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)

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.

Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?

“…As mentioned curcumin is least soluble in water with an estimated solubility of 11 ng/mL in alkaline conditions while it is readily soluble in lipids or fats. ,, Hence, efforts have been made to develop various lipid or phospholipid curcumin formulations and several of these formulations have shown tremendous potential as therapeutic agents . For example, Meriva, a lecithin delivery method for curcumin, has better tissue dispersion and bioavailability than the unformulated natural substance. , This novel second-generation formulation has been shown to be safe and well-tolerated at a dose of 250 mg/day to 4 g/day for a period of 7 days to 8 months and did not cause any side effects both in healthy subjects and patients. − Moreover, this formation has been shown to ameliorate metabolic disorders including diabetes-associated edema and microangiopathy, hypercholesterolemia, metabolic syndrome, and NAFLD. ,,− ,− In various clinical trials, this formulation reduced skin flux, peripheral edema, retinal edema, LDL-C, TC, TG, LDL-C, non-HDL-C, uric acid, BMI, waist circumference, hip circumference, AST, ALT, portal vein diameter, liver size, 3-methyl-2-oxovaleric acid, 3-citrate, hippurate, hydroxyisobutyrate, indoxyl sulfate, α-ketoglutarate, kynurenine, methylamine, succinate, trimethylamine, chenodeoxy cholic acid, lithocholic acid, taurocholic acid, leptin, MutL homologue 1 (MLH1), and MutS homologue 2 (MSH2), and increased adiponectin levels, zinc levels, Zinc to copper ratio, PO 2 , visual acuity, microcirculation score, in patients. ,,− ,, In another study, administration of Meriva (1 g/day) for 3 or 6 months caused a substantial reduction in MCP-1, IL-4, IFNγ, TBARS, p -cresyl sulfate, carbohydrate intake, protein intake, total fiber intake, phosphorus and potassium intake, and gut microbes such as Escherichia-Shigella, Enterobacter verrucomicrobia, Firmicutes, and improved other species of microbes including Lactobacillaceae spp., Lachnoclostridium spp., Lachnospiraceae family, and Prevotellaceae without side effects in patients suffering from chr...…”

“… , It also reduced the risk of development of T2D and Alzheimer’s disease in adults of age between 30 and 70 years . Another study showed that this formulation (1 g or 4g/day) reduced the severity of gulf war illness disease without any serious side effects . Moreover, Meriva along with fish oil reduced postprandial insulin levels in healthy subjects whereas Meriva with phytosterol reduced cardiovascular disease (CVD) risk in hypercholesterolemia patients. ,, …”

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials

“…Further, a double-blind, randomized clinical trial of curcumin cream (2%) applied for 10 days showed remarkably reduced episiotomy pain and increased wound healing . A pseudo-randomized crossover trial of escalating curcumin dose from 1 g/day to 4 g/day every 30 days showed reduced disease severity in patients with gulf war illness ( n = 39) of unknown etiology . In another study, 1000 mg/day of curcumin for 8 weeks reduced serum urate in 39 patients with hyperuricemia .…”

Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis

“…Curcumin and boswellic acids (as well as other constituents, such as maritime pine) were studied in combination for other indications in clinical trials in humans, including acute musculoskeletal pain, chronic kidney disease, benign thyroid nodules, diverticulitis, tendinopathy, and Gulf War syndrome. 107 – 112 In healthy adults with acute musculoskeletal pain, treatment with the combination of curcumin and boswellic acids or with acetaminophen for 7 days reduced pain intensity at a similar rate and to a similar level. 113 The only difference observed between the two groups was improved reduction in the affective domain of the McGill Pain Questionnaire in the curcumin and boswellic acids treatment group (8.57 times better, p = 0.027).…”