• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Metabolic Trap//Who got worse on l-tryptophan?

Martin aka paused||M.E.

Senior Member
Messages
2,291
They currently run a trial on the therapeutic effects of kynurenine, no reason to warn of it other than "there is insufficient evidence to recommend".

Assuming the IDO trap theory is correct, tryptophan would make things worse and enhance the IDO trap.
Hard to avoid taking it. But supplementing it seems to be bad then. Thank you!
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
I question now if a higher than normal serotonin level can be achieved with protein supplements like Whey (which helps me). Tryptophan is too little represented and the amino acids that use the same carrier (BBB) are too represented. So they should compete at the BBB. I assume that increased serotonin levels can only be achieved if tryptophan is taken in isolation and best consumed on an empty stomach, i.e. with an isolated intake and a quick portion. @nerd ?
 

nerd

Senior Member
Messages
863
I question now if a higher than normal serotonin level can be achieved with protein supplements like Whey (which helps me). Tryptophan is too little represented and the amino acids that use the same carrier (BBB) are too represented. So they should compete at the BBB. I assume that increased serotonin levels can only be achieved if tryptophan is taken in isolation and best consumed on an empty stomach, i.e. with an isolated intake and a quick portion. @nerd ?

Whey might help for many reasons, not necessarily due to tryptophan.

If you only want an increase in serotonin, 5-HTP would be the choice that doesn't affect the IDO trap.
 

Wanja

Senior Member
Messages
111
Location
Berlin, Germany
Whey might help for many reasons, not necessarily due to tryptophan.

If you only want an increase in serotonin, 5-HTP would be the choice that doesn't affect the IDO trap.

And i took a combination supp of HTP5, Tryptophan, b6 and Tyrosin... I wish i knew earlier about the trap theory...
But isit really possible that 5 days of taking 60 mg could have this amount of impact?
 
Messages
70
Whey might help for many reasons, not necessarily due to tryptophan.

If you only want an increase in serotonin, 5-HTP would be the choice that doesn't affect the IDO trap.

5-HTP could affect Trp levels in the cells by exerting a negative feedback on TPH enzyme which converts Trp to 5-HTP.
 

nerd

Senior Member
Messages
863
5-HTP could affect Trp levels in the cells by exerting a negative feedback on TPH enzyme which converts Trp to 5-HTP.

Yes. There are various feedback mechanisms. I wouldn't take 5-HTP either, but it's still better than tryptophan. Also from a quality perspective.
 

nerd

Senior Member
Messages
863
How would you increase low serotonin?

I also had a B6 deficiency. ME pathology increases the need for B6. B6 is necessary for serotonin. But I didn't really have very low serotonin. Not in the blood. Urine tests are confounded by creatinine in ME. I would only trust 24h urine tests as a ME patient.

BH4 also affects serotonin availability, just like B6. I wrote about it here:
Brain Kynurenine and BH4 Pathways: Relevance to the Pathophysiology and Treatment of Inflammation-Driven Depressive Symptoms
 

Wishful

Senior Member
Messages
5,679
Location
Alberta
For those of you thinking that bad reactions to TRP are due to the serotonin pathway, keep in mind that only 5% of the TRP in the brain goes down the serotonin pathway. The rest goes down the kynurenine pathway.

For me, TRP made my ME symptoms much worse, while 5-HTP had no effect on them, so my symptoms seem to be due to the kynurenine pathway.
 

Wanja

Senior Member
Messages
111
Location
Berlin, Germany
For those of you thinking that bad reactions to TRP are due to the serotonin pathway, keep in mind that only 5% of the TRP in the brain goes down the serotonin pathway. The rest goes down the kynurenine pathway.

For me, TRP made my ME symptoms much worse, while 5-HTP had no effect on them, so my symptoms seem to be due to the kynurenine pathway.

But isnt the problem with the metabolic trap that the tryptophan is not getting metabolized into kynurenine because of the broken IDO 2? And is then metabolized into serotonin instead?
 

rosie26

Senior Member
Messages
2,446
Location
NZ
When i took melantonin it was the horror.
I woke up the next morning feeling like a zombie. Brain fog was so insane i wws barely able to orientate myself.
@Wanja How many milligrams of melatonin were you taking? I started out on 1mg but ended up finding a quarter mg still did the same job. I found it very gentle with no hangover. I now no longer use melatonin though due to another health crisis 6 years ago - and not knowing whether it may have contributed.

As for 5-HTP I don't find it gentle enough. The one experience I had with it I found it too suddenly rough. The way it threw me to sleep and back out awake again three times in 15 seconds or so was really scary.
 

Mrparadise

Senior Member
Messages
119
Does anybody know if SSRI's are able to raise serotonin without affecting the IDO trap? I know that SSRI's are mostly useless but it is just a thought.
 

BrightCandle

Senior Member
Messages
1,147
Some meta review of melatonin suggested that 200-300mcg was the optimal dose for sleep and more made things worse. That seems to be the magic range and ideally you want the slow release type since it mimics the bodies process better.
 

Wanja

Senior Member
Messages
111
Location
Berlin, Germany
@Wanja How many milligrams of melatonin were you taking? I started out on 1mg but ended up finding a quarter mg still did the same job. I found it very gentle with no hangover. I now no longer use melatonin though due to another health crisis 6 years ago - and not knowing whether it may have contributed.

As for 5-HTP I don't find it gentle enough. The one experience I had with it I found it too suddenly rough. The way it threw me to sleep and back out awake again three times in 15 seconds or so was really scary.

I cant remember but i know that it skyrocket my brain fog. Not sure how much i took but never again since then
 

JES

Senior Member
Messages
1,320
Does anybody know if SSRI's are able to raise serotonin without affecting the IDO trap? I know that SSRI's are mostly useless but it is just a thought.

SSRI's actually reduce serotonin in long-term (ref). Here is another paper according to which extracellular serotonin levels eventually return following SSRI treatment, but serotonin synthesis and intracellular levels are reduced. It got me wondering: if the metabolic trap causes excess of serotonin, could SSRI's taken over a longer period help the situation?
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
SSRI's actually reduce serotonin in long-term (ref). Here is another paper according to which extracellular serotonin levels eventually return following SSRI treatment, but serotonin synthesis and intracellular levels are reduced. It got me wondering: if the metabolic trap causes excess of serotonin, could SSRI's taken over a longer period help the situation?
I did and it didn’t help.