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

Abstract

Black elderberry, used medicinally for centuries, decreased influenza duration by 4days 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 < 48h of at least 2 moderate-severity influenza symptoms and positive polymerase chain reaction influenza test. Patients from age 5 to 12years received placebo or 15ml (5.7g) elderberry extract orally twice a day for 5days; those > 12years received 15ml 4 times a day for 5days. Patients were permitted to choose to also receive the standard dosage of oseltamivir. Primary: days until all symptoms were none or mild for 21.5h. Secondary: days to complete symptom resolution for 24h. The 87 participants were randomized to receive placebo (n = 44) or elderberry (n = 43). The average age was 25 ± 20years, and 56% were male. The average number of days to reach all symptoms none or mild for 21.5h in the placebo group was 4.9 ± 2.8days 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 2days worse than with placebo taken alone. Our results contradict previous studies and demonstrate the need for further studies. NCT03410862.