A Potential Cause for the Precise Combination of GI Issues + Post-Exertional Malaise and Migraines
This short article has the potential to be highly impactful for the subset of people dealing with the following exact intersection of macroscopic bodily issues:
GI issues (e.g. IBS, IBD, SIBO, slow digestive motility, etc.)
post-exertional malaise (which we’ll call PEM, from now on, i.e. feeling real bad after exercise and other exertion),
and migraines.
These are all very common chronic symptoms, and they often go together. Their precise area of overlap sits in the microscopic domain of (1) energy metabolism and (2) vascular tone.
By energy metabolism, I mean the ubiquitous process by which your body uses various substrates (i.e. the food you consume, in the form of mainly macronutrients—carbs, protein, and fat—and micronutrients—vitamins, minerals, etc.) to produce usable energy for your cells, in the form of ATP.
By vascular tone, I mean the “tenseness” of your blood vessels, i.e. how wide or narrow they are, how “stiff” their walls are, and how well this width and stiffness is regulated.
Both of these microscopic processes are incredibly important to your overall health.
The former (energy metabolism) does almost absolutely everything, particularly by fueling thousands of different enzymatic reactions. Poor energy metabolism can lead to almost every single disease or symptom (migraines, fatigue, chronic pain, fatigue, poor sleep, brain fog, immune/autoimmune issues, etc. etc. etc.).
The latter (vascular tone) is extremely important for physical endurance/strength, cardiovascular health, brain health, and much more.
Now, in this particular trifecta—the combination of GI issues, PEM, and migraines—GI issues are more commonly prior to the latter two (though the following may act in alternative orderings as well).
Particularly, chronic GI issues, such as untreated SIBO or celiac or wheat/gluten sensitivity or Crohn/UC or IBS etc. all lead to energetic strain on your enterocytes, which are the cells lining your gut. That is, long-term existence of these digestive issues requires more energy expenditure by your gut cells, which ultimately depletes their primary fuel: Glutamine.
Glutamine is the most abundant amino acid in the body, and the gut cells use it as their primary source for the production of energy, allowing them to digest, counter immune threats, undergo peristalsis, etc. Over time, with chronic GI issues, the GI cells become rate-limited at glutamine and ultimately:
(1) cease to function effectively,
(2) reduce the amount of glutamine available for the rest of the body
and
(3) stop making enough citrulline.
Citrulline is another important amino acid in the body that is ultimately converted into arginine to make nitric oxide, which is the all-important regulator of vascular tension (the width/stiffness of your blood vessels).
And the citrulline in your body is mainly made from glutamine in your gut.
So you can see that long term GI stress ultimately reduces the whole-body availability of both glutamine and citrulline, which leads downstream to:
(1) post-exertional malaise
and
(2) migraines
(as well as sleep issues, cardiovascular issues, heat/cold intolerance, cold fingers/toes, etc.)
The reason for this is that, while GI cells are the main users of glutamine, muscle cells are the main storers of glutamine, i.e. most of the glutamine in your body is stored in your muscles, and they use that glutamine for the production of usable energy in times of stress (like exercise).
Less glutamine means less energy available to muscle cells and significant fatigue, muscle soreness, and poor growth after exercise.
And with less citrulline, your body is not able to make nitric oxide effectively and therefore will not be able to regulate the width and stiffness of your blood vessels correctly!
And poor vascular tension regulation is a recognized major contributor to migraines.
So ultimately:
(1) long term GI stress leads to (2) poor glutamine status leads to (3) poor citrulline production leads to (4) poor nitric oxide availability leads to (5) poor muscular functionand migraines.
Glutamine and citrulline are both pretty safe to supplement, but generally the dosages required are much higher than what people generally take, i.e. not just 5 grams for glutamine and 1 gram for citrulline. More like 20 grams for glutamine and 5-10 grams for citrulline, taken on an empty stomach.
There are downsides to both for a fraction of people:
In people sensitive to glutamate (neural overactivity), glutamine can be a real problem, and in people with HSV/HPV viral latency, citrulline can be a problem. In such case, you’ve got to keep doses low and spread out.
If this (educationally) helps you, shoot me and my team an email! (support@malekmd.com)
Disclaimer: The information in this post is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider with any questions about a medical condition or before making changes to your health regimen.
