BCAAs reducing PEM

[datadragon]

RBC tests always show my magnesium level is okay. I've been taking magnesium glycinate for years and years. I also take B6 daily, in the morning. If I take it at night, it gives me insomnia. And I take NAC daily, in the morning. Several years ago someone on PR posted that it helped with sleep because of its effect on glutamate, so I started taking it at night. At first it helped, and then it switched, causing insomnia. It took awhile to figure this one out but I finally did, with help from reddit.

Hi Mary yes you have had some non typical reactions such as insomnia or perhaps glutamate or glutamate/gaba balance being an additional issue to deal with for you beyond say just the core effect of nlrp3 inhibition lowering ifn-y and ability to lower wasf3 levels that should help many to focus on especially where something like a virus or fructose also in table sugar or heavy exercise is likely fueling nlrp3 activation in the earlier stages.

You can see if switching to magnesium sulfate works better then the glycinate in this case.

On b6 just remember to avoid pyridoxine which inhibits the active p5p form and stick to p5p but trying to take more of a rda dose not a large dose as during inflammation any zinc or mag deficiency can make it not go in the cell and become more inflammatory not anti inflammatory. However most recently it appears that zinc and magnesium are cofactors that also are needed for B6 entry into the cell I found as well, so zinc and magnesium deficiency/unavailability may further impair utilization of vitamin B6 during inflammation/infection states even when supplementing such as using the active form P5P. This may be why B6 levels become high instead during that time fueling serine and inflammation or immune response https://forums.phoenixrising.me/thr...duction-utilization.57030/page-3#post-2440317

 

[Mary]

@datadragon - I also take zinc and have for many years. I think you know that insomnia is a huge issue for most of us on this form. It goes hand-in-hand with MECFS.

 

[datadragon]

I also take zinc and have for many years. I think you know that insomnia is a huge issue for most of us on this form. It goes hand-in-hand with MECFS.

Let me make this much easier for you and others to understand. As far as Glycine's acute effects on glutamate, it can be directly used as a NMDA receptor ligand, on the glycine binding site. That means in some ways it is a glutamate supplement, allowing NMDA receptors to work in the first place. The N-methyl-D-aspartate receptor, is a glutamate receptor. So perhaps the form like a magnesium glycinate or solgar zinc glycinate (solgar chelated zinc) might not work well for this situation, why I suggested to try magnesium sulfate instead for example. Glutamine also can increase glutamate why I mentioned some other nlrp3 inhibitors

The mechanism by which wasf3 levels are causing the pem https://www.healthrising.org/blog/2023/08/16/nih-mitochondria-chronic-fatigue-syndrome/
can be helped for many with those nlrp3 inhibitors or ifn-y inhibitors, but then it’s not just er stress but infection inflammation glucose fructose heavy exercise etc all happen to converge to increase wasf3 levels via nlrp3 activation or increase in ifn-y. The additional issue has been that several nutrients go deficient during an infection/inflammation state or that nlrp3 activation such as zinc for example gets placed into the cell and its absorption is lowered both so it’s not easily restored without using a chelated form. . From there this can cause problem with vitamin b6 and other nutrients in a further cascade where it’s needed with b6 for example to convert it to the active form and get it into the cell, otherwise b6 would be more inflammatory rather than it’s usual anti inflammatory effects. So yes we may need an extra step like a chelated zinc that is not glycinate although I was hoping the lowering of inflammation would restore the zinc metabolism and lessen its additional requirement in some people.

 

[Wayne]

The only thing that has affected PEM at all are BCAAs, which decreased my PEM recovery from 2 - 3 days to 1 day.

Hi @Mary, do you remember @ljimbo423? Looks like he hasn't posted in a couple of years. But I just ran across a rather remarkable post he made on his experience with BCAAs which I thought you would find interesting.

 

[Mary]

Hi @Mary, do you remember @ljimbo423? Looks like he hasn't posted in a couple of years. But I just ran across a rather remarkable post he made on his experience with BCAAs which I thought you would find interesting.

Thanks @Wayne - I remember @ljimbo423 very well, he posted many times about how BCAAs helped him. And I know he took a much higher dose than I do. I know he hasn't been on the forum in quite awhile and I really hope he's doing okay! @ljimbo423 , if you see this, let us know how you're doing if you don't mind

I take 5 grams of BCAAs a day. Some years ago I increased my dose to maybe 8 or 9 grams and as I recall it gave me insomnia (!), what else! But, hmmm -- maybe I'll try increasing it again. I do take B1 and CoQ10, but not pantethine though I took that several years ago. I could try adding pantethine back into the mix. fwiw, I don't get "flu-like flares" - I do get sick quite a bit, but it's an actual bug, not a "flu-like flare", generally sinus-related, which astragalus and andrographis help with.

@Wayne, did you ever give the BCAAs a try using something besides the Nutricost brand, which I don't think is a good product? and also taking them on an empty stomach which I think helps?

 

[Wayne]

@Wayne, did you ever give the BCAAs a try using something besides the Nutricost brand, which I don't think is a good product? and also taking them on an empty stomach which I think helps?

Hi @Mary, I actually ordered the product you recommended a couple weeks ago. I initially took a single 1 gram capsule, and felt I noticed a slight "uplift". So I took another one 2-3 hours later. I then noticed some increased energy, and also definitely improved brain function.

So.... I threw caution to the wind, and took a 3rd capsule another 2-3 hours later. That kind of got my system "churning" a bit (as you can can guess--I overdid it). I remember feeling energized for the rest of the day. But then I seemed to be crashed a bit the next day (PEM I'm presuming).

So I stepped back, gave it a few days, and then started taking 1 capsule first thing in the morning. I didn't notice a lot, so I started adding another capsule in the evening. I still can't say whether or not it's making a difference. But my strategy is to keep upping it incrementally until I start getting a better sense of what it's doing.

As much as I know it's a good idea for me to start things incrementally, I've also found value in taking a good shot of something when I'm first trying it out, just to get a sense of how my body my react. So I got that initial take that it definitely did some good things, and I'm now settling into my more methodical approach. I think both these approaches have their merits, would you agree?

 

[hapl808]

So.... I threw caution to the wind, and took a 3rd capsule another 2-3 hours later. That kind of got my system "churning" a bit (as you can can guess--I overdid it). I remember feeling energized for the rest of the day. But then I seemed to be crashed a bit the next day (PEM I'm presuming).

The problem I've had with almost any intervention that allows me to do more is that it doesn't stop the crash. I took modafinil once (very low dose) and felt much less brain fog for 3-4 hours, but then had a 3-4 day crash.

I have the exact same BCAA and I take it sometimes, but honestly I've never noticed a difference. I might revisit at a higher dosage as usually I've only taken 1g-3g at a time, so maybe a 5g daily dosage would move the needle. It's a big bottle and I've noticed no negative effects, so probably worth trying.

Amino acids can be weird. I tried taurine in various dosages as it seemed to let me do slightly more, but it also seemed to make my crashes slightly worse (presumably just from doing more). I ended up stopping that. Glycine helps me a bit when my HR is elevated even more than usual. And so forth.

 

[Wayne]

Amino acids can be weird.

I agree, I've seen numerous accounts of how seemingly innocuously small amounts of just about any amino acid can cause quite a disruption for some people. But most amino acids seem to have a lot of potential as well, as evidenced by @ljimbo423 and @Mary's accounts of using BCAAs.

The amino acid I'm currently diligently trying to get my hands on so I can give it a try is Acetyl-DL-Leucine (ADLL) which is somewhat connected to BCAAs. I can't help but wonder whether people who do well with BCAAs might do even better by adding ADLL.

It's an amino acid specially formulated to cross the blood brain barrier, and has been used successfully and extensively in Europe since the 1950's for many of the health issues people with ME/CFS deal with. It's not available in the U.S., so I've spent the morning trying to figure out a way to have a forwarding company ship it to me from France (where it originated and where it's currently produced).

Below in the link is an overview of ADLL that I made up for my chiropractor, who specializes in brain concussions and associated balance and vertigo problems associated with them. He was astounded he'd never heard of this before, and immediately saw the huge potential for his patients. It's a reasonably priced supplement, and I'm planning on buy a good amount so I can give it a good try.

Spoiler: Acetyl-DL-Leucine Overview

Acetyl-DL-Leucine (ADLL): Neurostabilization and Clinical Potential

What is ADLL?

ADLL stands for acetyl-DL-leucine, a synthetic derivative of the essential amino acid leucine. It contains a racemic mixture of D- and L-enantiomers.

Originally developed in France, it is available by prescription and OTC under the brand name Tanganil for the treatment of vertigo and vestibular dysfunction. (Since 1957).

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Mechanism of Action

Unlike sedative medications, ADLL does not act on GABA receptors. Instead, it stabilizes neuronal membrane potentials, particularly in the cerebellum and brainstem.

This allows for improved sensory integration, balance, and neural signaling without sedation or cognitive dulling.

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Blood-Brain Barrier Permeability

A critical feature of ADLL's effectiveness is its ability to cross the blood-brain barrier efficiently.

The acetylation of leucine improves its lipophilicity, enabling it to enter the central nervous system in active form.

This property distinguishes it from many other amino acid derivatives and is likely a key factor in its clinical efficacy, especially for conditions involving brainstem, cerebellar, and cortical dysfunction.

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Neurological Applications and Evidence

• Ataxia: Studied in hereditary ataxias and Niemann-Pick type C, improving coordination, motor control, and mobility.
• Gait and Balance: Improves postural control and cerebellar function in clinical settings.
• Stroke Recovery: Anecdotal reports suggest benefit in restoring coordination and sensory integration post-stroke.
• Long COVID and ME/CFS: Users report improvement in brain fog, post-exertional fatigue, and dysautonomia.
• Vestibular Disorders: Widely prescribed in France for acute and chronic vertigo of both central and peripheral origin.
• Cognition and Sleep: Anecdotal reports describe improved mental clarity, working memory, and sleep quality, particularly in individuals with central hyperarousal or neuro-fatigue.

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Chiropractic and Functional Neurology Relevance

ADLL may complement neurostructural, chiropractic, and functional neurology approaches by:

• Supporting neuroplasticity
• Dampening maladaptive reflex arcs
• Enhancing CNS resilience and regulation

Its non-sedating action makes it especially useful alongside therapies that aim to reactivate intrinsic nervous system regulation.

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Reported Benefits (Clinical and Anecdotal)

• Reduced brain fog and mental fatigue
• Improved coordination and balance
• Enhanced cognitive clarity and working memory
• Better sleep onset and continuity
• Lower sensory overload and postural instability
• Support during benzodiazepine withdrawal recovery

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Safety and Access

• Well-tolerated, with minimal side effects
• Not associated with dependence or sedation
• Prescribed in France as Tanganil (500 mg), typically 2–3 times daily
• May be available for personal-use import via international pharmacies, depending on local regulations

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Suggested Search Terms
To learn more, search:

• "acetyl-DL-leucine"
• "Tanganil"
• "acetyl-D-leucine"
• "neurological amino acid treatment"
• "non-sedating vestibular modulator"

 

[Mary]

As much as I know it's a good idea for me to start things incrementally, I've also found value in taking a good shot of something when I'm first trying it out, just to get a sense of how my body my react. So I got that initial take that it definitely did some good things, and I'm now settling into my more methodical approach. I think both these approaches have their merits, would you agree?

I think I agree You did initially start low, which I think is very smart and then sort of gradually increased and now are trying to find your sweet spot. I remember when I first started B1 - I think I took 100 mg, it's a little hard to remember exactly how much - but it gave me such a marked boost in energy, followed by such severe fatigue, I can't fathom how I would have felt if I had started with a higher dose!

 

[Mary]

The problem I've had with almost any intervention that allows me to do more is that it doesn't stop the crash. I took modafinil once (very low dose) and felt much less brain fog for 3-4 hours, but then had a 3-4 day crash.

I have the exact same BCAA and I take it sometimes, but honestly I've never noticed a difference. I might revisit at a higher dosage as usually I've only taken 1g-3g at a time, so maybe a 5g daily dosage would move the needle. It's a big bottle and I've noticed no negative effects, so probably worth trying.

Yeah, BCAAs don't stop or prevent a crash for me, but they cut my PEM recovery time by more than half. And I think give me a little more energy, but I still crash like clockwork if I exceed my energy envelope. I still remember how it felt the first time my crash started lifting the same day it hit - it felt like a miracle, I couldn't believe it was happening. Usually my fatigue would steadily worsen throughout the day and evening of day 1, until you can't imagine tolerating any more, and very gradually the next day starting to lessen but oh so slowly and day 3, somewhat better but still going slow as molasses.

So getting it over with in one day is huge and worth taking the BCAAs for me. I've found I have to take them every day. I never get over my need for them.

 

[Mary]

The amino acid I'm currently diligently trying to get my hands on so I can give it a try is Acetyl-DL-Leucine (ADLL) which is somewhat connected to BCAAs. I can't help but wonder whether people who do well with BCAAs might do even better by adding ADLL.

Hi again @Wayne - I forgot about this and just saw the other thread where you wrote about it, and now I am very curious about it! If you manage to get your hands on some, please let me know, I may want to get some as well, and also will be very curious to see how you react! Thanks