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You are likely to benefit from methyation support. Despite the fact that you have some of the serious mutations, your comt and vdr taq status mean you should tolerate methylated substances quite well.
You have one, sometimes major, first priority mutation. The cbs 699 mutation is an upregulation, this means that your body pulls homocysteine into the transsulfuration pathway at an increased rate. This further slows down the methyl cycle and unfortunately can create more bad things like hydrogen sulfide and ammonia. Alot of people are intolerant of sulfur containing foods for this reason, one of the most prolific symptoms is brain fog. It puts more stress on the suox enzyme which can deplete molybdenum as well, as molybdenum is the rate limiting compound in the production of that enzyme. Unfortunately, a cbs upregulation also draws cysteine away from glutathione production. Low glutathione is a big, if not the largest, contributor to a state of toxicity and immune dysregulation in the body. Ramping up the methyl cycle creates more homocysteine, which can lead to more sulfur metabolites and make this problem worse or create one if it is not properly addressed. A sulfur free diet (i dont necessarily agree with removing meat from the diet in the way some people say to), a small amount of molybdenum to help the suox enzyme convert the bad sulfur compounds into good ones, and some yucca root to help mop up excess ammonia is the typical protocol. This should be done before addressing the methyl cycle.
MTHFR 677 is the gene most associated with methyl cycle inhibition and all that comes with it. A heterozygous mutation means about a 35% loss of enzyme function. Your body does not convert folate into the form required to generate SAMe (the bodies major methyl donor) as well as someone without this mutation. Methylfolate supplementation will bypass this mutation and is the best and easiest way to deal with this mutation.
Methyl B12 is the substance that is required to turn homocysteine into methionine (the precursor to SAMe). Methyl b12 is also required for other things in the body, such as nerve myelination (quite important). The MTRR gene encodes the information to produce the enzyme that methylates b12. Gene locations 66 AND 664 are the 2 most associated with lowered production of this enzyme, which slows down the methyl cycle. You are heterozygous for both. The MTR mutation is an upregulation and basically means you use the smaller amount of methyl b12 you are creating at a faster rate to turn homocysteine into methionine. This leaves less b12 for other functions. This can be bypassed by taking methyl b12.
From heartfixer on MAO-A:
Monoamine Oxidase A breaks down serotonin, a neurotransmitter that is generated from the dietary amino acid tryptophan, in a BH4 requiring reaction. Many anti-depressant drugs, including the SSRIs (Serotonin Selective Reuptake Inhibitors) work by blocking the breakdown of serotonin. Defects in serotonin metabolism have been associated with mood and neurological disorders. How best to address the MAO A R297R abnormality is not clear to me. As serotonin metabolism is adversely affected, individuals with the R297R defect should avoid large doses of high tryptophan foods (see appendix). High doses of St. John’s Wort, often taken to address depression, could lead to mood swings as serotonin levels fluctuate. Dr. Yasko recommends frequent dosing in small amounts of St. John’s Wort, 5HTP (a tryptophan metabolite), and the Mood S RNA formula if serotonin support is needed.
If it is an issue for you, there is some more information about this mutation on the web. Phoenixrising is a good website to get a better idea, though sometimes conflicting views can create confusion.
My personal recommendations:
Address the cbs mutation first. In some people that makes a world of difference. Also, adding turmeric supplementation can help increase the flow of cysteine into the production of glutathione according to Yasko. I suggest starting low and slow with methylfolate and methyl b12, like 50 or 100 mcgs of each, and work your way up. I would think that using b12/folate at a 2 to 1 ratio would be a good place to start. Adding a few hundred mgs of TMG will help pull homocysteine away from the transulfuration pathway, definitely add that in if you experience a benefit from cbs protocol, though its not a bad idea anyways. Some people experience start up symptoms, which are a usually general feeling of being upregulated or anxious. With an MAO-A mutation, your problems most likely would be related to that. In most it tapers off, but in some it can get gradually worse. Taking 50-100 mg of time release niacin will quench this. Study Dr Lynch, I tend to agree with his latest ideas on supplementing the methyl cycle. The need for potassium can increase dramatically when starting a methyl protocol. When it runs low it can create symptoms of muscle cramps/spasms, anxiety, ibs etc. Low potassium is called hypokalemia, some people can require up to or even more than 1000 mgs to quench those symptoms. Though, not all people get them. Also, starting a methylation protocol can make inflammation/sensitivities much worse, so these things should be under control before embarking on your methyl journey. As always, I recommend being under the supervision of a professional, the more experience they have with this, the better.
Keep us updated 🙂 Good luck!