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You are highly likely having some problems related to this area of the physiology. I hope you have a good doctor who knows their methylation stuff, you are likely going to be a tough case. The mthfr 3 and mtrr a66g are both large roadblocks but with homozygous mut’s with both 158 and 62 comt genes and mao a, you are probably not going to handle mb12 or methyl donors very well. Some people are exceptions to that rule, you wouldnt know until you tried.
Another cbs 699. Alot of chronically ill people have it but i didnt expect it to be this prevalent in this crowd. Try out the cbs protocol- no sulfur foods and add in some molybdenum and/or yucca root if you wish. If you feel better and clearer, you will know you’re expressing it and should stick with it. Its a first priority mutation anyway and you will tolerate any methyl supplementation better if it is a problem and has been resolved.
As far as the nos mut’, no one could put it better than heart fixer, I doubt there is anyone more familiar with its implications than him, here is what he has to say:
In a BH4 dependent reaction, Nitric Oxide Synthase (NOS) converts Arginine in to Nitric Oxide, the molecule that resists plaque formation, vasospasm, and abnormal clotting. If you can make and maintain Nitric Oxide then you will not develop cardiovascular disease. If you have cardiovascular disease and if we can successfully reboot your Nitric Oxide system, than we can stabilize your disease. Every maneuver in drug and non-drug cardiovascular medicine that improves patient symptomatic status and outcome works on this system. Every risk factor (or causative factor for cardiovascular disease) compromises Nitric Oxide generation or maintenance. NOS is also involved in ammonia detoxification, a job that distracts it from its Nitric Oxide generating duties and which uses up BH4. Without adequate levels of BH4 Nitric Oxide Synthase will not convert Arginine in to beneficial Nitric Oxide, but rather in to undesirable free radical species such as superoxide or peroxynitrite.
The NOS D298E abnormality codes for a dysfunctional NOS enzyme. It has trouble breaking down ammonia and it has trouble generating Nitric Oxide. NOS (+) individuals are at greater risk for developing all forms of cardiovascular disease, for experiencing adverse events, and for restenosis following balloon angioplasty. A component of “a positive family history of cardiovascular disease” is related to genes coding for high cholesterol, elevated lipoprotein (a), and iron over absorption. The rest likely relates to inherited abnormalities in NOS, ACE, and the other Methyl Cycle genes. If you are NOS (+) we will pay particular attention to maneuvers designed to lower your ammonia burden, and to address risk factors that compromise Nitric Oxide. As the products of a compromised or genetically abnormal NOS system are the free radicals superoxide and peroxynitrite, aggressive antioxidant supplementation makes sense here (while a broad spectrum program of antioxidant supplementation is always wise, we specifically use Vitamin C to neutralize superoxide and 5-methyl folate to neutralize peroxynitrite). I give two separate two hour presentations on Endothelial Dysfunction, which we have on cassette tape (we will likely have a DVD presentation available late next fall). BH4 supplementation has been demonstrated to improve Nitric Oxide generation and endothelial function in individuals with risk factors such as hyperlipidemia, and we presume that it will do the same in individuals with Methyl Cycle abnormalities.
Having both a cbs mut’ and nos mut’ is an ammonia double whammy, I urge you to try out some yucca root, you might really benefit from it. Do you have bad brain fog by chance?
This lady summed up the acat mut’ perfectly:
Again, this mutation, if it is being expressed and is causing a problem, needs a very good doctor that is very familiar and experienced with treating this particular area of the physiology to be properly treated.
If you have any emotional/ psychological issues, armed with the knowledge of the comt and mao a mut’s, you could possibly do well with some targeted supplementation regarding those. The couple of docs I talked to and follow regarding those will generally treat them last, fyi. Again, a doc very familiar with treating those conditions bio-medically will go a long way.
How familiar are you with the methyl cycle and all that goes with it? Have you been to heartfixers page and how well do you understand it? You could really use an ace doctor, if you dont have one, I might be able to help recommend one.
Just out of curiosity, what symptoms and conditions do you and your family have that are on the checklist I put together, if you dont mind?