Kynurenines Causing Central Fatigue

[Mary]

First, my brain is tired today so I don't have the energy to really think this out. Having said that, here's one article about lactic acid vs. inorganic phosphate as a cause of muscle fatigue: Muscle Fatigue: Lactic Acid or Inorganic Phosphate the Major Cause?

I've always associated the lactic acid burn (or what I assume is lactic acid burn) with fatigue. It's what I get when I crash, and I can tell my crash has lifted when all the achiness has lifted. I've had days when i'm very achy but not crashed, and again, I'm always more tired when achy. But maybe lactic acid is not the culprit, though it feels like it is.

Here's an article about baking soda improving athletic performance, but results seem to be inconclusive.
How Baking Soda Can Improve Athletic Performance . It cites two studies of athletes using baking soda pre-performance, one study showed improved performance and the other didn't.

This is where my fuzzy brain comes into play - I don't have the energy to look at the difference between the two studies closely but thought it might be interesting for those of you who do have the energy to look at this.

 

[Rufous McKinney]

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).

I managed to consistently do the BCAA's for a period of time and found them to be helpful. They seemed to reduce the amount of neurological issues I was having- due to failure to pace adequately. Exercise fatigue per se was not the issue.

 

[Rufous McKinney]

How Baking Soda Can Improve Athletic Performance . It cites two studies of athletes using baking soda pre-performance, one study showed improved performance and the other didn't.

I was doing the baking soda in the morning for a while - then I had this gastroperesis- and was sloshing around with too much liquid in my stomach- so I cut out drinking that baking soda water. I've not gone back to it.

Could this be effects tied to consuming more sodium itself, rather than the notion that its changing aciditiy someplace? The body is highly- homeostatic- and I doubt we can change our pH that easily.

 

[bthompsonjr1993]

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.

It’s really not hard to tell. I was a power lifter before I got CFS. I felt the burn of lactic acid for hours a day in the gym for 4 years before getting CFS. This is lactic acid. It’s the exact same unmistakable sensation, and it’s brought on by muscle exertion. The only difference is, now the lactic acid gets released when I simply lift my arm over my head, as opposed to it used to happen only after lifting tremendous amounts of weight or light weight for a tremendous amount of reps

 

[Pyrrhus]

It’s really not hard to tell. I was a power lifter before I got CFS. I felt the burn of lactic acid for hours a day in the gym for 4 years before getting CFS. This is lactic acid.

That's certainly a very recognizable sensation. It's definitely acid, but probably not lactic acid. The lactic acid hypothesis lasted many decades before people started to point out some of the problems with the lactic acid hypothesis, such as the fact that lactic acid is removed from muscles within minutes of overexertion, while the burning muscle sensation continues after the lactic acid has been removed from the muscle and sent to the liver.

These days, our best understanding of the muscle burning sensation directly after overexertion is a combination of two mechanisms. Firstly, the stressed mitochondria release H+ ions in addition to lactic acid, so the acidity of the muscle tissue rises even as the lactic acid is carried off. Secondly, stressed muscle cells can release extracellular ATP. (Whereas intracellular ATP is an energy source, extracellular ATP is a danger signal.) Both the increased acidity and the extracellular ATP are detected by nociceptors, which send a pain-like sensation to the brain. However, our understanding of these processes can change as more evidence comes to light.

Note that I am only talking about the muscle burning sensation you get directly after over-exertion. I am not talking about Delayed Onset Muscle Soreness (DOMS), which is the muscle burning sensation you get roughly two days after an intense strength training session. Nor am I talking about central pain/fatigue processes...

Hope this helps.

 

[Wishful]

Thanks @Pyrrhus , I'd been composing a response in my head, but I was going to have to say that I didn't know what caused the feeling of 'lactic acid burn'.

The other part of my reply was that even without knowing the precise factor that triggers the nerves, it's not as straightforward as a digital readout of lactic acid levels. The 'feeling of muscle pain' starts with a signal, passes along a transmission network with certain properties that affect the signal, and then gets processed by a neural network which has a complex mathematical function involving multiple inputs and feedback loops, which finally results in one or more neurons switching on the 'feeling'. I expect that even a small change in one or more of those factors can drastically change the 'feeling' in response to muscle use. Even with all the muscle chemicals remaining at their normal levels for a given amount of usage, one of those other factors could make the 'feeling' response much stronger. Since ME seems to alter glial cell functioning, it's reasonable to expect that those glial cells could make a person more sensitive to inputs, or even cause 'feelings of pain' without any actual inputs. My neuropathic pain seems to be in that category.

The bottom line is that we can't assume that our feelings are accurate representations of actual biochemical levels in our bodies. ME can screw around with the accuracy.

 

[bthompsonjr1993]

That's certainly a very recognizable sensation. It's definitely acid, but probably not lactic acid. The lactic acid hypothesis lasted many decades before people started to point out some of the problems with the lactic acid hypothesis, such as the fact that lactic acid is removed from muscles within minutes of overexertion, while the burning muscle sensation continues after the lactic acid has been removed from the muscle and sent to the liver.

These days, our best understanding of the muscle burning sensation directly after overexertion is a combination of two mechanisms. Firstly, the stressed mitochondria release H+ ions in addition to lactic acid, so the acidity of the muscle tissue rises even as the lactic acid is carried off. Secondly, stressed muscle cells can release extracellular ATP. (Whereas intracellular ATP is an energy source, extracellular ATP is a danger signal.) Both the increased acidity and the extracellular ATP are detected by nociceptors, which send a pain-like sensation to the brain. However, our understanding of these processes can change as more evidence comes to light.

Note that I am only talking about the muscle burning sensation you get directly after over-exertion. I am not talking about Delayed Onset Muscle Soreness (DOMS), which is the muscle burning sensation you get roughly two days after an intense strength training session. Nor am I talking about central pain/fatigue processes...

Hope this helps.

Okay if some other acid produces the same exact feeling as lactic acid that would make sense. But this is how it goes for me. If I raise my arms above my head, my shoulders burn like lactic acid. When I put them back down, they stop burning within a minute. However, if I do something like 50 weighted calf raises, whereas before I would have been only a little sore and for only 2 days, now I am very sore and for at least a full week.

 

[msf]

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).

Two is not a good sample. Also, it's helpful to post the studies you mention. Anyway, we obviously have different ideas about ME, so I think at a certain point its best to just hope that others find something that works for them.

 

[xebex]

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.

@Mary Do you notice the effect right away or is it something you need to take for a while before seeing improvements.

 

[Mary]

@Mary Do you notice the effect right away or is it something you need to take for a while before seeing improvements.

I noticed the effect in about 5 days, when I was crashed, and was very astonished to feel my crash, which ordinarily would have lasted at least 2 days, if not longer, start to lift late afternoon. I hadn't felt any different prior to then.

 

[xebex]

I noticed the effect in about 5 days, when I was crashed, and was very astonished to feel my crash, which ordinarily would have lasted at least 2 days, if not longer, start to lift late afternoon. I hadn't felt any different prior to then.

thanks!

 

[pattismith]

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).

In the wikipedia page for Central Nervous System fatigue, they list several neurochemical mecanisms and ways to improve it.

Quote from it:


Branched-chain amino acids[edit]
Several studies have attempted to decrease the synthesis of serotonin by administering branched-chain amino acids and inhibiting the transport of tryptophan across the blood brain barrier.[23] The studies performed resulted in little or no change in performance between increased BCAA intake and placebo groups. One study in particular administered a carbohydrate solution and a carbohydrate + BCAA solution.[24] Both of the groups were able to run for longer before fatigue compared to the water placebo group. However, both the carbohydrate and the carbohydrate + BCAA groups had no differences in their performance. Branch-chained amino acid supplementation has proven to have little to no effect on performance. There has been little success utilizing neurotransmitter precursors to control central nervous system fatigue.

One review hypothesized that the inconsistency with BCAA administration was the result of ammonia accumulation as a result of increased BCAA oxidation.[5]

 

[pattismith]

That's certainly a very recognizable sensation. It's definitely acid, but probably not lactic acid. The lactic acid hypothesis lasted many decades before people started to point out some of the problems with the lactic acid hypothesis, such as the fact that lactic acid is removed from muscles within minutes of overexertion, while the burning muscle sensation continues after the lactic acid has been removed from the muscle and sent to the liver.

These days, our best understanding of the muscle burning sensation directly after overexertion is a combination of two mechanisms. Firstly, the stressed mitochondria release H+ ions in addition to lactic acid, so the acidity of the muscle tissue rises even as the lactic acid is carried off. Secondly, stressed muscle cells can release extracellular ATP. (Whereas intracellular ATP is an energy source, extracellular ATP is a danger signal.) Both the increased acidity and the extracellular ATP are detected by nociceptors, which send a pain-like sensation to the brain. However, our understanding of these processes can change as more evidence comes to light.

Note that I am only talking about the muscle burning sensation you get directly after over-exertion. I am not talking about Delayed Onset Muscle Soreness (DOMS), which is the muscle burning sensation you get roughly two days after an intense strength training session. Nor am I talking about central pain/fatigue processes...

Hope this helps.

My ME/CFS/Fibro had a gradual onset starting around 20 old.
Muscle burning during exercise (especially sustained contraction) during and lasting some days after and associated fatigue /sleepiness/brain fog were among the symptoms.

After much thinking about it, I still have difficulties to say if it's a peripheral or a central neurologic process.

-Peripheral means excess peripheral nerves excitability when chemoreceptors/nociceptors are minimally stimulated

-Central means the nerve excitability is normal but it produces an abnormal and excessive brain reaction

In both cases, the problem is not the acid muscles exertion produces, it's the abnormal reaction of the nervous system.

 

[leokitten]

@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.

Hi @Mary - yep after doing a pass on this paper it does provide a hypothesis for why BCAAs might truly help, I remember you mentioned this supplement in another thread before. Might give it a try again.