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

Abstract

Background: 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.

Objective: To determine whether elderberry extract decreases influenza's duration and severity.

Design: 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.

Patients: 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.

Intervention: 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.

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

Results: 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).

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

Conclusions: 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.

Trial registration: NCT03410862.

Keywords: Sambucus nigra; elderberry; influenza; treatment.

Conflict of interest statement

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.

Figures

Fig. 1

Consort Flow Diagram.