New Research Shows Migraine Patients with Medication Overuse/Adaptation Headache May Have Leaky Gut

A recent study published in The Journal of Headache and Pain suggests a revealing link between chronic migraine, medication overuse/adaptation headache (MOH/MAH), and leaky gut syndrome.

What is leaky gut syndrome?

Leaky gut syndrome is based on the concept of increased intestinal permeability (hyperpermeability), where the intestinal lining lets larger molecules through that it normally would not, potentially including toxic ones.

It is a theory that intestinal hyperpermeability is not just a symptom of gastrointestinal diseases, but an underlying cause that can develop on its own and trigger inflammatory responses that lead to various diseases. However, there is little to no evidence that it is a disease itself or that it causes other diseases.

Intestinal hyperpermeability is a known feature of inflammatory bowel disease, celiac disease, and some other gastrointestinal conditions. In fact, it is generally considered a symptom, not a cause of these diseases.

The theory suggests things like diet, stress, etc. may cumulatively damage the intestinal lining over time leading to hyperpermeability. It is important to note that scientists are still unsure if this actually occurs.

There are no direct symptoms of intestinal hyperpermeability itself. Symptoms would be related to the underlying injury/condition causing damage to the intestinal lining.

There is also no standard test or medical diagnosis for leaky gut syndrome/intestinal hyperpermeability currently. However, some tests are being investigated to detect it.

Back to the study

In this study, researchers found evidence that women with chronic migraine plus MOH/MAH have impaired gut barrier integrity (it is important to note that every patient with MOH/MAH in this study used NSAIDs as their abortive of choice).

This was shown by elevated blood levels of:

• Lipopolysaccharide (LPS) - a toxin from gut bacteria
• LPS binding protein (LBP) - a marker of LPS exposure
• Vascular endothelial cadherin (VE-cadherin) - indicates a leaky gut vascular barrier

They also had higher levels of inflammatory molecules like IL-6, CGRP, and HMGB1 compared to migraine patients without medication overuse/adaptation or healthy controls.

Additionally, the frequency of irritable bowel syndrome (IBS) symptoms was higher in the chronic migraine group, further suggesting intestinal troubles.

Importantly, the degree of leaky gut and inflammation correlated with patients’ migraine frequency and severity. This raises the possibility that leaky gut could be involved in migraine chronification and medication overuse/adaptation headache.

What Does This Mean for Migraine Patients?

These findings open new avenues for understanding and treating medication overuse/adaptation headache and chronic migraine. If impaired gut health perpetuates inflammation and central sensitization in the brain, treating gut issues concomitantly with migraine may be beneficial.

The one glaring red flag in this study, however, is the fact that all the patients with MOH/MAH were using NSAIDs and we already know NSAIDs cause GI disturbances via several mechanisms:

1. NSAIDs inhibit cyclooxygenase enzymes (COX-1 and COX-2) which normally produce prostaglandins that help protect the stomach lining/mucosa. By reducing prostaglandins, NSAIDs impair this mucosal defense making the stomach more susceptible to injury and bleeding.
2. NSAIDs may also directly injure the epithelial cells of the stomach and duodenum, allowing acid, pepsin, and bile to irritate the exposed underlying tissue layers. This can cause inflammation, erosion, and ulcers.
3. Many NSAIDs are acidic in nature, so they can further aggravate the gastric mucosa already compromised by prostaglandin deficiency and direct cell injury. The acidic environment promotes inflammation and delays healing of existing ulcers.
4. By causing microscopic injury to the GI lining, NSAIDs allow increased intestinal permeability where bacteria and toxins can leak through into the bloodstream, potentially leading to further inflammation or infection.
5. Through changes in gut microbiota composition, NSAID use can increase growth of bacteria that release pro-inflammatory mediators, compounding intestinal inflammation.

Therefore, it is impossible to conclude that chronic migraine has any connections to increased intestinal permeability without more studies with patients with MOH/MAH due to other medications such as triptans. Yes, the degree of leaky gut did correlate with migraine frequency and severity, but that same metric likely also results in a proportional increase of NSAID use, which in turn causes more GI disturbances.