• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? (Kavyani, 2022)

Messages
600
Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease with a substantial social and economic impact on individuals and their community. Despite its importance and deteriorating impact, progresses in diagnosis and treatment of ME/CFS is limited. This is due to the unclear pathophysiology of the disease and consequently lack of prognostic biomarkers. To investigate pathophysiology of ME/CFS, several potential pathologic hallmarks have been investigated; however, these studies have failed to report a consistent result. These failures in introducing the underlying reason for ME/CFS have stimulated considering other possible contributing mechanisms such as tryptophan (TRP) metabolism and in particular kynurenine pathway (KP). KP plays a central role in cellular energy production through the production of nicotinamide adenine dinucleotide (NADH). In addition, this pathway has been shown to mediate immune response and neuroinflammation through its metabolites. This review, we will discuss the pathology and management of ME/CFS and provide evidence pertaining KP abnormalities and symptoms that are classic characteristics of ME/CFS. Targeting the KP regulation may provide innovative approaches to the management of ME/CFS.


https://link.springer.com/article/10.1007/s00018-022-04380-5
 
Messages
600
From Glass et al 2023:

While kynurenate is the only tryptophan compound with correlations in both the time point and the ratio sides of the heatmap, the differences seen in plasma and urine correlations in the other eight compounds, which appear at various locations in the tryptophan pathway, attest to a profound dysregulation of this pathway in the ME/CFS patients compared to the controls.
 

Wishful

Senior Member
Messages
5,808
Location
Alberta
Seems like a well-written article, covering known research and what works for a few PWME and what doesn't work for most (GET/CBT). I recommend this paper for patients trying to educate their doctors about ME.

Before I knew about ME, I assumed I had some sort of rare chronic neuroinflammation, and that the KP played a major role. I don't think it's quite that simple, since there are plenty of modulators of the KP, and none have proven to be reliable modulators of ME symptoms. Maybe it plays a role in downstream effects of the core problem. Maybe "profound dysregulation" is a bit overblown.
 

Wishful

Senior Member
Messages
5,808
Location
Alberta
Peroxynitrite scavengers make my ME symptoms worse. My theory for this is that ONOO- is the main factor controlling the lifespan of IDO, so less ONOO- means more TRP catalyzed into kynurenines, including QUIN, which might be responsible for the "feeling lousy" symptoms.
 

Violeta

Senior Member
Messages
3,009
Has this been talked about anywhere? I just accidentally found this.

"the role of HHV (human herpes virus) in modulating the tryptophan-kynurenine pathway"
 

Forummember9922

Senior Member
Messages
173
Has this been talked about anywhere? I just accidentally found this.

"the role of HHV (human herpes virus) in modulating the tryptophan-kynurenine pathway"
Definitely resonates with me. My onset was clearly right at the time of a HHV onset. Actually if you go to the reddit herpescureresearch there are tons of candidates in development. Some of them are new ways to attack the virus, or latent forms of the virus, others in development are broad spectrum anti-virals that could work against things like EBV too but it will take a lot of time. Off the top of my head theres cp-cov3, im-250, and some mrna herpes vaccines/theraputic vaccines in development. There are a lot of horses in the race. Pretilivir will probably be the first thing to hit the market that works in a different way than valtrex but will only first be available to immunocompromised. I would like to see data on Pretilivir in CFS patients.
 

Wishful

Senior Member
Messages
5,808
Location
Alberta
In some other thread, I pointed out that since ME alters immune system function, the abnormalities in viral activity in PWME might be effects of that alteration, rather than a cause of ME. Of course, it's also possible that the viral abnormalities are part of a feedback loop that keeps us in the ME state, or at least keeps the symptom severity higher than it would be otherwise.
 
Back