I think that it is not relevant only for the depressed ones, but for anyone with POIS.
Agreed. Thanks for the thoughtful posts guys...
Hi, Mellivora.
Thanks for your comment
Going a little further about the effect of inflammation in POIS, I have found many interesting scientific data suggesting that the inflammation response is not only responsible for what I call the first two clusters of symptoms ( allergy-like and flu-like symptoms), but also for the two other clusters of symptoms, the
niacin/kynurenic acid cluster of symptoms (cognitive symptoms, memory problems, difficulties with problems solving, brain fog, slowed thought processing....) and the
serotonin/quinolinic acid cluster of symptoms (emotional symptoms like anxiety, depressive mood, fatigue, lack of motivation, mood swings, irritability, low self-esteem, intense emotional reactions, social phobia,....). Those third and fourth clusters are both linked, in my hypotheses, to the effects of pro-inflammatory cytokines release (from the allergic/immune response at the core of POIS). Those immune messengers have a direct effect on the metabolism of the much important tryptophan amino acid metabolism. I am grateful that POIS sufferers benefit from ten of thousands of dollars of research that have been done in both cancer and depression, on the tryptophan metabolism, and on enzymes in the tryptomahn metabolic pathways as the IDO and TDO, because they are of interest in depression ( as illustrated by the article presented by Mellivora in this thread), and in cancer as well.
I was struck to realize that there was indeed two different enzymatic pathways in the kynurenine pathways that could explain those two different sets of symptoms, the cognitive and the emotional ones. This dual pathway could explain why some individual present only one cluster and not the other, or present both at different levels of severity in any unique individual. Each person has his personal metabolic specificities, based on their specific enzymatic levels of activities. If one particular enzymatic pathway is more active or less active, some symptoms may or may not appear. For example, in my own case, I have absolutely no cognitive symptoms (cluster 3), and have severe cluster 4, emotionnal symptoms. My particular POIS "configuration" is not of the more current type, as the majority of POISers have some cognitive symptoms, like brain fog, memory problems, or mental focus problems. My weakness is, like explain below, that my tryptophan is changed in quinolinic acid, and it seems that I do not produce much kynurenic acid. Sounds mysterious? Stay tuned...
I will try to explain clearly part of what I came to suspect as being part of the physiopathology of POIS. I attached to this message a very, very interesting figure that you can dig if you are interested about what I have just briefly presented. It is from a very interesting slides presentation that I really think you should take a look at :
http://fr.slideshare.net/adonissfera/tryptophan-and-madness . It explains the effect of pro-inflammatory cytokines like IL-1, IL-6, TNF-alpha, interferon-gamma, and others on the brain chemistry, via the alteration of the tryptophan metabolism, in particular by pushing it toward the kynurenine pathway (KP). What I have attached is slide no 17 of this serie. It is a great summary of what happens, and i you study it carefully, you will find how an inappropriate immune reaction producing lots of pro-inflammatory cytokines (las POIS may be, as postulated by dr Waldinger) can cause cognitive deficit, as well as anxiety, depression and other emotional symptoms.
Note that those two clusters come via a different enzymatic pathway - the KMO (kynurenine mono-oxygenase) enzyme leads to a higher concentration of quinolinic acid in the brain, showed as QUIN with an upside arrow, on the figure. This part leads to emotional symptoms ( high brain level of quinolinic acd are linked to depression, anxiety, and many psychiatric disorders -
https://en.wikipedia.org/wiki/Quinolinic_acid#Psychiatric_disorders ). That is the path I suspect is the most present in my personal POIS acute phase.
The other pathway, via the KAT enzyme (kynurenine amino transferase), leads to higher kynurenic acid concentration in the body, which lead to impaired memory and cognitive faculties (yes, including brain fog!) ( see
https://en.wikipedia.org/wiki/Kynurenic_acid#Role_in_disease and
http://phys.org/news199944356.html for more info about KYNA effects on cognition ) I personnally do not have a problem in this pathway, which seems stable for a reason I do not know yet, but many POISers do have increased production of kynurenic acid in their brain in POIS acute phase, I think.
Moreover, you will note in this figure that the overuse of tryptophan ( symbol = Trp) leads as well to less serotonin (symbol = 5-HT, upper right of the figure), which also contributes to emotional symptoms. This figure could have had also the same lowering mentionned for niacin, which is also made from Trp. Interesting, isn't it? Less niacin leads to more cognitive impairments - just take a look at the symptoms of pellagra, caused by a lack of niacin -
http://en.wikipedia.org/wiki/Pellagra The first two enzymes that are on the left of the figure, IDO and TDO, are those that are highly over-activated after O (according to what I understand), and are responsible for the massive transformation of Trp into kynurenine (symbol KYN), everywhere in the body. This KYN enters the brain, and there is tranformed either by the KMO or the KAT enzyme, depending of your own metabolic "personality".
As could be predicted from this figure, taking one hour pre-O substances that blocks IDO and TDO will prevent both the cognitive and emotional symptoms, by preventing the massive production of kynurenine from tryptophan. It is then a matter of finding the right combination of different substances at the right dosage, because some very simple substances acts as inhibitors for those enzymes ( like curcumin, polyphenols sources and other antioxidants, and some others). I have pretty much found the combination of substances that works for me. After a month, quite sure now that it has nothing to do with placebo effect. More about that soon.
In addition to the attached file, you can also take a look at
http://en.wikipedia.org/wiki/Kynurenine_pathway , a good starter to get used to all these enzymes name and pathways. Believe me, you may get to know all these names! When something matters to you, motivation to understand comes easily.
