25 year old female with cold urticaria for 2 years, feel unsure what to do anymore

[redsun]

I have not looked into the link between urticaria and dysautonomia but I do take a multivitamin that has thiamine hcl 25 mg every day.

I have never taken any of those antibiotics. I have only taken doxycycline every single time for Lyme disease, ehrlichiosis, etc.

This study says that dextromethorphan was their treatment. So cough medicine? I don’t have edema or pelvic pain, just cold urticaria. I don’t know if that would apply to me but it’s worth looking into.

I developed chronic anxiety from a young age due to abuse etc. I have always been a worrier for many different reasons. I was very jumpy, easily put into fight or flight, couldn’t handle caffeine. Of course having health issues and then anxiety about that is another stress.

I Never struggled with insomnia in my life until I was like 9 months into peating and then I got the covid vaccine against my will. Within a day or 2 after the first shot I felt like I had a thyroid storm or brain inflammation..?. My heart was constantly racing, I was in constant fight or flight and felt like I couldn’t breathe. my metabolism went super high and I was burning through calories like crazy. I lost 10-15 lbs in a month without trying at all. I couldn’t sleep, I could barely eat, I quit my job that I got the vaccine for. So I went to my doctor desperate for help. She prescribed me hydroxyzine. I didn’t take it for another 2 months where I continued to lose a pound or 2 per week, couldn’t sleep through the night, waking up every hour. I then gave in and tried the hydroxyzine before bed. I’ve taken it every night since then and i have been able to sleep through the night ever since then. I also have much lower anxiety levels throughout the day, and I gained the weight back that I lost that stressful time. I do plan on getting off of hydroxyzine eventually because it’s not recommended during pregnancy but I really want to get my health in order as much as I can before I get pregnant.

Usually with histamine issues you need to avoid multivitamins as many micronutrient in supplemental form (or in the higher quantities that are only found in supplements) can potentiate histamine activity directly or indirectly by their effects on other things. Most of the B vitamins can increase histamine activity except B12 and choline for the most part. B2 can have pro and anti-histamine effects. Manganese and also selenium are problematic as well. Zinc excess is problematic as it is a GABA antagonist which will increase glutamate activity which will then stimulate histamine but in normal intakes it is beneficial.

I remember at a time where I was taking doses of thiamine in the hundreds of milligrams for over a week until I realized it was causing severe histamine reactions to the point where I could barely sleep because of runny nose, sneezing, itching, watery eyes and it was intolerable during the day. I found out that thiamine is a histamine liberator and needs to be avoided for those with histamine issues or those prone to mast cell activation. Even low doses of thiamine (25 mg a day) for prolonged periods of time will do the same thing to me. Not everyone is prone to the typical histamine reactions like I described. This can easily show up as worsening urticaria even without those other symptoms. Everyone reacts differently but you be unintentionally worsening symptoms.

 

[mostlylurking]

Usually with histamine issues you need to avoid multivitamins as many micronutrient in supplemental form (or in the higher quantities that are only found in supplements) can potentiate histamine activity directly or indirectly by their effects on other things. Most of the B vitamins can increase histamine activity except B12 and choline for the most part. B2 can have pro and anti-histamine effects. Manganese and also selenium are problematic as well. Zinc excess is problematic as it is a GABA antagonist which will increase glutamate activity which will then stimulate histamine but in normal intakes it is beneficial.

I remember at a time where I was taking doses of thiamine in the hundreds of milligrams for over a week until I realized it was causing severe histamine reactions to the point where I could barely sleep because of runny nose, sneezing, itching, watery eyes and it was intolerable during the day. I found out that thiamine is a histamine liberator and needs to be avoided for those with histamine issues or those prone to mast cell activation. Even low doses of thiamine (25 mg a day) for prolonged periods of time will do the same thing to me. Not everyone is prone to the typical histamine reactions like I described. This can easily show up as worsening urticaria even without those other symptoms. Everyone reacts differently but you be unintentionally worsening symptoms.

This is a debatable subject.
Here's some nicely packaged information I just came across here: Thiamine deficiency and Histamine Intolerance. Is there a link?

-start of paste-
Yes, there's a link between mast cells, histamine intolerance and thiamine deficiency.

Using your smoked fish episode as a starting point....

Smoked foods contain sodium sulfite which triggers mast cell degranulation.

Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation
Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation - PubMed

Histamine Intolerance Originates in the Gut
Histamine Intolerance Originates in the Gut

And...

All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases


Thiamine has been scientifically shown to modulate mast cell degranulation.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy
Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy - PubMed


"These data suggest that mast cell degranulation is a very early response induced by TD (Thiamine Deficiency)..."
And...
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats - PubMed

"These data present a new finding that thiamine deficiency affects the central histaminergic neuron system as well as other monoaminergic systems."

And...

Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats - PubMed

"...the increased histamine levels in the hypothalamus, especially those in its anterior region, are closely related to the hypothermia in thiamine-deficient rats."

"What does the hypothalamus do?"

Hypothalamus: Function, hormones, and disorders

Mast cells releasing histamine is part of the immune response to antigens like gluten, casein, or viruses like Covid.

Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19
Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19 - PubMed

High dose Thiamine is used to quench the out of control immune response in Covid patients.

Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile.


Europe PMC


"Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role."


Cobalamine, Vitamin C, Pyridoxine, and Folate help get rid of the histamine, while Thiamine helps calm the immune response. Niacin and Riboflavin are also needed to help the other B vitamins do their jobs. A B Complex supplement should contain all eight of the essential B vitamins. Thiamine needs magnesium to work properly, so a magnesium supplement would be beneficial.


Oh, there's calcium in cooked green leafy vegetables that is better absorbed than the calcium in dairy.

Liver is a great source of all the B vitamins and important minerals like iron and zinc.


-end of paste-

 

[redsun]

This is a debatable subject.
Here's some nicely packaged information I just came across here: Thiamine deficiency and Histamine Intolerance. Is there a link?

-start of paste-
Yes, there's a link between mast cells, histamine intolerance and thiamine deficiency.

Using your smoked fish episode as a starting point....

Smoked foods contain sodium sulfite which triggers mast cell degranulation.

Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation
Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation - PubMed

Histamine Intolerance Originates in the Gut
Histamine Intolerance Originates in the Gut

And...

All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases


Thiamine has been scientifically shown to modulate mast cell degranulation.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy
Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy - PubMed


"These data suggest that mast cell degranulation is a very early response induced by TD (Thiamine Deficiency)..."
And...
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats - PubMed

"These data present a new finding that thiamine deficiency affects the central histaminergic neuron system as well as other monoaminergic systems."

And...

Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats - PubMed

"...the increased histamine levels in the hypothalamus, especially those in its anterior region, are closely related to the hypothermia in thiamine-deficient rats."

"What does the hypothalamus do?"

Hypothalamus: Function, hormones, and disorders

Mast cells releasing histamine is part of the immune response to antigens like gluten, casein, or viruses like Covid.

Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19
Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19 - PubMed

High dose Thiamine is used to quench the out of control immune response in Covid patients.

Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile.


Europe PMC


"Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role."


Cobalamine, Vitamin C, Pyridoxine, and Folate help get rid of the histamine, while Thiamine helps calm the immune response. Niacin and Riboflavin are also needed to help the other B vitamins do their jobs. A B Complex supplement should contain all eight of the essential B vitamins. Thiamine needs magnesium to work properly, so a magnesium supplement would be beneficial.


Oh, there's calcium in cooked green leafy vegetables that is better absorbed than the calcium in dairy.

Liver is a great source of all the B vitamins and important minerals like iron and zinc.


-end of paste-

Inhibition of human and canine diamine oxidase by drugs used in an intensive care unit: relevance for clinical side effects? - PubMed

Three hundred and forty-one drugs, commonly used in intensive care units (ICU), were chosen for an investigation of possible activation or inhibition of the histamine metabolizing enzyme diamine oxidase (DAO). After examination of 164 substances, using both canine and human DAO in an in vitro...

pubmed.ncbi.nlm.nih.gov

Full PDF of the study, which tested multiple drugs below. The table on page 2 showing clear inhibition of DAO by thiamine:

 

[summergirl]

Usually with histamine issues you need to avoid multivitamins as many micronutrient in supplemental form (or in the higher quantities that are only found in supplements) can potentiate histamine activity directly or indirectly by their effects on other things. Most of the B vitamins can increase histamine activity except B12 and choline for the most part. B2 can have pro and anti-histamine effects. Manganese and also selenium are problematic as well. Zinc excess is problematic as it is a GABA antagonist which will increase glutamate activity which will then stimulate histamine but in normal intakes it is beneficial.

I remember at a time where I was taking doses of thiamine in the hundreds of milligrams for over a week until I realized it was causing severe histamine reactions to the point where I could barely sleep because of runny nose, sneezing, itching, watery eyes and it was intolerable during the day. I found out that thiamine is a histamine liberator and needs to be avoided for those with histamine issues or those prone to mast cell activation. Even low doses of thiamine (25 mg a day) for prolonged periods of time will do the same thing to me. Not everyone is prone to the typical histamine reactions like I described. This can easily show up as worsening urticaria even without those other symptoms. Everyone reacts differently but you be unintentionally worsening symptoms.

Hi redsun,
I did not take a multivitamin (or b complex) for over a year during my cold U reactions. I just added the multivitamin into my diet a few months ago and I’ve seen really no positive or negative change in my cold reactions. Maybe more hair growth on my head and improved skin and stronger nails. But Honestly my hair nails and skin are always improving for me since I started peating.

In regards to why I started taking the multi, I wanted a more efficient way to get some zinc and selenium (for thyroid) etc into me because I felt that I was having tons of copper in my diet and limited zinc because I frequently forgot about eating oysters. The amount of zinc in the multi is only 7.5 mg of zinc bysglycinate chelate. I don’t think it is excessive. Some zinc is needed because it inhibits the release of histamine from mast cells.

I just feel like there are so many different directions I could look whether it’s viral infections, endotoxin, thyroid, estrogen dominance, pcos, gluten, chronic stress, leaky gut, deficiencies, and my genetics. I also live in an old house that has mold on the bathroom ceiling and all the windows that I do clean off it but reappears. I also have had somewhat wonky digestion ever since I got on accutane. I know a lot of histamine issues originate in the gut and with the lack of DAO enzyme.

I’m so lost and not sure which direction to go anymore.

 

[redsun]

Hi redsun,
I did not take a multivitamin (or b complex) for over a year during my cold U reactions. I just added the multivitamin into my diet a few months ago and I’ve seen really no positive or negative change in my cold reactions. Maybe more hair growth on my head and improved skin and stronger nails. But Honestly my hair nails and skin are always improving for me since I started peating.

In regards to why I started taking the multi, I wanted a more efficient way to get some zinc and selenium (for thyroid) etc into me because I felt that I was having tons of copper in my diet and limited zinc because I frequently forgot about eating oysters. The amount of zinc in the multi is only 7.5 mg of zinc bysglycinate chelate. I don’t think it is excessive. Some zinc is needed because it inhibits the release of histamine from mast cells.

I just feel like there are so many different directions I could look whether it’s viral infections, endotoxin, thyroid, estrogen dominance, pcos, gluten, chronic stress, leaky gut, deficiencies, and my genetics. Or something that I haven’t even thought of yet. my concern is that it’s a combination of basically every one of those issues.

I’m so lost and not sure which direction to go anymore.

Try the TMG for a few weeks and see if it improves. Thats the most direct solution so it makes sense to start there.

 

[summergirl]

Try the TMG for a few weeks and see if it improves. Thats the most direct solution so it makes sense to start there.

I will look into buying TMG and I will update here whether I’ve seen any change or not. Thank you!

 

[mostlylurking]

Try the TMG for a few weeks and see if it improves. Thats the most direct solution so it makes sense to start there.

You can try TMG (also known as Betaine Anhydrous).

@summergirl

TMG? This TMG? TMG (Trimethylglycine) - Information; Why it is Recommended

"An extract from sugar beets, TMG is a natural polysaccharide and a good source of methyl groups that promotes healthier levels of the powerful pro-oxidant and free radical generator homocysteine. Homocysteine is a toxic end product of the metabolism (methylation) of methionine (an essential amino acid) and is now known to be a leading cause of heart and artery disease."

Sorry, you lost me. I'm a fan of Ray Peat's wisdom. Ray Peat didn't recommend increasing methylation. He was concerned that the anti-cancer gene would get turned off by methylation.

Ray Peat, PhD on Carbon Dioxide, Longevity, and Regeneration – Functional Performance Systems (FPS)

"A mole rat has never been known to develop cancer. Their serum C-reactive protein is extremely low, indicating that they are resistant to inflammation. In humans and other animals that are susceptible to cancer, one of the genes that is likely to be silenced by stress, aging, and methylation is p53, a tumor-suppressor gene."


View: https://youtu.be/jwVDzaH4XZ4?t=2760

 

[redsun]

@summergirl

TMG? This TMG? TMG (Trimethylglycine) - Information; Why it is Recommended

"An extract from sugar beets, TMG is a natural polysaccharide and a good source of methyl groups that promotes healthier levels of the powerful pro-oxidant and free radical generator homocysteine. Homocysteine is a toxic end product of the metabolism (methylation) of methionine (an essential amino acid) and is now known to be a leading cause of heart and artery disease."

Sorry, you lost me. I'm a fan of Ray Peat's wisdom. Ray Peat didn't recommend increasing methylation. He was concerned that the anti-cancer gene would get turned off by methylation.

Ray Peat, PhD on Carbon Dioxide, Longevity, and Regeneration – Functional Performance Systems (FPS)

"A mole rat has never been known to develop cancer. Their serum C-reactive protein is extremely low, indicating that they are resistant to inflammation. In humans and other animals that are susceptible to cancer, one of the genes that is likely to be silenced by stress, aging, and methylation is p53, a tumor-suppressor gene."


View: https://youtu.be/jwVDzaH4XZ4?t=2760

Of course I lost you, you are a one trick pony. There is so much to human biochemistry and here you are parroting the same thing over and over again. I have never seen you not recommend thiamine for anything. You are a broken record.

You are suggesting the thing I recommend to someone is actually dangerous and toxic. This is very wrong.

Yes TMG, as in betaine, a naturally occuring compound in the body that is made endogenously from the oxidation of choline via choline oxidase to be used in methylation and also in water balance in cells. How do you think you deactivate histamine, catecholamines, make melatonin, make phosphatidylcholine endogenously, creatine, synthesize DNA, synthesize myelin, and regulate gene expression? Methylation.

Due to the fact that genetic mutations dealing with methylation enzymes are common, TMG actually is a good way to prevent the elevation in homocysteine that can occur because of them. These gene mutations can predispose someone to histamine intolerance. This is why TMG is also used to lower histamine. It is unbelievably simple and not to mention safe. Theres more that can be done but TMG is a simple way to get started.

TMG is used in BHMT to recycle methionine and become DMG. And after that it will also make 3 methylenetetrahydrofolates which can be converted to methylfolates which will also be used to recycle homocysteine. There is no homocysteine made from the TMG itself. It literally recycles it and lowers it. And the link you are using to refute me actually proves my point for me. Maybe read past the first paragraph next time?

"Multiple studies have demonstrated that medium to high levels of plasma homocysteine are associated with increased risk of heart disease, cerebrovascular disease and peripheral artery disease. In one study, daily treatment with TMG, folic acid and choline normalized homocysteine levels in 17 of 19 patients. [1] TMG lowers homocysteine levels with and without vitamins B12, B6 and folic acid."

Enough about TMG, on to the more pressing matter. This overly basic understanding of biochemical processes which perpetuates ignorance is the bane of health forums. Yes excess homocysteine is bad, but did you know very low homocysteine is also bad? Of course you didn't. You want lowish homocysteine but you don't want it nonexistent, you still need it. Low homocysteine will compromise your ability to synthesize taurine, sulfate, cysteine, and glutathione (which needs cysteine), all required compounds in the human body. We want to have to some homocysteine but we want it being converted to important compounds.

When someone deals with manifestations of excess histamine such as urticaria, supporting methylation will almost always improve the condition. Often these people need more methyl groups not less due their genetics. This is not going to promote cancer. Its like saying dietary choline promotes cancer, which becomes TMG in the body anyways to be used in methylation. The body makes its own TMG all the time from choline. We shouldn't consume choline either then. We will all get organ failure, fatty liver, severe dysautonomia, and muscle damage from choline deficiency but at least we can't get cancer...

There is no black and white on what someone does and does not need. Each human has individual needs and thus every health situation has different possible solutions and treatments. You cannot just slap some thiamine on them like a band-aid on every problem. This applies to methylation, this applies to iron, this applies to PUFA, this applies to the use of pharma drugs even, this applies to every health related topic full-stop. There is nuance to everything and if you haven't realized that by now, I don't think you ever will.

 

[mostlylurking]

There is nuance to everything

Yep, and it's extremely difficult to safely diagnose a stranger asking for help on a forum.

And the link you are using to refute me actually proves my point for me. Maybe read past the first paragraph next time?

I read the first paragraph, and the chance of damaging the circulatory system via your proposal did flash out at me; the stranger on the forum that you have never laid eyes on did mention that they did have the covid injection, which is known to attack/cause inflammation of the circulatory system. Seemed important to point out that issue.

Health chemistry is very complicated. Everyone carries a load of toxins that affect their health and their own personal body chemistry. People tend to take notice of what helps them personally. You rely on your personal experiences; I rely on mine. When I'm faced with new health care information that is complicated, I make it a point to research what Ray Peat has said about it. Ray was consistent in his position that increasing methylation is never something he would recommend.

 

[summergirl]

Of course I lost you, you are a one trick pony. There is so much to human biochemistry and here you are parroting the same thing over and over again. I have never seen you not recommend thiamine for anything. You are a broken record.

You are suggesting the thing I recommend to someone is actually dangerous and toxic. This is very wrong.

Yes TMG, as in betaine, a naturally occuring compound in the body that is made endogenously from the oxidation of choline via choline oxidase to be used in methylation and also in water balance in cells. How do you think you deactivate histamine, catecholamines, make melatonin, make phosphatidylcholine endogenously, creatine, synthesize DNA, synthesize myelin, and regulate gene expression? Methylation.

Due to the fact that genetic mutations dealing with methylation enzymes are common, TMG actually is a good way to prevent the elevation in homocysteine that can occur because of them. These gene mutations can predispose someone to histamine intolerance. This is why TMG is also used to lower histamine. It is unbelievably simple and not to mention safe. Theres more that can be done but TMG is a simple way to get started.

TMG is used in BHMT to recycle methionine and become DMG. And after that it will also make 3 methylenetetrahydrofolates which can be converted to methylfolates which will also be used to recycle homocysteine. There is no homocysteine made from the TMG itself. It literally recycles it and lowers it. And the link you are using to refute me actually proves my point for me. Maybe read past the first paragraph next time?

"Multiple studies have demonstrated that medium to high levels of plasma homocysteine are associated with increased risk of heart disease, cerebrovascular disease and peripheral artery disease. In one study, daily treatment with TMG, folic acid and choline normalized homocysteine levels in 17 of 19 patients. [1] TMG lowers homocysteine levels with and without vitamins B12, B6 and folic acid."

Enough about TMG, on to the more pressing matter. This overly basic understanding of biochemical processes which perpetuates ignorance is the bane of health forums. Yes excess homocysteine is bad, but did you know very low homocysteine is also bad? Of course you didn't. You want lowish homocysteine but you don't want it nonexistent, you still need it. Low homocysteine will compromise your ability to synthesize taurine, sulfate, cysteine, and glutathione (which needs cysteine), all required compounds in the human body. We want to have to some homocysteine but we want it being converted to important compounds.

When someone deals with manifestations of excess histamine such as urticaria, supporting methylation will almost always improve the condition. Often these people need more methyl groups not less due their genetics. This is not going to promote cancer. Its like saying dietary choline promotes cancer, which becomes TMG in the body anyways to be used in methylation. The body makes its own TMG all the time from choline. We shouldn't consume choline either then. We will all get organ failure, fatty liver, severe dysautonomia, and muscle damage from choline deficiency but at least we can't get cancer...

There is no black and white on what someone does and does not need. Each human has individual needs and thus every health situation has different possible solutions and treatments. You cannot just slap some thiamine on them like a band-aid on every problem. This applies to methylation, this applies to iron, this applies to PUFA, this applies to the use of pharma drugs even, this applies to every health related topic full-stop. There is nuance to everything and if you haven't realized that by now, I don't think you ever will.

I did some digging last night. I downloaded my raw dna sequence from 23 and me and then I searched for some genetic mutations that decrease methylation / increase histamine intolerance.
I am heterozygous for all of these mutations:
COMT V158M
COMT H62H
VDR BSM
VDR Taq
MTHFR C677T
MTR A2756G
MTRR A66G
MTRR K350A
BHMT-02
I know these mutations are common, they’re present in like 30% of white people. So I don’t think I’m completely screwed. But there is a lot of different information I’m coming across when reading about each of these mutations. I’m sure it has had an impact on my ability to methylate. For years I’ve only bought methylated b vitamins though.

 

[redsun]

Yep, and it's extremely difficult to safely diagnose a stranger asking for help on a forum.

I read the first paragraph, and the chance of damaging the circulatory system via your proposal did flash out at me; the stranger on the forum that you have never laid eyes on did mention that they did have the covid injection, which is known to attack/cause inflammation of the circulatory system. Seemed important to point out that issue.

Health chemistry is very complicated. Everyone carries a load of toxins that affect their health and their own personal body chemistry. People tend to take notice of what helps them personally. You rely on your personal experiences; I rely on mine. When I'm faced with new health care information that is complicated, I make it a point to research what Ray Peat has said about it. Ray was consistent in his position that increasing methylation is never something he would recommend.

Except if you knew TMG has never been shown to raise homocysteine and in fact it alone is enough to lower it, you would have never said that.

I already know what Ray has said about basically most all of the topics he has covered. And I don't ignore it and oftentimes I will recommend stuff if it makes sense in context , but I use knowledge from research and other health experts. You should never rely too heavily on one expert. You always miss the whole story.

I did some digging last night. I downloaded my raw dna sequence from 23 and me and then I searched for some genetic mutations that decrease methylation / increase histamine intolerance.
I am heterozygous for all of these mutations:
COMT V158M
COMT H62H
VDR BSM
VDR Taq
MTHFR C677T
MTR A2756G
MTRR A66G
MTRR K350A
BHMT-02
I know these mutations are common, they’re present in like 30% of white people. So I don’t think I’m completely screwed. But there is a lot of different information I’m coming across when reading about each of these mutations. I’m sure it has had an impact on my ability to methylate. For years I’ve only bought methylated b vitamins though.

Methylated B vitamins do not add methyl groups. They are in their active forms, but research has shown all forms of activated vitamins are cleaved (lose their phosphate group) in the small intestine when they reach the gut to be absorbed. So for example, Riboflavin 5 phosphate is cleaved in the gut to just free riboflavin. Pyridoxal 5 phosphate is cleaved to pyridoxal. Methyl B12 and methylfolate would provide some methyl, but the actual quantity of methyl from the amount you find in supplements is quite low and would not make much of a difference if any.

You likely need more methyl groups, hence TMG. Activated vitamins will not make a difference here because they dont actually add a substantial amount of methyl.

 

[ThazMYchocolate]

Methylated B vitamins do not add methyl groups. They are in their active forms, but research has shown all forms of activated vitamins are cleaved (lose their phosphate group) in the small intestine when they reach the gut to be absorbed. So for example, Riboflavin 5 phosphate is cleaved in the gut to just free riboflavin. Pyridoxal 5 phosphate is cleaved to pyridoxal. Methyl B12 and methylfolate would provide some methyl, but the actual quantity of methyl from the amount you find in supplements is quite low and would not make much of a difference if any.

You likely need more methyl groups, hence TMG. Activated vitamins will not make a difference here because they dont actually add a substantial amount of methyl.

So when I take methylated B vitamins, I get severely agitated, edgy, anxious and that sort of thing. It doesn't happen in non-methylated versions, which I take pretty big doses of sometimes. What do you think is happening to me, if not getting over-methylated by the methyl groups in them?

 

[ThazMYchocolate]

There is nuance to everything and if you haven't realized that by now, I don't think you ever will.

You may very well be correct in everything you say, but if you address people like they are beneath you I doubt you will get any converts. It's hard for me, at least, to read through your comments because of the air of condescension woven throughout. It's like you could be a brilliant doctor, but have no bedside manner, sometimes you see...being kind to people is more medicine than the prescription. Meaning HOW you talk to people (and make them feel) is more important than how right you are.

 

[redsun]

So when I take methylated B vitamins, I get severely agitated, edgy, anxious and that sort of thing. It doesn't happen in non-methylated versions, which I take pretty big doses of sometimes. What do you think is happening to me, if not getting over-methylated by the methyl groups in them?

B vitamins themselves are very stimulatory in supplemental quantities. But if you are overmethylated or sympathetic dominant, even small amounts of methyl can cause overstimulation and its associated symptoms such as anxiety. Or it could be a specific active vitamin is causing the problem, for example P5P vs pyridoxine HCL will elicit different reactions.

You may very well be correct in everything you say, but if you address people like they are beneath you I doubt you will get any converts. It's hard for me, at least, to read through your comments because of the air of condescension woven throughout. It's like you could be a brilliant doctor, but have no bedside manner, sometimes you see...being kind to people is more medicine than the prescription. Meaning HOW you talk to people (and make them feel) is more important than how right you are.

That is a fair critique. Except I don't write condescendingly like this ever. This is a specific, recurrent issue with this particular user. You are a newcomer so this seems unprovoked. I assure you it is not.

 

[ThazMYchocolate]

B vitamins themselves are very stimulatory in supplemental quantities. But if you are overmethylated or sympathetic dominant, even small amounts of methyl can cause overstimulation and its associated symptoms such as anxiety. Or it could be a specific active vitamin is causing the problem, for example P5P vs pyridoxine HCL will elicit different reactions.

It was the methyl b12 specifically that I think was the worst, maybe the methyl folate as well. I have p5p in my non-methyl b-complex and no issues with it. I take separately folinic acid and hydroxocobalamin and I don't do those every day. But they don't give me the awful feels like the methyl b12/b9.

I also gave my son Renzo's kids vitamins which have methylated B's and I noticed that he was emotionally volatile on them. So I don't know a good vitamin to give my kids anymore. I don't feel like he eats well...mostly chicken tenders (i know, pufa ). I wish I could make him eat healthy and that daddy was on board with no pufa. At least I can get him to drink a glass of milk or 2 a day (he is in kindergarten).

I don't think I have tried the methylated type since I have fixed my thyroid issues, so maybe it would be less of an issue now? My husband hated the methyl-b's as well, even more so than me! I think I remember they gave me headaches too.

 

[mostlylurking]

That is a fair critique. Except I don't write condescendingly like this ever. This is a specific, recurrent issue with this particular user. You are a newcomer so this seems unprovoked. I assure you it is not.

I just can't seem to help myself. High dose thiamine hcl gave me my life back after 30+ years of fibromyalgia/CFS, which included being almost universally reactive to almost all foods and environmental toxins, which was caused by heavy metal poisoning. Some here refer to me (in an endearing manner) as MostlyThiamine. Here's a little something I found to share with you and have a GREAT day! High Dose Thiamine Therapy for Parkinson's Disease Helps Patients Reverse Symptoms. Why? This novel, promising therapy from Italy is little known in the United States, but is being prescribed by neurologist Antonio Constantini with good success.

Two Solutions to Improve the Function of the Methylation Cycle​

1. Since the methylation cycle has been compromised or even side lined completely, a therapy that appears to offer promise (in light of Dr. Costantini’s research) is to take  mega doses of vitamin B1 (thiamine). This supports that ability of the methylation cycle to process the essential conversions to enzymes. “Normal levels†are insufficient to activate the cycle. Most of the unused reside from B1 is simply eliminated rather than used to product the enzymes.
2. Quieting an overactive sympathetic nervous system by dealing with stressful situations with calm and balance and reducing persistent anxiety will directly contribute to bringing a compromised methylation cycle “back on line”. In doing so, Â we add extra “hard drive” and “processing power” that the body now can use to convert the B vitamins to enzymes. Â Once the methylation cycle becomes fully functional, a high dose of B vitamins should no longer be required or necessary.

Robert Rodgers PhD
Road to Recovery from Parkinsons Disease
Road to Recovery from Parkinsons Disease – Natural Therapies for Parkinson's Disease

 

[Ania]

Hi all,
My name is Sarah, I am a 25 year old female. I have been lurking on this forum for 2 years and it is so sad that I finally was able to join the forum about a week ago, and that same day I discovered that Ray Peat passed away.

I apologize for how long this is probably going to be. I will try to make it as brief as I can. I developed cold urticaria around December of 2020. I was on a hike in the winter and I got itchy bumps all over my legs and hands. I thought it must have been something I ate, but then it happened every single time any part of me got cold, ever since then. My face, hands, arms, legs, stomach, anything that is exposed to cold temperatures for more than a few minutes will turn red and develop hives a few minutes into rewarming. Now I can't swim in cold water, etc. because I could develop anaphylaxis (which I thankfully have never had before).

I took accutane in 2019-2020, and got off of accutane in July. By August I discovered Ray Peat, and started loosely "peating" by the fall. I was increasing carbs, reintroducing dairy after 7 years of avoiding it, decreasing PUFAs. A few months later, in Dec 2020, my reactions to the cold started.

I did not see my PCP for my cold urticaria until the spring of 2021 and I did not see an allergist until spring of 2022. The allergist suspected that I developed cold urticaria because of a mycoplasma pneumonia infection, though I did not remember ever being sick. He tested me for mycoplasma pneumonia IgG and IgM and my titers were high so I was positive for that, even though the time of the testing was almost 2 years after developing the reaction to cold. The allergist said he doesn't know how long I will react to the cold, and he recommended me to take zyrtec 4 times per day and famotidine 2x per day but I have not done that. He also recommended xolair injections which I considered for a while and then decided not to pursue.

Some factors in my life that I believe are relevant:
- I had a physical/emotional trauma from my father my whole childhood
- I have had significant anxiety probably mostly related to that trauma, ever since I was about 5
- I had lyme disease 3 times as a teenager, and ehrlichiosis once, all from tick bites.
- I was bullied a lot in school because I had bad acne since I was 12 and I was socially anxious and awkward, this caused a lot of additional stress
- I got the covid vaccine against my will when my work mandated it to keep my job in healthcare, though I had already had cold urticaria for 6 months by that point
- I was diagnosed with PCOS when I was 19, which I know is related to thyroid function, stress, and estrogen, and all those issues can cause urticaria issues
- I have known estrogen dominance from DUTCH testing in 2019, and I did a repeat dutch test in 2021 after 1 year of "peating" and all of my levels improved (stress hormones went down a LOT, testosterone excess went down, progesterone went up)
- I still had estrogen dominance in my 2021 DUTCH test.
- For birth control I do fertility awareness method, and I do ovulate every month since 2020 and I get my period every 32-35 days which is a huge improvement as I used to rarely ovulate and my period would skip every few months.
- I know that stress hormones like cortisol are immune suppressants. They were off the charts in my 2019 DUTCH test. When I finally lowered my stress levels significantly by eating more pro-metabolically, I wonder if that allowed my autoimmune condition (cold urticaria) to show itself.

I can attach screen shots of my DUTCH tests from 2019 and 2021 if that would be helpful.

When I gave in and took accutane for 9 months in 2019-2020, it was because my acne was severe. At the time of starting accutane I was doing low carb, high fat and intermittent fasting. I was eating tons of nuts and seeds and nut butters instead of carbs, taking fish oil, avoiding fruit and almost all carbs, which I don't do any of that now. My hair was falling out, my face was puffy, my acne was horrible, and I was in denial that all the "healthy" fats could cause that, so I kept telling myself my symptoms were just because I didn't take my carbs low enough for PCOS, and I was convinced for about 2 years that low carb, close to keto, and intermittent fasting was best for insulin resistance which was the "root cause" of PCOS, but I now know insulin resistance is just a symptom of a bigger metabolic problem.

I had thyroid testing done in spring of 2022 because I was convinced my cold U and my PCOS must be related to my thyroid. My results came back "normal" i will add those numbers here:

TSH.

1.06 uIU/ML

0.400 - 4.100 uIU/ML

Free Thyroxin

1.0 NG/DL

0.80 - 1.90 NG/DL

Free T3

3.3 PG/ML

2.2 - 4.2 PG/ML

Thyroid Peroxidase Antibody

10 IU/ML

<35 IU/ML

Thyroglobulin Antibody

<15 IU/mL

0 - 115 IU/mL

Long story short if anyone has any advice for me, what to try, what to eat, what to test, please let me know. My PCP, allergist, and endocrinologist, have nothing to offer me except telling me to take antihistamines and avoid cold. I do take hydroxyzine daily only at night and it helps with sleep and anxiety as well as the itchiness of the reactions.
Other supplements I take:
Inositol 1 tsp 2x per day
vitamin D3 5,000 IU a few times per week
vitamin K2 a few times per week
vitamin E every day with dinner
beef liver capsules
magnesium glycinate every night

I try to not let my stress and anxiety overwhelm me. I spend a lot of time in nature (though it's harder now in the winter because it's cold).
I spend time with my boyfriend and people that love me. I try to stay hopeful that my body can heal itself and wants to heal itself. I try to tell myself I am resilient and young and I will be ok.

I developed chronic urticaria at the age of 18. It was not connected to cold. However to this day I do not know what triggers it.
For the last thirty years I have been on antihistamines. For a long time it was Zyrtec, but about 4-5 years ago I switched to cyproheptadine 1 mg daily. Many years after first symptoms I discovered I had Lyme disease, who knows for how long. I also developed many other symptoms like rheumatoid arthritis, which proved to be connected to food sensitivities. Now I control it with diet. I can get sensitive to any food or drink if I ingest it more than once daily. My immune system treats it as a danger offender and starts attacking it. Once I develop sensitivity, it is irreversible. When I recognized this pattern, I was already left with very few foods.
I have learned how to function. But urticaria never disappeared,(although it is very well controlled with antihistamines).I thought about connection with lime, because not long ago I met someone who had almost exactly the same symptoms as mine. And the person said she had lime disease. I started thinking that lime can probably influence immune system so that it stars to act irrationally and goes crazy.
Mine is totally screwed.
You said you had lime 3 times.
Did you treat your lime immediately each time?
Are you sure you got rid of it?
I would check it if I were you.

 

[summergirl]

I developed chronic urticaria at the age of 18. It was not connected to cold. However to this day I do not know what triggers it.
For the last thirty years I have been on antihistamines. For a long time it was Zyrtec, but about 4-5 years ago I switched to cyproheptadine 1 mg daily. Many years after first symptoms I discovered I had Lyme disease, who knows for how long. I also developed many other symptoms like rheumatoid arthritis, which proved to be connected to food sensitivities. Now I control it with diet. I can get sensitive to any food or drink if I ingest it more than once daily. My immune system treats it as a danger offender and starts attacking it. Once I develop sensitivity, it is irreversible. When I recognized this pattern, I was already left with very few foods.
I have learned how to function. But urticaria never disappeared,(although it is very well controlled with antihistamines).I thought about connection with lime, because not long ago I met someone who had almost exactly the same symptoms as mine. And the person said she had lime disease. I started thinking that lime can probably influence immune system so that it stars to act irrationally and goes crazy.
Mine is totally screwed.
You said you had lime 3 times.
Did you treat your lime immediately each time?
Are you sure you got rid of it?
I would check it if I were you.

I have had my blood rechecked for Lyme a few times due to the symptoms I have been dealing with over the years. It always comes back negative. But I have a lot of antibodies because I’ve had Lyme so many times so it sometimes comes out equivocal. (Because they are just testing for antibodies and can’t tell if it’s an active infection)

When I had ehrlichiosis (it was a bacteria from a tick in my blood eating my white blood cells and platelets leaving me with a suppressed immune system and petichae on my legs)

I literally felt like I had blood cancer for 9 months when I had ehrlichiosis, before I finally went to the doctor. I was a junior in high school and I was trying to just get through SAT’s etc. it had to get to the point that I had colds and flus constantly, I had a low body temp like 97.2 for months, then I donated blood at school, basically passed out, then that day I developed a 102-103 fever that lasted 2 weeks, I had chronically low blood pressure, splitting headaches that felt like my brain was going to explode, THEN I went to the doctor. Then I was tested for tick diseases and it took them 2 weeks and they figured out it was ehrlichiosis.

With Lyme I think I had it treated fairly quickly each time. Because the symptoms came on so fast and obvious. I don’t remember if my antibiotic course was long enough each time I was treated. I took doxycycline each time. I have no idea if I have chronic Lyme or chronic ehrlichiosis

Now that we are talking about this, I think I should be re-tested or maybe try to seek out a Lyme specialist

 

[mostlylurking]

I developed cold urticaria around December of 2020.

I developed chronic urticaria at the age of 18.

I just wanted to share an article with you both that includes another perspective on urticaria. It's written by Dr. Derrick Lonsdale and is posted here.

Here's part of it:
"After the second injection she developed urticaria. This was again a signal through the autonomic system that delivered a message to histamine releasing cells in the skin.

Oxidative Stress and the Brain​

Let me try to explain these symptoms because I can assure you that they are all related to the brain. In particular, I am referring to the limbic system of the brain, that part of the brain that computes our adaptive mechanisms through the autonomic nervous and endocrine systems. The reference to the hippocampus makes it clear that the limbic system is involved because this is an important organ within that system. We can sum up the situation by saying that this young lady is now maladapted to her physical and mental environment.

When this part of the brain suffers from reduced energy efficiency from defective oxidative metabolism in mitochondria, it becomes erratic in the way it reacts to input signals delivered through the sensory system. This continuous process of brain and body signaling is how we adapt to our environment throughout life. We have to go back to the writings of Hans Selye whose professional career was spent in studying the effect of physical stress in animal systems. He reported his work as “The General Adaptation Syndrome” and referred to the diseases of mankind as the diseases of adaptation. I would have preferred to call it the diseases of maladaptation. What Selye emphasized throughout his writings was that it was consumption of energy that was required for adapting and its failure resulted in the syndrome that he described.


Now we know that the mitochondria are responsible for producing energy required for this, the General Adaptation Syndrome makes perfect sense. When Selye was doing his work, the biochemistry of energy metabolism was in its infancy. Now we have much more information about oxidative metabolism and energy production. Until recently, any mitochondrial dysfunction was considered to be invariably genetic in origin. We are now aware that it can be acquired as a result of environmental stress that results in insufficient energy to meet the mental or physical demand."

"We are suffering from an epidemic of biochemical rather than psychological disease. Of course there is a genetic principle behind it; there always is! The smarter the child the greater the dietary risk. This should be fairly obvious to anybody because, like our cars, the better the car the better the fuel has to be. Because the brain, central nervous system and the heart are the most oxygen consuming tissues in the whole body, it is hardly surprising that they are the first to succumb. They are the organs most affected by vitamin B1 deficiency that causes beriberi. This vitamin, like a spark plug in a car, is a necessity to the oxidation of glucose, the primary fuel used by our cells, particularly in brain. Of course, it is not the only non caloric nutrient required, but its association with energy metabolism is clearly dominant."

-end paste-

more via the link above.

 

[L_C]

Of course I lost you, you are a one trick pony. There is so much to human biochemistry and here you are parroting the same thing over and over again. I have never seen you not recommend thiamine for anything. You are a broken record.

You are suggesting the thing I recommend to someone is actually dangerous and toxic. This is very wrong.

Yes TMG, as in betaine, a naturally occuring compound in the body that is made endogenously from the oxidation of choline via choline oxidase to be used in methylation and also in water balance in cells. How do you think you deactivate histamine, catecholamines, make melatonin, make phosphatidylcholine endogenously, creatine, synthesize DNA, synthesize myelin, and regulate gene expression? Methylation.

Due to the fact that genetic mutations dealing with methylation enzymes are common, TMG actually is a good way to prevent the elevation in homocysteine that can occur because of them. These gene mutations can predispose someone to histamine intolerance. This is why TMG is also used to lower histamine. It is unbelievably simple and not to mention safe. Theres more that can be done but TMG is a simple way to get started.

TMG is used in BHMT to recycle methionine and become DMG. And after that it will also make 3 methylenetetrahydrofolates which can be converted to methylfolates which will also be used to recycle homocysteine. There is no homocysteine made from the TMG itself. It literally recycles it and lowers it. And the link you are using to refute me actually proves my point for me. Maybe read past the first paragraph next time?

"Multiple studies have demonstrated that medium to high levels of plasma homocysteine are associated with increased risk of heart disease, cerebrovascular disease and peripheral artery disease. In one study, daily treatment with TMG, folic acid and choline normalized homocysteine levels in 17 of 19 patients. [1] TMG lowers homocysteine levels with and without vitamins B12, B6 and folic acid."

Enough about TMG, on to the more pressing matter. This overly basic understanding of biochemical processes which perpetuates ignorance is the bane of health forums. Yes excess homocysteine is bad, but did you know very low homocysteine is also bad? Of course you didn't. You want lowish homocysteine but you don't want it nonexistent, you still need it. Low homocysteine will compromise your ability to synthesize taurine, sulfate, cysteine, and glutathione (which needs cysteine), all required compounds in the human body. We want to have to some homocysteine but we want it being converted to important compounds.

When someone deals with manifestations of excess histamine such as urticaria, supporting methylation will almost always improve the condition. Often these people need more methyl groups not less due their genetics. This is not going to promote cancer. Its like saying dietary choline promotes cancer, which becomes TMG in the body anyways to be used in methylation. The body makes its own TMG all the time from choline. We shouldn't consume choline either then. We will all get organ failure, fatty liver, severe dysautonomia, and muscle damage from choline deficiency but at least we can't get cancer...

There is no black and white on what someone does and does not need. Each human has individual needs and thus every health situation has different possible solutions and treatments. You cannot just slap some thiamine on them like a band-aid on every problem. This applies to methylation, this applies to iron, this applies to PUFA, this applies to the use of pharma drugs even, this applies to every health related topic full-stop. There is nuance to everything and if you haven't realized that by now, I don't think you ever will.

What biochemistry book would you recommend for the beginners? Thank you.