that led to her discovery of the key active ingredient in elderberry.

"I became interested in the natural healing elements of elderberry when I did by PHD on it in Switzerland," Mumcuoglu told ISRAEL21c. "I isolated the active substances from the elderberry and tested them against the flu virus, and found them to be effective. After finishing my studies, I came back to Israel and continued to work on research for another 10 years or so at the Hadassah Medical Center in Jerusalem."

According to Mumcuoglu, the black elderberry has been known since the 5th century BCE and was mentioned in the writings of Hippocrates, Dioscurides and Plinius. It can be found in every pharmacopoeia. Elderberry wine was traditionally used for influenza and the ill effects of the chills, and the juice of the black elderberry has historically been an invaluable remedy.

After assessing its effectiveness against the flu during her research, which was conducted in collaboration with the Department of Virology, Hebrew University School of Medicine, Mumcuoglu decided to commercialize an elderberry supplement she named Sambucol, and founded Razei bar in 1992. Mumcuoglu was able to test her products on actual patients during a flu epidemic in souther Israel in the winter of 1992-93. The results were very encouraging. Within 24 hours, 20% of those patients taking Sambucol had dramatic improvements in symptoms like fever, muscle aches and pains and coughing. By the second day, 73% were improved and by day three, 90%. In the untreated group, only 16% felt better after two days. The majority of that group took almost a week to begin feeling better.

Another double-blind placebo-controlled clinical study was conducted using Sambucol during an outbreak of influenza B Panama. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the Sambucol treated group within 2 days. A complete cure was achieved within 2 to 3 days in nearly 90% of the Sambucol treated group and within at least 6 days in the placebo group.

And most recently, in a randomized, double blind, placebo-controlled study conducted in Norway, Sambucol was shown to significantly reduce the duration of the flu by approximately four days. The use of rescue medication (pain relievers, etc.) was significantly less in the group receiving Sambucol than in the placebo group.

The study concluded that Sambucol stimulates the healthy immune system by increasing production of inflammatory cytokines. Cytokine production was measured using monocytes derived from the blood of 12 healthy volunteers, which were incubated with four different Sambucol products: Sambucol Black Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System, and Sambucol for Kids.

Mumcuoglo refused to divulge the exact makeup of Sambucol and what makes it different from other elderberry extracts, but stressed that Sambucol stands alone among elderberry extracts.

"I was the first to introduce the elderberry in the U.S., and now there are about 70 copycats. But to our credit, we still have about 80% of the market. We have a very special recipe. It's very easy to destroy the active element, that's most of those other products aren't effective," she said.

Even though the product is produced and manufactured in Israel, the elderberries are imported from Europe, as the Middle East does not offer the proper climate for growing them.

Sambucol costs $12 for 30 lozenges, and it can be found in just about any health food store throughout the U.S. It's distributed by Nature's Way Products. Besides the U.S., Sambucol is currently sold in Canada, United Kingdom, Holland, Belgium, Norway, Denmark, Israel, South Korea, Singapore and New Zealand.

"I think that Sambucol has a great role to play - it really can save lives. To my knowledge, it's the only product that can cut the flu in half, before complications have a chance of setting in. At least 30,000 deaths are reported due to flu complications every year in the US.," Mumcuoglo said.

"I'm very concerned over what is going to happen there. Half the population that has been receiving the vaccine will not get it this year, and a lot of them will get sick, transfer the flu to their families and friends. It's important to pass the message on - You need to stem the flu immediately, as soon as your experience a symptom."

Research data from studies conducted around the world have proven Sambucol® to be effective in shortening the duration and lessening symptoms of influenza A and B. Below are some research highlights:

Effect of Sambucol® on several strains of Influenza virus.
Sambucol®, a standardized extract, is a preparation based on the berries of the Black Elder, used as herbal remedy for influenza virus infections. It contains a potent antiviral compound, AntiVirin® as well as a high amount of three flavonoids (Bronnum-Hansen and Hansen, 1983). The flavonoids are naturally occurring plant antioxidants.

Laboratory tests:
Sambucol® was shown to reduce hemagglutination and inhibited replication of human influenza virus type A, type B and animal strains from swine and turkeys in cell cultures.

Clinical Study:

A double-blind placebo-controlled clinical study was conducted during an outbreak of influenza B Panama. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the Sambucol® treated group within 2 days. A complete cure was achieved within 2 to 3 days in nearly 90% of the Sambucol® treated group and within at least 6 days in the placebo group. "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", Z. Zakay-Rones et al. J. Alt Compl
Med 1995;1:361-369.

Second clinical study on flu
In a randomized, double blind, placebo-controlled study conducted in Norway, Sambucol® was shown to significantly reduce the duration of the flu by approximately four days. The use of rescue medication (pain relievers, etc.) was significantly less in the group receiving Sambucol® than in the placebo group. "Randomized study on the efficacy and safety of an oral elderberry extract in the treatment of influenza A and B virus infections" Thom Erling & Therje Wollan, J. Int. Med. Res., 2004;32(2):132-140.

Herbal alternatives to keep the flu at bay
10/27/2004- The shortage of flu vaccine has forced millions of Americans to seek alternatives and the supplements industry has not been slow in coming forward with suggestions.The American Botanical Council suggests some herbals that manufacturers may want to think about turning into immune boosting supplements.

The ABC believes that certain herbs can help healthy adults protect themselves against flu, diminish flu symptoms, and/or shorten flu intensity and duration, especially when taken at the first sign of flu symptoms.

According to Mark Blumenthal, ABC founder and executive director, there are a handful of herbs with proven safety that can help improve the body’s immune functions. In this group he include echinacea, elderberry and the Chinese herb andrographis.


However, as Blumenthal notes, there is not total agreement in the scientific world as to the effectiveness of echinacea.

One recent Canadian clinical trial showed that the herbal extract lowered respiratory tract symptoms in people with colds.

Calgary-based Factors R & D Technologies in collaboration with researchers at the universities of Alberta, British Columbia and Dalhousie in Nova Scotia, as well as the Heinrich-Hein University in Düsseldorf, Germany and the Karl-Franzens University in Graz, Austria used an echinacea extract phytopharmaceutical to produce Echinilin, which they used in the tests.

“When clinical trial participants were given Echinilin, we saw an immediate and sustained increase in natural killer cells which target virus infected cells and destroys them,” said Dr. Richard Barton, co-director of the human clinical studies. ”This indicates that their immune system had been stimulated to target and destroy the viruses. The end result was an immediate and marked reduction in both severity of symptoms and duration of the infection.”

Other researchers, though, are still undecided about the ability echinacea to reduce symptoms of the common cold and help patients recover faster.

A study published in June in the Archives of Internal Medicine (164:1237-1241), for example, showed that the herbal remedy had no effect on severity of symptoms and the time taken to recover from a cold compared to those given placebo.

The findings were based on a trial of 120 adults, who took 300 milligrams of an echinacea juice preparation daily at the first sign of a cold, and supported the results of a study in children last year.

This trial, published in the Journal of the American Medical Association, found that echinacea did not reduce the severity or duration of infections although it did appear to cut the number of respiratory tract infections in the children.

Elderberry Extract

In a Norwegian study, published last year, scientists were able to demonstrate that patients receiving elderberry extract Sambucol recovered from the flu four days earlier than patients in the control group.

The study, which appeared in The Journal of International Medical Research, showed that on average, flu patients given Sambucol recovered in 3.1 days compared to 7.1 days for those given placebo.

The remedy, manufactured from Sambucus nigra L. by Israel-based Razei Bar Industries, is currently available in the US, Canada, United Kingdom, Holland, Belgium, Norway, Denmark, Israel, South Korea, Singapore and New Zealand.

A previous study published by The Journal of Alternative and Complementary Medicine had found that nearly 90 per cent of flu patients given Sambucol were completely free of symptoms within two to three days, as compared to at least six days with placebo.

Black elderberry has not, however, been tested as a flu preventative, nor is it intended as a substitute for flu vaccine.

"Some of the best things about elderberry are its mildness, its safety, and its great taste,” said Blumenthal, adding that this makes it a good remedy for children too.

The ABC plans soon to publish a monograph on elderberry based on the scientific literature pertaining to this herb and will include the clinical and laboratory research documenting the beneficial immune-stimulating properties of elderberry preparations.


The third herbal that Blumenthal sees as having pronounced benefits for the immune system is andrographis.

A recent published review of 11 clinical trials shows that andrographis is safe and effective in treating upper respiratory tract infections associated with colds and flus, said the ABC.

“Unfortunately, despite its good record of being scientifically documented for its safety and benefits, it has not yet become popular in the US, although it is available from a few manufacturers,” said Blumenthal.  copyrighted - needs reworded.

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