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Tryptophan and IDO Trap Theory

LaurelB

Senior Member
Messages
139
I am sure this has been discussed elsewhere, but I had trouble finding the answer. My doctor recently suggested an amino acid blend which has tryptophan in it. My question is, is that a concern given the IDO trap theory of high tryptophan/low kynurenine in ME/CFS? Does anyone know of an amino acid blend (besides BCAAs) that does not have tryptophan? Thanks for any input.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
Your response to amino acids will be specific to you. If eating a meal high in amino acids makes you feel worse, you'll need to test the acids separately. TRP made my ME symptoms worse early in my ME; proline made me feel worse a year or so ago (thankfully that passed).

My opinion is that if a normal high-protein meal doesn't make you feel better, a packaged blend probably won't either. If you really need one amino acid at a much higher rate than the others, a blend won't help.

A wild guess: the amino acid blend is your doctor's answer to "feeling fatigued". Well, PWME aren't fatigued, we have something that seems somewhat similar to normal fatigue, but has a different mechanism, so the normal fatigue treatments are generally worthless.
 

LaurelB

Senior Member
Messages
139
Thank you for your reply. My doctor's suggestion is due to the fact I'm bedridden with ME and have been for years, and thus have a lot of muscle atrophy. She feels I need as much help as I can get to prevent further atrophy, especially since I can't exercise or move much. I expressed concern about tryptophan in relation to the IDO trap (which she is aware of) but she feels I need some kind of amino acid blend regardless. I was wondering if Dr. Phair had ever mentioned if this was a bad idea or not. I've taken amino acid blends in the past with no change in symptoms, but now that I'm aware of the IDO trap theory, I just don't want to take something that could further that problem (assuming the theory holds true).
 

BrightCandle

Senior Member
Messages
1,147
If they haven't helped in the past they probably wont now but it likely wont hurt. I was concerned about it for a while based on the IDO trap theory but Trypothan and amino acids generally don't have anything but a positive impact for me and it makes me think that the theory is wrong or our intake doesn't matter. Some people have very strong reactions to glutimate but your milage will vary.

Rather than BCAA+ powders the other option is something like Whey protein isolate. Pretty much anyone will tolerate the isolate form even if lactose intolerant and it wont kick off the soya/pea protein intolerance of the vegetarian protein powders but it too will put protein into your body which can aid your muscles.

Based on what we know about ME/CFS burning protein for energy there is a decent chance that with time this might give you a bit more energy, it does usually for me.
 

Judee

Psalm 46:1-3
Messages
4,461
Location
Great Lakes
Some people here really do well with the BCAA and the amino blends. I'm one that doesn't.

For me I think it makes an excess of ammonia in my muscles and I get really bad burning cramps especially in my neck, shoulders and down my spine within a very short time after taking them.

The last time I tried it was a couple days of misery. Ornithine, which is supposed to lower ammonia, did counter the reaction by about 60% but still the remaining discomfort lingered.

I don't have any issues with eating meat though but that's typical for me. Often, I've found that when I can't take a supplement to get a nutrient, I can usually tolerate it in food form as long as I don't have an allergy or sensitivity to that particular food.

Like Wishful said, everyone's reaction will be different. Mary's posts on BCAA's make it sound like she gets a boost from them.
 

LaurelB

Senior Member
Messages
139
Thanks for the comments, everyone. I generally don't have problems with amino acids and have taken them before. It's just now that I know about the IDO trap theory, I am concerned that, if it proves true, then I could be slowly making that trap/imbalance worse over time, and I'm wondering if he ever spoke about that at all.
 

LaurelB

Senior Member
Messages
139
Thank you so much! That was very helpful. Especially this quote: "Our concern about Trp supplements is not about the fate of trapped cells; we are just worried that you could push more cells into the trap and make the disease worse. "
 
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Mary

Moderator Resource
Messages
17,335
Location
Southern California
@LaurelB - why are you excluding BCAAs from consideration? They've made a huge difference for me, cutting my PEM recovery time by more than half, and have done so for I think 8 years (I'm losing track!) When I get low in them, I start to backslide very quickly. And a high protein diet does not have the same effect. I've eaten lots of protein for many years but protein never touched my PEM. Here are a couple of articles which discuss how BCAAs help offset our excess tryptophan:

A Brief but Updated Scientific Look at the "F" Word: Fatigue (ncf-net.org)
Chronic Fatigue Syndrome -- Part II (dynamicchiropractic.com)
Amino acids and central fatigue - PubMed (nih.gov)
Role for Branched-Chain Amino Acids in Reducing Central Fatigue | The Journal of Nutrition | Oxford Academic (oup.com)

If your doctor hasn't already done one, I'd ask her to do an amino acid test which will show what amino acids you may be deficient in. This is how I started taking BCAAs - an amino acid profile showed low leucine (very abnormal I've read) and borderline high tryptophan. This I think would help guide you and your doctor in what to do here.
 

LaurelB

Senior Member
Messages
139
Oh, I'm not excluding BCAAs at all. I was on them and plan on going back on them. It's just that my doctor felt I needed a more complete amino acid blend. But I'm wary of taking anything with tryptophan, so was asking if there are any blends that exclude trypto (besides BCAAs, which I was already on). Sorry I was not clear.

I did have an amino acid test many years ago, but perhaps I should do so again.
 

JES

Senior Member
Messages
1,320
Thank you so much! That was very helpful. Especially this quote: "Our concern about Trp supplements is not about the fate of trapped cells; we are just worried that you could push more cells into the trap and make the disease worse. "

The metabolic trap theory is still at hypothesis stage along with a hundred or more other hypotheses of possible mechanisms behind ME/CFS. Whilst I found the metabolic trap hypothesis interesting, Phair has recently been looking at something called the itaconate shunt and I have a feeling this wouldn't be the direction they are heading in if they are so confident in the metabolic trap hypothesis.

It would probably make sense to avoid tryptophan if real life ME/CFS was as simple as the metabolic trap hypothesis, but I feel that's rather or very unlikely. You get a certain amount of tryptophan from diet as well either way and eliminating that is difficult. I had a bad reaction to 5-HTP form of tryptophan, but got none of those same negative side effects from plain tryptophan.
 

LaurelB

Senior Member
Messages
139
Thanks. I'm aware of Phair's itaconate shunt theory and watched his most recent video on it. I could be wrong but my understanding from his first presentation is that the itaconate shunt theory helps to also explain the metabolic trap theory; it doesn't preclude it. I do realize these are both just hypotheses among hundreds that may not prove to be true. However, I have been bedridden for over 20 years and have tried 100s of different medications and supplements in that time, most of which made me worse and not one of which has ever helped. So I am very cautious in taking anything that may worsen my condition right now. The amino acid complex my doctor originally suggested had a daily serving of 5 grams of tryptophan (much more than you would get from food). It just doesn't seem worth the risk to me until we have a better answer on whether this theory may pan out or not. Upon reading more about the theory, my doctor has since agreed. We will stick with BCAAs for now.
 
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Messages
600
Anyone know anything about the OMF kynurenine clinical trial? They had it on their web page for a long time but now its listed under "previous", indicating that this trial is done. Are they not going to release a paper on this, doesnt matter if it failed i just want to know whats going on...
 

pattismith

Senior Member
Messages
3,931
Some people here really do well with the BCAA and the amino blends. I'm one that doesn't.

For me I think it makes an excess of ammonia in my muscles and I get really bad burning cramps especially in my neck, shoulders and down my spine within a very short time after taking them.

The last time I tried it was a couple days of misery. Ornithine, which is supposed to lower ammonia, did counter the reaction by about 60% but still the remaining discomfort lingered.

Did you try Arginine + Citrulline supplementation? This is recognized ammonia detox is some diseases like Urea Cycle disorders and Mitochondrial diseases;

Here what they do in French Hospitals:

1680637644296.png

Diapositive 1 (aphp.fr)
 

Judee

Psalm 46:1-3
Messages
4,461
Location
Great Lakes
Did you try Arginine + Citrulline supplementation

Yeah, I have tried them. I can take Arginine in a combo supplement with the Ornithine but don't do well on the Citrulline or the Arginine as a sole ingredient supplement.

This supplement seems to help me the best for clearing ammonia and w/o side effects: https://www.swansonvitamins.com/p/swanson-condition-specific-formulas-ghr-essentials-120-caps

Edit: I keep also wanting to try sodium benzoate as @BrightCandle said he also thought it reduced ammonia.
 
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pattismith

Senior Member
Messages
3,931
Yeah, I have tried them. I can take Arginine in a combo supplement with the Ornithine but don't do well on the Citrulline or the Arginine as a sole ingredient supplement.

This supplement seems to help me the best for clearing ammonia and w/o side effects: https://www.swansonvitamins.com/p/swanson-condition-specific-formulas-ghr-essentials-120-caps
the medical therapy for UCD /hyperammonemia is Arginine/Citrulline 1/1 ratio of, did you try a combo of these two?

Arginine-Citrulline Sustain™ , 120 Tablets - Jarrow Formulas

...
 

Judee

Psalm 46:1-3
Messages
4,461
Location
Great Lakes
the medical therapy for UCD /hyperammonemia is Arginine/Citrulline 1/1 ratio of, did you try a combo of these two?

Arginine-Citrulline Sustain™ , 120 Tablets - Jarrow Formulas

I'm a little nervous to try because I don't remember the reactions I had to them individually (something to do with my heart or bp or reynauds iirc) but next time I'm feeling like I have too much of a build up of extra ammonia (usually because of burning spinal muscles or because of a migraine) I will try to remember to test it and see.
 
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