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Article

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

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Department of Psychology, University of Alabama at Birmingham, CH 233, 1300 University Boulevard, Birmingham, AL 35233, USA
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Department of Psychology, Virginia Commonwealth University, White House, 806 West Franklin Street, Richmond, VA 23284, USA
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Department of Psychology, Vanderbilt University, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240-7817, USA
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School of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand
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Double Oak Mountain Pharmacy, 5510 Highway 280, Suite 123, Birmingham, AL 35242, USA
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UAB School of Medicine, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35223, USA
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Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, BMR2-208, 901 19th Street South, Birmingham, AL 35205, USA
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Author to whom correspondence should be addressed.
Academic Editors: Beatrice A. Golomb and Paul B. Tchounwou
Int. J. Environ. Res. Public Health 2021, 18(5), 2483; https://doi.org/10.3390/ijerph18052483
Received: 31 December 2020 / Revised: 21 February 2021 / Accepted: 23 February 2021 / Published: 3 March 2021
(This article belongs to the Special Issue Gulf War Illness, A Drug and Environmentally-Triggered Condition)
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. View Full-Text
Keywords: resveratrol; luteolin; fisetin resveratrol; luteolin; fisetin
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MDPI and ACS Style

Hodgin, K.S.; Donovan, E.K.; Kekes-Szabo, S.; Lin, J.C.; Feick, J.; Massey, R.L.; Ness, T.J.; Younger, J.W. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). Int. J. Environ. Res. Public Health 2021, 18, 2483. https://doi.org/10.3390/ijerph18052483

AMA Style

Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, Ness TJ, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). International Journal of Environmental Research and Public Health. 2021; 18(5):2483. https://doi.org/10.3390/ijerph18052483

Chicago/Turabian Style

Hodgin, Kathleen S., Emily K. Donovan, Sophia Kekes-Szabo, Joanne C. Lin, Joseph Feick, Rebecca L. Massey, Timothy J. Ness, and Jarred W. Younger. 2021. "A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea)" International Journal of Environmental Research and Public Health 18, no. 5: 2483. https://doi.org/10.3390/ijerph18052483

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