Many Mentally Ill Have Histamine-methylation Ratio Imbalance

[Ben]

I tried Benadryl last night to see how it effect me, expecting positive effects. I found that it gives me the same helpless, depressed, feeling as caffeine. It lasts until the next day.

Ben, what dose of Benadryl did you take? I had a similar horrible experience at a 50mg dose which lasted over 24 hours, but at only 12.5mg it had almost the opposite effect.

The Last Psychiatrist wrote an article on the pharmacology of Benadryl, which explains that at different doses it doesn't just have different strengths, but acts as a totally different drug:

The drug has the most affinity for H1 receptors, sure, but look what else it does. M1 blockade (dry mouth, constipation, confusion.) It also has significant NE and serotonin reuptake blockade. Basically, the FDA decided to pick only one of these four properties and slap it on the box, in the same way as labeling a TV dinner as "Rice."

The Last Psychiatrist: Treating Insomnia With Less

I took 3 tablets in total, which I think is 75 mg. By opposite effect, what in particular do you mean? Better mood and more physical and mental energy? Funny that 12.5 mg would have the best effect on someone if each tablet is 25 mg.

 

[Suikerbuik]

A quick reply on what I mean with system and ignorance, besides scientific community - mindset (ego) and putting an immense value on publishing papers.

I also mean that it is us, ourselves, too. We want science to come up with a medicine, so we suffer as little as possible (fear for pain is common for everyone). We expect science to cure cancer or at least make it not deadly. We want everything arranged and secured for tomorrow, because of OUR fears for the uncertainties. We want everything as easy as possible because most of don't want to think about this.

We need to take our own responsibility too, maybe people on this forum came to realise this and do. Most people don't. Who wants to give in on things while ours neighbours possibly won't? It's not only science that is wrong, anyway we're going a bit off topic now :).

 

[CellularIconoclast]

I took 3 tablets in total, which I think is 75 mg. By opposite effect, what in particular do you mean? Better mood and more physical and mental energy? Funny that 12.5 mg would have the best effect on someone if each tablet is 25 mg.

When I took the 50mg dose I felt depressed, had severe brain fog, and no energy as well as mild visual hallucinations (walls moving, etc.).

The 12.5mg dose was while having allergy like symptoms from intestinal bloating, likely from gut histamine production. I had brain fog, a headache, runny nose, etc. This small dose seemed to eliminate the psychological symptoms, but I can't prove it wasn't a placebo effect.

 

[Kasper]

@Ben Did you know that histamine H3 antagonists have very similar effects as modafinil has ? It seems like H1,H2 and H3 antogonist all work very differently.

 

[mouse]

I found that the advice for treating histamine by increasing methylation only works for a subset of people with high histamine, and that increasing methylation worsens histamine for others. This is well known for a long time as one can find advice to limit folates and other methyl doners in those with high histamine if one looks for it. The preponderance of posts and blogs from those who have high histamine and cannot improve despite increasing methylation is another sign of the limitations of this simplistic theory. I can reliably increase my histamine problems by increasing almost any aspect of methylation, including copper, and have seen the same happen to a friend who also has high histamine.

I found the comments about high-histamine-low-copper people amusing as I haven't yet engaged in killing people.

 

[Ben]

I found that the advice for treating histamine by increasing methylation only works for a subset of people with high histamine, and that increasing methylation worsens histamine for others. This is well known for a long time as one can find advice to limit folates and other methyl doners in those with high histamine if one looks for it. The preponderance of posts and blogs from those who have high histamine and cannot improve despite increasing methylation is another sign of the limitations of this simplistic theory. I can reliably increase my histamine problems by increasing almost any aspect of methylation, including copper, and have seen the same happen to a friend who also has high histamine.

I found the comments about high-histamine-low-copper people amusing as I haven't yet engaged in killing people.

Histadelics are often overloaded with folate. It traps methyl groups by creating methyl-tetrahydrofolate, worsening their ability to metabolize histamine. So apparently you weren't increasing methylation, but reducing it further. How do you know you have low methylation and high histamine anyway? Did you even test your copper and absolute basophil levels?

Not that I recommend methyl donors. Restriction of methyl donors has great benefits like longer lifespan, and methylation of DNA is a normal aspect of aging. There are different ways to reduce histamine and its actions, and shift the imbalance. Then there are substances healthy in general. CO2, for example, demethylates DNA, and reduces both histamine and serotonin.

 

[Sirkama]

Are there any other good anti-histamines? Cyproheptadine is seemingly unavailable in Norway.

 

[Suikerbuik]

Even though it is not completely related to the initial subject. I can't resist posting this here, regarding the discussion we had.

http://www.nytimes.com/2014/05/15/h...sex-bias-in-early-studies.html?src=rechp&_r=0

For decades, scientists have embarked on the long journey toward a medical breakthrough by first experimenting on laboratory animals. Mice or rats, pigs or dogs, they were usually male: Researchers avoided using female animals for fear that their reproductive cycles and hormone fluctuations would confound the results of delicately calibrated experiments.

That laboratory tradition has had enormous consequences for women. Name a new drug or treatment, and odds are researchers know far more about its effect on men than on women. From sleeping pills to statins, women have been blindsided by side effects and dosage miscalculations that were not discovered until after the product hit the market.

Now the National Institutes of Health says that this routine gender bias in basic research must end.

“Every cell has a sex,” Dr. Clayton said in a telephone interview. “Each cell is either male or female, and that genetic difference results in different biochemical processes within those cells.”

Margaret McCarthy, a neuroscientist at the University of Maryland School of Medicine who studies sex differences, agreed that the new policies will meet resistance. “The reactions will range from hostile — ‘You can’t make me do that’ — to, ‘Oh, I don’t want to control for the estrous cycle,’ ” she said.

 

[Blossom]

Are there any other good anti-histamines? Cyproheptadine is seemingly unavailable in Norway.

You could look into benadryl (diphenhydramine) it is a first generation H1 antihistamine that some forum members use. Forum member 5magicbeans mentioned doxylamine as another option in a previous post.

 

[Kasper]

What about quercetine ?

 

[charlie]

Ray Peat mentioned atropine in his newest newsletter. Awesome newsletter, btw.

 

[mouse]

I found that the advice for treating histamine by increasing methylation only works for a subset of people with high histamine, and that increasing methylation worsens histamine for others. This is well known for a long time as one can find advice to limit folates and other methyl doners in those with high histamine if one looks for it. The preponderance of posts and blogs from those who have high histamine and cannot improve despite increasing methylation is another sign of the limitations of this simplistic theory. I can reliably increase my histamine problems by increasing almost any aspect of methylation, including copper, and have seen the same happen to a friend who also has high histamine.

I found the comments about high-histamine-low-copper people amusing as I haven't yet engaged in killing people.

Histadelics are often overloaded with folate. It traps methyl groups by creating methyl-tetrahydrofolate, worsening their ability to metabolize histamine. So apparently you weren't increasing methylation, but reducing it further. How do you know you have low methylation and high histamine anyway? Did you even test your copper and absolute basophil levels?

Not that I recommend methyl donors. Restriction of methyl donors has great benefits like longer lifespan, and methylation of DNA is a normal aspect of aging. There are different ways to reduce histamine and its actions, and shift the imbalance. Then there are substances healthy in general. CO2, for example, demethylates DNA, and reduces both histamine and serotonin.

This methyl-trap is in reference to a deficiency of mb12 in relation to mthf. mb12 is one methylation supplement that worsens histamine, hence methyl trapping isn't the culprit.

I'm not sure where you got the idea that restriction of methyl doners is beneficial. This sounds like another excessively simplistic and incorrect idea. There's more than a few papers in pubmed that refer to undermethylation in relation with various illnesses. My reading suggests that the appropriate methylation of appropriate things is more important than gross levels of methylation.

 

[pboy]

Charlie...did he mention it in a positive or negative light? Im quite interested because I actually seem to function better when I take in more methyl donors and less nightshades (atropine) I find they make me a bit nervous feeling and mess with breathing. I cant recall ray talking much about acetylcholine and methylation much...but in terms of why he considers caffeine similar to a vitamin, I assume its because it can spare b6 b9 b12 choline and betaine via its methyl donating capability. The excess purine base becomes uric acid before excretion and based on what ray says on other osmolality increasing molecules he might also consider that a metabolically useful function. But you hear many things about uric acid being negative as far as joints and kidney health are concerned

 

[charlie]

"Shock, inflammation, resistance, epigenetics" May 2014

"Drugs, such as atropine and cyproheptadine, which limit the reduction of body temperature, are also protective against shock(Irwin, et al., 1999; Fuentes, et al., 2006; Zhang, et al., 1992)"

I guess this wasn't really directly related to the discussion in this thread, but I just remember him mentioning cyproheptadine and atropine together. Also, atropine has been coming up recently in discussions here a couple times.

 

[Blossom]

Here is a quote from Peat on the topic of methylation for his January 2014 newsletter.
Ray wrote:

Genetic fadism in medicine has been increasing because of advertising for genetic tests sold directly to the public. Many people have been disturbed to learn that they have a "mutation" in a gene called MTHFR. This is an extremely common variation in a gene that relates to the activity of an enzyme that regulates methylation, i.e., the attachment of single carbon atoms to a great variety of molecules in the body.

People who have the less active form of the enzyme have a slightly higher requirement for one of the b vitamins, folate (which is found in fruits, vegetables, milk, cheese, eggs, liver,etc.) Several other nutrients, vitamins b2, b6 and b12 are involved in the regulation of folate and methylation. Large numbers of people have begun using a variety of supplements that are supposed to increase the bodies methylation capacity. Oddly it seems that the testing companies, as well as most of the doctors talking about the methylation system, haven't been talking about the association of that"mutant gene" with a much lower risk of cancer. In recent years excess methylation of DNA has been associated with stress, cancer, and aging. Choline, an important methyl donor, has been associated with prostate cancer risk (Assad,etc all.,2012).

 

[Kray]

Here is a quote from Peat on the topic of methylation for his January 2014 newsletter.
Ray wrote:

Genetic fadism in medicine has been increasing because of advertising for genetic tests sold directly to the public. Many people have been disturbed to learn that they have a "mutation" in a gene called MTHFR. This is an extremely common variation in a gene that relates to the activity of an enzyme that regulates methylation, i.e., the attachment of single carbon atoms to a great variety of molecules in the body.

People who have the less active form of the enzyme have a slightly higher requirement for one of the b vitamins, folate (which is found in fruits, vegetables, milk, cheese, eggs, liver,etc.) Several other nutrients, vitamins b2, b6 and b12 are involved in the regulation of folate and methylation. Large numbers of people have begun using a variety of supplements that are supposed to increase the bodies methylation capacity. Oddly it seems that the testing companies, as well as most of the doctors talking about the methylation system, haven't been talking about the association of that"mutant gene" with a much lower risk of cancer. In recent years excess methylation of DNA has been associated with stress, cancer, and aging. Choline, an important methyl donor, has been associated with prostate cancer risk (Assad,etc all.,2012).

Can someone translate for me? What is the opinion, that it is best to look for them in this form if you have methyl. problems, or no, regardless? I have used these and they contain both phosphorylated and methylated forms. I don't know what this all means. I bought them mainly because they had no fillers and seemed high quality. Can you help me understand this better? :?

http://www.iherb.com/Metabolic-Maintena ... =null&ic=1

Many thanks,
C-lady

 

[Ben]

I'm not sure what significance phosphorylation has for vitamins, but avoid methyl donors, like methylated vitamins. Methyl donors are not good because they increase DNA methylation and suppress genes like anticancer genes. DNA methylation is also a normal part of the aging process. If you have a problem with high histamine, try out antihistamines, anticholinergics, copper or copper-containing foods like oysters, and avoid excessive amounts of protein, particularly muscle meat, because the L-histidine gets converted into histamine in the body.

 

[Kray]

I'm not sure what significance phosphorylation has for vitamins, but avoid methyl donors, like methylated vitamins. Methyl donors are not good because they increase DNA methylation and suppress genes like anticancer genes. DNA methylation is also a normal part of the aging process. If you have a problem with high histamine, try out antihistamines, anticholinergics, copper or copper-containing foods like oysters, and avoid excessive amounts of protein, particularly muscle meat, because the L-histidine gets converted into histamine in the body.

Ben,

Ok, now I see the concerns for methylation others may have been describing. Does this include P5P (B6)? What other particular B vitamins are methylated forms, if you happen to know?

What would be considered "excessive" amounts of muscle meat? What is your understanding of an upper tolerable limit of daily protein?

Thanks-

 

[Ben]

Folate as MTHF (methyltetrahydrofolate)and vitamin B12 as methylcobalamin are the only ones I'm aware of being used.

When it comes to protein intake, it largely depends on your metabolic rate and amount of physical activity (especially weight-training). I don't think it's a good idea to limit protein in general, but limit muscle meat. Instead, consume more of the protein as milk or cheese, or ideally, gelatinous foods. Fruits like pears, apples, and oranges tend to contain low histidine as well.

I found that skipping high-protein foods before bedtime gives me lucid dreams. RP recommends more protein in the morning, and more fat and sugar at night. So if you're going to limit protein a little bit, limit it around bedtime.

 

[Kray]

Folate as MTHF (methyltetrahydrofolate)and vitamin B12 as methylcobalamin are the only ones I'm aware of being used.

When it comes to protein intake, it largely depends on your metabolic rate and amount of physical activity (especially weight-training). I don't think it's a good idea to limit protein in general, but limit muscle meat. Instead, consume more of the protein as milk or cheese, or ideally, gelatinous foods. Fruits like pears, apples, and oranges tend to contain low histidine as well.

I found that skipping high-protein foods before bedtime gives me lucid dreams. RP recommends more protein in the morning, and more fat and sugar at night. So if you're going to limit protein a little bit, limit it around bedtime.

Thanks for the feedback. I guess the meat/histidine issue is individual to the person. How often do you eat muscle meat? Does having gelatin along with it help, such as lamb w/shanks, as Peat suggests? I usually have all the protein sources on a daily basis that you mention. Of total protein, muscle meat probably makes up about 25% of that, usually with some gelatin at some point each day. Does that seem reasonable?

I agree that I feel better with more protein during the busy hours and more carb/fats at night. :)