Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial, 2021, Nee et al

https://pubmed.ncbi.nlm.nih.gov/34319275/

2021 Nov 1;116(11):2279-2285.
doi: 10.14309/ajg.0000000000001395.
Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial
Judy Nee 1, Sarah Ballou 1, John M Kelley 2 3, Ted J Kaptchuk 2, William Hirsch 1, Jesse Katon 1, Vivian Cheng 1, Vikram Rangan 1, Anthony Lembo 1, Johanna Iturrino 1
Affiliations
Affiliations

• 1Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
• 2Program in Placebo Studies, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
• 3Department of Psychology, Endicott College, Beverly, Massachusetts, USA.

• PMID: 34319275
  
• DOI: 10.14309/ajg.0000000000001395

Abstract


Introduction: Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms.

Methods: In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint.

Results: A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure.

Discussion: Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

 

It would have been so straightforward to have given numbers of participants, I wonder why they didn’t.

The possibility of minty burps might might be a problem for the blinding.

 

I’ve tried them too Trish, which is how I know of the possibility. I don’t know how common it may be, not very I should think, but in my experience it’s not impossible. I don’t remember how many times in my case as it’s a long time ago. It could have been just once. It was just a thought.

 

But what if the peppermint oil works through taste and smell - like onions make you cry and curry makes you sweat?

I drink peppermint because the taste makes the drink refreshing. My autonomic nervous system must think it is good.

 

I remember trying peppermint about 40 years ago. I can't remember what form it was in. It irritated my innards dreadfully.

 

That's one interpretation. The other, more rational, would be that whatever they use to evaluate clinical significance is not reliable, or natural improvements are common enough to occur, which would be consistent with a more likely microbial infection being dealt with over time, making the first problem even worse and invalidating any attributions to psychosocial mumbo-jumbo.

So why would a large trial be needed? Oh, right, this is a jobs program and no one actually cares about results. My bad. Keep at it, they probably could go on for centuries doing the same stuff since no one but the patients care.

 

Impossible to tell without the full report but yes - method here is key, together with unaddressed confounds.

Peppermint is physiologically active, anyone who has ever sucked a tic tac knows that it gives a burning sensation to the mouth so looking at peppermint for medical use isn't about resolving effect or no effect, but about useful effect or not. This study may be right in saying that "the overall quality of previous studies is low, and findings have been heterogeneous" but a raw treatment versus placebo isn't going to resolve the limitations of previous studies:

Review article: The physiologic effects and safety of Peppermint Oil and its efficacy in irritable bowel syndrome and other functional disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814329/

IBS is subject to behavioural changes, especially changes in diet, and this provides a large potential confound because most people find dietary restriction a bigger pain than having gut discomfort and even when an IBS sufferer knows what foods they need to avoid to keep symptoms to a minimum, life and boredom mean that sticking to the limitations of say FODMAP avoidance just doesn't happen with 100% compliance.

When entered into a medical trial that offers the possibility of symptom relief, trial participants may respond behaviourally in different ways, some may use the discipline of the trial to plan their meals more carefully, to take a more regimented approach to avoidance of know problem foods and to the inclusion of beneficial foods, and maybe to take a more diligent approach exercise etc. Other participants may take the opposite approach, giving up restrictions on the basis that the pills are going to help whatever. Unless data is collected on these behavioural responses then they will appear in the study results as unaddressed confounds. In the case of a more disciplined approach to dietary management amongst participants receiving the placebo, the confound will be seen as a boost to the placebo effect.

It may only require a fairly small divergence between the behavioural extremes within the study group to produce a heavily confounded result.

It's worth noting that the nature of the treatment - enteric coated peppermint gel, (in the UK the most commonly available form is sold as Colpermin) - does require a degree of dietary regimentation in that each capsule need to be taken between meals so, taking one capsule three times a day means timing food intake across the day with at least a modicum of discipline. If taken too close to a meal, the enteric coating may breakdown in the stomach and the active ingredient - the peppermint gel - fail to reach the small intestine, this can also cause GERD like problems. Presumably all participants were given instructions that required meal planning and therefore better compliance with any avoidance/inclusion protocol.

Edit for readability

 

Interesting points, @CRG.
Certainly all improvements in a placebo arm shouldn’t be attributed to a true placebo effect.

An important issue is what might bring out different levels of fastidiousness in the active and placebo arms.
It would seem to be theoretically possible that people who got some improvement with an active therapy might become less fastidious in other elements of their condition’s management. They might be willing to cope with a certain level of symptom burden. While the placebo group might remain at a more fastidious level.
However, it certainly wouldn’t be my first interpretation of data.

The point about not taking it correctly so that one could end up with a suboptimal dosage is also interesting.