I've been corresponding with Dr Pfair. I also had the thought that maybe we can lower our tryptophan levels, or lower absorption rates, to naturally boost kynurenine. But based on our discussion, I doubt we can self-treat and fix the metabolic trap that way at this point.
DIET: There is no reason to believe a low tryptophan diet will work. First of all, low tryptophan in the blood or CSF does not lead to lower levels in the cells. You would think it might, but apparently the affinity levels are so strong for tryptophan within the cells (mM as low as 1), that the cells are not going to just slough off tryptophan because levels are low outside the cells. And the whole point of the high levels in the cell is that the kynurenine is not being produced, meaning very low catabolism of tryptophan in the cell. Translation: the cells are not using their tryptophan so starving them of more won't help since they already have an over-supply, they are not using much of it right now, they do not like letting tryptophan go.
ABSORPTION: This is an alternative to changing the diet, why not simply block tryptophan uptake. This is easy, just take BCAAs, which compete with tryptophan for absorption. This is known to work, has been used before with other tryptophan related disorders. I even tried it for a few days. It made a tiny difference, maybe, but it was unstable, one day better, one day neutral or maybe a little worse. Anyway, Dr Phair had already considered this idea. He does not think blocking tryptophan absorption would work either for lowering levels inside cells, but since I had tried it, we discussed. He said blocking uptake would definitely lower levels in serum and CSF, but probably not in cells. However, the advantage of this approach is that you don't starve yourself of other nutrients, BCAAs can be taken along with meals with tryptophan. But again, I've tried it and may try again but only to replicate. And I don't recommend this if people are sensitive to amino supplements (some are from soy). This is probably a fairly safe thing to try, but again, like the diet approach, unlikely to work.
There is an entire ecosystem here, the kynurenine pathway is complicated. I read around a bit and started to wonder if it is a good idea to boost it too much, or rapidly, in CFS patients. What if it would be intolerable? Do we want to start up metabolic processes our bodies have shut down, possibly for a reason. For example, high kynurenine levels are known to increase cancer risk. Hmmm. Also, the kynurenine pathway can be influenced by the adrenal system. It is certainly possible that low adrenals or problems with cortisol regulation have a significant effect on kynurenine levels. So what if adrenal exhaustion plays a role in low kynurenine levels? Would forcing kynurenine higher have a positive or negative effect on the adrenals? (I have no idea, just pointing out there are more interrelationships here that could be important for CFS that need to be considered)
Some other thoughts... Tryptophan's major function is in the liver, it is processed by TDO enzymes there. Only 5% or so of our tryptophan is used outside the liver and processed by IDO. Therefore, lowering tryptophan levels could have an effect on liver function. This has been studied, but I did not look at the studies in depth, however, I think we need to consider possible side-effects of altering the tryptophan system rapidly or too much.
Other points. The kynurenine pathway has been studied with suicidal patients and is definitely disrupted for them. Just a point worth mentioning.
This is very basic research. I think it is great to have some progress, a reason to keep hope alive and keep funding flowing to the researchers. But I am trying to stay realistic also, and remember the many previous research findings that seemed to be about to change everything, and did nothing... So trying to stay grounded, hope this post was not too negative, but just feeling cautionary today. Hopeful still, but with guarded optimism.
