A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom ( Ganoderma lucidum), Stinging Nettle ( Urtica dioica), and Epimedium ( Epimedium sagittatum)

Jarred Younger, Emily K Donovan, Kathleen S Hodgin, Timothy J Ness, Jarred Younger, Emily K Donovan, Kathleen S Hodgin, Timothy J Ness

Abstract

This report is third in a three-part clinical trial series screening potential treatments for Gulf War Illness (GWI). The goal of the project was to rapidly identify agents to prioritize for further efficacy research. We used a placebo-controlled, pseudo-randomized, crossover design to test the effects of reishi mushroom (Ganoderma lucidum), stinging nettle (Uritca dioica), and epimedium (Epimedium sagittatum) in 29 men with GWI. Participants completed 30 days of symptom reports for baseline, then a botanical line consisting of 30 days of placebo, followed by 30 days each of lower-dose and higher-dose botanical. After completing a botanical line, participants were randomized to complete the protocol with another botanical, until they completed three botanical trials. GWI symptom severity, pain, and fatigue were contrasted between the four conditions (baseline, placebo, lower-dose, higher dose) using linear mixed models. GWI symptom severity was unchanged from placebo in the reishi lower-dose condition (p = 0.603), and was higher in the higher-dose condition (p = 0.012). Symptom severity was not decreased from placebo with lower-dose stinging nettle (p = 0.604), but was significantly decreased with higher-dose stinging nettle (p = 0.048). Epimedium showed no significant decreases of GWI symptoms in the lower (p = 0.936) or higher (p = 0.183) dose conditions. Stinging nettle, especially at higher daily dosages, may help reduce the symptoms of GWI. Epimedium does not appear to beneficially affect GWI symptom severity, and reishi may exaggerate symptoms in some GWI sufferers. These results are in a small sample and are preliminary. Further research is required to determine if stinging nettle is indeed helpful for the treatment of GWI, and what dosage is optimal. This trial was registered on ClinicalTrials.gov (NCT02909686).

Keywords: epimedium; reishi; stinging nettle.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study event flow. Participants took three of the tested compounds in the following order: placebo, lower-dose botanical, and higher-dose botanical.
Figure 2
Figure 2
CONSORT Flow diagram. The three participants who discontinued botanicals provided sufficient data to be included in analyses. Four participants could not be included in analyses due to unusable outcome responses (two reported only “zeros” for GWI severity, and two gave all retrospective reports).
Figure 3
Figure 3
Main treatment effects of reishi, stinging nettle, and epimedium on GWI symptom severity. Average symptom levels (0–100) are presented for the baseline, placebo, lower-dose, and higher-dose conditions. * = significantly lower than baseline, *# = significantly lower than baseline and placebo (p’s < 0.05).

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