A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin ( Curcuma longa), Boswellia ( Boswellia serrata), and French Maritime Pine Bark ( Pinus pinaster)

Emily K Donovan, Sophia Kekes-Szabo, Joanne C Lin, Rebecca L Massey, James D Cobb, Kathleen S Hodgin, Timothy J Ness, Carl Hangee-Bauer, Jarred W Younger, Emily K Donovan, Sophia Kekes-Szabo, Joanne C Lin, Rebecca L Massey, James D Cobb, Kathleen S Hodgin, Timothy J Ness, Carl Hangee-Bauer, Jarred W Younger

Abstract

This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/- 3 days of baseline symptom reports, followed by 30 +/- 3 days of placebo, 30 +/- 3 days of lower-dose botanical, and 30 +/- 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

Keywords: boswellia; curcumin; maritime pine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study protocol. Each participant completed testing of up to three botanicals. Some participants opted to re-enroll in the study protocol after completion, resulting in a maximum of six botanical assignments. For each botanical, there was a placebo condition, followed by lower-dose botanical and higher-dose botanical conditions. The period of time between visits was 30 +/− 3 days.
Figure 2
Figure 2
CONSORT Flow diagram. Twenty individuals were randomized to at least one of the treatments covered in this report.
Figure 3
Figure 3
Main treatment effects of curcumin, boswellia, and maritime pine on Gulf War Illness (GWI) symptom severity. Average symptom levels (0–100) are presented for the baseline, placebo, lower-dose, and higher-dose conditions. * significantly lower than baseline (p < 0.05). *# significantly lower than baseline and placebo (p < 0.05).

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