Community symposium on molecular basis of ME/CFS at Stanford Discussion Thread

[raghav]

@jaybee00 I gave the link so that you will have an idea of the prices of various generics available in India. You can try contacting some exported through Indiamart. Here is the link https://dir.indiamart.com/search.mp...e+injection+20+mgml&src=as-kwd:kwd=glatiramer I think one or more of these distributors will be willing to export to US. I dont know how the US customs will handle this. Regarding the pricing you can talk to them through phone and get a quote. As @junkcrap50 said it has to be kept refrigerated at all times till you use it. Anyway I am scared of the severe allergy that it can cause like shortness of breath and chest pain, which some sites say are common side effects.

 

[raghav]

@Rachel Riggs Do you have to take the drug on a daily basis? or is twice a week or so sufficient ? Did it relieve mental fatigue also ? Did you have any GI symptoms and did it help with those symptoms ? Sorry to bother you with too many questions.

 

[dreamydays]

I have started a low tryptophan diet: grapes, apple, pineapple, mandarin, carrot, gelatine based sweets (wine gums and marshmallow), some specialist low protein rice and biscuits, collagen and my guilty pleasure... non-alcoholic wine.

Too early to say, have also order IFN-g boosting tablets. Next step get a reliable importer for capoxone. I think its ok out of the fridge for 7 days.

 

[raghav]

IFN-g boosting tablet ? What brand is that ?

 

[dreamydays]

I should have said IFN-y which is Interferon Gamma. Its called Kagocel

 

[raghav]

Ok. thanks.

 

[raghav]

Can it be taken on a long term basis ?

 

[dreamydays]

It's used in Russia for cold and flu over the counter. I am not expecting it to be strong. They have an english website https://www.kagocel.ru/en/

 

[Moof]

@jaybee00 Anyway I am scared of the severe allergy that it can cause like shortness of breath and chest pain, which some sites say are common side effects.

I reckon you're wise to be worried about taking it unsupervised. Severe allergic reactions can kill people in just a few minutes, and as we've heard in a tragic UK case this week, Epi-pens don't always work. I realise it's possible to be severely allergic to almost anything, including usually harmless substances found in virtually every home – but taking a drug by injection that's known to cause allergies sounds particularly scary. I think I'd rather give the scientists time to do their research first...I so hope it does turn out to be helpful, though!

 

[Learner1]

I should have said IFN-y which is Interferon Gamma. Its called Kagocel

How do you know you need it? I recently had a cytokine test and mine was high...

 

[melihtas]

I have started a low tryptophan diet: grapes, apple, pineapple, mandarin, carrot, gelatine based sweets (wine gums and marshmallow), some specialist low protein rice and biscuits, collagen and my guilty pleasure... non-alcoholic wine.

If you don't have enough protein in your diet, your body will start wasting muscle and since your muscle contains a lot of tryptophan you won't achieve a low tryptophan diet. You will lose muscle for nothing.

To prevent muscle wasting you need to add beef gelatine (sweets are not enough) or BCAA and CLA amino acid blends into your diet.

Without tryptophan your serotonin levels will drop too, so I think taking 5-HTP might be a good idea.

 

[dreamydays]

I am having collagen powder which is essentially the same as beef gelatine, I might also add some BCAA. If my mood or sleep changes I will add 5-HTP. I have no idea if this is helping as I was already on an upward curve.

@Learner1 IFN-y induces IDO, so the idea is to try an push upward against the metabolic trap. I think most severe patients are already high in IFN-y. If it makes me feel worse I will discontinue immediately.

 

[Learner1]

I am having collagen powder which is essentially the same as beef gelatine, I might also add some BCAA. If my mood or sleep changes I will add 5-HTP. I have no idea if this is helping as I was already on an upward curve.

I am not 100% sure of all of the intricacies of all of this, but prior to ME/CFS, my tryptophan level was normal. I developed ME\CFS after being on high dose melatonin for 2 years and then 5-HTP for sleep, and my tryptophan level became high when all my other aminos were low.

@Learner1 IFN-y induces IDO, so the idea is to try an push upward against the metabolic trap. I think most severe patients are already high in IFN-y. If it makes me feel worse I will discontinue immediately.

I am not severe, but am mild/moderate. A
Diagnostics Solutions Cytokine Panel was fairly inexpensive and showed the high IFN-gamma... I'm a little gunshy of all of this right now, and think getting good data before going off and experimenting might be a prudent step, as if something goes wrong, you can at least know what the test conditions were before trying something else.

 

[Tally]

I thought one can't change intracellular tryptophan levels with diet?

prior to ME/CFS, my tryptophan level was normal.

Was that intracellular or in blood?

 

[dreamydays]

I don't think we know what will happen if a ultra low tryptophan diet is consumed. I am just hoping by not adding to intracellular levels then I might be able to clear some. If not I will just lose a few pounds of extra weight lol.

 

[frozenborderline]

If you don't have enough protein in your diet, your body will start wasting muscle and since your muscle contains a lot of tryptophan you won't achieve a low tryptophan diet. You will lose muscle for nothing.

To prevent muscle wasting you need to add beef gelatine (sweets are not enough) or BCAA and CLA amino acid blends into your diet.

Without tryptophan your serotonin levels will drop too, so I think taking 5-HTP might be a good idea.

I agree with the first part. Probably increasing proteins that are in gelatin and BCAAs is great. 5HTP is possibly dangerous. It could be somewhat benign to take once in awhile but taking it regularly could cause cardiac fibrosis

 

[GodGenghis]

@Learner1 IFN-y induces IDO, so the idea is to try an push upward against the metabolic trap. I think most severe patients are already high in IFN-y. If it makes me feel worse I will discontinue immediately.

Why do you suppose most severe patients are already high in IFN-y? I dont know much about such things. It just seems counterintuitive since IFN-y upregulateS IDO.

 

[junkcrap50]

My MS diagnosis was weak, I had very few lesions, all of which would resolve over time. Also, I noted that I was way sicker with much more diverse symptoms than those I knew with MS. The interesting thing to note is that there is no definitive diagnosis for MS, just as is the case with ME/CFS. It's a clinical diagnosis based on MRI's with space and time, and clearly mistakes are made. My point is that MS is not so different than ME/CFS in that way, yet the MS population is treated so much differently...

Do you know Rachel of any other CFS/ME patients who have taken Copaxone? And how they responded to it?

 

[keepontruckin]

I wonder if Copaxone could help with multiple chemical sensitivity. Rachel, if you had mcs, did you have a sense that it improved?

 

[nandixon]

The gene IDO2 does seem to be important, but you think this isn’t much to do with tryptophan?

I'm definitely not saying that. I'm saying that, if I understand the timeline correctly: Phair/the Ron Davis team noticed that the IDO2 gene might be a potential problem from the severely ill patients study. Phair then came up with the idea that a defective IDO2 might mean that tryptophan isn't getting properly catabolized if the tryptophan levels rise high enough to significantly inhibit the IDO1 enzyme - because there's not a working IDO2 enzyme as a backup. The team then did some tracer experiments that appear to show that indeed (intracellular) tryptophan levels are inappropriately increased and kynurenine decreased just as you'd expect. Bingo! So now they're thinking that the metabolic trap idea (i.e., an inhibited IDO1 with no IDO2 as backup) might very well be correct.

The possible problem, though, is that the Michaelis-Menten chart that Phair presented appears to indicate they may be giving IDO2 a much greater affinity (~200 μM) for tryptophan than what the literature is saying (i.e., ~7000 to 9000 μM). If that's true, then there’s likely no metabolic trap, per se, because even a perfectly working IDO2 enzyme isn't likely to help enough because its ability to catabolize tryptophan is so poor at physiological levels. But like I said previously, maybe I'm misinterpreting something.

IDO2 was only discovered in 2007, and at that time, if I remember correctly, it was thought it basically had the same function as IDO1, i.e., a (redundant) enzyme that catabolizes tryptophan. It's become apparent though, that it's role is much more likely to be immunomodulatory or regulatory (including with respect to IDO1). And that's consistent with its poor enzymatic ability (although it's possible that its true substrate hasn't been determined yet).

So IDO2 might very well be important with respect to tryptophan but, from what I can tell, probably indirectly and not by directly catabolizing it.