BCAAs reducing PEM

Hip

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@Mary, I was doing some online research into isoleucine, which is one of the three amino acids in BCAAs, and I came across this interesting article on examine.com, which says:
[Isoleucine] is able to significantly increase glucose uptake and the usage of glucose during exercise
Leucine also appears to have this ability, but due to leucine stimulating a protein known as S6K (required for protein synthesis) leucine reduces its own efficacy by hindering insulin-stimulated uptake. In other words, while isoleucine and leucine both stimulate glucose uptake, leucine then shoots itself in the foot and hinders itself while isoleucine just acts in a predictable and linear manner.
So perhaps the isoleucine component in BCAA is the one that actually has the PEM-reducing effect: because if we assume that PEM involves blockages in energy metabolism, then isoleucine appears to be the BCAA which most helps support energy metabolism.

BCAA contains the amino acids leucine, isoleucine and valine in the ratio 2:1:1. So that means only 25% of your BCAA is isoleucine. So if it is the case that isoleucine is doing all the anti-PEM work, the other aminos might not offer much benefit.

So it's possible you might get more bang for your buck by using pure isoleucine, in place of BCAA.



The reason I was researching into isoleucine is because I just discovered it stimulates the release of certain antiviral and antibacterial compounds in the body called beta-defensins. These beta-defensins have been shown effective against the enteroviruses and herpesviruses found in ME/CFS. So it possible that isoleucine supplementation may have a useful antiviral effect for ME/CFS patients.

Thus isoleucine potentially may have two beneficial effects in ME/CFS: improving energy metabolism as well as having some antiviral effects.
 

Mary

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So it's possible you might get more bang for your buck by using pure isoleucine, in place of BCAA.
@Hip, that's so interesting! Thanks so much for tagging me. :thumbsup: Right now is not a good time for me, but sometime soon I'll do an experiment and just see if isoleucine alone makes a difference. Or I might stick with the BCAAs but then add in extra isoleucine to see if it helps. I'm afraid to change it much because the BCAAS made such a big difference for me! :sluggish:

There is one other thing though about the possible mechanism of action of BCAAs, and that is the effect of BCAAs on tryptophan in the brain.

In a nutshell, these researchers proved that by inhibiting the L-system transporter, experiments verified that BCAA's and/or BCH suppressed the uptake of tryptophan thereby alleviating fatigue in the central nervous system and thus improved endurance capacity in the animals tested
http://www.ncf-net.org/forum/Fword.htm

http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=41341

Studies in human subjects have shown that the plasma ratio of free tryptophan/BCAA increases during and, particularly, after sustained exercise. This would favour the transport of tryptophan into the brain and also the synthesis and release of 5-HT which may lead to central fatigue. Attempts have been made to influence the 5-HT level by giving BCAA to human subjects during different types of sustained heavy exercise. The results indicate that ingestion of BCAA reduces the perceived exertion and mental fatigue during exercise and improves cognitive performance after the exercise.
http://www.ncbi.nlm.nih.gov/pubmed/11310928

http://jn.nutrition.org/content/136/2/544S.full

In any event, it's definitely worth looking into and a little self-experimenting! :nerd:
 

Hip

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sometime soon I'll do an experiment and just see if isoleucine alone makes a difference
I am going order some isoleucine for myself, as I am keen to try it.

Interestingly, that examine.com article may explain an odd phenomenon I noticed years ago when taking a different BCAA: leucine. I found that leucine, taken at a dose of around 5 grams daily, would produce an immediate benefit, and I'd feel slightly improved and energized within hours. Nothing spectacular, it was a mild general energy boost, but noticeable and welcome.

But after only around 2 or 3 days, I found those benefits would disappear, even though I would continue to take the same leucine dose daily. I never really figured out why. If I stopped leucine for a while, and then restarted it, I'd get the same phenomenon: a noticeable boost for the first day, but then it would disappear.

However, that article may explain the basis of this phenomenon, since it says that leucine stimulates energy production from glucose, but then leucine shoots itself in the foot, and hinders it own action.

Whereas it says isoleucine stimulates a sustained energy production from glucose, without hindering it's own action. So I am guessing isoleucine will provide me with the same energy boost I got from leucine, but without petering out the next day.



There is one other thing though about the possible mechanism of action of BCAAs, and that is the effect of BCAAs on tryptophan in the brain.
Yes, I guess that is another possible explanation for the benefits of BCAAs. I don't know much about this serotonin link to fatigue myself. When taking serotonin-boosting supplements like 5-HTP and high dose inositol, I have not seen any increase in fatigue. But I think the fatigue effect may involve serotonin being present in certain areas of the brain.
 
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Mary

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I am going order some isoleucine for myself, as I am keen to try it.
It is so worth a try - keep us posted!
I found that leucine, taken at a dose of around 5 grams daily, would produce an immediate benefit,
But after only around 2 or 3 days, I found those benefits would disappear, even though I would continue to take the same leucine dose daily. I never really figured out why. If I stopped leucine for a while, and then restarted it, I'd get the same phenomenon: a noticeable boost for the first day, but then it would disappear.
Something very similar happened to me with NADH. I remember the year it happened - 2004- it was so remarkable. A daily dose of 20 mg. (pricey but oh well) taken for about a week I think, suddenly gave me a great boost in energy and not only energy, but I stopped crashing for about 10 days. In other words, I could do as much as I wanted without crashing. It felt like a miracle. And then, after about 10 days, it just stopped. I tried it off and on again for several years but never got that benefit again and could never figure out why. Something similar happened to me with l-carnitine in 2002.

FWIW, I first became interested in BCAAs when my leucine was found to be low on Nutreval testing, and I was told that it was very unusual to have low leucine, just not a normal type of deficiency. I don't remember what my isoleucine levels were but I think I'll look them up just to see.

Anyways, I am definitely putting isoleucine next on my List of Things to Try! :)
 

ljimbo423

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@ljimbo423 - I thought you might find the posts by Hip above (#82 and #85 - the numbers are at the bottom of each post) very interesting - :nerd:
That's interesting that isoleucine increases glucose uptake and the usage of glucose during exercise. Looks like I've got some homework to do.:)

I thought it was helping by being used as fuel for the Krebs cycle, after the PDH enzyme. Allowing the mitochondria to work better and more ATP to be created.

Assuming Fluge and Mella are right about the PDH enzyme being inhibited by PDK's in ME/CFS.

Isoleucine might be helping in both ways. I'm really interested in how you and Hip do with the Isoleucine alone.

I've been thinking about trying it in addition to the BCAA's I take but it hasn't gotten past being just a thought yet!:)
 

ljimbo423

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I found that leucine, taken at a dose of around 5 grams daily, would produce an immediate benefit, and I'd feel slightly improved and energized within hours. Nothing spectacular, it was a mild general energy boost, but noticeable and welcome.
When I started taking BCAA's, I only noticed a slight increase in energy at 5-10 grams. At 10-15, the increase in energy was very clear.

At 20 grams a day, I felt like a different person it gave me so much energy but it gave me insomnia so I had to reduce the dose.

You might want to try a higher dose of Isoleucine to see if it works for you. Good luck with it!
 

Mary

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I've been thinking about trying it in addition to the BCAA's I take but it hasn't gotten past being just a thought yet!:)
That's my first inclination. I have personal things going on right now I have to deal with but I hope in a week or two to give the isoleucine a try. The BCAAs did boost my energy a little in the beginning, though I really can't remember if it lasted. But the chief benefit I got, and STILL HAVE, is that they cut my PEM recovery time in half. That hasn't changed in 4 years. However, the BCAAs did NOT increase my energy window - what I can do safely without crashing (all these energy variables!) Still pretty limited, but recovery time is much better.

Anyways, I think right now I would be too afraid of increasing my PEM recovery time if switched just to isoleucine, so will probably at first, any rate, just add some extra isoleucine. I'll have to do more reading too!
 

Hip

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At 20 grams a day, I felt like a different person it gave me so much energy but it gave me insomnia so I had to reduce the dose.
That's very interesting. 20 grams of BCAA would contain 5 grams of isoleucine. That's the isoleucine dose I will aim for; it will also be comparable to the 5 grams of leucine that I used to take.

I've just bought some isoleucine from purebulk.com; there's a 15% discount code operational at present: MILITARY15 which worked for me. It will take a couple of weeks to get to the UK though. I couldn't find any pure isoleucine for sale in the UK or Europe, so it seems like an unusual amino acid which is not often bought.