Stanford Community Symposium 2018: Phair, Metabolic traps, Tryptophan trap

Back in the mid 1980's, on a doctor's recommendation, I took L-tryptophan for sleep once - and only once. That night, I had the weirdest dream experience of my life. It was like I was rapidly shifting between random images - fragments of dreams which only lasted a second. The worst aspect was that I couldn't get out of the "dream," even though I wanted to. There's a famous animation called "An American Time Capsule" that captures that kind of rapid image change, but I won't link to it here because it's basically an exercise in sensory overload.

I haven't seen the conference video yet - (my internet connection is apparently too slow for live 720), but tryptophan is an essential amino acid and the precursor molecule to tryptophol (there are several steps). Tryptophol is the molecule that trypanosomes produce which seems to be the behind some of the effects of sleeping sickness.

In 1989, the sale of over the counter L-tryptophan was abruptly halted in the US and other countries when 1,500 users of L-tryptophan of came down with Eosinophilia–myalgia syndrome (EMS). Thirty-seven people died. The cause of the "outbreak" was thought to be contaminants introduced into a batch produced by one Japanese manufacturer, but some cases had occurred up to 3 years earlier. The exact link between L-tryptophan and EMS remains unknown. [This paper suggests there is genetic risk factor.]

In the US, the FDA began removing restrictions on L-tryptophan in 2001, lifting the general import ban in 2005.

 

Mady Hornig talks about issues with tryptophan as part of this presentation, http://microbediscovery.org/2016/03...ing-science-in-mecfs-at-conference-in-sweden/

 

IDO2 top related transcription factors foxo1a and foxo1
Source Genecards also African trapanosomes gets mentioned and PKC

 

I've had that experience with melatonin. Tryptophan is the precursor to melatonin.

 

According to the hypothesis, SSRIs would make things worse.

See:
https://www.ncbi.nlm.nih.gov/pubmed/10721121

 

This is really interesting. Also, reading more about tryptophol, I see that it's also present in some alcohols and is created by candida: https://en.m.wikipedia.org/wiki/Tryptophol

Could these convergences explain some of the secondary symptoms (IBS/GI problems, alcohol intolerance, etc)?

Obviously, these are all preliminary findings that need follow-up, but I think it chimes with some of what we know anecdotally. Whether it's a generalised issue or only a factor for a subgroup is yet to be seen.

 

I was responding to Forbin's comment above:

Forbin's comment suggested that this metabolic trap might be linked to Ron's other comments about trypanosomes. I was just making huge leaps in logic.

 

I just wanted to ask this very question as well. I vaguely remember reading something about how an increase in IDO is necessary for the maternal immune system to not attack the fetus, and blocking it with 1-methyl-tryptophan leads to a t-cell mediated attack on the fetal tissue. There must be some 'flag' thingy set (or reset) here.

Another obvious question would be why IDO activity is dysregulated in the first place, because we don't want to find out we can easily fix this with an IDO2 inducer and then die to whatever was the reason for this stuff not working in the first place.

I hope someone who knows more about this will chime in...

 

https://www.ncbi.nlm.nih.gov/pubmed/10721121

I note it’s from scientists in the biochemistry department at Oxford. We had scientists in the UK. What happened?


ETA: somehow the post did not transfer fully. Please see @Trish For abstract in short sections. #27

 

Some Reality check here :

- What percentage of pregnant women with ME/CFS goes into remission?

-Are there women that have an increase of Symptoms or got ME/CFS after/during pregnancy ?

-If lowering levels of Tryptophan during pregnancy is the reason , wouldn’t some of us have an amelioration of symptoms by minimising Tryptophan food sources intake?

 

From what I’ve read, 30% get better during the pregnancy (but doesn’t last), 30% feel no difference, and 30% get worse. I’ve seen these numbers many times, but I have no idea where they come from or how accurate they are.

The leading hypothesis is that the increased blood volume helps, but I have a hard time seeing how that could make someone worse.

What happens during pregnancy doesn’t appear to dictate what happens after the pregnancy. Some get better, some get worse, some stay the same. Again, I’ve seen this mention a lot but don’t know what it is based on.

 

Apocryphally, the other way around!

 

I think the variable results in pregnancy have to do with the fact that our basic disease is a problem with energy production. In MS, where the illness is based on an immune problem, pregnancy may cause a remission by it's action on the immune system.

In ME, any improvement caused by the immune system could easily be swamped by the increase in energy needed to cope with, say, throwing up or the increased weight, never mind all the other physical and social problems that pregnancy brings.

Whether pregnancy makes someone feel better or worse is down to a complex interaction of factors which will be very difficult to disentangle.

 

It seems to me that this links to what the CII team found in this paper? https://www.nature.com/articles/s41598-018-28477-9, discussion thread https://www.s4me.info/threads/insig...ehensive-metabolomics-2018-lipkin-et-al.4873/

In it they say

Seems to me that they are talking about the same thing?

They say on the subject of serotonin

 

@Simon M , any thoughts?

 

So what does this mean? Is it likely this is a side-effect of long-term amitriptyline use (or similar)? If not, would long-term use of these drugs worsen the problem?