Help! I Need To Control My Kynurenic Acid Level

[Texon]

Guys, it’s my last theory and it’s been very encouraging since I started to read about kynurenine pathway.

SSRIs increases KAT activity and reduces KMO activity. This leads to excess ‘kynurenic acid’ and low ‘quinolinic acid’. The first one is a NMDA antagonist, dopamine negative regulator and a7 cholinergic receptor antagonist. The second one is mostly the opposite of it.

I won’t mention all of my problems in this post, in short, I have ‘terrible’ cognitive, emotional and motor dysfunction, also which is progressively worsening day by day.

I seriously need some help. I don’t know if this because a neuroinflammation or a enzyme downregulation, I don’t actually care. I just want to fix them all. I’m open for all suggestions.

New insight into the antidepressants action: modulation of kynurenine pathway by increasing the kynurenic acid/3-hydroxykynurenine ratio. - PubMed - NCBI

- I can’t get any antibitotic without a prescription
- Most of the supplements are unavailable and can’t be ordered from abroad

@haidut I am not a scientist or doctor, but IMHO these are definitely symptoms of neuroinflammation probably caused by defective tryptophan metabolism. Have you looked into B12 (B12d.org) and thiamine/B1 (Dr. Derrick Lonsdale, MD) deficiencies, which also contain this symptom set? Quinolinic acid is a potent neurotoxin along with glutamate, etc. So not sure you want to reduce kynurenic acid. This is the last thing I would want to do. Current science seems to indicate only 2 pathways, i.e., tryptophan>niacin>nad, OR, tryptophan>quinolinic acid due to lack of nad/disruption of the kynurenine pathway. I share this set of symptoms btw, and it is hellacious trying to get to the bottom of them. I have to be very careful with methyl donors as well. You may want to consider foods such as dairy, all grains and so on as aggravating factors as well. I think these are issues often overlooked.

 

[Astolfo]

@haidut I am not a scientist or doctor, but IMHO these are definitely symptoms of neuroinflammation probably caused by defective tryptophan metabolism. Have you looked into B12 (B12d.org) and thiamine/B1 (Dr. Derrick Lonsdale, MD) deficiencies, which also contain this symptom set? Quinolinic acid is a potent neurotoxin along with glutamate, etc. So not sure you want to reduce kynurenic acid. This is the last thing I would want to do. Current science seems to indicate only 2 pathways, i.e., tryptophan>niacin>nad, OR, tryptophan>quinolinic acid due to lack of nad/disruption of the kynurenine pathway. I share this set of symptoms btw, and it is hellacious trying to get to the bottom of them. I have to be very careful with methyl donors as well. You may want to consider foods such as dairy, all grains and so on as aggravating factors as well. I think these are issues often overlooked.

Thanks so much for the reply. I think I couldn't understand well, did you mean that my tryptophan metabolism producing more than enough quinolinic acid? If so, why I'm getting more and more calm while my brain gets more damaged every day? There is a inverse paralellism between my sypmtoms and my anxiety levels. Quinolinic acid is excitatory, so it should have been the opposite.

Also, should I cut the dairies or eat more of them? I cut off taking any dairy a few months ago because of my gut problems. I got terrible gut noise and bloating problem from the pssd, and I thought it was bacterial. I was wrong, It's all connected to the disease I'm have. And the gut problems increase everytime when I ejeculate or take some cyptoheptadine (I don't take it anymore).

The cognitive and sensory problems are so bad now. I may not able to explain it fully, but if you want to know how it feels like, I can say that it feels like being in a dream 7/24. My brain feels like it's melted, and I really can't use my brain, I cannot even tell how big the difference is because of the huge gap between my normal base and now.

Looking to the monitor or panels feels like looking to the sun. My eyes and visual perception literally destroyed.

 

[Texon]

Thanks so much for the reply. I think I couldn't understand well, did you mean that my tryptophan metabolism producing more than enough quinolinic acid? If so, why I'm getting more and more calm while my brain gets more damaged every day? There is a inverse paralellism between my sypmtoms and my anxiety levels. Quinolinic acid is excitatory, so it should have been the opposite.

Also, should I cut the dairies or eat more of them? I cut off taking any dairy a few months ago because of my gut problems. I got terrible gut noise and bloating problem from the pssd, and I thought it was bacterial. I was wrong, It's all connected to the disease I'm have. And the gut problems increase everytime when I ejeculate or take some cyptoheptadine (I don't take it anymore).

The cognitive and sensory problems are so bad now. I may not able to explain it fully, but if you want to know how it feels like, I can say that it feels like being in a dream 7/24. My brain feels like it's melted, and I really can't use my brain, I cannot even tell how big the difference is because of the huge gap between my normal base and now.

Looking to the monitor or panels feels like looking to the sun. My eyes and visual perception literally destroyed.

Wow that's a lot of stuff going on. I think excluding dairy is a good idea too, as it contains casomorphin which is an opiate chemical. I couldn't tolerate cyproheptadine either. The reference to symptoms after ejaculation makes me think of possible prolactin overload. Have you had any recent exposures to any molds or chemical toxins? Do you have any functional medicine docs in your area? It sure sounds like you might need to visit an ER asap.

 

[Texon]

Thanks so much for the reply. I think I couldn't understand well, did you mean that my tryptophan metabolism producing more than enough quinolinic acid? If so, why I'm getting more and more calm while my brain gets more damaged every day? There is a inverse paralellism between my sypmtoms and my anxiety levels. Quinolinic acid is excitatory, so it should have been the opposite.

Also, should I cut the dairies or eat more of them? I cut off taking any dairy a few months ago because of my gut problems. I got terrible gut noise and bloating problem from the pssd, and I thought it was bacterial. I was wrong, It's all connected to the disease I'm have. And the gut problems increase everytime when I ejeculate or take some cyptoheptadine (I don't take it anymore).

The cognitive and sensory problems are so bad now. I may not able to explain it fully, but if you want to know how it feels like, I can say that it feels like being in a dream 7/24. My brain feels like it's melted, and I really can't use my brain, I cannot even tell how big the difference is because of the huge gap between my normal base and now.

Looking to the monitor or panels feels like looking to the sun. My eyes and visual perception literally destroyed.

Another thought...could this be some sort of serotonin poisoning from the ssri's? I can't tolerate them either.

 

[Astolfo]

Have you had any recent exposures to any molds or chemical toxins? Do you have any functional medicine docs in your area? It sure sounds like you might need to visit an ER asap.

1- no
2- no

I went to hospital several times in just one year. Maybe more than 15 times. Anybody did not believed to me. Even my family don't believe me either.

Another thought...could this be some sort of serotonin poisoning from the ssri's? I can't tolerate them either.

Perhaps. But this doesn't explain properly that why it's progressive and why did I not get any single windows.

 

[Texon]

1- no
2- no

I went to hospital several times in just one year. Maybe more than 15 times. Anybody did not believed to me. Even my family don't believe me either.




Perhaps. But this doesn't explain properly that why it's progressive and why did I not get any single windows.

@haidut
Man, I can sympathize for sure. My family thinks I am off my rocker....I meant to ask, could you have a severe sensitivity to electromagnetic frequencies//EMF's. I just heard today that wifi and watching blue screens all the time without blue blocking glasses can seriously lower testosterone. Could you possibly be dealing with undiagnosed hormonal issues?

As I write this (in front of my wireless laptop computer), I feel very weird (heavy head, anxiety over nothing, no motivation) after having just a cup of oolong tea and a couple of spoons of sugar (caffeine/glutamate from the sugar?). I feel like I am getting so sensitive to so many things it's going to be difficult to find anything to eat. This has been ongoing, but I believe the whole thing started very recently with a reaction to steamed beets a couple of days ago (overdose of nitric oxide/oxalic acid?), and then was made massively worse when I switched to oatmeal for breakfast (gluten/gliadin?) a few days in a row. Plus, I had a couple of glasses of milk yesterday after not having any for weeks (severe glutamate/casein sensitivity...very severe?). Maybe it's just going to take several days for the milk effects to wear off?

My current state reminds me of when I took some colostrum powder a long time ago thinking it was a healthy supplement, only to feel like I was losing all motor function from my waist down. I never touched it again after that. My daughter thinks I am spiking my blood sugar and insulin is driving sugar too low in my brain. I tend to think its glutamate reactivity and quinolinic acid simply because I tested positive for the quinolinic acid issue according to an organic acids test done by Great Western Labs in Wichita, KS. Plus, I was one of the Eosinophilia Myalgia Syndrome victims in 1990 supposedly caused by contaminated tryptophan (they've never been able to duplicate the disease in the labs).

Haidut...could something as simple as aspirin, niacinamide, etc., be curative in cases of brain inflammation which these symptoms seem to indicate. I'm also thinking of the possibility of low dose naltrexone to maybe act like a "reset button"....that is if it doesn't set me off to "crazy land" as well.

 

[Astolfo]

@Texon Yeah, naltrexone would be very useful in our cases. But it's not possible to get one, it's too expensive here and I need a prescription. My family doesn't help me either, as they are not believing me.

I had taken aspirine and B complex for a while. Didn't get any improvement from them.

 

[Goobz]

I have a similar set of symptoms and came to the same conclusion regarding the pathway - too much kynurenic acid. I’ll post properly later but I’m on my phone atm.

Have you taken estrogen blocking drugs like AIs, at all? My issues started after being prescribed letrozole

Both quinoloic acid and kynurenic acid come from the kynurenine pathway and I believe our best may be to turn off this pathway systemically at the liver. This pathway is turned on to degrade tryptophan to produce NAD+, a vitamin b3 metabolite.

It is controlled by an enzyme called tryptophan 2 3 dioxygenase (TDO) and TDO inhibitors are one of the latest things for Alzheimer’s and other neurodegenerative illnesses. TDO inhibitors in animal studies seem to prevent the protein accumulating neurodegenerative diseases.

The natural TDO inhibitor in human is estradiol and I believe melatonin and niacinamide as well.

The kynurenine pathway can also be activated locally / in specific areas of inflammation. This enzyme is indole 2 3 dioxygenase IDO and is part of the immune system. Many pathogens rely on tryptophan for their growth, and starving this response is induced to try to stave the cells of tryptophan and make it commit suicide via apoptosis. However in the case of pathogens such as Lyme or chlamydia pneumoniae, they simply switch to a non metabolic “cryptic” state until the danger has passed and thus evade the immune system.

IDO inhibitors tend to be things like cannabis and resveratrol and plant compounds.

With both IDO and TDO inhibitors you theoretically run the risk of NAD depletion, so my current thinking is to take a form of NAD booster / form of vitamin b3, along with a TDO inhibitor. In my mind that way you’re getting adequate NAD without having to get it via the kynurenine pathway and getting the toxic byproducts thereof (kynureninic acid, quinolonic acid ). But just my opinion at the moment I may be completely off.

 

[Texon]

@Texon Yeah, naltrexone would be very useful in our cases. But it's not possible to get one, it's too expensive here and I need a prescription. My family doesn't help me either, as they are not believing me.

I had taken aspirine and B complex for a while. Didn't get any improvement from them.

@Goobz... Astolfo, if you are ever able to get the 50mg naltrexone prescription pill, you can crush it and dilute it in filtered or distilled water to whatever strength you want. Just last night, I took 100 mgs each of niacin hcl and thiamine hcl with dinner. I had also taken the same niacin at other times during the day. Flushed very strongly from the niacin at dinner but immediately felt more balanced than I have in several days. Fell asleep for 2.5 hrs around 8, woke up at 10:30, went back to sleep around 12, then woke up at 4:30. Although niacin causes a significant flush, I now wonder if it serves to somehow deplete excess histamine which is beneficial in the long run? Be careful to include methyl B12 or TMG as needed if you don't methylate well because niacins are methyl sinks. Dr. Abram Hoffer MD psychiatrist (suggest reading everything you can about him) cured hundreds of schizophrenics with niacins as a foundation protocol. He said people subjected to severe prolonged stressors needed much higher doses indefinitely. Near the end of his life in his 90s, he summed it all up to say, "If you want to live a long time, take niacin."

 

[Astolfo]

@Goobz My estradiol came as 42, it was inside the range but was also close to the upper limit. So, there is no problem with my estradiol levels. At the last test, I saw that my estradiol went down to 30s, it's still in the range though.

Is there anything you can suggest me to take? I have B complex at home (it contains niacinamie instead of niacin though). I must say that it's pain in the butt to buy some supplements in my country. They are so expensive and there not much diversity. I can't also buy anything from abroad without paying taxes and I need prescription.

@Texon

I wish I could get some N. I will try but I don't ever think I can get that money or get my family believed to me.
I'm currently taking 400 mcg of beclamethasone dipropionate(aerosol) and 5 mg desloratadine daily because of my eustachian tube dysfunction. I wonder if they have any negative effect on me because I read that corticosteroids have permanent cognitive and metabolic effects, especiall on childrens.

Although, I don't think I should complement about it, while I'm already in a terrible cogntitively impaired state.

 

[Goobz]

@Goobz My estradiol came as 42, it was inside the range but was also close to the upper limit. So, there is no problem with my estradiol levels. At the last test, I saw that my estradiol went down to 30s, it's still in the range though.

Is there anything you can suggest me to take? I have B complex at home (it contains niacinamie instead of niacin though). I must say that it's pain in the butt to buy some supplements in my country. They are so expensive and there not much diversity. I can't also buy anything from abroad without paying taxes and I need prescription.

@Texon

I wish I could get some N. I will try but I don't ever think I can get that money or get my family believed to me.
I'm currently taking 400 mcg of beclamethasone dipropionate(aerosol) and 5 mg desloratadine daily because of my eustachian tube dysfunction. I wonder if they have any negative effect on me because I read that corticosteroids have permanent cognitive and metabolic effects, especiall on childrens.

Although, I don't think I should complement about it, while I'm already in a terrible cogntitively impaired state.

There are obvıously goıng to be too many varıables for me to gıve you much of value over the ınternet

But I also had ıssues after usıng steroıd nasal sprays - I belıeve the caused an overgrowth of a certaın fungus ın my nasal cavıty and thıs was came up on a swab a long tıme afterwards. So I would see ıf a doctor could do a swab for you

Apart from that I am lookıng at the amıno acıd phenylalanıne myself because of the fungus ın questıon - ıt secretes ochratoxın a whıch competes wıth phenylalanıne, and takıng phenylalanıne along wıth ıt has been shown to reduce absorptıon.

However ınterestıngly enough out of all the amıno acıds tested, phenylalanıne was the one that blocked kynurenıc acıd buıld up the best. Check the graph and the study here.
Amino acids inhibit kynurenic acid formation via suppression of kynurenine uptake or kynurenic acid synthesis in rat brain in vitro. - PubMed - NCBI

Nıacın or other NAD boosters, along wıth KAT or TDO ınhıbıtors or other thıngs that block the buıld up, may be helpful. But really, all thıs bıochemıstry ıs way too complıcated to say for sure and I belıeve you can probably hurt yourself by guessıng and takıng supplements. So ı wouldnt go out and just take supplements to experıment.

Try to get to the bottom of whats causıng the problem fırst. Thats what Im tryıng to do and ıts been a very slow process.

Im at an ınternet cafe wıth a foreıgn keyboard so excuse my strange paragraphs and characters.

 

[Astolfo]

So I would see ıf a doctor could do a swab for you

It was very quick. I got extreme sleepines effect from fluoxetine, just after a few days of half dose usage. So, this is probably not something related to fungus overgrowth or any bacterial problem, I guess.

Try to get to the bottom of whats causıng the problem fırst. Thats what Im tryıng to do and ıts been a very slow process.

Im at an ınternet cafe wıth a foreıgn keyboard so excuse my strange paragraphs and characters.

It's really not a problem, I'm really glad you're giving me some answers.

I really wanted to find out what is causing the problem. But there is literally anything I could find. Any single clue, I don't have.

I'm just assuming that it's some type of neurological inflammation or an immune attack*.

*: Why? Because I think fluoxetine wreck havoc on my glucocorticoid system. glucocorticoids are one of the most powerful anti-inflamatory things in the body. Overly upregulated GR(receptor) means there will be excess feedback signal. And, the final outcome is low glucocorticoid signalling.

Also I want to tell something more. I was taking triamcinolone acetonid, while I started to fluoxetine. It was only been a few days though, I didn't use that spray for a long time and had cut off when I started to take antidepressant.

My cortisol was 8.72, it's just 0.02 upper than the minimum limit. Now, after a few months later, I took another test and it's now 12. %50 increased but my problems still worsening. I'm barely talk even with my family because I'm having really hard times while finding which word I will say and pronouncing it properly.
It took so much time to write this, I hope you understand.

 

[lampofred]

Have you ever tried niacinamide?

 

[Goobz]

Until İ get more time to post more and more clearly than last time, this article would be worth reading. İt mentions various causes of the kynurenine pathway being activated. The focus is on the dangers of quın. acıd not kyn acid... and a focus on toxins such as mold, but the cause of both being elevated can be the same

Mary Ackerley: The Brain on Fire: The role of toxic mold in triggering psychiatric symptoms | Dr. Ritchie Shoemaker

 

[Astolfo]

@Goobz Thanks so much for the link. But, it's clearly impossible for me to read that now. I'm barely able to read sentences even in my main language. It's been very long time since I don't make any research about my problem, back then, I was still able to read pubmed articles but it's not possible now.

 

[Goobz]

No worries - it’s actually not very informative for this kyn pathway anyway, she actually only mentions he quin acid pathway briefly. I think I got it mixed up with another article

But it’s worth reading for potential causes of the pathway malfunctioning.

For now, maybe try get off the steroids and try to treat anxiety as much as possible, focus on relaxing, diet, sleep. Stress turns on the kyn pathway in general.

 

[Astolfo]

@Goobz I found very interesting articles about (serotonin, tryptophan, kynurenine, gut, brain and inflammation). Appearently, all of them is related to each other. I tried to read it but couldn't even stand for a five minutes. I couldn't read nor memorize any of the sentences.
Please, may you look at these articles?

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome

Brain Kynurenine and BH4 Pathways: Relevance to the Pathophysiology and Treatment of Inflammation-Driven Depressive Symptoms

It may explain my unexplained gut bloating, progressive cognitive deterioration, myoclonic jerks etc. It's an autoimmune reaction either because of serotonin or glucocorticoid receptor imbalance. Fluoxetine messes with both of them.

Building block of "happiness hormone" is key to controlling immunity in cancer and auto-immune diseases

 

[Goobz]

@Goobz I found very interesting articles about (serotonin, tryptophan, kynurenine, gut, brain and inflammation). Appearently, all of them is related to each other. I tried to read it but couldn't even stand for a five minutes. I couldn't read nor memorize any of the sentences.
Please, may you look at these articles?

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome

Brain Kynurenine and BH4 Pathways: Relevance to the Pathophysiology and Treatment of Inflammation-Driven Depressive Symptoms

It may explain my unexplained gut bloating, progressive cognitive deterioration, myoclonic jerks etc. It's an autoimmune reaction either because of serotonin or glucocorticoid receptor imbalance. Fluoxetine messes with both of them.

Building block of "happiness hormone" is key to controlling immunity in cancer and auto-immune diseases

I’ll read them and post something when I get the chance, they look interesting thanks.

In the meantime, just quick suggestion - have you tried red light therapy? It’s very good for brain health in general, and very powerful, and seems like a good defensive strategy for brain problems. You could use it whilst working things out further.

 

[Astolfo]

I’ll read them and post something when I get the chance, they look interesting thanks.

In the meantime, just quick suggestion - have you tried red light therapy? It’s very good for brain health in general, and very powerful, and seems like a good defensive strategy for brain problems. You could use it whilst working things out further.

Thanks...
I thought trying red light therapy, but those special red LEDs are not being sold here. I'm currently trying 100 mg aspirin daily, it has some effects but not sure if it's in a good way or not. It definitely has emotional blunting effects.

In case of you haven't read this yet:

Oxindole