A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol ( Polygonum cuspidatum ), Luteolin, and Fisetin ( Rhus succedanea ).

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101238455 Publication Model: Electronic Cited Medium: Internet ISSN: 1660-4601 (Electronic) Linking ISSN: 16604601 NLM ISO Abbreviation: Int J Environ Res Public Health Subsets: MEDLINE

Original Publication: Basel : MDPI, c2004-

Fallopia japonica* ; Persian Gulf Syndrome* ; Rhus*; Cross-Over Studies ; Flavonols ; Gulf War ; Humans ; Luteolin/therapeutic use ; Male ; Resveratrol

A chronic multi-symptom illness of unknown etiology, Gulf War Illness (GWI) affects 175,000 to 250,000 veterans of the Gulf War. Because inflammation has suspected involvement in the pathophysiology of GWI, botanical treatments that target inflammation may be beneficial in reducing symptoms. No FDA-approved treatments currently exist for GWI, and rapid prioritization of agents for future efficacy testing is important. This study is part of a larger project that screened nine different botanical compounds with purported anti-inflammatory properties for potential treatment of GWI. We tested three botanicals (resveratrol [ Polygonum cuspidatum ], luteolin, and fisetin [ Rhus succedanea ]) on symptom severity of GWI in this placebo-controlled, pseudo-randomized clinical trial. Twenty-one male veterans with GWI completed the study protocol, which consisted of 1 month (30 days ± 3) of baseline symptom reports, 1 month of placebo, 1 month of lower-dose botanical, and 1 month of higher-dose botanical. Participants completed up to 3 different botanicals, repeating the placebo, lower-dose, and higher-dose cycle for each botanical assigned. Linear mixed models were used for analyses. Resveratrol reduced GWI symptom severity significantly more than placebo at both the lower ( p = 0.035) and higher ( p = 0.004) dosages. Luteolin did not decrease symptom severity more than placebo at either the lower ( p = 0.718) or higher dosages ( p = 0.492). Similarly, fisetin did not reduce symptom severity at either the lower ( p = 0.504) or higher ( p = 0.616) dosages. Preliminary findings from this screening study suggest that resveratrol may be beneficial in reducing symptoms of GWI and should be prioritized for future testing. Larger trials are required to determine efficacy, response rates, durability of effects, safety, and optimal dosage. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

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UL1 TR003096 United States TR NCATS NIH HHS

Keywords: fisetin; luteolin; resveratrol

ClinicalTrials.gov NCT02909686

0 (Flavonols)
KUX1ZNC9J2 (Luteolin)
OO2ABO9578 (fisetin)
Q369O8926L (Resveratrol)

Date Created: 20210403 Date Completed: 20210423 Latest Revision: 20210423

20240829

PMC7967624

10.3390/ijerph18052483

33802381