Reviewed: Lopresti AL, Smith SJ. An investigation into the anxiety-relieving and mood-enhancing effects of Echinacea angustifolia (EP107™): A randomised, double-blind, placebo-controlled study. J Affect Disord. October 2021;293:229-237. doi: 10.1016/j.jad.2021.06.054.
Echinacea (Echinacea purpurea and E. angustifolia, Asteraceae) is a well-known herbal preventative and treatment option for the common cold and upper respiratory tract infections. Echinacea also has been reported to improve immune function and protect against other viral, bacterial, and fungal infections. Two human trials, published in 2013 and 2020, suggest anxiolytic effects and provide some clinical evidence for what has been reported in animal models.1,2 In both trials, AnxioCalm® (Terry Naturally Vitamins; Green Bay, Wisconsin), an herbal supplement containing the E. angustifolia extract EP107™, was used. The purpose of this 2021 three-arm, parallel-group, randomized, double-blind, placebo-controlled trial was to examine the efficacy and tolerability of AnxioCalm at two different doses for the treatment of symptoms of mild to moderate anxiety in healthy adults.
Participants
Participants were recruited between May and June 2020 throughout Australia using social media advertisements. The study included healthy men and women (18-65 years old) with a total Clinically Useful Anxiety Outcome Scale (CUXOS) score between 11 and 40, indicating mild to moderate anxiety. Participants were required to be non-smokers and medication-free for four weeks before the beginning of the study, not use pain-relieving medications more than once a week, have a body mass index (BMI) between 18 and 35 kg/m2, and be fluent in English. Researchers excluded people who consumed more than 14 alcoholic drinks per week, had a current or 12-month history of illicit drug abuse, took supplements that could influence the study outcomes, were diagnosed with a medical condition (other than anxiety), and were pregnant, lactating, or intending to become pregnant.
A total of 339 individuals were assessed for eligibility. Of those, 231 were excluded for not meeting inclusion criteria (n = 211) or not completing the initial questionnaire (n = 20). The remaining 108 participants were randomly assigned to the high-dose echinacea (HDE, n = 37), low-dose echinacea (LDE, n = 36), and placebo (n = 35) groups. Four participants in the HDE group discontinued the study due to digestive complaints (n = 1), beginning medication (n = 1), and undisclosed reasons (n = 2). Four in the LDE group discontinued due to digestive complaints (n = 1) and undisclosed reasons (n = 3). In the placebo group, seven did not complete the study for undisclosed reasons. Ninety-three people completed the study.
Materials and Assessments
Each AnxioCalm tablet contained 20 mg of EP107. The placebo tablets contained cellulose powder and the same excipients as the active tablets. Both tablets were identical in appearance.
Participants were mailed a six-week supply of tablets and instructed to take the tablets with or without food. The HDE group consumed two 20-mg AnxioCalm tablets twice daily (total daily dose of 80 mg), and the LDE group took one placebo tablet and one 20-mg AnxioCalm tablet (total daily dose of 40 mg of the active ingredient).
Participants were required to complete online versions of the CUXOS, Positive and Negative Affect Schedule (PANAS, a self-reported measure of positive and negative emotions), Short Form-36 (SF-36, a quality-of-life assessment), and the Bergen Insomnia Scale (BIS) at baseline and weeks 1, 2, 4, and 6, except the SF-36 and BIS, which were completed at all intervals except week 1. The CUXOS was the primary outcome measure. The other tests were secondary outcome measures. Adverse events were recorded at weeks 1, 2, 4, and 6.
A total of eight participants from the placebo (n = 2), LDE (n = 3), and HDE (n = 3) groups failed to consume the minimum required tablets. However, data from these participants were included because removal of their results did not significantly influence the outcomes. There were no statistical differences between groups at baseline, except in the HDE group, which had a significantly lower PANAS positive affect score (P = 0.012) than the LDE and placebo groups.
Results
In all groups, the CUXOS total scores and CUXOS psychological and somatic scores reduced over time. No group differences were significant for any of the CUXOS scores at any timepoint.
The PANAS positive affect score significantly increased and the negative affect score significantly decreased in the LDE group compared with baseline. Similar results were observed in the HDE group: The PANAS positive affect score significantly increased (P = 0.001), and the negative affect score significantly decreased (P < 0.001). In the placebo group, a significant reduction in the PANAS negative affect score was shown (P = 0.03); however, the change in the PANAS positive affect score was not significant compared to baseline. Between-group analysis showed a significant difference in the change of PANAS positive affect score between the LDE and placebo groups (P = 0.005) and the HDE and placebo groups (P = 0.048). A significant change in the PANAS negative affect score between the placebo and LDE (P = 0.001) and placebo and HDE (P = 0.041) also was observed.
Significant improvements in several SF-36 scores (role limitation due to emotional problems, energy/fatigue, emotional wellbeing, and social function) were observed in the LDE group compared to baseline. In the HDE group, significant improvements also were seen in some SF-36 scores (role limitation due to emotional problems, emotional wellbeing, and social function) compared to baseline. The placebo group showed a statistically significant improvement in energy/fatigue scores on the SF-36 compared to baseline. Between-group analysis showed a significant change in the SF-36 emotional wellbeing score between the placebo and LDE (P = 0.043) groups and the placebo and HDE (P = 0.046) groups. In the HDE group, a significant change in the SF-36 social function score (P = 0.043) and general health score (P = 0.49) was observed when compared to placebo.
The BIS score significantly reduced in all groups compared to baseline (P < 0.001 for all), indicating an improvement in insomnia symptoms. However, there were no significant between-group differences.
No major adverse events were reported. The frequency of adverse events was similar in all three groups. However, digestive complaints, particularly nausea, were more prevalent in the HDE group (n = 4). The mean adherence to the protocol in participants that completed the study was 93%.
Conclusion
Several limitations of this study should be noted. The two echinacea doses had similar effects in the study; therefore, an optimal dose has yet to be determined. The study was conducted during the COVID-19 pandemic, when many people may have been experiencing an increase in stress and anxiety, which could have impacted the findings.
The authors concluded that AnxioCalm supplementation over six weeks may reduce symptoms of anxiety and improve emotional wellbeing in healthy adults, though there were no significant differences between groups on the primary variable, the CUXOS score. They recommended further research to examine the potential anxiolytic and antidepressant effects of short- and long-term use of echinacea.
References
- Haller J, Freund TF, Pelczer KG, Füredi J, Krecsak L, Zámbori J. The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers. Phytother Res. 2013;27(1):54-61. doi: 10.1002/ptr.4677.
- Haller J, Krecsak L, Zámbori J. Double-blind placebo controlled trial of the anxiolytic effects of a standardized echinacea extract. Phytother Res. 2020;34(3):660-668. doi: 10.1002/ptr.6558.