Kynurenines Causing Central Fatigue

[Wishful]

https://journals.sagepub.com/doi/full/10.1177/1178646920936279

The title is: Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit

The paper is about what causes central fatigue, and there's a nice explanation of the three types of fatigue and why serotonin and lactic acid are not the cause of fatigue. Their conclusion: "Neuroactive tryptophan metabolites are a major cause of central fatigue." This is a lengthy paper (tough for us with central fatigue) but I think it's a must-read for those interested in central fatigue and the role of kynurenines in ME.

I admit I'm biased about the paper because it fits what I've observed with my ME, and the vague hypotheses I'd arrived at.

 

[andyguitar]

You might find this research interesting @Wishful even though its from a while back.

 

[sometexan84]

This sounds like part of the IDO2 Metabolic Trap hypothesis, where IDO2 is impaired due to mutation, leading to higher levels of Tryptophan that IDO1 can't handle, thus triggering the trap.

And now they're studying the increase of thrombospondin-1 (TSP-1) and how that's causing fatigue. Possibly because of too much Tryptophan.

Study of Thrombospondin-1 (TSP1) in ME / CFS pathogenesis (STOP-ME)

 

[Hip]

Interesting that this paper says branched-chain amino acids (BCAAs) have been proposed to alleviate exercise-induced fatigue: @Mary found BCAAs reduce PEM (see PEM Busters thread).

 

[Wishful]

I did notice the bit about BCAAs, and ignored it because they didn't do anything for me, other than blocking increased symptoms from TRP. However, I'm not sure that I took BCAAs when I had PEM or was expecting PEM, so I'm not sure that they wouldn't have helped. Do you recall any other members saying that BCAAs reduce their PEM symptoms?

 

[Mary]

@Wishful - in this post I mentioned a few articles which talk about BCAAs and tryptophan and central fatigue.

To be more accurate, the BCAAs reduce my PEM recovery time. They cut it by more than half, which is huge. They have helped several other members here - e.g., @ljimbo423 and I've seen several other members say that BCAAs have helped them, either with energy or PEM.

 

[ljimbo423]

@Wishful

BCAA's help me quite a bit. Although I didn't notice much of a difference in energy until I got up to about 10 grams a day. I now take 13 grams every day.

They make a big difference in my energy levels and because of that, help a lot with the fatigue I get with PEM. They also improve my brain fog some but they seem to help more with energy.

Like anything though, they help some people but others get little to no benefit from them. I use to think they were working on improving my mitochondrial function but now I think it might have more to do with serotonin, etc. and central fatigue.

 

[andyguitar]

Like anything though, they help some people but others get little to no benefit from them

Have you come across any posts (anywhere-not just on PR) about people having an adverse reaction to BCCAs @ljimbo423 ?

 

[ljimbo423]

Have you come across any posts (anywhere-not just on PR) about people having an adverse reaction to BCCAs @ljimbo423 ?

None outside of PR that I can remember. I have read 1-2 posts of people feeling much worse from BCAA's here. Generally speaking they seem to be well tolerated.

Most of the side effects I read from people are from them causing insomnia. Either from too high a dose, taking it too late in the day or because they had a heightened sensitivity too them. This seems to be fairly common.

 

[andyguitar]

Because there are some big variations in what people report as being helpfull I can't help wondering if some have me/cfs and FM, and the BCAA are helping the FM more than me/cfs. As this paper says there are deficiencies of BCAA in FM.

 

[sb4]

@BrightCandle You saying that high Tryp foods cause a worsening of your symptoms and not increased carbs?

Pretty sure @Wishful did near zero Tryp for a year without much improvement.

 

[msf]

https://journals.sagepub.com/doi/full/10.1177/1178646920936279

The title is: Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit

The paper is about what causes central fatigue, and there's a nice explanation of the three types of fatigue and why serotonin and lactic acid are not the cause of fatigue. Their conclusion: "Neuroactive tryptophan metabolites are a major cause of central fatigue." This is a lengthy paper (tough for us with central fatigue) but I think it's a must-read for those interested in central fatigue and the role of kynurenines in ME.

I admit I'm biased about the paper because it fits what I've observed with my ME, and the vague hypotheses I'd arrived at.

Lactic acid may not cause fatigue, but I am pretty sure that it, or byproducts of the reaction that produces it, cause the lactic-acid feeling in my legs and arms.

 

[Wishful]

Lactic acid may not cause fatigue, but I am pretty sure that it, or byproducts of the reaction that produces it, cause the lactic-acid feeling in my legs and arms.

Hard to tell, unless you actually measure lactic acid levels. Even then, the feeling could be caused by something that also correlates with lactic acid, with the acid not being the actual cause. Maybe someday there'll be a paper properly proving what the truth is.

 

[msf]

Hard to tell, unless you actually measure lactic acid levels. Even then, the feeling could be caused by something that also correlates with lactic acid, with the acid not being the actual cause. Maybe someday there'll be a paper properly proving what the truth is.

I've done that, they were above normal levels. Plus everything I have tried that should have an effect on lactic acid (most obviously sodium bicarbonate) has an effect. At some point, if it walks like a duck, etc.

 

[Wishful]

Plus everything I have tried that should have an effect on lactic acid (most obviously sodium bicarbonate) has an effect.

Even that's not actual proof. I haven't researched it, but I don't see how taking bicarbonate would significantly affect lactic acid levels in muscle tissue. It would react with the acid in a test tube, but swallowing some would just cause the stomach to release more HCl. If you take things that you are convinced will reduce lactic acid and thus make you feel better, the placebo effect may be in effect.

I'm not arguing that lactic acid isn't responsible for your sensations, I'm just arguing that it isn't solid proof, and that there could be other explanations. However, if some treatment makes you feel better, it doesn't matter how it works, unless you're basing other decisions on a certain theory which may be wrong.

 

[msf]

Even that's not actual proof. I haven't researched it, but I don't see how taking bicarbonate would significantly affect lactic acid levels in muscle tissue. It would react with the acid in a test tube, but swallowing some would just cause the stomach to release more HCl. If you take things that you are convinced will reduce lactic acid and thus make you feel better, the placebo effect may be in effect.

I'm not arguing that lactic acid isn't responsible for your sensations, I'm just arguing that it isn't solid proof, and that there could be other explanations. However, if some treatment makes you feel better, it doesn't matter how it works, unless you're basing other decisions on a certain theory which may be wrong.

sodium bicarbonate has been consistently shown to improve exercise performance, and that the explanation for this that these studies offer is that it counteracts acidosis. some studies state that bicarbonate may actually cause intracellular acidosis (even though it causes alkalinization of the blood), this seems to actually be necessary for normal energy production in muscles during exercise.

I appreciate your point about the proof being in the pudding though: bicarbonate helps me exercise, just as it helps healthy people,

 

[Wishful]

google sodium bicarbonate + effects + exercise. If you had, you would have found that it has been consistently shown to improve exercise performance, and that the explanation for this that these studies offer is that it counteracts acidosis.

I did that. I found two peer-reviewed papers, and found that the results were inconclusive, and didn't show a direct supplement/lactic-acid link. I ignored the non-peer-reviews articles, because those have conflicts of interest (articles with positive findings get better advertising revenue).

 

[xebex]

@Wishful - in this post I mentioned a few articles which talk about BCAAs and tryptophan and central fatigue.

To be more accurate, the BCAAs reduce my PEM recovery time. They cut it by more than half, which is huge. They have helped several other members here - e.g., @ljimbo423 and I've seen several other members say that BCAAs have helped them, either with energy or PEM.

@Mary can you send a link to the BCAAs you use? I have some pills that have like 1g of BCAAS not very helpful if you're finding you need 10!

thanks

 

[Mary]

Hi @xebex - I take a combination of two products. I do this because I split my BCAAs into 2 doses and though the powder is more cost-effective, if I'm out doing errands it's easy to carry pills with me to take.

I take about 2/3 scoop of this first thing in the morning, which = 4000 mg:

and then I take 6 of these capsules late morning on an empty stomach. 2 capsules = 1000 mg., so 6 capsules = 3000 mg

I've increased my dose a little.

 

[xebex]

Thank you Mary