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.
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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