High dose folate induced derealization?

mad539

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Hello,

i'm now three years in a derealized state and still trying to find out what exactly happend back then that i went into that state in the first place. It started 2019 and thankfully i have many written notes in a notebook to reconstruct what happend back then. It seems my derealization happend in a timespan of around a month.

I have looked into this again with more detail, and in this month this all happend:
- After a high homocysteine test result (while trying to optimize my health), i took 400µg folic acid (not methylated) and 20 mg B6 as pyridoxine, fish oil, K2, B12, Zinc, Magnesium
- I started becoming self employed as software engineer
- I started having doubts about my current relationship
- I started using digestive enzymes
- Started experimenting with high dose folate (1-3mg)

While doing all that, i started having symptoms (from the notes i took):
- carbohydrate and alcohol interolance
- pressure on the throat, especially when eating carbs
- sight issues (went to the optician multiple times because my glasses are blurry, but they were fine)
- muscle weakness
- memory issues
- derealization
- becoming sick easily, especially when drinking alcohol
- doing high stress excercise (like HIIT) makes me feverish/sick the next day

Then my journey into hundreds of different supplements, many many lab tests and many different diets began. I could fix most of these issues with diet and some supplements, but never went out of the derealized state. I some times have glimpses back into reality when smelling some smells or remembering old memories, but they are only seconds long.

I have some MTHFR mutations, and after taking the methylfolate (1-3 mg), i first felt really great and good for around a week, but then it switched over to a kind of depressed state. I can't remember it exactly, but looking at the buy and shipping date of the 5-MTHF and my impatientness for new supplements, i assume i must have taken it straight after receiving it and it matches the symptoms timeline. So i assume it might be the 5-MTHF which induced the symptoms.

I took 5-MTHF on and off later and went deep into the MTHFR topic and trying to titrate the vitamins in the right proportion, but never felt right on them, so i stopped and never took 5-MTHF again.

Could it be that the high dose folate induced very fast some kind of vitamin deficency? I'm already taking high dose B1 (benfo and hcl) and it really helped with carbohydrate interolance, but never focused on the other B's.

I wondered if that even is possible. Maybe some of you guys have some experience. Anyway, i appreciate any help.
 
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mad539

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Actually no. But I reduced all supplements to the essential ones i "think" are helping me, and stopped fiddling around. Still there are some that helped me tremendously: #1 for me is boron, which helped my digestive issues extremely. But most of the time i don't have any clue how all the vitamins interact and noticed sometimes that by taking "that" vitamin i was acutally hurting myself.

The biggest changes still come from excercising and the right foods (or not eating the bad ones).

Thanks for the book recommendation, it looks very promising.
 
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mad539

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I've read the book, very interesting. I stopped all supplements and going to make the blood tests (especially whole blood histamine) as described in the book next week. Then i can find out in what category i'm in (over- or undermethylated, pyrrole disorder, ..).

What i noticed in the last three years:
- I got more and more histamine interolant
- Foods i could tolerate in the past like eggs, are now making problems
- SAMe (tried it only once) makes my dissociation 500% worse
- The best i've felt was when i forgot the supplements for one day and only ate carbs (low protein)
- While taking B6 (while DPDR started) as pyridoxine my B6 blood levels were extremly high even years after stopping and didn't go down
 

Tim Lundeen

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It sounds like you are a high-methylator, and that folate makes it worse; being sensitive to SAMe is pretty definitive. (I don't know how this relates to pyrrole, whether it excludes it or could be both.) Methionine in the diet can overdrive methylation, make things worse (e.g. eggs). My suggestion for folate is to get it from food only; legumes are the best source, soak them 3+ hours or overnight, and use a pressure cooker to minimize lectins.
 
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mad539

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My first lab came back:

Folate9.7 nmol/L8.83 - 60.8
Homocysteine10.8 µmol/L<10
Iron75 µg/dL35 - 168
Transferrin2.7 g/L2.0 - 3.6
Transferrin-Saturation19.7 %16.0 - 45.0
Ferritin185 nmol/L30 - 400

So folate is definitive low and homocysteine high. My neutrophils are under the range and my lymphozytes are over range, but it's like this for many years.
Strange that transferrin-saturation is so low. What could that be? Ferritin looks normal.

It sounds like you are a high-methylator, and that folate makes it worse; being sensitive to SAMe is pretty definitive. (I don't know how this relates to pyrrole, whether it excludes it or could be both.) Methionine in the diet can overdrive methylation, make things worse (e.g. eggs). My suggestion for folate is to get it from food only; legumes are the best source, soak them 3+ hours or overnight, and use a pressure cooker to minimize lectins.

Shouldn't that mean i'm an undermethylator? Eating a diet with high methionine makes my symptoms worse, maybe because the methionine accumulates and can't be fast enough "converted"? I've tried in the last days a diet with less protein as normal, and i'm feeling better. Clearer head, better articulation and feeling better overall.

I'm now going to test whole blood histamine, zinc and copper status and b6. Also b2, because many of my symptoms clear up when taking riboflavin (sore throat, cracks in the corner of the mouth).
 

Tim Lundeen

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Seems like if you were an undermethylator, you wouldn't be sensitive to SAMe.

Folate is on the low end, Walsh says that high methylators need more folate, which balances methyl groups. You could try eating more legumes, to make sure you get enough from diet. Homocysteine is high, maybe more folate would reduce it.

Ferritin is higher than "optimal ferritin levels for cardiovascular mortality reduction range from 20 to 100 ng mL" Optimal serum ferritin level range: iron status measure and inflammatory biomarker -- might also come down with enough folate, or by using lactoferrin and/or IP6 to reduce iron stores. Higher ferritin can also raise blood glucose levels.

Did you check fasting blood glucose? Could get a meter and start checking that at home, it's good/quick feedback. Should be 83 when you wake up (less is ok, but means your body is having trouble maintaining ideal for some reason).

Riboflavin also raises neurotransmitter levels by reducing COMT, but as with all things suggest low doses, could try small doses, maybe 3 to 5 mg of riboflavin 5' phosphate. Taking it with thiamin (a few mg) and biotin (50-100ug) might be helpful.
 
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mad539

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I will try legumes, and if i don't tolerate them, i start using chicken liver which should be very high in folate.

Here are some blood sugar related labs:
Glucose85 mg/dL75.0 - 115
Insulin2.06 mU/L2.6 - 24.9
HOMA0.43
HbA1c5.4 %4.8 - 6.1

Three years ago i became very carbohydrate sensitive, but high dose thiamine (thiamine hcl and benfotiamine) helped with that. I always assumed i'm insulin resistant and have some metabolic disorder, but the HOMA Index doesn't indicate that. Still strange that my HbA1c is so high, even i'm never over 150gr carbs a day a very long time (years).

I just remember i had very high levels of B6 for a long time, until i started supplementing most b-vitamins but without B6. Then it started to come down:
1655830476373.png

This is the reddit post i made:

View: https://www.reddit.com/r/Nootropics/comments/iavg2l/vitamin_b6_toxicity_reduction_per_year/


I wonder if the high B6 level drove some processes in overdrive and depleted other vitamins.

Thanks for your help.
 
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Tim Lundeen

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Interesting, thanks!

I suspect that eating low carb results in a slightly higher HbA1c because glucose is always slightly elevated by high fat intake, which slows carb clearance. The result is very low insulin, good blood glucose control, but higher average blood glucose than if it falls to normal more quickly. When I was eating this way, I lost about 40 pounds without any effort, but couldn't lose the last 10 of visceral fat until I switched to a very low fat, high carb diet (which gives excellent blood glucose control). These extremely-low-fat diets (less than 10% fat, 15% protein) are not healthy long-term, but can reset carb and fat tolerance.

Curious that you could take methylated b vits but be sensitive to SAMe. Maybe these methylated supplements are related to derealization? I suspect that both methylated and acetylated supplements mess people up.
 

joaquin

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Why would you say your HbA1c is so high? 5.4 is not bad at all.
 

joaquin

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I suspect that both methylated and acetylated supplements mess people up.
I would concur. I switched from DMG to regular Glycine years ago and it made a difference.
 
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mad539

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Interesting, thanks!

I suspect that eating low carb results in a slightly higher HbA1c because glucose is always slightly elevated by high fat intake, which slows carb clearance. The result is very low insulin, good blood glucose control, but higher average blood glucose than if it falls to normal more quickly. When I was eating this way, I lost about 40 pounds without any effort, but couldn't lose the last 10 of visceral fat until I switched to a very low fat, high carb diet (which gives excellent blood glucose control). These extremely-low-fat diets (less than 10% fat, 15% protein) are not healthy long-term, but can reset carb and fat tolerance.

Curious that you could take methylated b vits but be sensitive to SAMe. Maybe these methylated supplements are related to derealization? I suspect that both methylated and acetylated supplements mess people up.
Thats very interesting! The methylated folate and b12 made issues too and i don't take them anymore. But they seemed to help reducing the high b6 level.

Because of the really fast (ramped up) onset of derealization and the (now) three year long chronic state with nearly no variation in severity (besides tinkering with vitamins) i think it must have overloaded something. I still suspect it must have something to do with the b6.

Last week i tried a lowish dose of 10-30 mg b6 as p-5-p and immediately got nightmares at night. It seems my derealization is also worse since taking the b6. I'm curious what my b6 level is going to be after the blood test.

It also seems that pyridoxine inhibits normal b6 function:

Why would you say your HbA1c is so high? 5.4 is not bad at all.
I just thought it should be lower because of my low carbohydrate intake. At least it is a bit away from diabetes.
 

Tim Lundeen

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Not sure that 10mg p-5-p is "low" :): Maybe 0.1mg is low, or maybe 0.5. Sensitive people can have issues with 1mg... I dilute a larger dose in water, down to 0.1mg/drop, so it's easy to try lower doses. Legumes have helpful B6 content.

Interesting that pyroxidine blocks p-5-p. I wonder if some of the high-dose pyroxidine protocols are actually reducing overactive p-5-p levels...
 
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mad539

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You're right, 10 mg is high but looking at other supplements they always come in insane amounts like 50 or 100 mg per capsule. I had to look for a supplement with "only" 10 mg :)
There are even groups (e.g. Vitamin B6 Toxicity) that discuss this specific b6 toxicitiy issue, mainly because they used pyroxidine instead of p-5-p. It would be interesting to find out why some have issues with this form and others don't.
 
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mad539

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I just want to throw this in before i forget it:
- My whole life i get skin painful cracks on the fingers and heels from all different kind of foods (they look like this: View: https://imgur.com/a/2Fyl1s9). This happens very fast after i ate a food (30-45 minutes) and when it's bad i even bleeds. After trying to track it down, my main suspicion are high fat meals. Eating very low fat meals never creates these issues.
- When drinking alcohol, i get a very rough voice and can't speak right. Sometimes it took days for it to resolve. Also i get extreme fatigue, but not always.
- I get pressure on the throat, which is kind of a pre-stage of the rough voice i get.
- I sometimes get cracked corners of the mouth and mouth ulcers when it's bad (painful white spots)

Last week i tried B2 again in lowish dosage (1.5mg 3x a day) and i just noticed that my voice didn't crack at all, even when drinking alcohol. I had better energy and better alcohol tolerance. I also remember that eating fatty fish (salmon) helps my skin, maybe because of the b2 content which is high in salmon.

Maybe the chronic high b6 drove everything in overdrive and depleted B2. I never really supplemented with B2, because the "normal" doses like 50 mg always created allergic issues.

I'm now pretty confident that i have some kind of chronic b2 deficency. I hope tomorrow the blood lab will show it.
 

Recoen

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I've read the book, very interesting. I stopped all supplements and going to make the blood tests (especially whole blood histamine) as described in the book next week. Then i can find out in what category i'm in (over- or undermethylated, pyrrole disorder, ..).

What i noticed in the last three years:
- I got more and more histamine interolant
- Foods i could tolerate in the past like eggs, are now making problems
- SAMe (tried it only once) makes my dissociation 500% worse
- The best i've felt was when i forgot the supplements for one day and only ate carbs (low protein)
- While taking B6 (while DPDR started) as pyridoxine my B6 blood levels were extremly high even years after stopping and didn't go down
Serotonin
 

Recoen

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You're right, 10 mg is high but looking at other supplements they always come in insane amounts like 50 or 100 mg per capsule. I had to look for a supplement with "only" 10 mg :)
There are even groups (e.g. Vitamin B6 Toxicity) that discuss this specific b6 toxicitiy issue, mainly because they used pyroxidine instead of p-5-p. It would be interesting to find out why some have issues with this form and others don't.
Arguably ALP. The Dessert harvest b complex has no B6 in it.
 

Recoen

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I just want to throw this in before i forget it:
- My whole life i get skin painful cracks on the fingers and heels from all different kind of foods (they look like this: View: https://imgur.com/a/2Fyl1s9). This happens very fast after i ate a food (30-45 minutes) and when it's bad i even bleeds. After trying to track it down, my main suspicion are high fat meals. Eating very low fat meals never creates these issues.
- When drinking alcohol, i get a very rough voice and can't speak right. Sometimes it took days for it to resolve. Also i get extreme fatigue, but not always.
- I get pressure on the throat, which is kind of a pre-stage of the rough voice i get.
- I sometimes get cracked corners of the mouth and mouth ulcers when it's bad (painful white spots)

Last week i tried B2 again in lowish dosage (1.5mg 3x a day) and i just noticed that my voice didn't crack at all, even when drinking alcohol. I had better energy and better alcohol tolerance. I also remember that eating fatty fish (salmon) helps my skin, maybe because of the b2 content which is high in salmon.

Maybe the chronic high b6 drove everything in overdrive and depleted B2. I never really supplemented with B2, because the "normal" doses like 50 mg always created allergic issues.

I'm now pretty confident that i have some kind of chronic b2 deficency. I hope tomorrow the blood lab will show it.
Serum B vitamin labs are more indicative of recent intake/ absorption (with some exceptions).
 
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mad539

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Serotonin
Could you explain what you mean?

Arguably ALP. The Dessert harvest b complex has no B6 in it.
You mean alkaline phosphatase? I only have one lab test with AP in it, in it were in range: 50 U/I (range: 40-130)
The lab was taken 5 months after the start of my derealization and around 6-7 months after my intake of pyroxidine.

Serum B vitamin labs are more indicative of recent intake/ absorption (with some exceptions).
I've requested whole blood riboflavin. I always look into chris masterjohns "Testing Nutritional Status" PDF when testing for vitamins, he says it should be low in deficency. I also stopped all vitamins around 1 week prior.
 
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mad539

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My results are in:
Manganese5.5 µg/L5.0 - 12.4
Copper13.5 µmol/L10.2 - 26.0
Coeruloplasmin0.23 g/L0.20 - 0.60
Zinc14.0 µmol/L9.2 - 19.9
Glycine1.2 mg/dL1.2 - 3.2
Methionine0.4 mg/dL0.2 - 0.7
Vitamin B289.5 µg/L40 - 140
Vitamin B6341 nmol/L20.0 - 121
Histamine<0.3 µg/L<1.0


And here again my labs from some posts above:
Folate9.7 nmol/L8.83 - 60.8
Homocysteine10.8 µmol/L<10
Iron75 µg/dL35 - 168
Transferrin2.7 g/L2.0 - 3.6
Transferrin-Saturation19.7 %16.0 - 45.0
Ferritin185 nmol/L30 - 400


Here are my thoughts on the results:

- Mangenese is low and supplementation might improve my glucose metabolism. It's not too low, but it shouldn't hurt

- Zinc and copper are both in range. Coeruloplasmin is low, but i have to research what this exactly means.

- The B2 is in range, but i'm still supplementing with low doses (like 1-2 mg a day) just to be sure.

- Interesstingly, the methionine and histamine are both normal. I even ate high histamine foods (chocolate, wine) and had the morning after (i thought) "high histamine" symptoms while taking the blood test. But strangely, they are low?

- Glycine is low and i think i will try supplementing with glycine or try to get it from food.

- After not taking any B6 for around one week, my B6 is still sky high (3x the reference range!). It is even higher than 3 years ago, which is crazy. After trying B6 again and noticing a worsening of symptoms of my derealization, this might be the main issue or a part of it. Can the high b6 come from food?

- My homocysteine is high too, and i'm very sure i'm not b12 deficient (multiple tests over the last years, with plasma b12 tests, MMA, e.g...). What's left is folate, which is low(ish). I have issues with methylfolate, so i'm going to try folinic acid (e.g. this).

I had good results by taking everything from a b-complex but just without B6 (thanks Recoen for recommending a b complex without b6 in it) to lower b6, so this is what i'm going to do. Maybe this is why i'm feeling a bit better when i don't eat high amounts of meat: Most of the time i eat chicken which is high in b6.
 
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