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impossible
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Deep1111;52311 wrote: Hi impossible, can you please interpret my results as well? If you can suggest me what supplements should I take to bypass mutation ?

These are my homozygous mutations (red):
COMT V158M
COMT H62H
VDR Bsm
VDR Taq

These are my heterozygous mutations ( yellow):
MTHFR A1298C
MTRR R415T
AHCY-01
AHCY-02
AHCY-19
CBS C699T
CBS A360A

Thanks in advance
Deep

Yours is pretty simple. You are the perfect example as to why a person should get a test done before they supplement methyl substances.

You dont have any noteworthy holdups in either your folate or methionine cycles, congratulations. You have mutations that are noteworthy, however, in another way. Your body is quite lethargic when it comes to breaking down dopamine and norepinephrine. The body “deactivates” them by attaching a methyl group to them. Because of this downregulation of useage of methyl groups, it would be incredibly easy for you to have too many methyl groups in your body. For this reason, you should stay away from not just methyl forms of vitamins, but it would probably be a good idea for you to stay away from methyl donors in general, you run the risk of becoming “overmethylated” very easily. You can find lists online. A hetero 1298 mutation isnt a huge deal, made even less problematic by your comt mutations. Low 1298= low bh4. Bh4 is required to make some neurotransmitters, since your not breaking dopamine down, your also not using up as much bh4 to make it. You might want to look up dopamine precursors, even dietary, and see if avoiding them helps you feel better if it is a problem for you. Tics, panic disorder, and bipolar disorder can all be related to too much dopamine, among other things im sure.

Your cbs 699 mutation could be causing you some problems, which would become worse if you started spinning the cycle faster with supplementation. That is actually an upregulation that basically results in the body making too many sulfur compounds, even toxic ones, and ammonia. This can have quite profound negative effects in some people, particularly those that are homozygotes. Treatment basically consists of minimizing or not eating sulfur compounds and if necessary supplementing with small amounts of molybdenum which the body needs to convert toxic sulfites into non toxic sulfates, and yucca root, which mops up ammonia.

Here is what heartfixer says about it:

CBS initiates the trans-sulfuration pathway, converting homocysteine in to cystathionine and its downstream metabolites. This is the most important Methyl Cycle defect and is present in 90% of the patients who we have tested. The CBS defect is an up regulation. CBS is operating at up to ten times its normal rate. Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. The C699T and (to a somewhat lesser extent) A360A defects are associated with CBS up regulation. Homozygotes (+/+) will be more severely affected than will be individuals heterozygous (+/-) for a CBS abnormality. We treat CBS ( +) individuals with dietary animal protein and sulfate restriction and supplements designed to neutralize ammonia and speed up clearance of sulfite/sulfate. Laboratory findings consist of an elevated urine sulfate level, a low or low normal blood homocysteine level, an elevated or high normal blood ammonia level, and positive findings of ammonia, sulfite, or sulfite upon Asyra testing. My initial observation is that individuals with high heavy metal burdens upon provocative challenge testing are likely to be CBS positive. CBS (+) individuals will be intolerant to sulfur containing drugs, nutritionals, and foodstuffs (I am +/- for CBS A360A and cannot tolerate DMPS or glucosamine sulfate. A cold beer tastes great but I do not like wine, which is high in sulfite).

Biochemistry – The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate, which stimulate the stress/cortisol “fight or flight” response), excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia), hydrogen sulfide (producing “brain fog”), and alpha-keto glutarate (leading to “excitotoxicity”). The G6PDH enzyme system may be affected, leading to abnormalities in sugar control. Methylation intermediates will “fall through this drain”, so the entire system suffers; our defenses against viral invasion and toxicity suffer. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy.

Ammonia is produced during the metabolism of dietary protein. The CBS up regulation drains methyl cycle intermediates in to ammonia, more ammonia than your system can handle. Ammonia detoxification is metabolically expense, using up two molecules of BH4 per molecule of ammonia. BH4 is necessary to generate neurotransmitters (dopamine, serotonin, and norepinephrine) and nitric oxide, our key vasoprotective molecule. Thus it is easy to see how a CBS up regulation, by generating ammonia and depleting BH4, can set you up for neurological, psychological, and cardiovascular disease states. We cannot change your DNA. We cannot stop CBS from generating excess ammonia, but if we restrict animal protein in your diet, we can decrease your ammonia burden, preserving BH4, such that you can start making neurotransmitters and nitric oxide again – in other words, we can compensate for your genetic challenge. The herb Yucca, Dr. Yasko’s Ammonia support RNA product, and supplementation with charcoal and carnitine will bind up or neutralize ammonia, and add to your dietary efforts.

Sulfite is neurotoxic. Sulfite will be over produced by the CBS up regulation, and then requires conversion in to the less toxic sulfate molecule by the enzyme Sulfite Oxidase (SUOX). SUOX can easily be overwhelmed. Molybdenum is required for SUOX function, and is typically depleted in CBS (+/+) or (+/-) individuals. Molybdenum supplementation (3 drops or 75 mcg of e-lyte Molybdenum twice a day), Boron 3 mg/day, Vitamin E succinate 400 IU/day, and hydroxy-B12 2000 mcg/day are also utilized to speed up SUOX activity.

While sulfate is less toxic than is sulfite, it will stimulate the adrenergic (fight or flight) limb of the autonomic nervous system and stimulate a cortisol stress response, revving you up into an unrelenting biochemical overdrive. If you have a CBS defect, we need to restrict your sulfur intake, at least until your urine sulfate (and your body sulfate burden) has decreased. The amino acids methionine, taurine, and cysteine all contain sulfur; they are concentrated in animal protein (thus the restriction on animal protein intake). Many nutritional supplements (MSM, N-acetyl cysteine, glutathione) that are good for most people are a problem for you. While certain aspects of your health will benefit from these agents, they will add to your sulfate/sulfite overload problem, adversely affecting the Methyl Cycle Defect that is the common denominator to all of your health problems. Many drugs are loaded with sulfur (sulfates, sulfites, metabolically active sulfur), so if you are CBS positive and I treat your hypertension with the diuretic hydrochlorothiazide, your diabetes with the sulfonylurea drug glipizide, and your urinary tract infection with a sulfa containing antibiotic, I will be lowering your blood pressure, lowering your blood sugar, and clearing bacteria from your bladder, but I will also be adding to your sulfate burden, compromising your biochemistry, and contributing to an ongoing decline in your health. I will be treating the manifestations of an underlying problem and at the same time adding to the underlying problem. If I treat your Mercury overload with DMSA or DMPS, I will remove a toxin from your body, but if you are CBS (+), I will be adding to your sulfate/sulfite pool, and sulfate/sulfite overload due to the CBS up regulation is likely playing a key role in your sensitivity to heavy metals and/or your inability to clear them. We can avoid this. We can hold sulfur containing agents until your sulfate burden has come under control. Learn all you can about the sulfur content of foodstuffs, supplements, and prescription drugs. Sulfites and Chronic Disease by Rick Williams (available at the office or at http://www.readingtarget.com/nosulfites) is an invaluable resource. Do not expect us to know the sulfur content of foodstuffs. Some tips on low sulfur eating are included at the end of this document, but do not expect us to tell you what to eat. We can’t do this. We do not have this knowledge. Please attend our monthly Methyl Cycle support groups meetings, and you may sign up for individual (or group) dietary change counseling. It is your responsibility to become expert in this area. I will work with you to phase out high-sulfur drugs and nutritionals from your program, but don’t expect me to get in right every time – please study your food, drug, and supplement labels.

Excitotoxicity – The CBS up regulation leads to excess production of alpha-ketoglutarate, which is converted in to glutamate, a stimulatory neurotransmitter. Under normal circumstances, glutamate will be converted in to GABA, a calming neurotransmitter, but the enzyme systems that convert glutamate in to GABA are compromised by lead and mercury, the clearance of which seems to be compromised in individuals with methyl cycle defects (here is a situation where dysfunction of a genetically abnormal enzyme leads to acquired dysfunction of a genetically normal enzyme system). The result is “excitotoxicity”, stimulatory behavior in autistic kids (“stims”) and anxiety and sleeplessness in adults. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on Excitotoxicity to follow; diet tips in appendix) and by supplementing you with GABA, aiming to restore GABA:Glutamate balance. GABA is initiated at 500 mg once or twice a day, advancing the dose as you see fit by your response.

The VDR (Vitamin D Receptor) Fok defect affects blood sugar control and pancreatic function. It does not affect dopamine metabolism. Dr. Yasko recommends Vitamin K and generalized support of pancreatic function and sugar regulation (low carbohydrate diet, supplementation with chromium, etc.) when the VDR Fok abnormality is an issue.

Methylation is only one chapter of the book, you should get the other panels too.

Just out of curiosity, have you ever had symptoms that would relate to the slowed breakdown of those neurotransmitters and if so what were/are they?