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Couple of questions

Discussion in 'Genetic Testing and SNPs' started by dbkita, Apr 10, 2013.

  1. caledonia

    caledonia

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    I'm hetero for CBS C699T, but also hetero for at least 3 of the BHMT SNPs. The BHMT SNPs are supposed to be able to cause a CBS like problem, even if you don't have CBS. So if a hetero C699T isn't supposed to be that bad, maybe the addition of several BHMTs in my case is why I was having such problems.
     
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  2. Valentijn

    Valentijn Activity Level: 3

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    5) SUOX S370S (SUOX base pair 1110) seems to have been confused with SUOX S370Y (SUOX base pair 1109).

    There's very little info on either, but basically S370Y is of interest because the mutation was found in someone deceased due to major SUOX malfunction. And that's not too surprising since it's a missense mutation. S370S was looked at in some of the studies which included S370Y, and S370S was found to be innocent of any SUOX-related wrong-doing.

    So it seems like a case of mistaken identity.

    6) CBS A360A and CBS N212N have no impact based on any of the research I've been able to find.

    7) BHMT-01, BHMT-02, and BHMT-04 have no impact based on any of the research I've been able to find.

    8) MTRR R415T, MTRR S257T, and MTRR A664A have no impact based on any of the research I've been able to find.

    9)MTR A2756G seems to be reporting the risk backwards - possibly based in increased cancer risk, rather than looking at methylation functionality (which feeds cancer too).

    10) ACAT1-02 has no impact based on any of the research I've been able to find.

    11) VDR Taq and VDR Bsm are clustered SNPs where everyone with a certain variant of one will have a certain variant of the other. Yet the results are/were listed as opposing variants being the risky ones. Thus everyone would be +/+ for one and -/- for the other, or +/- for both.
     
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  3. Lotus97

    Lotus97 Senior Member

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    Does Yasko explain why this is? Or what to do about it? It certainly would explain why I've been having problems too since mine don't seem to be from overmethylation.
     
  4. Star-Anise

    Star-Anise Senior Member

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    Lotus97
    Lotus this is what I found:
    She explains it further here somewhat:
    http://dramyyasko.com/wp-content/uploads/2010/06/39-A1-BHMT8.pdf
    The key aspect appears to be stress that influences BMHT's ability to BHMT gene convert homocysteine to methionine - see page 8.

    BHMT/homocysteine/sulphur seems to be a subject of continued research, & the relationship doesn't seem to be entirely understood, but there does seem to be a relationship:
    http://www.ncbi.nlm.nih.gov/pubmed/22775318

    Apparently, once formed, homocysteine can be removed from the body in only two ways:
    a) it can be remade into methionine through a process remethylation
    b) homocysteine can be made into the amino acid cysteine through a transulfuration process that requires two enzymes to work in concert with vitamin B6.

    Cysteine is a sulphur containing amino acid. And in healthy conditions the liver converts dietary L-cysteine into glutathione, taurine, sulfate, cystine, and allows a tolerated amount of unconverted L-cysteine to circulate in blood for direct uptake by body cells and organs.Excessive levels of L-cysteine are controlled by the liver using the enzyme CDO to decompose the amino acid to non-toxic and rapidly excretable sulfate. http://www.cfsn.com/sulph.html

    So it seems that BMHT + impaired ability to deal with heightened cysteine/sulfates + whatever other lovely snps (methyl related, sulphur metabolism) related one may have that influences the whole process of methionine synthesis versus homocysteine buildup = potential buildup of sulphur byproducts.

    That's my two bits...

    In my observations, I feel much better limiting sulphur. I don't know my snps yet, but will share the day I get 23andme results back! :) However, there seems to be a group that don't feel better when they eliminate strictly follow CBS protocol for a long time. The whole situation is complicated. I would be wary of entirely discounting CBS or BHMT mutations as a whole. But I don't think they are the be all to end all either. It all works together.

    All the best!
    S
     
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  5. abporter

    abporter

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    This pdf ends in mid-sentence. (?)
     
  6. abporter

    abporter

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    I have a CBS C99T homozygous mutation. I have injected a methyl B12/folate/P5P compounded mixture subcutaneously and have felt better, although I did not check my sulphate or ammonia levels (I did not know I had a mutation until this past week). So I'm not sure if I need to be concerned about addressing my CBS mutation first.
     
  7. Jay1218

    Jay1218

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    Hey everyone,

    I'm new here and recently found out I have one abnormal copy of C677T and one abnormal copy of A1298C (I believe this means compound heterozygous?)

    The test unfortunately didn't check for any CBS mutations or any others, but my holistic doctor started me on FolaPro and B-Supreme to help with the methylation issues. The first week-week and a half I seemed to be doing okay (not 100% but slightly better than before).

    Towards the end of the second week and going into the 3rd though, I started feeling really crappy (headaches, nausea, brain fog, anxiety). These would come and go and I would have periods of the day where I felt good and other periods where it would get bad.

    I think it may have been over-methylation and I mentioned all this to my doctor so she recommended coming off the FolaPro and said it sounds like I might actually have a CBS mutation too.

    I ordered the test from 23andme to see if it is indeed a CBS mutation but it looks like that can take up to 8 weeks to get your results back.

    So my question is this:

    While I wait for the test results, should I try a CBS protocol anyway just to see if it helps? I feel crappy most of the time now and I really would hate to wait 8 weeks to find out for sure. Every day is starting to suck for me so if there's no potential negative aspects of doing a CBS protocol even though it isn' confirmed yet, do you think I should try it out?

    Also, I read through this whole thread and there seems to be a lot of conflicting information. I'm not very good with all the science stuff, so can someone tell me what the current, most effective CBS protocol is at this time? I've read everything from yucca to molybdenum, charcoal, ammonia support, boron, vitamin e, CoQ10, and a bunch of other recommendations.

    It's all very overwhelming right now and I'm not sure where to start.

    Oh and the reason why I didn't get the test done through my doctor or schedule a visit to go over this is I found out my insurance isn't covering my visits so I was having to pay out of pocket which gets expensive. So my only option right now is unfortunately to try some stuff out and see what works.

    I just feel stuck. I tried treating the MTHFR abnormalities and that obviously screwed something up so now I need to fix whatever is going on.

    Thanks in advance.
     
  8. Freddd

    Freddd Senior Member

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    Hi Jay,

    If methylation starts up many people almost immediately have induced deficiencies. The first two are usually paradoxical folate insufficiency and low serum potassium. After that often come zinc, or magnesium, or vitamin D or half a dozen others. So the solution is more L-methylfolate and/or more potassium, titrated until the symptoms disappear. It works for a lot of people. It happens to a large percentage of people who start methylation. It means you have started healing and forming cells. That places more demand on the body's supplies of nutrients. It's sad that more people don't recognize the signs of success.


    Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with cyanocobalamin it is very common with methylb12 and adensosylb12 and less so with hydroxycobalamin..
    IBS – Steady constipation , Nausea, Vomiting, Paralyzed Ileum, Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness, Abnormal heart rhythms (dysrhythmias), Increased pulse rate, Increased blood pressure, Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.
    Group 2a - Both
    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation
    Group 2b – Either or both
    Headache, Increased malaise, Fatigue
    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency
    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.
     
  9. Jay1218

    Jay1218

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    Hi Fred,

    Thanks for responding here.

    That's definitely interesting and I didn't think of that. So how do I know for sure if my symptoms are actually a result of me starting to heal like you said and they really aren't being caused by a CBS mutation like my doctor thinks it could be? Is there anything else I can do to get a better idea aside from waiting for test results?

    I guess I'm stuck now on whether to keep going with the L-methylfolate and risk getting even worse or to stop taking it/cut back on it until I know for sure which will take weeks or months.

    Today for example, I cut back to 400 mcg methylfolate and I've been feeling sick all day. Hard for me to know whether it's from too much or too little. Yesterday I took 3 pills which was 2.4 mg and also felt pretty sick, but I have taken 3 pills before and was fine so it's extremely random.

    Another thing I forgot to mention in my original post is that I have been gradually increasing the folate every week since I started. So the first week I took 1x pill per day (each pill is 800 mcg), the second week 2x per day, 3rd week 3x, and that's as far as I have gotten so far.

    Normally I space them apart throughout the day, but there were a couple times where I tried to take 2 in the morning together and I planned on taking the 3rd one later, but both times I took the 2 together I ended up feeling crappy those days (yesterday was one of them).

    I also had a night about a week ago where I got extremely dizzy as soon as I turned the lights off to go to sleep. This turned to a severe case of insomnia and anxiety. I didn't fall asleep until 8am so I was literally just laying in bed restless for like 8 hours before I finally drifted off.

    As for potassium, should I be taking it in supplement form or just getting more through my diet? I generally eat 2 bananas every day so not sure if that's enough or I need more.

    Is there anything else you recommend to go along with the methylfolate and b-supreme that I'm on that may help with these symptoms? I've been thinking of following this protocol here: http://mthfr.net/mthfr-c677t-mutation-basic-protocol/2012/02/24/ what do you think of it?

    Lastly, should I try getting right back to 3x pills per day like I was doing or should I start over at a small dose and work back up?

    Sorry for so many questions, I'm just in information overload at the moment and trying to figure out what's best.

    Thanks again.

     
  10. Valentijn

    Valentijn Activity Level: 3

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    It means there's a 50% chance that you're compound heterozygous. Basically it requires that each problematic allele from each SNP be on a different strand of the gene. Hence you'd have to have one copy from each parent. But 23andMe does not indicate which strand SNPs are in, and shows alleles in alphabetical order instead.

    So you're either at 65% of normal methylfolate production if not compound heterozygous, or you're at 30% of normal production if you are compound heterozygous. Either way, supplementing methylfolate is a good idea.

    The CBS mutations are all pretty harmless, aside from the supposedly "good" versions resulting in higher homocysteine and heart disease risks. CBS SNPs shouldn't be causing problems, but that's not to say that a "CBS protocol" won't help, albeit for reasons unrelated to the SNPs.

    But there is likely to be plenty of other information in your 23andMe results that will be useful.
     
  11. Freddd

    Freddd Senior Member

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    Hi Jay,

    For one thing, jumping the dose all around of l-methylfolate doesn't help. The largest failing of 60 years of b12 and folate research is that they never, in all those decades, actually mapped out the pathways of healing from b12 and folate deficiency. With the research the way they did it, if by some chance the folic acid or CyCbl or HyCbl worked well enough for the person and they had healing turn on with immediate low potassium and low folate, they were out of the study for intolerable side effects. So the actual way things go for healing has never been officially identified. The low folate was never identified, and the low potassium was identified correctly and marked "rare".


    The only way I know is that I was at a different board when I got hit with low potassium and it was no mystery there. We all just used potassium, no fuss no muss and lots of healing. I'm healed. I have rehabilitated as well as my age and other injuries have allowed me. I had some heavy mileage even without these illnesses. I have seen hundreds of others also become re-enabled, healed from FMS and CFS with some co-morbidities remaining but able to rehabilitate and go back to work. People who heal, generally will have had to use potassium and additional folate. Then they can stop struggling with those symptoms and get on with healing. Otherwise the person will struggle with those symptoms and things get more and more messed up and unmanageable as they thrash from here to there trying every fad that doesn't work. Maybe the identical low folate and low potassium symptoms have other causes. If so then the ones that respond to potassium and folate, when they have the appropriate symptoms, are the people who are more likely to heal. Who knows what cause and effect are. Good luck.
     
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  12. Jay1218

    Jay1218

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    Thanks guys.

    Fred, I normally don't jump all over the place with the methylfolate. I was gradually increasing it every week but the only reason I dropped to 400 mcg yesterday is because I thought I was over methylated so I wanted to cut back. Maybe that wasn't the best idea in hindsight but it was what I thought I was supposed to do.

    Regarding B12, how should I be taking that? From what I read in some of your other posts, we should be taking both MeB12 and another one that starts with an A. Is there a specific brand that works better than others?

    Same with the potassium. What type of dosage should I be taking and is it only when I notice symptoms from the methylfolate or should I just be taking it throughout the day?
     
  13. Freddd

    Freddd Senior Member

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    Hi Jay,

    A balance of both varieties of b12, AdoCbl (adenosylcobalamin) and MeCbl works best but the exact balance varies. The Anabol Naturals Dibencozide works well.

    I find I have to take 1200-2000mg of potassium a day. Towards the low end I have to take extra doses of 300-400mg each day or two whereas currently 2000mg keeps me steady as a rock for now. I take the NOW foods potassium gluconate. Sometimes I also have use potassium chloride I put into capsules to eat with food and can fit 500mg in one capsule instead of 5 pills of gluconate.
     

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