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Methylation diagnostic impact on supplements

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I have researched the Pfeiffer clinic site on methylate (a histamine test is done to determine this). I have commented for some time that certain supplements are good or bad depending on this diagnostic. The site is fragmented, so I took excerpts and combined them. What it shows is that the same supplements that help one category, actually hurt another. So please be careful!







1. UNDERMETHYLATED, high histamines


GOOD: methionine, SAMe, Calcium, Magnesium, B-6, Inositol, TMG, zinc.


BAD: Folic Acid, B-12, Choline, DMAE, copper




2. OVERMETHYLATED, low histamines


GOOD: Folic Acid, B-12, DMAE, B-3


BAD: methionine, SAMe, Inositol








Notes compiled from all over his site:






UNDER METHYLATED = HIGH HISTAMINES, elevated basophils histamine ( > 70)


Conditions associated with undermethylation: Anorexia, Bulemia, shopping/gambling disorders, depression, schizo-affective disorder, delusions, oppositional-defiant disorder, OCD. most exhibit seasonal allergies, perfectionism, strong wills, slenderness, OCD tendencies, high libido, etc.


hives more undermethylated





methionine and/or SAM are wonderful for high-histamine (undermethylated) persons.


(undermethylated) persons thrive on methionine, SAMe, Ca and Mg, but get much worse if they take folates & B-12 which can increase methyl trapping. Generally, OCD patients respond nicely to methonine, SAMe, calcium, magnesium, B-6, Inositol, TMG, and zinc.



more than 40% of all clinically depressed men are undermethylated and benefit from therapies which enhance methylation.

High bloodhistamine indicates undermethylation, low serotonin levels




Most OCD patients (both obsessive thoughts AND compulsive actions) exhibit undermethylation and associated low levels of serotonin, dopamine, and norepinephrine. Choline is anti-dopaminergic and often makes OCD patients worse. Most OCD patients get worse if given supplements of DMAE, choline, copper, or folic acid.


Inositol is usually very helpful for UNDERMETHYLATED, HIGH HISTAMINE patients. This includes nearly every OCD patient we have seen. Inositol usually provides calming throughout the day and ability to settle down to sleep at night, for these patients.


Some practitioners like to tinker with the SAM cycle to promote conversion of homocysteine to methionine, but this can deplete the cystathione pathway and result in deficiencies of glutathione, cysteine, etc. Some persons have a genetic enzyme weakness which can disrupt the SAM cycle


Undermethylated adults typically require 2,000 - 3,000 mg/day of methionine for several months to see good results. Also, augmenting nutrients such as calcium, magnesium, B-6, and zinc are essential.


Personally, I believe the use of SAMe is the quickest way to help an undermethylated, high-histamine person.








Overmethylated persons generally exhibit anxiety, absence of seasonal allergies, presence of food/chemical sensitivities, dry eyes, low perspiration, artistic/music interests/abilities, intolerance to Prozac and other SSRI's, etc.


Conditions associated with overmethylation: Anxiety/Panic disorders, anxious depression, hyperactivity, learning disabilities, low motivation, "space cadet" syndrome, paranoid schizophrenia, hallucinations. (Oct 3, 2003)






?Over methylated do well on B-12 and folates?? ??


methionine and/or SAMe usually harm low-histamine (overmethylated persons)




Many anxious children are overmethylated and thrive on DMAE which passes the blood-brain barrier and enhances acetylcholine (which suppresses dopamine). Since DMAE tends to lower Dopamine, Norepinephrine, and Noradrenaline..... anxiety may be lessened and expressive language improved. Of course, DMAE is effective only for children who have a genetic tendency for elevated levels of these three neurotransmitters.


DMAE is usually indicated for children who are "space cadets" who have high anxiety, little motivation for learning, and poor organization. DMG is usually indicated for intense children who are strong willed, competitive, and exhibit obsessive/compulsive tendencies. (Oct 1, 2003)


On the other hand, OVERMETHYLATED patients usually derive little or no benefit from Inositol, and may experience very nasty side effects from it.


another 15% or so are overmethylated and need to head for the other goal line...... namely avoidance of methylating supplements and use of folate therapy.




histamine deficiency. After studying the metabolism of more than 20,000 schizophrenics he learned that this

"low histamine" syndrome was common in anxiety, panic disorders, and classical paranoid schizophrenia. His enormous biochemistry database revealed that most histapenics suffered from (1) copper overload and (2) deficiency of folic acid and/or B-12. More importantly, he found that aggressive therapy using folic acid, B-12, and B-3 (note: niacin) usually produced dramatic improvements in these persons.






Use caution if you have depression or bipolar disorder and are taking or considering taking inositol. There is a possibility that manic episodes may occur.

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Very Confusing as my son has TS, ADD and OCD. What is good for the ADD, may not be good for the OCD. In the ADD Formula by Buried Treasure found at www.lifelinefoods.com there is DMAE and Phosphatidyl Choline. Also finding vitimans without preservatives so far both I know of available to me have choline, B12 and copper.


I know this ADD formula is helping him, I notice a difference if I run out and he doesn't have it for awhile, but it doesn't do anything for the OCD. What if you have symptoms from both lists, how do you determine if you are high or low?

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The symptoms are very overlapping, I agree. It is very confusing to do it by symptoms!


Re the histamine test, I think that Direct health care only does the pyroluria test. They referred me to http://www.labcorp.com/ for the histamine test, but it needs a doctor's signature. I am going through Pfeiffer next week.


Still the pyroluria test alone is a great start. So often these things are comorbid, which complicates things. That's why I like the histamine test.



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I have been reading a great book called "optimum nutrition for the mind" by Patrick Holford. He is an english guy who I believe was trained by Pfieffer himself. He has a web site called: www.mentalhealthproject.com where you can fill out a questionaire with all your symptoms and it will suggest which tests you should have done. Quite interesting (except is you are answering for a child - it asks questions about your sex life - a bit hard for a 12 year old??!!??)


Anyway, he doesn't mention Tourette's at all in his book, but for symptoms of undermethylation it add lots of other symptoms:


Sneeze in sunlight

Cry/salivate or get nauseated easily

Abnormal fears/compulsions/rituals

Light sleeper

Fast metabolism

Depression or suicidal thoughts

Produce lots of body heat

Little body hair and lean build

Large ears or long fingers and toes

Good tolerence of alcohol

Inner tension or driven feeling

shy or oversensitive as a child

Obsessive or compulsive tendencies


At another place in the book he says histamine causes allergic reactions (which we knew, right) but also causes a tendencecy to hyperactivity. He also says you produce too much saliva and therefore tend to have no or only a few cavities.


I know at Pfieffer they do a test for absolute basophils, but in Holford's book he says that if you have a standard blood test (I guess this is what we call a full blood count in Australia) and your "basophil count" was high, this is an indicator of high histamine status.


His recommendation is 2g vitamin c as this is an antihistamine, 15mg zinc, 5mg manganese and at least 50mg of b6. He said is you have undesirable symptoms, also supplement 500 mg calcium and 500 mg methionine morning and night. He says the calcium releases the bodies stores of calcium and the methionine detoxifies the histamine by ading methyl to it.



He goes into more details about overmethylation as well, but my little one is having a hissy fit in the other room, so I must go.



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This is great stuff! I would love to hear the over methylated summary too--for contrast. Please do post it! I know that they don't ever discuss tics--someday our stats will be tracked also--our kids have so many of the same underlying conditions.


I know about the basophil test (Direct health care does it). I thought it was step 1) histamine test, step 2 as needed for confirmation basophil test. I think Nancy E said Pfeiffer did the histamine test.


I need to ask Pfeiffer about manganese. They recommend it with the zinc (too litte zinc can cause depression, too much zinc can cause depression, so the manganese is needed), but then they say that manganese isn't good for people with Tourettes! I don't know if that applies to tic syndromes.


Just like Omega 3's are desirable, but for some with pyroluria it is actually bad. So many factors to balance, it is such a challenge.


I like Pfeiffer because they record data on 1000's of patients and try hard to be so organized in creating subcategories. Though their site is a maze....




ps Please do post the other info. I thought that 'anxious depression' was over methylated, while normal depression was undermethylated.


I want to have this test done for myself too.

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The baby is asleep now, so....


Holford suggests overmethylation symptoms are:


More body hair

More liklihood of being overweight

rare headaches or allergies

high pain threshold

suspicious nature


extreme fears, phobias and paranoia


I believe from what he says, it is more the copper overload causing the symptoms for this profile.


Did you go to www.mentalhealthproject.com ?


I was fascinated. I did the questionaire, and I know what my problems are, and it picked it perfectly. I suggested a thyroid problem, and yes, I am having issues with this at the moment.


My son's came up undermethylated at about 70% and pyroluria only 30% (but i wanted to check it out anyway after all the success's I had heard about here) and when we did that test, it was negative, only 5.4 so I want to ask the doctor for the full blood count as I cannot find anyone here in Australia that does the absolute Basophils or whole blood histamine.


First I am trying to get rid of all the additives as per my conversations with Auslare. I can't believe all the additives that cause problems. i thought we were doing really well on cutting the stuff out. We are also trying gluten/casien free, but not really seeing much difference with it.



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I don't know how I missed that link--it is awesome!! Thanks!!


Others here--great test there, and info on causes of various conditions and supplements recommended


Mine showed 'no major imbalances'. Of course, if I had taken this test a few years back...it would have been different. My highest things were

Heavy Metal Toxicity (which I definitely have), and

High Homocysteine (which I suspect, based on my own reading of symptoms).


I really want both my son and I to have the homocysteine and histamine tests done.



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A friend sent me a link from the Dr. McCandless board. Sorry no link.


This may explain why Pfeiffer didn't give Nancy the methalothonien (sp). Remember, this basically is used for autism and we are looking at it for other issues as well.


This all of course relates to the MT promotion therapy, which they claim can resolve the diet restrictions, mercury and yeast issues.






Methylcobalamin: We have learned about even more benefits of the methylcobalamin than we knew at the last conference, and the evidence is that 90% of our kids benefit to some extent, some remarkably so, with injectable M-B12, and many of them without other treatments per Dr.

Neubrander's experiment of giving it to children immediately when they first come see him and during awaiting the results of the other routine testing.

I believe every child deserves an adequate trial of this treatment, and evidence so far is that other ways of getting it may be somewhat beneficial for a few kids, but the difference in the kids getting the injections is impressive.


Methionine: I have been hearing of some bad reactions to large dose methionine, and asked Jon Pangborn about it. He feels that methionine in large doses is not a good idea for this reason: Methionine's metabolism gets stuck at SAM, and some then goes to methionine sulfoxide until the SAH-Hcy-Met synthase log jam is opened up (possibly by methylcobalamin).

Methylation cannot be pushed by methionine when S-adenosylhomocysteine is elevated. SAM can't push it either; not until SAH is normalized. And after SAH is normalized, more recycle of Hcy to Met and more Met should occur, making large doses of Met unnecessary. Methionine acts as a reducing agent, but bottom line is: there are lots of safer antioxidants like vitamin C and GSH.


I would suggest this not be used unless your doc recommends and supervises it.


Further notes from Dr. Deth re high dose methionine: "There are overlaps

between methylation problems in schizophrenia and methylation problems in autism. One of the most robust observations (replicated in ten different

studies) is that the administration of high doses of methionine can elicit acute psychotic reactions in schizophrenics, while having no such effect in normal individuals. Increasing methionine levels above normal would impair dopamine-stimulated phospholipids methylation, since the D4 receptor and methionine both compete for MAT activity." On this same topic, Teresa Binstock writes: "The fact that gastro/nutritional pathologies might alter these (methionine) pathways is exciting. The possibility that, by altering fetal nutrient profiles, placental irregularities might alter these pathways is exciting. But willy nilly rushing forth to therapize a specific child by manipulating these interrelated pathways seems fraught with risk for at least a small subgroup. Manipulations at the level of histones and epigenetics ought be highly respected because such manipulations are altering a fundamental element within mammalian life (the histone and epigenetic modification). Another notation by Dr. Shaw offering another reason for possible toxicity: "Methionine can be converted by abnormal gut flora to methanethiol, one of the most toxic gases there is. Methanethiol has been implicated as a significant factor in hepatic coma. The toxic effect of methanethiol is amplified in the presence of elevated ammonia which has also been reported in autism by Drs. Boris and Bradstreet."


...A very recent article in Am J Med Genet, 2004 May, 15;127B(1):51-9, Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation, by Abdolmaleky, HM et al from Dept. of Psychiatry, Harvare Med Sch at Mass Metal Health Center, Boston, MA.


Some selected notes from the abstract: Fine-tuning of neuronal connections during development is regulated through environmental interactions. Some fine-tuning occurs through changes in gene expression and/or epigenetic gene-specific DNA methylation states. Known epigenetic mechanisms include RNA inhibition, RNA modification, and DNA rearrangement. Exposure memory expressed as epigenetic DNA modifications allows genomic plasticity and short-term adaptation of each generation to their environment.

Environmental factors that affect DNA methylation include diet, proteins, drugs, and hormones. Induced methylation changes may produce altered gene response upon subsequent hormonal stimulation. The gene-specific DNA methylation state may be preserved upon transmissioin through mitosis and meiosis. An increasing amount of data implicates a role for DNA methylation in multi-factorial psychiatric disorders. For example, 1-methionine treatment can exacerbate psychosis, while valproate, a drug producing hypomethylated DNA, reduces such symptoms.


Authors state that more studies are needed to define the role of methylomics and other epigenetic phenomena in the nervous system.


Best wishes to all! Dr. JM

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Hi all,


In response to Claire's quote from the website - Alternative Mental Health - I found the website VERY interesting. I did want to mention that on the site I noticed this under the OCD topic:


"A word of caution --- Manganese supplements tend to aggravate Tourette's Syndrome, and can also worsen the symptoms of OCD."


I was not aware that manganese could present these issues and just wanted to share this with others.


Just a quick history:


My son's tics had dissappeared completely over the summer and he was basically tic free for a little over 3 months. Then about a month ago his eye blinking began again along with a vocal tic. They have been present for about 4 wks and he also has had a cold/cough which turned out to be strep. He's now on anitbiotics and I think all the stress between the illness and the antibiotics have made it worse as he's also developed a little hop.


I now have realized that after he received his first flu shot (Oct. '02) is when he developed his first tic - a sort of nasal expelling sound which we thought was related to sinus problems. We treated it with Flonase and using a humidifier and it subsided a lot. It disappeared completely by late spring 03. I gave him the flu shot again last fall '03 again (sadly, I had no knowledge of themerisol) -by around the end of Nov. the nasal tic began again. It subsided until around end of Jan '04 when he developed a vocal tic. That was when we first realized all this may be related to a tic disorder. His tic continued to diminish thru the spring and then we had none over the summer.


I am very interested in the histamine test and also having him tested for heavy metals.. just in the process of finding the right doctor.


Best to all and thanks to everyone for sharing your knowledge,



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Hi Renee,


Yes, I love that site! I had read about the manganese and asked them about it. They said since my son's trigger was only screens it wasn't a normal tic syndrome (remember he doesn't have any now), so manganese was okay.


Basically their view seemed to be If TS, don't use it. Most here are in between---she seemed to feel that if you use manganese watch closely for tics or worsening.


Good luck finding the right doctor. I don't believe in 'perfect' doctors--we still need to do our research. But ours was a godsend. Look at this site--the vast majority who have been searching have gained improvement.



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Guest Guest_Kimberly


My daughter's tests from Pfeiffer showed she does have elevated histamine (undermethylation). One of the supplements prescribed for her is Methyl B12 Sublingual 1000mcg. I had heard from several sources that B12 isn't good for people with tics. I thought one of the causes of tics is that their level of dopamine is too high. The paper I was given from Pfeiffer says that undermethylation results in LOW levels of serotonin, DOPAMINE, and other neurotransmitters. In your research have you found that kids with tics have high levels of dopamine or low levels? I am confused on this and would love any feedback you can give me.



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I have never heard of that Kimberly. Only that B12/folate was not great for undermethylated people--and that came from Pfeiffer. Yet they 'prescribed' it for your and Nancy's children. Go figure!


We do B12 with no issues.


I think this undermethylation is very common in this group. Please let us know if you notice improvement or not with the treatment.



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  • 3 weeks later...

Hi! This panel is new to me. But I just had my son evaluated at pheiffer and his results were pyloguria, high histamine, malabsorption and heavy metal. He was previously diagnosed HF Autism or PDD. I have not yet started their vitamin regeme yet but have ordered and waiting for them to come in. I have been using some vitamins to experiement myself. Finding lots of improvement on the Calcium/Magnesium and B12 w/Folic. I've just ordered a B12 without Folic and looking forward to trying it out. Also, have noticed a big improvement on the Casin/Gluten Free diet although it seems almost impossible. I try to cut these foods down but not completely out and that has seemed to help. I have also recieved a enzyme chewable and I'm hoping he will take it. That is supposed to help on the malapsorptions of these proteins. When I try these others I will let you know.


Nancy Smith

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