Elderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 and Above: a Randomized, Double-Blind, Placebo-Controlled Trial



Black elderberry, used medicinally for centuries, decreased influenza duration by 4 days in three previous peer-reviewed trials. US elderberry sales, possibly related to a “high severity” and “high activity” influenza season from January to March 2018, more than doubled from 2017 to 2018 to > $100 million.


To determine whether elderberry extract decreases influenza’s duration and severity.


FDA-approved, investigator-initiated, Investigational New Drug, double-blind, randomized, placebo-controlled trial. Conducted January 2018–April 2019 in three emergency rooms, two suburban and one urban, in the Midwestern Health System.


Eighty-seven consecutive, consenting patients, over age four, with < 48 h of at least 2 moderate-severity influenza symptoms and positive polymerase chain reaction influenza test.


Patients from age 5 to 12 years received placebo or 15 ml (5.7 g) elderberry extract orally twice a day for 5 days; those > 12 years received 15 ml 4 times a day for 5 days. Patients were permitted to choose to also receive the standard dosage of oseltamivir.


Primary: days until all symptoms were none or mild for 21.5 h. Secondary: days to complete symptom resolution for 24 h.


The 87 participants were randomized to receive placebo (n = 44) or elderberry (n = 43). The average age was 25 ± 20 years, and 56% were male. The average number of days to reach all symptoms none or mild for 21.5 h in the placebo group was 4.9 ± 2.8 days compared to 5.3 ± 3.6 in the elderberry group (p = 0.57). The average number of days to complete resolution was 8.7 ± 3.8 and 8.6 ± 3.9 in the placebo and elderberry group, respectively (p = 0.87).


Small sample size, but powered > 0.90 to detect 2-day benefit of elderberry versus placebo.


We found no evidence that elderberry benefits the duration or severity of influenza. Post hoc analysis suggested primary outcomes with elderberry taken alone (without oseltamivir) were 2 days worse than with placebo taken alone. Our results contradict previous studies and demonstrate the need for further studies.

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Funding was provided by the Wendel Family Foundation, the Research Program Committee of the Cleveland Clinic, and Cleveland Clinic Children’s. Study medication and placebo, and no financial support, was provided by PharmaCare. PharmaCare and the other funding sources were not otherwise involved with the design of the study; the collection, analysis, and interpretation of the data; and the decision to approve publication of the finished manuscript. PharmaCare did have the opportunity to review this article prior to submission for publication as per a Materials Transfer Agreement with Cleveland Clinic.

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Michael Macknin, MD, Professor Emeritus of Pediatrics, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, author and principal investigator, was responsible for the conception, design, and interpretation of the work. Kathy Wolski, MPH, Lead Biostatistician, C5 Research, Cleveland Clinic, author, performed the biostatistics for this study. Jeffrey Negrey, MA, Research Coordinator, Clinical Research Unit, Cleveland Clinic, author. Sharon Mace, MD, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, author. All authors were involved in the acquisition of data for the work, drafting of the work or revising it critically for important intellectual content, and final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors would like to acknowledge everyone who contributed significantly to this work. Stephanie Stoianoff, MBA, BSHA, Research Coordinator, helped with enrollment of patients, patient follow-up, and data entry. Wendy Spencer, RN, Research Coordinator Cleveland Clinic Children’s, helped with enrollment of patients. Megan Villareal, BA, helped coordinate the contributions of the Clinical Research Unit study coordinators. Deborah Gladish, BA, and Karen Myers provided data management support; Craig Balog, BS, provided programming support, Gerry McConnell, BSN, RN, provided monitoring, and Tammy Gamble provided administrative support. These individuals are paid employees of C5 Research at Cleveland Clinic. John Petrich, RPh MS, Investigational Drug Service Department of Pharmacy Cleveland Clinic, received study medications and helped with blinding and proper storage and end-of-study disposal of all study medications. Amy Moore, BA, provided medical editing support from the Department of Scientific Publications at Cleveland Clinic. Lukas Kost, MD, and Aiman Altaqui, MD, of Cleveland Clinic also helped with patient enrollment. Kristen Beck, B.A., introduced the P.I., MM, to the elderberry for influenza peer-reviewed literature. Michelle Medina, MD, provided invaluable support as department chairman. The medical teams, including the laboratory staff, in the three participating emergency rooms provided essential support for this project.

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Correspondence to Michael Macknin MD.

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Conflict of Interest

Dr. Macknin reports he has been a vegan for 10 years, and the Wendel Family Foundation is supportive of plant-based nutrition. Dr. Macknin also explored the possibility of pursuing a patent for a drug combining oseltamivir and elderberry extract. The Innovations Department at the Cleveland Clinic expressed the belief this combination was not patentable. Therefore, Dr. Macknin will not pursue a patent, but he encourages others to study this combination. No other authors report any conflicts of interest relative to this manuscript.

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Macknin, M., Wolski, K., Negrey, J. et al. Elderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 and Above: a Randomized, Double-Blind, Placebo-Controlled Trial. J GEN INTERN MED 35, 3271–3277 (2020). https://doi.org/10.1007/s11606-020-06170-w

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  • elderberry
  • Sambucus nigra
  • influenza
  • treatment