A close friend sent me the following information and told that these symptoms apply to him extremely well. Knowing him, I tend to agree. If he is right and indeed has "Under-methylation/HISTADELIA" why can't he use antihistamines? I looked up the proposed treatments within the limited time and knowledge I have and none seem to mention antihistamines...?! Any drugs out there at all that can help?
Thanks



>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Under-methylation/HISTADELIA

Individuals with high-histamine levels may be due to a metabolic imbalance that results from under-methylation. As a consequence, these individuals overproduce and retain excessive levels of histamine. Histamine is a substance in the body that has wide ranging effects. There are receptors for histamine in the brain, stomach, skin, lungs, mucus membranes, blood vessels, etc. For some individuals, high levels of blood histamine (called histadelia) have psychological, behavioral, and cognitive symptoms.



Many patients with obsessive-compulsive tendencies, "oppositional-defiant disorder," or seasonal depression are under-methylated, which is associated with low serotonin levels. Often with inhalant allergies, frequent headaches, perfectionism, competitiveness and other distinctive symptoms and traits. Tend to be very low in calcium, magnesium, methionine, and vitamin B-6 with excessive levels of folic acid. People with histadelics have a positive effect from SSRIs and other serotonin-enhancing medications (Paxil, Zoloft, Prozac, Celexa, Effexor, etc.) because methylation is a step in the manufacture of mood stabilizing neurotransmitters. Unfortunately, histadelics often have nasty side effects with these medications.



Histamine excess can be manifest as asthma, vasomotor rhinitis, allergic skin disorders with pruritis, excess stomach acid production (acts as a gastric hormone to stimulate flow of HCl), saliva, tears, and thin nasal and bronchial secretions, and certain types of vascular headaches. This is the basis of anti-histamine medications. Excessive histamine results because of the inadequate methylation in liver detoxification. Histamine opposes adrenalin in its effects and as expected fatigue occurs just as it occurs in adrenal exhaustion.



Biochemical treatment revolves around antifolates, especially calcium and methionine. Certain forms of buffered vitamin C can help by providing calcium and ascorbic acid. Three to six months of nutrient therapy are usually needed to correct this chemical imbalance. As in most biochemical therapies, the symptoms usually return if treatment is stopped.



Methylation is involved in DNA synthesis, masking and unmasking of DNA, detoxification, heavy mental detoxification, nerve myelination, carnitine and coenzyme Q 10 synthesis. The relationship of mood and behavior to Histadelia is due to the fact that methylation is involved in neurotransmitter synthesis.

As kneejerk reflex I tend to agree, at least in part.

High histimine also manifests in premature ejaculation in men....an effect usually alleviated by the addition of varying degrees of methionine. However, females with anorgasmia, histimine has helped in many cases....of course, one would need to exercise caution is taking histimine until they can be sure they don't have an allergic reaction.

Hmm... I don't know why antihistamines aren't used. I'm sure it wouldn't hurt if he tried them. I think it's better to use one that doesn't cross the BBB like reactin, but that won't change histamine activity in the brain.

Because the unwanted mental effects from histamine are derived from the H3 receptor, using a selective antagonist for it would be preffered. When the H3 receptor is activated it inhibits the release of a wide range of neurotransmitters including DA, NE, GABA, 5HT, and ACh. Unfortunately there are no commercially available H3 antagonists, although 2 are being researched:

http://en.wikipedia.org/wiki/ABT-239
http://en.wikipedia.org/wiki/Thioperamide

Just FYI: the hypothalamic histamine H1 receptor plays some role in feeding rhythms and mediates the effects of leptin, at least in rats.

Why not attack the methylation problem directly.

http://www.hsfighters.com/ has methylfolate available without a prescription.


If there is any validity to the above quote, then that seems like a case of MTHFR SNP, which makes methylfolate even more attractive.

Just some ideas.

Betahistine (Lacour and Sterkers, 2001). ?

Yeah, betahistine would be perfect. Don't know how I missed that one

Just 'cause there's no where else to put it

Thanks so much for all of these great responses.

The paper attached -unless I am reading it wrong- states that histamine reduces food intake and hunger through Leptin mediated pathways in the brain. Unfortunately this individual has very high appetite and will never feel full. Given that, can we still speculate that he has too much histamine? Is there some kind of unusual disorder in literature where the hypothalamus is exposed to too little histamine while the rest of the brain and nervous system gets too much....?


RE Betahistine; is this a selective H3 antgonist which crosses the BB barrier? If anyone has any suggestion with regards to where to get this cheaply and easily please PM. No, I am not going to feed this to anyone just yet. But if later, after further deliberation, this continues to look like a good option, it would be ideal to know how to get some.

You read it right.

Could H1/H3 downregulate when exposed to chronic high histamine levels? Since histamine acts downstream of leptin, leptin resistance could explain the appetite(?).

Don't understand the ins-and-outs of what's goig on here. It's late - just dug up the first betahistine abstacts I found .

Ned Tijdschr Geneeskd. 2004 Nov 20;148(47):2338-41.Links
[Delirium in a 73-year-old man after many years of unwise use of betahistine][Article in Dutch]

A 73-year-old man was admitted because of delirium that had already persisted for 5 days. The physical examination and extensive tests did not reveal any somatic pathology. The only drug he used was betahistine, taken for several years because of supposed Ménière's disease. After withdrawal of betahistine and treatment with haloperidol the patient recovered completely within a few days. A new delirium was induced when, after discharge from the hospital, betahistine was restarted because of dizziness. There was again a complete remission after betahistine was stopped and haloperidol was restarted. Betahistine is not known to induce delirium, but an investigation in side-effects databases did reveal several cases in which delirium might have been present, even though the term was not actually used. In this case, delirium was possibly caused by the combination of an elevated betahistine plasma level and a damaged blood-brain barrier due to cerebral infarctions, which were revealed by CT and MRI.

Betahistine dihydrochloride interaction with the histaminergic system in the cat: neurochemical and molecular mechanisms.

Brahim Tighilet, Suzanne Trottier, Christiane Mourre, Carole Chotard, Michel Lacour
UMR 6149 "Neurobiologie Intégrative et Adaptative", Université de Provence/CNRS, 52 Faculté de Saint Jérôme-Case 361, F-13397 Cedex 20, Marseille, France. tighilet@up.univ-mrs.fr
Drugs interfering with the histaminergic system facilitate behavioral recovery after vestibular lesion, likely by increasing histamine turnover and release. The effects of betahistine (structural analogue of histamine) on the histaminergic system were tested by quantifying messenger RNA for histidine decarboxylase (enzyme synthesizing histamine) by in situ hybridization and binding to histamine H(3) receptors (mediating, namely, histamine autoinhibition) using a histamine H(3) receptor agonist ([(3)H]N-alpha-methylhistamine) and radioautography methods. Experiments were done in brain sections of control cats (N=6) and cats treated with betahistine for 1 (N=6) or 3 (N=6) weeks. Betahistine treatment induced symmetrical changes with up-regulation of histidine decarboxylase mRNA in the tuberomammillary nucleus and reduction of [(3)H]N-alpha-methylhistamine labeling in both the tuberomammillary nucleus, the vestibular nuclei complex and nuclei of the inferior olive. These findings suggest that betahistine upregulates histamine turnover and release, very likely by blocking presynaptic histamine H(3) receptors, and induces histamine H(3) receptor downregulation. This action on the histaminergic system could explain the effectiveness of betahistine in the treatment of vertigo and vestibular disease.

J M Arrang, M Garbarg, T T Quach, Dam Trung TuongM, E Yeramian, J C Schwartz
The actions of betahistine (N alpha-methyl-2-pyridylethylamine) on brain histamine receptors were investigated in a series of biological models.

[3H]Mepyramine binding to H1-receptors in membranes from guinea-pig cerebellum was inhibited by betahistine with a Ki value of 31 microM. The binding of [3H]mepyramine in brain of the living mouse was inhibited by betahistine in high dosages (150-300 mg/kg). In slices from mouse cerebral cortex, betahistine induced [3H]glycogen hydrolysis in a concentration-dependent manner with an EC50 value of 9.0 microM with a maximal effect 57% that of histamine. Mepyramine and triprolidine, two H1-receptor antagonists, inhibited the betahistine-induced glycogenolysis with Ki values of 28 nM and 7 nM respectively. In slices from guinea-pig hippocampus, betahistine stimulated the accumulation of cyclic AMP in the presence of 5 microM impromidine, a H2-receptor agonist. The maximal effect represented 22% of that elicited by histamine at the H1-receptor and the EC50 value was 32.4 microM. Mepyramine at 0.1 microM partially blocked the response to betahistine. Together these various observations indicate that betahistine is a partial agonist at cerebral H1-receptors. Finally, betahistine was not an agonist at histamine H3-autoreceptors but was a rather potent antagonist of the inhibitory effect of exogenous histamine on [3H]histamine release elicited by K+ depolarisation in slices from rat cerebral cortex (Ki = 6.9 microM).

What are the advantages/disadvantages of the common methyl donors; folate, TMG, SAM-E, methionine?

Folate-- if you are in the 50% of the population that is at least heterozygous for the MTHFR polymorphism, then you can't convert folate into MTHF efficiently. If you are homozygous, well you'd probably be fucked.

TMG--secondary pathway

SAMe-expensive, and without adequate MTHF ultimately results in homocysteine.

Best option= L-methylfolate(MTHF).

Metafolin(MTHF) is available above 800mcg by prescription, at 800 available from hsfighters.com and metagenics(fola-pro).

Since many people in this forum use/have used SSRIs it is worth pointing out that folate influences/predicts response to anti-depressants and that Deplin(7.5mg MTHF) is approved as an adjunct for anti-depressants in the US. www.deplin.com has some interesting info.

I read somewhere that folic acid was bad for people with under-methylation...

Lynx have you tried the MTHF? Notice anything compared to the usuals?

I am just trying it now, and have stopped taking my normal multi which has folic acid, and I really think it is making a difference. I don't know why I didn't do this before, because I know that I am heterozygous for the MTHFR polymorphism.

I am finding that my current 5mg/lexapro + 300mg/wellbutrin is fucking kicking ass. However, I have to note that I live pretty far north in the SAD zone, and the light is coming back. Also, I just switched from Carlson/Nordic regular mixed fish oil to Carlson DHA. So, there are a lot of factors. However, all together I am feeling great.

This is from a Charles Poliquin article at T-Nation.

"If your urine reeks after eating asparagus, congratulations! You officially have a genetic defect and can't methylate asparagine properly. Apparently, prevalence of this defect is on the rise in the US and is a red flag for Parkinson's disease, Alzheimers, and prostate cancer amongst others. Try jacking up your methyl donors such as folic acid and B12 to turn off that gene."

Is this valid? Mine always has after eating asparagus and still does despite adequate amounts of folate, B12 and a gram of TMG per day.

I haven't looked at the cofactors required for asparaginase so i don't know about that, however, 50% of the population is heterozygous for MTHFR, meaning you can't convert folic acid to MTHF efficiently.

asparagus only?

my pee smells after eating asparagus, and also after eating tuna

in tuna's case, what is the cause? under-methylation? tks

Here's something from Wikipedia.......

Some of the constituents of asparagus are metabolized and excreted in the urine, giving it a distinctive smell. This is due to various sulfur-containing degradation products (e.g. thiols and thioesters) and ammonia. Recent studies suggest that every individual produces the odorous compounds upon eating, but that only about 40% of individuals have the genes required to smell them.[10][11] The speed of onset of urine smell is rapid, and has been estimated to occur within 15-30 minutes from ingestion

If this is so, then Poliquin's statement is moot regarding urine odor being an indicator of methylation.
But, is it possible that methylation allows the expression of the gene required to smell these particular compounds?

gee

would we be concerned about unusually high blood levels of this product encouraging excessive methylation, and/or the problematic changes that occurred in rats?

I believe that so far the rat research used SAMe, which will ultimately become homocysteine without MTHF around to recycle it. If there is other research let me know.

??????????????????

In the meantime, I have looked at Betahistine and it certainly appears promising.

In addition, Dilantin (Phenytoin) is coming up quite often as a cure for depression caused by excess histamine. For example: http://www.healthrecovery.com/HRC_2006/Dep...ler_coaster.htm
(do a search for Dilantin)

Finally, I have asked my friend why he wasn't taking anti-histamines and he said that when he did as a teenager, it gave him some arrhythmia and he was thus taken off of them.

So, we have those 3 choices. It appears that 1 and 2 would be better. Which of the first 2 would you recommend? For now, we are looking for maximum efficacy to first and foremost test whether this MOA will work. If it does, we can then focus more on long-term dangers of using such a medicine. Without the usefulness of the drug being established, I think we shouldn't worry too much about the hypothetical case of what would happen if these are used for the long-run.

Thanks to all

Wow, I haven't heard any talk of Dilantin for many years. Jack Dreyfus, founder of the Dreyfus Fund, was a major proponent of this drug after it helped him with severe endogenous anxiety back in the mid 1960's. He established the Dreyfus Medical Foundation to study and promote the use of Dilantin for psychiatric disorders.

http://www.remarkablemedicine.com/

Hey Sub7,

I think you have another option, that is to rebalance the methylation/histamine.

Indeed...

What I am proposing is the following.

Step 1: Get a script for either medication and see if they make a big difference.
Step 2: -if they do, we will conclude that the problem is indeed caused by histamine and work on the methylation issue so that we can reduce the dose of the drug, and maybe even eliminate it
- if the drug doesn't work, the issue is likely not methylation/histamine related

In the past i've strongly suspected myself to be histapenic, based sollely on my intolerance of SAMe, Inositol & CoQ10, all of which make me feel very manic and anxious. On the other hand I;ve allways had very strong histamine reactions to the smallest stimuli (simply brushing a fingernail accross my forehead, back or chest will leave a histamine filled elevated trail / bump) and have allways had plenty of alergies to pretty much anything, which kind of makes me think I may be histadelic. Today I did the niacin flush test (http://www.latitudes.org/forums/lofiversion/index.php?t2056.html, no idea how correct this is, feel free to comment), and it indicated high histamine, so i;ve gone ahead and ordered 2 weeks supply of betahistine. I'll keep you updated of any results.

Hmmmmm……no explanation of what you meant by gee.
Is it short for gee whiz?
Perhaps said as a sarcastic remark for my stating something incorrectly or so obvious and simple to a cognoscenti such as you, graatch?

no, I liked your comment, and I said "gee" because I became confused and curious

In looking up info on histadelia, I'm running across info on niacin. I keep seeing pseudo-science-ish sites claiming that schizophrenics have high histamine, and that the niacin flush is in part due to high histamine, but...




And "if" the niacin flush really is related to histamine release (ie "50 mg nicotinic acid -> flush), then why wouldn't you take 50 mg ED until you acclimate due to sufficient release, thus lowering histamine levels ("histamine exhaustion", if you will), then up to 75 mg, 100mg, until you have to take 100-150 mg to achieve a flush, thus indicating normal histamine levels?

Bust.

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.
Prostaglandins (Prostaglandins) 1989 Aug; 38(2): 263-74

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.

Guess I misinterpreted your "gee" and got a bit confrontational. My bad.
Most of you guys know WAY more than I do. I just try to learn and offer a tidbit here and there if I can.

Article by Dr. Amy Yasko. "Biomolecular Nutrigenomic Analysis of the Methylation Cycle".

http://www.holistichealth.com/Publications...300F4B835B.html

I've since read some criticism of her mission, methods and credentials. But, that's Maloney's opinion. http://www.maloneymedical.com/id86.html

Never the less, it might be of interest.

OK Ladies and Gentlemen,

Here is an update: He started taking Methionine (500 mg 4 times a day, for a total of 2,000 mg/day) and it made a big difference, absolutely great improvement...
As the next step, he will talk to his doctor about Betahistine as well as Dilantin. My suggestion was to get a small amount of both and try them for a brief period each before going back to the doc for a reevaluation.

Can you please suggest a dosing regimen if one were to do such an experiment? Would it be sufficient to try each of these for a week with a few days off in between? Or would you need to be on these things for a longer period of time to assess their full effects? Also is it sufficient to take a few days off from the first before repeating the same experiment with the second medicine or would a longer break be required?

Thanks to all

What are his improvements, specifically?

His racing mind has calmed down a great deal and excess itchiness on arms and around the nose area subsided. The depressive episodes which used to occur every 4-5th day (and last half a day to a full day) haven't surfaced in 15 days; the resulting improvement in his mood is remarkable...

If he takes methionine he should control homocysteine right?. It is recommended to take TMG, B6 and folic acid,but from your post folate is not good.

Why methionine and not SAMe?.

YOU'RE DOING IT WRONG. Moar double-blind placebo experiments with moar subjects and a control group, amirite?

"High or low histamine levels are considered by some of the alternative medicine community to be health issues; this is not accepted by the mainstream medical community."

"this is not accepted by the mainstream medical community"

"this is not accepted"

"not accepted"

Can you please explain? Do you mean that histamine cannot be to high or too low? No matter what one's serum histamine levels are, there can never be any adverse consequences?

According to this site: http://www.nutritional-healing.com.au/cont...ical%20Subtypes,
and this site: http://www.alternativementalhealth.com/articles/walshFL.htm, people with high histamine shouldn't take DMAE, choline, centrophenoxine, etc., because it increases acetylcholine which "lowers dopamine, norepenephrine, and noradrenaline." I've actually tested myself, and my histamine levels are quite high. Further, I've found benefit from antidepressants and SAM-e. However, I'm skeptical about this claim regarding acetylcholine, since this supposed suppression would not be of aid to a lot of people with ADD, and I know a lot of people here have ADD and have supplemented with a choline source. Such a trial should result in disaster, but I'm guessing that it hasn't. So, my question is whether the claim that acetylcholine reduces other neurotransmitter levels is bull. What do you think?

Jason

It's not entirely bullshit -- acetylcholine definitely suppresses dopaminergic transmission (and vice versa) in some contexts. This is one reason anticholinergics are sometimes used in Parkinson's disease, where dopamine has flown the coop -- the imbalance between the two systems is thought to cause certain symptoms.

And there's no question that histamine encourages acetylcholine release in some contexts.

But it's all a lot more complex -- this is why I don't know how useful the histadelia stuff is. The interaction varies depending on the specific system or area of the brain we examine.

For these reasons, though, I do think that cholinergics alone are generally not so helpful for ADD. They may have more use when used in conjunction with a dopaminergic ... some people speak of a downstream anticholinergic effect from methylphenidate. I'm not sure how much validity this has.

Note that in this post I'm referring to muscarinic acetylcholine, not nicotinic acetylcholine (of which nicotine is an agonist) which is thought to actually have (in some contexts!) an antagonistic relationship with muscarinic acetylcholine ...

I read somewhere, probably not a scholarly resource, that rabbits, for their size, have an unusually high resistance to opioids of all kinds, and also that this was somehow linked to their extremely high levels of blood histamine.

We also know that nicotine ---> endogenous opioid release downstream, eh?

When I take enough alpha-gpc, it's almost like an anti-opioid, inasmuch as I need to be doing something rewarding at all times or I become dysphoric, whereas opioids seem to "let me be" and I can lie around, or fly a kite, or whatever.

Update: So I've got my shipment and betahistine and ran it for a few days @ 48mg/ day without any noticeable results. Then I recieved my shipment of methionine and have been taking it for almost a week @ 2200mg+ per day and that shit is awesome! I feel full of beans, clear headed and happy. i did not expect it to work anywhere near as well, as i;ve tried SAMe few years back and did not like it.
Question, methionine raises homocysteine right? I am currently taking a whole lot of b6 (40mg or so a day), what else should I be supplementing with?

Folate and B12

You sir are entirely correctly, however:

1. Histadelia is still a fantasy internet illness
2. Even if histadelia wasn't a fantasy internet illness, a generalized set of non-specific symptoms doesn't entitle one to make a definitive diagnosis in the absence of a medical professional

Honestly everything people describe here could also be a symptom of hypothyroidism. Of course, you wouldn't know that, unless you got a blood test. Similarly, you don't know what your histamine levels are until you get a blood test.

Even if you believe histadelia is as real of an entity as hypothyroidism, you must appreciate that hypothyroidism also shares symptoms with other problems (hypogonadism, sleep problems, depression, chronic infection, etc) and distinguishing between them can only be done through testing and observation.

Posting up images that have the word "SCIENCE" written over them and trying to sound scientific is nice but your own statement is extremely unscientific. How in the world have you proven a negative? How did you reach the conclusion that someone CANNOT suffer symptoms due to excess histamine?

FYI, the individual I described has already been diagnosed with high histamine levels and as a child was put on anti-histamines which he then had to stop due to arrhythmia (as I already had explained in my earlier post).

Long Live Scieeeeence

I never stated some wildly divergent level of histamine isn't going to cause you problems, but the fact remains histadelia is still a fantasy internet illness.

Science is knowledge gained through observation. Not shit some alt-health fag made up you e-diagnose yourself with, without testing at all.

If you really want to help whoever the dude is, get him a fucking blood test, making assumptions / playing doctor is going to be very unreliable and get you more placebo effects than anything. But the greater harm is not allowing the guy to actually be diagnosed/treated through the medical system, such as it is. Again, how the fuck do you know he doesn't have hypothyroidism? You don't, and neither would a doctor, UNTIL THEY DID SOME MOTHERFUCKING TESTING.

PS,



OH YEAH BABY, I CAN PASTE IN 4CHAN IMAGES.

Why don't you read what I already wrote twice in this thread. He has been diagnosed with excess levels of histamine as I said. I will ask him to dig up the blood results for precise numbers. I wrote this already.

...and "the greater harm is not allowing the guy to actually be diagnosed/treated through the medical system"
what? you serious? how the hell did you conclude I am not allowing the guy to be diagnosed by the health system? As I indicated very very clearly, he sent me a link, which I posted here. After discussions in this thread, I told him about methionine and he bought some from his local Vitamin Shoppe. That's all there is to it. He is seeing a few doctors actually and I would have to be stupid to tell him that he should stop seeing them.

again, if you read what I wrote first, your comments would make more sense.