• 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.

Glutathione Precursor Cross Comparison

Lotus97

Senior Member
Messages
2,041
Location
United States
Good slides from:

Dr Deth: Redox Methylation in the Gut, Brain, and Immune System power point presentation.


Check out the path of Cysteine, and Cystine.


You can see EAAT3 also.
That's interesting. It sort of goes along with Rich's theory about excitotoxicity due to a drop in glutathione in the astrocytes. That thing about cysteine in the CSF concerns me since one of the places Lyme borrelia like to hang out is in the spinal fluid and they consume cysteine. One thing I'm wondering is about amino acids from food. I seem to remember reading somewhere that people with CFS/ME have a harder time absorbing amino acids from food. If that is true (and hopefully someone following this thread can confirm that) then that would mean we're getting less cysteine and methionine from our food so less glutathione and methylation. Also, less lysine and methionine would mean less carnitine.
 

Jarod

Senior Member
Messages
784
Location
planet earth
That thing about cysteine in the CSF concerns me since one of the places Lyme borrelia like to hang out is in the spinal fluid and they consume cysteine.

interesting. give off a nasty bi-product by any chance?

One thing I'm wondering is about amino acids from food. I seem to remember reading somewhere that people with CFS/ME have a harder time absorbing amino acids from food.

If you look around, you will see that there is a number of papers researching if special amino acids help people with liver disease.

However, I believe the NAC can glutathione in my situation from past experience(some people are worried because lead or mercury), for me...it is a just a matter of how to get it to where it needs to go. Had some stomach or liver issue where I can't tolerate NAC anymore.
 

Hip

Senior Member
Messages
17,858
I have often thought I should do this. In the past it would not have helped because of my cycles - I would be a totally different person from one day to the next -- for instance, one day susceptible to MSGtoxicity, the next not (I was crying inside many times for sheer frustration of never knowing what each day would bring).

Do you have a form you use to determine how you feel to put it into perspective with every other day? I have thought I should make a form where I can just check thinsg off or rate things on some scale...but it would have to list a boatload of symtoms so I could check yes/no if I had them that day.

I find that a very good way to record the benefits that a drug or supplement may be providing is to observe and write down when you do something a little out of the ordinary, over and above your normal capabilities.

For example, if you find that you are suddenly able to do 12 hours concentration a day on a task, when normally you would only be able to do 6 or 8 hours a day, then write that down in your journal. Write something short and simple like "Was able to spend the whole day online, researching into xyz without feeling at all mentally exhausted. This is very unusual for me".

Then when you come back to look at your notes in your journal, in a few months time, you will say to yourself "wow", what on Earth was I taking at that time to give me that much brain power?! And then you start to look back at the medications you took on that day, or on the day before, or throughout the week before, in order to figure out what it was that gave you this boost in concentration abilities. It is usually fairly easy to spot what supplement or drug was producing the benefits, as that will usually be the one you had just started taking at that point.

The trouble I find with ME/CFS is that when you do start feeling better, you often just take this for granted, and you never really ask why. It's crazy, but I find you just accept feeling better like you accept good the weather: if a nice sunny day arrives, you just enjoy it, and that's it, with no further ado. That attitude is fine for the weather, but can be a disastrous attitude for ME/CFS, as you can miss the benefits of some very good medications, if you just take feeling better for granted.

Keeping a simple daily medications journal is I think vitally important for ME/CFS for three reasons: (1) because as just explained, we tend to take feeling better for granted and don't analyze why; (2) we have very bad memories due to ME/CFS, so we will quickly forget or put out of mind drugs or supplements that have been of benefit; (3) there can be significant day to day variations in ME/CFS symptoms anyway, which can confuse the issue, but if your journal shows that on days you took supplement X, you nearly always had an improvement in some symptom, then eventually you will see the pattern.

Everyone has their own particular problematic ME/CFS symptoms they want to address. In my case, for example, I have particular problems with brain fog and mental stamina, sound sensitivities, anxiety disorder, ADHD-like symptoms, and IBS-D, and so I am always on the lookout for any improvements in any of these symptoms when I experiment with any drug or supplement.

I find I often start to look back historically in my medications journal when I have taken a turn for the worse for a few weeks, and then reading my written record of times of better heath not only raises my morale, but often usually gives me some very useful clues as to what supplements or drugs I need to take in order to get back to that state of better health.

I originally started writing my notes on paper (in a large diary with half a page per day), as I thought this would be the simplest and easiest approach. But later I switched to using a simple word processor document to record each day's supplements, because I found most of the time, I would be taking roughly the same medications each day, so I realized that with a word processor, it was very easy to just copy the previous day's set of medications, and paste this same set into the current day's entry.

I can upload an example page of my word processor document journal if you like.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I believe this is the study Rich was referring to about Glutathione in the brain depleted in ME/CFS. It also goes along with the diagram Jarod posted earlier.
http://www.ncbi.nlm.nih.gov/pubmed/22281935

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.
Abstract
Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using (1)H MRSI, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD). In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction. Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) (1)H MRSI to measure CSF lactate; (ii) single-voxel (1)H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) (31)P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction. We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.
 

Jarod

Senior Member
Messages
784
Location
planet earth
Here's a good one.



The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures.

Chen Y, Swanson RA.
Source

Department of Neurology, University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121, USA.

Abstract

Cysteine availability is normally the rate-limiting factor in glutathione synthesis. How neurons obtain cysteine from extracellular space is not well established. Here we used mouse cortical neuron cultures to examine the role of the excitatory amino acid transporters (EAATs) in neuronal cysteine uptake. The cultured neurons expressed both EAAT2 and EAAT3. Cysteine uptake was predominantly (> 85%) Na+-dependent, with an apparent Km of 37 microm. Cysteine uptake was reduced by the EAAT substrates l-glutamate and l-aspartate and by synthetic EAAT inhibitors. The non-selective EAAT inhibitor threo-beta-hydroxyaspartate had a significantly greater maximal inhibitory effect than did the EAAT2-selective inhibitor, dihydrokainate, indicating uptake by both EAAT2 and EAAT3. Serine, a substrate of ASC uptake system, had negligible effects on cysteine uptake at 10-fold excess concentrations. To assess the functional importance of EAAT-mediated cysteine uptake in neuronal glutathione synthesis, cultures were treated with diethylmaleate to deplete glutathione, then incubated with cysteine in the presence or absence of EAAT inhibitors. Threo-beta-benzyloxyaspartate and the non-transportable inhibitor threo-beta-hydroxyaspartate both inhibited the cysteine-dependent glutathione synthesis. The findings suggest that neuronal EAAT activity can be a rate-limiting step for neuronal glutathione synthesis and that the primary function of EAATs expressed by neurons in vivo may be to transport cysteine.

 

xjhuez

Senior Member
Messages
175
Rice protein improves oxidative stress by regulating glutathione metabolism and attenuating oxidative damage to lipids and proteins in rats

Taken together, these findings strongly suggest that SAAs (methionine and l-cysteine) are essential compounds for the defense against oxidative stress. Thus, the higher content of SAAs in rice protein might represent a possible mechanism through which RP enhances oxidative stress, primarily through the modulation of GSH metabolism, further highlighting the key role of SAAs in the antioxidant status.