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Connecting the dots ... Is ME/CFS a complex fungal intolerance? (part 3)

This is the third blog in a series on my theory that a major ME/CFS pathology may be a complex fungal intolerance. If you have not read the introduction and part 2, that is recommended before reading this post. This is a speculative theory and experience sharing and not to be considered medical advice.

Just for a quick review, in part 2 I introduced the topic of tryptophol, an alcohol produced by Candida from its metabolism of tryptophan. This alcohol has been identified as a major component of African sleeping sickness, also called African Trypanosomiasis (AT). The fact that it can also be produced by Candida under certain conditions is noteworthy due to the metabolic similarities between AT and ME/CFS. And the fact that the conditions where the most tryptophol can be produced by Candida are found in the small intestine is also noteworthy. This gives us a testable pathology and a treatment target. And this also raises many questions. I would like to address some of the questions I often get regarding this theory:

How do you know if you have a tryptophol problem? I have not found a way to directly measure tryptophol levels yet during the time intervals when it would likely be produced in the small intestine. So for now I am making an inferrence based on symptoms, the genetic metabolic trap hypothesis, and treatment response. While using a Candida treatment targeted at the small intestine, several ME/CFS patients have now experienced positive results and some significant symptom reversal that can be directly related to a change in the tryptophan and melatonin system so that may be indirect evidence. And there are plans to measure microbiota changes and hormone levels that would be altered by tryptophol, particularly melatonin, before and after treatments.

What is the treatment for tryptophol? There is currently no antidote to tryptophol that I am aware of, so one of the reasons for this blog is to spark interest and hopefully treatment ideas. The likely treatment target is to lower tryptophol production by Candida. That would logically involve lowering it's precursor tryptophan levels in the small intestine, as well as lowering overall Candida levels there. There are many anti-Candida treatments that would target many parts of the body. I have run a small test and several other patients have as well, including lowering tryptophan levels, dietary measures including anti-fungal foods, using pH sensitive antifungals that target Candida specifically in the small intestine, using anti-Candida probiotics, and supporting healthy stomach acid levels to limit flow of Candida into the small intestine. I plan to blog about this experience soon.

Are there clinical tests for this? I have not been able to find clinical tests for Candida that could identify an infection limited to the small intestine, and I've also found no clinical tests to show the levels of tryptophol. Most likely there is a research assay somewhere for tryptophol, based on the studies that have been produced, perhaps for blood levels. But that may or may not be helpful. There are clinical tests for bacterial overgrowth in the small intestine (SIBO), involving testing the breath for hydrogen levels, but nothing similar I can find for Candida. And there are plenty of stool tests for Candida but those are not specific to the small intestine. In fact, you can find a Candida test for almost every part of the body except the small intestine. So this pathology would likely be left undiagnosed and untreated in most patients. If anyone reading this knows of tests that could target these criteria, I would love to hear about them.

Are there parallels between African Trypanosomiasis and ME/CFS? We can certainly explore the literature to see if there are parallels. Metabolic similarities include sepsis, and I won't cover that as it is beyond my background and has been mentioned already in a Stanford ME/CFS symposium, so I am making the assumption the metabolic parallels are significant. But what about the symptom parallels? The general symptoms of AT are generally attributed to the very high levels of tryptophol being produced by the tryposomal parasite as it progresses through the body and into the nervous system. The disease starts in the subcutaneous tissues, blood and lymph. Over time it eventually gets into the nervous system and the brain. Due to the production of tryptophol all over the body during the infection, AT involves a much higher level of tryptophol than would likely be produced by Candida only in the small intestine, so tryptophol symptoms are most likely milder in ME/CFS than in AT. Also, not all of the AT symptoms may be the result of tryptophol as the trypanosomal parasite may disrupt the host in other ways. These are AT symptoms according to the W.H.O., also according to the US CDC, and a few related sources and a few online AT resources.

AT symptoms, with comments for ME/CFS in parentheses ( ) :

-Confusion (brain fog)
-Problems with coordination and slurring of speech (loss of motor function)
–Mania (adrenal looping, or running on adrenaline, wired-but-tired)
–Daytime slumber and night-time insomnia (dysautonomia, reversed circadian rhythms)
–Parkisonism and cerebellar signs (issues related to the brainstem perhaps)

Here are a few more that require no comments:

-Fever
-Severe headaches
-Irritability
-Extreme fatigue, and easy fatigabillity
-Swollen lymph nodes
-Aching muscles and joints
-Itching
-Weakness
-Cardiovascular problems
-Neurological problems

There may be more parallels, this is just a quick sample. The point is that there is enough similarity that I believe we should at least consider the possibility that ME/CFS patients are being exposed to tryptophol via activity of Candida in the small intestine.

Many of us have treated Candida without success, how is this different? This is an important question that I’ve heard repeatedly as I have discussed this theory with people. Most Candida treatments are either topical or systemic. Meaning, we are treating just the surface skin we can get to, with lotions or medications. Or, we are treating the entire body by taking a drug (Diflucan, one of the azoles, Nystatin, etc), or an anti-candida herb (Oregano, garlic, etc) or nutrient (coconut oil, etc), or an anti-candida diet. If you treat the entire body, you will experience a large die-off, from Candida everywhere. This is often attributed to the detox load from die-off, but there is another interesting explanation. Candida has quorum sensing, and it knows when its numbers go down. So if you kill it, it immediately starts growing back up to its stable saturation level, and that happens quickly, it can double its population in a few hours. Candida also is highly adaptive and mobile and can literally hide from treatments, or change its metabolism to avoid an antiparasitic. In fact many antifungal drugs are no longer effective against some of the newer strains. So this is not a simple fungus to treat even under the best conditions. In my experience, most attempts by ME/CFS patients to treat Candida fail, unless you are very diligent, and very patient, and rotate many different treatments. But in the past we have not specifically targeted the small intestine, and that may be a simpler problem to solve in terms of die-off tolerance.

How could Candida get into our small intestine? That is supposed to be a relatively sterile location in the GI system, at least in ideal conditions. This is a good question and I have not found anything specific, although the SIBO research may give some ideas. I have wondered whether low stomach acid levels may be partly to blame. Or overgrowth coming back to the small intestine from further down the digestive tract.

Why would Candida be active in our small intestine? This is another good question, even if Candida gets in the small intestine, due to the alkalinity there and the rapid flow of broken-down food combined with pancreatic fluids, one would think there would be little opportunity for Candida. One possibility is that motility is slow for ME/CFS patients in the small intestine. Perhaps due to weak connective tissues, muscle atrophy, or neurological damage. In one mouse study, a high stress level associated with pending trauma was shown to significantly slow down small intestinal motility, so that could be a factor in some cases. In this study the mice could see a live hungry cat through a partition in their cage, and their small intestinal motility slowed down significantly.

Is tryptophol found in ME/CFS patients in metabolomic studies? According to Dr Robert Navioux, mass spectrometry studies do show tryptophol can be present in both some ME/CFS patients and controls (private conversation). There may be specific preconditions that make ME/CFS patients more vulnerable to the effects of tryptophol. This is an area that needs more exploration.

Where does the Candida get access to tryptophan to make tryptophol? This is a very important question and I suspect may be at the heart of the unique vulnerability of ME/CFS patients. The metabolic trap is one explanation, elevated tryptophan levels in the cells lining the small intestine. Another possibility is high dietary tryptophan levels, particularly a diet that includes high tryptophan meats such as pork, beef, and poultry. But even a regular diet might suffice as a source of tryptophan with lower intestinal motility or gastroparesis in the stomach that pushes food into the small intestine too slowly, giving the Candida more access to the tryptophan.

Why would ME/CFS patients be so vulnerable to Candida in the small intestine? There could be several reasons, some have been covered already. We could have immune problems defending against Candida, there are some known bad genes for Candida, such as the FUT2 gene. Or a connective tissue disorder in the small intestine, as the outer tissue in the small intestine must connect with smooth muscles. Another possibility is gastroparesis slowing the stomach contraction, pushing the food into the small intestine too slowly. And of course, the metabolic trap, with bad IDO2 enzyme genes allowing cellular tryptophan levels to go too high on the inner layers of the small intestine, leading to more tryptophol production. This brings up an interesting possibility I mentioned in the introduction, that if the metabolic trap is active, the IDO1 enzymes may be less active, which would directly reduce the ability to manage candida loads. There could be other flora problems that have biased the GI system towards fungal over-activity or overgrowth. Another issue would be how the tryptophol gets into the bloodstream and brain, which could also involve tissue disorders or a leaky gut.

Now on to Part 4 …

Comments

Kurt, this is fascinating. I definitely have a Candida connection: CDSA showed multiple strains of yeast, and more recent mycotoxins test showed very high levels of 4 different types. I seem to fit the profile of AT (slurred speech, difficulty walking, wired-but-tired plus many others). I have done multiple anti-fungal treatments - they are the only things I have tried over 11 years which have given me some improvement, but the benefits are limited and don't last. Looking forward to the next part with great interest.
 
Kurt, this is fascinating. I definitely have a Candida connection: CDSA showed multiple strains of yeast, and more recent mycotoxins test showed very high levels of 4 different types. I seem to fit the profile of AT (slurred speech, difficulty walking, wired-but-tired plus many others). I have done multiple anti-fungal treatments - they are the only things I have tried over 11 years which have given me some improvement, but the benefits are limited and don't last. Looking forward to the next part with great interest.
I also tried to fight Candida for years, with modest success. But this time is very different, and I believe it is due to targeting the small intestine. Which I believe takes a certain combination of treatments (I'm working on posting that next).
 
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Just read some information about taurine supplements, recommending NOT to swallow it if candida is suspect. You had recommended to me in a previous post, not to swallow GABA supplement, for the same reason. Would you agree? Are there other amino acids that could also be feeding candida? For example I take 2gm of lysine daily.
 
Hi Kurt, thanks for the great information! I tried to find some literature regarding trytophol and came across this articles. This article suggests that tryptophol is actually pathogenic to Candida and reduces its colonies.
https://pubmed.ncbi.nlm.nih.gov/31217414/
I am familiar with that study and plan to address the topic in a future post. I am putting together summaries of all the research articles that together produce this theory. It might be a very long post.

Tryptophol is a weaker quorum sensing chemical than farnesol. Also, it is possible that tryptophol is somehow getting directly into the bloodstream. But it is also possible that tryptophol is a double-edged sword, both helping manage candida overgrowth and poisoning our autonomic nervous system at the same time.
 
Just read some information about taurine supplements, recommending NOT to swallow it if candida is suspect. You had recommended to me in a previous post, not to swallow GABA supplement, for the same reason. Would you agree? Are there other amino acids that could also be feeding candida? For example I take 2gm of lysine daily.
I also take lysine daily. I had not seen that about taurine. This might be a good topic for the candida forum.
 
Also just read, two things I’m taking for reflux, DG licorice root and marshmallow root are anti-candida.
 
Also just read, two things I’m taking for reflux, DG licorice root and marshmallow root are anti-candida.
Yes, that's what I kept finding again and again. Most of the treatments that I thought were working on all sorts of different pathologies were just working against Candida. Candida is a very resilient opponent but there are many ways to defend against it. And fortunately for us, there is a wealth of research already into Candida.
 
very impressive theory, have you been able to discuss this with any of the researcher like Ron Davis?
 
"Or overgrowth coming back to the small intestine from further down the digestive tract."
That sounds like it would be consistent with some of the dramatic improvements (and subsequent relapses) after fecal transplant.
 

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