BCAAs reducing PEM

[Mary]

I've found the brands vary wildly. It can be hard to get good ones.

Yeah, they do vary. I pretty much stick with one brand for BCAAs, optimum nutrition. I’ve been buying it on Amazon for many years and it’s consistently good. A couple of times I’ve tried to go with something cheaper and it’s never worked out.

 

[bad1080]

I've found the brands vary wildly. It can be hard to get good ones.

what's the difference and how do you tell them apart?

 

[Mary]

@L'engle - one more thing about buying good BCAAs - I said above that I've been buying Optimum Nutrition brand BCAAs for many years on Amazon, and it's consistently good. However, one time after buying it on Amazon I noticed thereafter that I started to go downhill - crashing easier, taking longer to recover. I contacted Amazon, fearing I'd received a counterfeit product and Amazon had me contact the manufacturer (Optimum Nutrition), which requested a picture of the batch code I believe, and it turned out that it was counterfeit - it wasn't their number - and Amazon refunded my money. Since that time, I've been careful (when I remember to do it! ) to make sure that the seller is either Amazon or Optimum Nutrition, which I think is pretty safe, instead of one of those oddball sellers you've never heard of before.

 

[Mary]

what's the difference and how do you tell them apart?

I've found a brand that works for me and I stick with it - Optimum Nutrition. See my post above about buying it on Amazon.

There are other good brands and the only way I know to tell if they're effective is to try them. Generally if something is a lot cheaper, it's not been good - it doesn't help me the way Optimum Nutrition brand does. And if something is equally good as ON, it's usually about the same price.

 

[Wayne]

Hi @Mary -- Have you by any chance ever tried Nutricost brand? I just noticed I've purchased it four times since 2019. I've been meaning to give this a try again (I have product right now), but the taste has been a deterrent. Plus, I can't say that I've noticed anything significant--though it's now been months at least since I last tried it.

I think I'll try this Nutricost again, and try to pay closer attention to how it affects me. I don't know that I've tried it on an empty stomach like you described in one of your recent posts. Also, do you do a flavored kind, or have you discovered a way to get past the pretty awful taste? -- BTW, that was some pretty serious sleuthing you did discovering that counterfeit batch!

 

[L'engle]

what's the difference and how do you tell them apart?

I just don't get any benefit from taking them, even in larger quantities. A single capsule of NOW brand gives me a noticeable improvement in physical energy. An entire scoop of the other brand I tried (PVL) didn't do much.

 

[Mary]

Hi @Mary -- Have you by any chance ever tried Nutricost brand?

I did buy it once according to Amazon, though I don't remember doing it. Nutricost is one of the cheapest brands that I've seen, so I am guessing that my one-time purchase of Nutricost BCAAs was not a good experience. I wouldn't try this brand again. And I almost always buy BCAAs in capsule form. I take so many supplements and it would be too much work to dissolve them, so taste is not an issue for me.

So again, I recommend the Optimum Nutrition BCAAs. They cost more, but they work. I seriously doubt if the Nutricost product would be as good. I wouldn't spend the money on them.

About taking them on an empty stomach - I've read many places that it's best to take amino acids on an empty stomach and here's what your favorite source (AI ) has to say about this: https://www.google.com/search?q=ami...wQxOS42uAfAEMIHBjAuMjMuMsgHMg&sclient=gws-wiz

If you really want to give them a fair try, I would make sure to use a known good brand AND to take enough of it AND to take it on an empty stomach.

 

[datadragon]

Glutamine limits NLRP3 inflammasome activation​

https://pubmed.ncbi.nlm.nih.gov/40296302/

See here for more to understand
https://forums.phoenixrising.me/threads/your-experience-with-hbot.93182/post-2480465

Also from that study, We further observed reduced generation of endogenous itaconate by glutamine deprivation and verified that both exogenous supplementation of itaconate derivative and increased endogenous itaconate production by overexpressing immune-responsive gene 1 [IRG1; also known as aconitate decarboxylase 1 (ACOD1)] could replace glutamine to inhibit the NLRP3 inflammasome.

This is the same Itaconate/ACOD1 Dr Phair had been discussing. See my post here for additional info

https://forums.phoenixrising.me/thr...possible-treatment-for-cfs.37244/post-2451853

 

[Mary]

@datadragon - what does your above post have to do with BCAAs reducing PEM? Could you explain in simple language for lay people like me?

 

[datadragon]

@datadragon - what does your above post have to do with BCAAs reducing PEM? Could you explain in simple language for lay people like me?

started taking BCAAs - the product I took also had glutamine added (http://www.iherb.com/MRM-BCAA-G-600...lc=en-US&w=mrm bcaa g 6000&rc=30&sr=null&ic=1) and within a couple of days my energy increased and then I recovered from a crash some 20 hours sooner than I typically do

Hi Mary, you mentioned the added glutamine. NLRP3 activation would naturally have led to increase of ER Stress, WASF3 levels and Exercise Intolerance/PEM. NLRP3 increases IL-1b/IL-6, INF-y which leads to that WASF3 increase. Glutamine inhibits the nlrp3 activation and subsequent Inf-y and pem/exercise intolerance. Just showing why it was generally working and more to learn how me/cfs is caused and potentially treatable.

 

[Mary]

Thanks @datadragon - actually I only took the product that had glutamine added in for a relatively short time as it started contributing to insomnia (!) I haven't taken glutamine for many years now, but the BCAAs still limit my PEM to one day, as long as I don't seriously overdo it.

 

[Viala]

Hey @Mary, I took BCAAs for a while and noticed that they helped a lot with my cognitive PEM, but after taking them for a month even small doses make me very sleepy so I stopped. Recently I tried it again and I still can't take them, which is a shame because it is obvious that they are helping. Do you know what can be causing this reaction?

 

[Mary]

Hi @Viala - I think usually the opposite tends to happen - if they're taken late in the day, they're known to interfere with sleep.

I wonder - are there are any other ingredients in the product you take? e.g., any flavoring, or other amino acids you might be reacting to? How much were you taking?

And if they seem "pure" without unnecessary additives, do you think you could take them at night? Maybe they could still help cognitively and help you sleep too.

I just googled "bcaa makes me sleepy" and here is what AI said: https://www.google.com/search?q=bcaa+makes+me+sleepy&sca_esv=b5fad06473769e67&sxsrf=AE3TifPLjfz3Azq6zqFI5sD2vUpy9Uwf1A:1753454591089&source=hp&ei=_5eDaJCkA_a3qtsPusT18AY&iflsig=AOw8s4IAAAAAaIOmD5BiaQ10YvUf_6EhTIq8ezEd4rMz&oq=bcaa&gs_lp=Egdnd3Mtd2l6IgRiY2FhKgIIAjIEECMYJzINEAAYgAQYsQMYQxiKBTIKEAAYgAQYQxiKBTINEAAYgAQYsQMYQxiKBTINEAAYgAQYsQMYQxiKBTINEAAYgAQYsQMYQxiKBTINEAAYgAQYsQMYFBiHAjIKEAAYgAQYQxiKBTINEAAYgAQYsQMYQxiKBTIIEAAYgAQYsQNI9S9QAFioE3ACeACQAQGYAZ0CoAGoCaoBBTQuMi4yuAEByAEA-AEBmAIJoAKDCMICChAjGIAEGCcYigXCAgoQLhiABBgnGIoFwgILEAAYgAQYkQIYigXCAgoQLhiABBhDGIoFwgIOEC4YgAQYsQMYgwEYigXCAg4QLhiABBixAxjRAxjHAcICERAuGIAEGLEDGNEDGIMBGMcBwgIHECMYsQIYJ8ICDhAAGIAEGJECGLEDGIoFwgIKEAAYgAQYsQMYCsICBxAAGIAEGArCAgoQLhiABBjlBBgKwgIFEAAYgATCAgsQABiABBixAxiDAcICCxAuGIAEGMcBGK8BwgIIEC4YgAQY5QTCAhMQLhiABBixAxjRAxhDGMcBGIoFwgIREC4YgAQYsQMYgwEYxwEYrwGYAwCSBwc1LjMuMC4xoAe4WLIHBzMuMy4wLjG4B_QHwgcHMC4xLjcuMcgHOA&sclient=gws-wiz

If BCAAs block tryptophan's entry into the brain, it can lead to reduced serotonin production, which might result in sleepiness or fatigue in some individuals.

I think actually this is the mechanism which causes BCAAs to help with energy for many persons with ME/CFS - their interference with tryptophan in the brain: https://pubmed.ncbi.nlm.nih.gov/11310928/

I think you are having the opposite reaction of most people - but maybe you could try them at night and see what happens - if you're lucky, they'll help with cognitive PEM AND sleep!

ETA: or maybe try increasing serotonin? I take 5-htp (100 mg.) at night before bed and it helps with sleep but maybe you could try it in the morning . . . just throwing out ideas here!

 

[Viala]

@Mary Thanks! I took my BCAAs in the early afternoon and tryptophan in the evening, I never tested taking BCAA before sleep, I will try that

The capsules are 500mg and the only ingredient is stearic acid, so it should be fine. I didn't take more than 2 capsules, I remember that you take higher amounts. This sleepiness started to happen after one month, before that BCAAs worked like a charm. I could focus on instructional videos for many hours, it was almost like before ME, I could read for many hours, and then one day half an hour after taking them I couldn't keep my eyes open, even on 160mg. I think BCAAs are important, need to figure this out.

I wish some supplements would work exactly the same on all of us, no paradoxical reactions, and here's yet another mystery to be solved.

 

[datadragon]

Thanks @datadragon - actually I only took the product that had glutamine added in for a relatively short time as it started contributing to insomnia (!) I haven't taken glutamine for many years now, but the BCAAs still limit my PEM to one day, as long as I don't seriously overdo it.

You could first see if glutamine by itself rather than bcaa does better for you with the pem based on mechanism of action to ultimately lower wasf3, inf-y and pem. it’s good to now know that many of the things people had mentioned regularly as contributors such as infection, Heavy exercise, high glucose and fructose, er stress I found all happen to converge to be able to increase inf-y and wasf3 levels. This leads to the pem and exercise intolerance.

https://www.healthrising.org/blog/2023/08/16/nih-mitochondria-chronic-fatigue-syndrome/

https://forums.phoenixrising.me/threads/your-experience-with-hbot.93182/post-2480465

If BCAAs block tryptophan's entry into the brain, it can lead to reduced serotonin production, which might result in sleepiness or fatigue in some individuals.

I think actually this is the mechanism which causes BCAAs to help with energy for many persons with ME/CFS - their interference with tryptophan in the brain: https://pubmed.ncbi.nlm.nih.gov/11310928/

BCAA (Branched Chain Amino Acids) leucine, isoleucine, and valine can restore orexin levels after brain injury[6].​

Orexins are activated by high protein diets [4]. The top three aminoacids that activate orexins are glycine, aspartate and cysteine [5].​

This can either lead to lowering of er stress and then wasf3 or lowering of glucose and then wasf3.

https://pubmed.ncbi.nlm.nih.gov/33576468/
https://forums.phoenixrising.me/threads/lion-diet.89555/post-2438991
https://www.bensnaturalhealth.com/blog/diabetes-health/l-leucine-supplements-for-diabetes/

https://forums.phoenixrising.me/threads/eating-sweets-exhausts-me.91481/post-2452529
https://forums.phoenixrising.me/thr...nfa-itaconate-shunt-part-2.89388/post-2438998

 

[Mary]

You could first see if glutamine by itself rather than bcaa does better for you with the pem based on mechanism of action to ultimately lower wasf3, inf-y and pem

I did take glutamine on its own several years ago (in addition to the BCAAs) - but - it caused insomnia so I had to stop taking it. I think it did help with energy a little bit, though it did not stop PEM. But - I've had trouble with insomnia for over 20 years. I can't take supplements or drugs which make it worse, and glutamine ended up making it worse for me. Glutamine is a precursor for both glutamate and GABA and it seems to be a crapshoot whether it's going to make sleep better or worse.

 

[datadragon]

I did take glutamine on its own several years ago (in addition to the BCAAs) - but - it caused insomnia so I had to stop taking it. I think it did help with energy a little bit, though it did not stop PEM. But - I've had trouble with insomnia for over 20 years. I can't take supplements or drugs which make it worse, and glutamine ended up making it worse for me. Glutamine is a precursor for both glutamate and GABA and it seems to be a crapshoot whether it's going to make sleep better or worse.

As you apparently got more energy from methylene blue which is another of many that inhibits nlrp3 just a couple below for example, perhaps that or another nlrp3 inhibitor would work was the thought. Look up supplement + nlrp3 in future. Glutamine during the day giving insomnia if that is what you tried or wish to try again without bcaas alone this time as a test reminds that sometimes it can have multiple effects to consider.

Many in vitro and in vivo studies have proved that melatonin alleviates NLRP3 inflammasome activity via various intracellular signaling pathways. Another I remember you tried https://pmc.ncbi.nlm.nih.gov/articles/PMC8300798

hyperbaric oxygen therapy alleviates the activation of NLRP3 inflammasome​

https://pmc.ncbi.nlm.nih.gov/articles/PMC5646971/
methylene blue also inhibits the NLRP3 inflammasome activation by the way. https://www.nature.com/articles/s41598-017-12635-6

Riboflavin vitamin b2 inhibits nlrp3
https://www.nature.com/articles/s41598-020-76251-7

Butyrate lowers nlrp3,, propionate, acetate increases
https://www.sciencedirect.com/science/article/pii/S2213231718300247

Far infrared radiation (as found in PEMF mat from what I read possibly the device you tried also) inhibited the NLRP3 inflammasome as well also apparently so these all have similar mechanism of action. https://pubmed.ncbi.nlm.nih.gov/26864306/

Ketamine is one of many that may work for ME/CFS due to inhibition of NLRP3 https://pubmed.ncbi.nlm.nih.gov/35925279/ as well as mentioned some benefit to restore impaired myelination https://forums.phoenixrising.me/thr...ic-fatigue-syndrome.91144/page-3#post-2451679

NAC has been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. NAC has been used to replenish glutathione stores and increase the proliferative response of T cells - N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH). https://www.sciencedirect.com/science/article/pii/S0306987720308811 https://pubmed.ncbi.nlm.nih.gov/32504923/

Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation - NLRP3 Inflammasome activation is limited by Exogenous GSH (Glutathione) and augmented in the presence of GSTO1-1 which suggests deglutathionylation as a possible process required for NLRP3 activation. https://www.cell.com/cell-reports/pdf/S2211-1247(19)31127-1.pdf. So maybe S-Acetyl L-Glutathione

Azithromycin accelerated NLRP3 transcript decay https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-017-0608-8.pdf

Palmitoylethanolamide PEA, doxycycline, and colchicine which all inhibit the NLRP3 inflammasome that have shown benefits may be effective.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8472716/
https://pmc.ncbi.nlm.nih.gov/articles/PMC8466018/

https://pmc.ncbi.nlm.nih.gov/articles/PMC10013297/
Suramin happens to be another NLRP3 inhibito
Consistently, apyrase (extracellular ATP scavenger), suramin (P2 receptor inhibitor), TNP-ATP (P2X receptor antagonist), and 5-BDBD (P2X4 inhibitor) downregulate NLRP3 expression https://www.nature.com/articles/s41401-022-00886-7

Zinc deficiency activates nlrp3 and er stress but would need to try chelated zinc like solgar chelated zinc.
https://www.nature.com/articles/cddis2013547
Zinc deficiency evokes the endoplasmic reticulum (ER)-stress response https://pubmed.ncbi.nlm.nih.gov/23748779/
Zinc inhibits iNOS promoter activity. NF-kB silencing abolishes cytokine-induced iNOS expression. Zinc inhibits the transactivation activity of NFκB.https://www.sciencedirect.com/science/article/pii/S2213231714000834

P2X7 receptor (P2X7R) is required for secretion of IL-1, and can be blocked by divalent cations such as magnesium (Mg). We demonstrated that Magnesium sulfate is efficacious in blocking IL-1-mediated-inflammation in HUVECs via downregulation of P2X7Rs on HUVECs https://pubmed.ncbi.nlm.nih.gov/31493768/ epsom salt bath or foot soak or dr Clark makes pills for example

Anakinra is a bio-engineered form of the naturally occurring interleukin-1 receptor antagonist (IL-1ra) that blocks the action of interleukin-1. It is routinely used in patients with autoimmune and inflammatory disorders and MAS. Within the IL-1 family of cytokines, several inhibitory mechanisms are in place to prevent runaway inflammation induced by IL-1α or IL-1β. The main mechanism is the IL-1 receptor antagonist (IL-1Ra), which blocks the IL-1R1 and prevents binding of IL-1α and IL-1β. In contrast to JAKinibs, anakinra will not directly block the IFN-STAT1/STAT2 pathway critical for host defense against viral infections. Third, in contrast to tocilizumab (an IL-6 inhibitor), it targets and inhibits the core mechanism in the pathogenesis of MAS, namely the hyperactive inflammasome loop https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03166-0. This may block inf-y

 

[Mary]

@datadragon - methylene blue also gave me insomnia. Several things have boosted my energy but (1) either the effects don't last, or (2) they give me insomnia. Nothing has extended my energy envelope even though I may feel better before having to stop. My activity window is roughly 4 hours of light activity, so I'll feel better during those 4 hours with methylene blue and sometimes cellfood, glutamine, etc. but those 4 hours don't increase. And again, glutamine DURING THE DAY and methylene blue during the day also, at a very small dose, ended up giving me insomnia.

Nothing has defeated PEM for me. The only thing that has affected PEM at all are BCAAs, which decreased my PEM recovery from 2 - 3 days to 1 day.

 

[datadragon]

methylene blue also gave me insomnia. Several things have boosted my energy but (1) either the effects don't last, or (2) they give me insomnia.

You could see if the specific form magnesium sulfate helps alone based on what you posted or when insomnia is present, either epsom salt bath or pill since you also mentioned it being potentially low as well.
https://a.co/d/9RIBVId. Does a banana containing some vitamin B6 help insomnia or some p5p active form not pyridoxine form taken in tiny amount like a small portion of pill or capsule to get around rda level not big dose. It’s needed for glutamate to gaba. Vitamin B6 converts a small amount of the tryptophan in your body to niacin, or vitamin B3, and serotonin, a neurotransmitter that helps regulate sleep patterns. By failing to obtain an adequate amount of dietary vitamin B6 , the body's metabolism of tryptophan may be disturbed. This may limit the amount of serotonin in the body, potentially leading to disturbed sleep patterns and insomnia. Next can try solgar chelated zinc cut in like 1/4 tablet not entire tablet. Can try one at a time.

Nac maybe as it lowers nlrp3 but N-acetylcysteine (NAC) is known to modulate glutamate levels in the brain, which can help improve conditions related to glutamate dysregulation. It acts by restoring the balance of glutamate, so at least not increasing as the glutamine

 

[Mary]

@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.