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Not PANDAS, but histadelia we think


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Hi - it was the integrative dr that rec the following but dr keller says go with it and is also looking at using TMG (betaine)

 

we are using 5 mthf (methylated folic acid), B6 with some some magnesium in it and B12. The integrative dr rec'd hydroxy B12 so as not to overmethylate but I'm not sure I get the reasoning and we are changing to methylcobalamin B12. dr keller reckons we should really be using B12 injections as most b12 cycles thru ur system in 4 hours or so whereas injectable lasts for 4 days. DD may not go for that so we are doing sublingual 4 times per day (when we remember).

 

We may use TMG if she recs. it uses an alternate pathway to methylate. TMG is trimethylglycine and was wondering about it and that case study you posted about glycine being used to effectively treat the boy's symptoms... my chem is way too crap to work out the relationship.. could it be loading enough glycine into the system that even crap methylators can use it to rebalance. I'm probably way off mark and showing my scientific ingnorance :)

 

I can see why adding normal folic acid or hydroxy B12 may cause issues as it may lead to more build up of un methylated products...

 

I've found a couple of studies linking histamine and glutamate interations in the brain .. do you know anything in that area? you seem to be the glutamate guru :)

 

But I thought B12 increases histamine levels, which we already have an abundance of. :huh: I guess I need to read that stuff again, ^_^

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From wikipedia -

 

 

The major step in the methylation cycle is the remethylation of homocysteine, which can occur via either of two pathways. The major pathway involves the enzyme methionine synthase, which requires vitamin B12 as a cofactor, and also depends indirectly on folate and various other B vitamins. The minor pathway involves betaine-homocysteine methyltransferase and requires TMG as a cofactor. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms.

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My son respnded well to Benadryl, doesn't even make him sleepy (side note, some kids respond negatively to Benadryl, every child is different). However, I didn't like having to give it to him sometimes 3 times a day on bad allergy days. We have now switched to D-Hist Jr and that helps him.

 

Has your son had a recent sinus infection? Keep an eye open for that. We have had allergy induced sinus infections in my house before. If PANDAS/PITAND, sinus infections can worsen symptoms too.

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Can someone explain how all the methylination stuff results in PANDAS? Or is it just implicated in ocd in general?

 

MaggiesMoon will have to explain the link her doc saw between histadelia and Pandas. But methylation I crudely understand it is just how well your body's chemistry lab is working. It's a discussion around how well or how poorly your body uses available enzymes, minerals and such to conduct its daily chemical transactions. It's basically a look at how well a particular body system is running. It's impact on overall health runs far and wide yet I don't believe it's specific to one ailment. I've seen it discussed on pyroluria, autism and mercury detox forums. My general takeaway is that is your have a poorly functioning methylation system, you're going to struggle with health and ridding your body of toxins and antigens - whether that be allergens, fungus, bacteria or pollutants.

 

What I really like about DUT's link is that is discusses how an under or over-methylating system can respond to one group of supplements vs. another. As we've added B6, zinc and other things recently, my son has improved. It seems to be addressing an underlying need of his body, regardless of what infection or toxin he may be fighting. I'm starting to appreciate that this is a "core" of good health structure that may be life long, beyond disease labels. Very interesting.

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Ok DUT - you are going to have to educate me please. Take pity on a poor art major...Can you give me a methylation for dummies explanation? I mean, I think I get the very very basic idea. But can you give me a tutorial? I think this is good stuff and might be really important - I just don't know what it means! :wacko:

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Hi - I'm awful at explaining and would probably cock it up anyway but this link is a fairly easy and visual explanation.

 

http://www.ceu-usa.com/courses/WC001/test_drive/methylation_cycle.htm

 

I don't get it totally but from what I've read it is important in very many body systems and it would seem to be important in neurotransmitter production (serotonin, dopamine, norepinephrine, melatonin too) and detoxing. it is also a step needed for methionine prodcution and consquently glutathione and is important for scavenging free radicals in oxidative damage.

 

our dd who is compound heterozygote and so has one alelle wrong on two genes, has low metabolites for serotonin, dopa, norepin and is an awful sleeper without melatonin. She also is high histamine not tested but symptom wise would seem variably but always high It will be interesting to see how she does on this regimen...

 

 

I'm trying to get a handle on the immune implications but am wondering if for some the increased histamine production alone (for the under methylators) is the initiating trigger for autoimmune, as is touted in some reasearch (increase H2 -> autoimmunity ...saw a paper where ranitidine aka zantac was used to decrease psoriasis symptoms).

 

 

 

Sorry if this isn't clear but neither is my understanding :)

 

Our PANDAS savvy ped says to especially consider mthfr if you have familial issues with heart/arteries/clots etc due to the increased homocysteine levels...

 

We also have a family history of salicylate sensitivity and assume same in dd as she appears to have problems with yellow food colouring which cross reacts like aspirin according to our immunologist. I suspect she may have more than one impaired pathway methylation and possibly sulphation but I ain't even thought of opening that can yet :-)

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Back to the original topic re histadelia -

 

some foods are high in histamine and some are histamine promoters. Milk is one that is especially high and I've read that some people are histamine sensitive and that a proportion of those who believe they are lactose intolerant are in fact histamine sensitive. Not sure how this could or even would feed into PANDAS looking symptoms but thought it worth a mention....

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oooh - found this which to me was very interesting, as one of my dd's mthfr gene polymorphisms is the A1298C one. She also looks as though she would benefit from biopterin supplementaion from testing and this explains why.. I've italicised the bits I found super interesting and bolded the bit in one of the last sentences that could explain why mthfr means more infections. None of this is substantiated in any way but I intend to go look for some real research etc that might back this up.. found it on some ADHD forum... here it is anyway for what it's worth

 

The A1298C mutation in the MTHFr enzyme affects the conversion of dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4). Less amounts of BH4 will therefore put a strain on the conversion of trytophan to serotonin and tyrosine to dopamine. This will lead to low levels of neurotransmitters such as dopamine, norepinephrine, serotonin and melatonin.In addition the activity level of the COMT enzyme will further affect the levels of dopamine and norepinephrine.

 

COMT: Catechol-O-MethylTransferase is the enzyme involved in the metabolism of dopamine and norepinephrine into subsequent compounds such as HVA and VMA. The rate of activity of COMT will determine how fast these neurotransmitters will be broken down. Mutations in the COMT enzyme (COMT ++ or COMT +-) actually slow down the activity of the enzyme. Normal COMT activity (no mutations) is depicted as COMT --

Mutations in the COMT enzyme will slow down the breakdown of dopamine, therefore individuals who are COMT ++ or +- have higher (as in good) levels of dopamine compared to COMT -- individuals who are rapidly draining their dopamine stores. This condition is further exacerbated if the individual has the A1298C mutation (++ or +-) because their dopamine levels are low to begin with (remember these individuals have less BH4, so less dopamine gets made).

 

Undermethylators: Dr.Amy categorizes individuals who are COMT -- as undermethylators.

One of the ways the COMT enzyme breaks down dopamine is by using a methyl group donated by SAMe (remember it is the universal methyl donor). Therefore a COMT -- individual will be in constant need of methyl groups as they are rapidly metabolizing dopamine. This puts a strain on the Methylation cycle as the demand on SAMe for methyl groups is increased. Think of this as COMT constantly demanding methyl groups from SAMe. If there are issues in the Methylation cycle or Folate cycle that affect the levels of SAMe (which in turn is dependent on the levels of methionine), there will be less methyl groups to begin with and even less to go around. It is like a domino affect. A break or strain in one cycle has a ripple effect on the rest as they are all co-dependent. Less methyl groups -> less methylation -> less RNA/DNA/protein synthesis/heavier viral load due to lack of methylation etc.

 

Overmethylators: These are the individuals who are COMT ++. Mutations make the COMT enzyme slower, so it will not break down dopamine as rapidly. Since it is slower in metabolizing dopamine, its demand for methyl groups is also reduced. Subsequently there is less of a strain on SAMe for methyl groups. So there will be relatively more methyl groups available for other biochemical reactions and to go around the various cycles.

 

Remember these are just relative terms. An undermethylator is low in methyl groups and an overmethylator has a higher store of them, in comparison. Remember one of the reasons we are in this predicament with autism is because we have problems with methylation, regardless of the under or over status.

 

In addition the strain on the BH4 cycle, the amount of BH4 will also affect the functioning of the Urea cycle. BH4 is the rate limiting factor for the Urea cycle. Two molecules of BH4 are necessary to drive the Urea cycle. One molecule will in turn generate peroxynitrite and if the individual has no BH4 left, super oxide is formed. Peroxynitrite and super oxide in combination cause damage to neurons when they accumulate in excess. . Peroxynitrite is a potent oxidant, which is capable of DNA strand scission (breaks open the bonds that keep the two DNA strands bound in a double-helix) , and nitrating tyrosine, all of which wreak havoc on the nervous system, especially a developing nervous system as in children. The ability to detoxify superoxide is facilitated by the enzyme superoxidedismutase (SOD).

 

Urea Cycle: Urea is the chief nitrogenous waste of mammals. Most of our nitrogenous waste comes from the breakdown of amino acids. Breakdown of amino acids results in the production of ammonia (NH3). Ammonia is a toxic compound that is converted into its safer counterpart urea, by enzymes in the liver. Urea is then eliminated by our kidneys. Essentially the urea cycle involves the conversion of ammonia into urea with the help of the intermediates listed below.

Arginine from our diet or from protein metabolism is converted to ornithine and urea by the enzyme Arginase. Ornithine is then converted to citrulline by ornithine transcabamoylase. This is the reaction on the far left side of the pathway diagram. Citrulline is converted back to arginine. This cycling of Arginine through the various intermediates is what converts ammonia to urea.

Arginine is also required for the production of Nitric Oxide (NO) by the enzyme nitric oxide synthase (NOS or eNOS). This reaction is dependent on the levels of BH4 available from the BH4 cycle. Remember two molecules of BH4 are needed to generate Citrulline and NO. One molecule of BH4 will in turn generate peroxynitrite and if there is no BH4, super oxide is formed. If we do not have enough BH4 to go around because of the A1298C mutation, we are going to have trouble with ammonia. Because ammonia is dangerous to the body, any BH4 we have is going to be used to try to get rid of the ammonia rather than to be making neurotransmitters like serotonin and dopamine. Furthermore mutations in the NOS (eNOS) exacerbate the situation as they will affect the synthesis of NO. NO is needed for several functions including secretion of certain hormones, addressing inflammation, killing pathogens etc.In essence if the limited supply of BH4 puts a strain on the functioning of this pathway, excess ammonia will accumulate as there is not enough BH4 to help convert it to urea. In addition the lack of BH4 also creates damaging free radicals like peroxynitrite and super oxide (SOD is needed to detoxify superoxide). Read more: http://adhdldsupport.proboards.com/index.cgi?board=alt&action=display&thread=1126#ixzz1b6k6thkJ

 

 

Sorry if this is off topic from the original question but didn't know what else to do with it....

Edited by dut
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