A Placebo-Controlled (..) Trial of Botanical Agents for [GWI]: Curcumin (..), Boswellia (..), and French Maritime Pine Bark (..), 2021, Donovan et.al

[Utsikt]

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)

Spoiler: Authors

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

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.

Web | DOI | PMC | PDF | International Journal of Environmental Research and Public Health

 

[Utsikt]

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).

 

[Liie]

Interesting to see that placebo had such clear effect.

How well is placebo usually constructed to really resemble the real thing?

I'm thinking that curcumin is pretty distinctive, being so yellow. So maybe participants could tell when they got placebo, which caused the effect. It's hard to imagine any other reason for why placebo didn't have an effect for curcumin.

It would be interesting if participants were asked which branch they though they were in after the trial.

And it would be sensible for the investigators to verify that participants can't tell the placebo and the real thing apart beforehand, and report the results of that.

 

[Liie]

Aha, it's from Jarred Younger. He sometimes speaks about these substances in his videos.

 

[Trish]

It looks from those graphs that the main difference between the tests was that the placebo in the curcumin trial didn't register any improvement, whereas the other two trials the placebo showed as much effect as the treatment.

So if the placebo in the curcumin trial had worked the same way as in the other trials, none of the treatments would seem to be effective.

 

[forestglip]

The blinding is interesting. Each patient received the placebo first, then the low dose at the next visit, then the high dose at the visit after that.

The patients were unaware of this schedule, but the research personnel weren't.

For each botanical, participants followed the same protocol: one month (30 +/− 3 days) of placebo, one month (30 +/− 3 days) of lower-dose botanical, and one month (30 +/− 3 days) of higher-dose botanical. Study participants were blinded to both the assigned botanicals and administration protocol (placebo, lower-dose, higher-dose).

Research personnel were blinded to the assigned botanicals but not to the administration protocol.

 

[Utsikt]

The blinding is interesting. Each patient received the placebo first, then the low dose at the next visit, then the high dose at the visit after that.

The patients were unaware of this schedule, but the research personnel weren't.

Unfortunately they didn’t assess the how successful the blinding was. Curcumin will change the colour of your urine, so that might have tipped them off.

The differences between placebo and the botanicals were also very small. They mention in the methods section that small effects probably don’t matter to pwGWI, but they don’t address it in the discussions:

The trials were not powered to detect small (Cohen’s d = 0.25) effects, with only 0.42 predicted power. Small effects, however, were not expected to have important clinical impacts on GWI.