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.

References:

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.