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My 23andme results are in, need your help

Discussion in 'Genetic Testing and SNPs' started by Peyt, Aug 6, 2014.

  1. Peyt

    Peyt

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    Hi All,

    I finally got my results back from 23andme and went ahead and ran it through geneticgene,

    OMG! I have 5 +/+ genes and so many +/-

    This is over-whelming for me !

    Here are the mutations:

    +/+

    COMT V158M +/+

    COMT H62H +/+

    VDR Taq +/+

    MAO A R297R +/+

    CBS A360A +/+



    +/-

    VDR Bsm +/-

    MTHFR 03 P39P +/-

    MTHFR A1298C +/-

    MTR A2756G +/-



    MTRR A66G +/-

    MTRR A664A +/-





    Here are the supplements I currently take based on the recommendations are Dr. Mensah and a little tweaking of my own:

    1. B6 100mg

    2. P5P 100mg

    3. EPO 1000mg

    4. Zinc 50mg

    5. Manganese 10mg

    6. Folic Acid/ B12 800mcg/25mg

    7. Vitamin D 5000mg

    8. Natural Calm (Magnesium) 1 tea spoon at night

    9. Niacinamide 1000mg



    Dr. Menssah had originally recommended 3 x Folic Acid 800mcg but after taking is for a couple of weeks I started getting bad headaches and nucia and I started feeling really bad. So I had to reduce to 1 x 800mcg, so I wonder if that is the correct form of folate I need to be taking because 1 per day really does not do anything. The 3 per day was making my depression go away and make me feel positive, but then as I said I guess I over loaded and had to reduce it.



    Any thoughts would be greatly appreciate it,
    God Bless,
    Peyt




    Reply
  2. Critterina

    Critterina Senior Member

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    Peyt,

    The first thing that worries me is that you're taking both B6 and P5P, 100 mg each. P5P is the active form of Vitamin B6, so you are getting 200 mg total. Toxicity is rare, but can start at 100 mg. There is only one case of it starting lower than that. Toxicity often shows up as peripheral neuropathy. Think about taking only one of these. Because I can't convert to the active form, I always suggest that in case you are like me, use the P5P and skip the B6 in the pyridoxine hydrochloride form.

    With the MTHFR A1298C SNP, methylfolate will likely help you a lot more than folic acid. It helps activate the BH4 enzyme for making serotonin, and low serotonin causes depression.

    I don't know what kind of B12 you are taking. There are different types of cobalamin: cyano, methyl, adenosyl, and hydroxy(l). Generally, if people can tolerate the methylcobalamin, that's preferred for starting methylation. If they don't tolerate it, they use the hydroxy form. You have the MTRR +/-, so you're not extremely efficient at converting the hydroxy form to the active methyl form, but with your other +/+s, you just have to take what you tolerate. I like having it be a separate supplement from the folate supplement, so you can adjust the ratios to suit yourself.

    My last thought it that looks like a lot of niacinamide. Maybe you have good reason to take it, but it seems like a fraction of that (5 mg? 10 mg? 20 mg?) would be enough. Too much of some of the B vitamins interferes with the methylation cycle; I don't remember if this is one of them or not.

    Best of health to you!
    Critterina
    taniaaust1 and Valentijn like this.
  3. Peyt

    Peyt

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    Hi Critterina, thanks so much for your post,
    the Folic Acid I take is by Now, it's this one: http://www.amazon.com/Foods-Folic-A...qid=1407389411&sr=8-1&keywords=folic acid now

    Which brand folate do you recommend?
    As far as Niacinamide, the smallest dose is usually 250mg and most manufacturers make the capsules with 500mg, so I don't think those small doses even exist. You might be looking at Nician or another form of B3, but Niacinamide is the gentle none-flush form of Nician. Anyways, If I don't take 1000mg a day my headaches will make me go crazy. 1000mg is the correct dose that works for me, anything less and I have to take tylonal for my headaches which is worst than anything.

    Anyways, someone in another forum suggested taking Ornithine which is suppose to help with CBS. I am going to add that to my regimine and also I am open to any suggestions on other forms of Folate that could work for me.
    Thanks so much
    Peyt
  4. Critterina

    Critterina Senior Member

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    Hi @Peyt ,

    I have two brands of methylfolate. Solgar is the "tried and true" brand. It seems that a lot of people on this forum use and recommend it, and some have tried other brands to find them less effective. Today I started taking the PipingRock brand. They both have the Metfolin(R) product in them, so I'm hoping they will be the same quality.

    Niacinamine - this is where you know your body and what works for you. Do what works. Enough said. I was using sublingual tablets - very expensive.

    I really can't figure out how ornithine would help with the CBS. I'm not saying that it doesn't, just that I don't get it at all. Ornithine I know best from the urea cycle. The biopterin cycle, folate cycle, and methyl cycle all come between the urea cycle and the sulfur cycle, so I'm confused. I am reluctant to mess with the urea cycle, even though I always test low serum arginine, because if you mess it up, you can get the bad oxidizers (peryoxynitrate and superoxide), particularly if you are low in BH4 (often true for us MTHFR A1298C people) or have the superoxide dismutase (SOD) mutation. To me, it's not worth the risk.

    One of the things you should know about is that CBS mutation does not cause problems in everybody. Even though you are ++, the CBS you have is the milder mutation, the A360A. If you want, you could test for sulfur problems, but if it were me, I would go by my answers to these questions: Does eating eggs or onions bother you? Have I tested for low methionine? If you say no to the first question, I wouldn't even bother with the second question. If you say yes to both, then get some test strips. Let me know if you plan to do this, as I have some I'm not using.

    I know this is all confusing, but just take it slowly. I know I wanted to fix everything at once. Twice I took the exact opposite of what I needed, and it slowed down what I needed to speed up or vice versa. It's not a good place to be! And just to give you some perspective, I think that most people here would trade the few SNPs you have for theirs. Essentially, with some methylfolate and some of the right form of B12 (methylcobalamin if you can tolerate it, hydroxycobalamin if you can't), and of course the niacinamide that you apparently need, and maybe some Vitamin D3 thrown in if you test low (and do get tested), you'll likely cover most of your bases.

    One word of caution - the MAO +/+ and the COMTs may (and I'm not saying will, just "may") make you prone to mood swings when these cycles start up. If that happens (it didn't to me), stop and start over with 1/10th or 1/100th of the dosage that gave you problems, then work your way up slowly. Lots of people here can give you advice about "starting low and going slow(ly)"

    Best of health to you,
    Critterina
  5. Peyt

    Peyt

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    Thanks for your reply Critterina,
    Just to give an update,
    I did order some strips which I should get in a few days. I also stopped my Folic Acid and ordered some Hydroxy B12 which apparently is the right kind for my type of SNPs. I have also started on a supplement called Yucca which I open the capsule and pour it on my food. I do feel like I get less bloating with this supplement, but not sure if it's helping with lowering Sulfur or Ammonia. I will know once I get the strips and start measuring the sulfur.
    Critterina likes this.
  6. Critterina

    Critterina Senior Member

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    @Peyt ,
    I'll be watching to see what the sulfate/sulfite strips show you. Are you feeling any better without the folic acid? Probably a good call on the hydroxy - as you only have +/- on the MTRR and you do have some of the SNPs that people associate with trouble with the methylB12.
  7. Peyt

    Peyt

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    When I was taking folic acid 3x a day , I felt my anxiety had lifted and I was more social and happy. But then after a couple of weeks I felt wired up and headaches came on, as if I was doing too much, so I lowered it to once a day, and then completely stopped. Now that I have stopped the Folic Acid, I am back to being down and sluggish. I wonder if it was because the Folic Acid I was taking was combined with the wrong type of B12 and now that I got the Hydroxy B12 I am tempted to go buy another brand of Folic Acid that is not combined with B12.

    BTW, I have been taking the HydroxyB12, and I have not felt any improvements at all.
    Ailsa and Critterina like this.
  8. Critterina

    Critterina Senior Member

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    Hey @Peyt ,

    Let me spin a story...I'm not saying it's true. I'm just looking to see whether there is a plausible explanation for what you describe based on your SNPs.

    OK, you have MTHFR A1298C +/-, so you may tend toward anxiety and/or depression, all other things being equal. The methylfolate has to be in larger quantities than the folinic acid to drive the reaction in the direction that will help your neurotransmitters make serotonin to combat this tendency.

    You also have MTRR A66G +/-, which prevents methylfolate from being used in the methionine cycle, making more of it available to support the reaction that makes serotonin...until you start taking B12.

    When you took folic acid, you felt better at first. The folic acid was being turned into methylfolate (some of the steps are naturally slow, but you don't have SNPs that significantly slow it down). You had more methylfolate to be turned back into folinic acid - maybe you take the folic acid, it surges toward methylfolate, then between doses the equilibrium supports some of the backward reaction, and your anxiety lifts a bit.

    You continued taking folic acid and it built up in your system (hypothetically, still). From http://www.drugs.com/folic_acid.html: Overdose symptoms may include numbness or tingling, mouth or tongue pain, weakness, tired feeling confusion, or trouble concentrating. Not a perfect match for what you describe, but similar to feeling like you've done too much, perhaps?

    So you stopped taking the folic acid, so you don't have the extra methylfolate at times, and you feel sluggish and 'down', which if it means depression, is exactly what I'd expect to happen with less methylfolate.

    On top of that, you're using hydroxyB12, which directs methylfolate to the methyl cycle, so you have even less methylfolate for serotonin production. (This ignores the possible moderating effect that when B12 directs methylfolate to the methyl cycle, it produces SAMe, which is also used to make neurotransmitters.)

    That may be a tall tale, but it's a possibility for how things might have been working with you.

    ****

    OK, so what I would recommend is that you do not buy any type of folic acid, but buy methylfolate. It will make the reaction go the right way. I agree with you that you want it to be a brand without B12 in it, so you can increase one without increasing the other. Try Solgar brand if you can find it.

    You were taking 800 mcg folic acid 3x/day, and you said that was too much. You could try to take 800 mcg methylfolate. (Solgar sells it in this strength). Maybe not 3x/day at first. Maybe 1x? Choose something you're comfortable with and see how you do. Increase when you know you're ok with it.

    You also said you were taking 25 mg of B12. That seems like a lot, although not a lot survives the gut if you're swallowing it. How much hydroxyB12 are you taking now? Is it sublingual? I would think 1 to 5 mg/day sublingual would be plenty. Again, choose something, take careful notes, and see how you do. And of course, let us know.

    Critterina
    Peyt likes this.
  9. Peyt

    Peyt

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    Critterina,
    Thanks so much for your suggestions. I made a mistake on the dosage I wrote on the B12 that was in the Folic Acid supplement.. It's 25mcg, not 25mg! which is not much. The new HydroxyB12 is only 1 mg and I take 1 every morning(it's only been 2 days).
    Critterina likes this.
  10. Critterina

    Critterina Senior Member

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    Whew! I'm glad, although I have taken 25 mg of methylB12 before, just to see if I got a reaction (I didn't.)

    I'll be looking forward to seeing how you do on the methylfolate, without changing your B12. I am optimistic that you will notice a difference.
  11. Peyt

    Peyt

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    Before I knew about 23andme and Yasko or any other one of those genetic tests, I used Dr. Walsh's protocol and it helped me about 70% improve my symptoms. His protocol is based on a Histamine and Pyrroluria test that he runs which shows if a person has excess histamine or deficiency histamine, it also shows Pyrrole and Zinc, Copper deficiency or excess. Then depending on the test results, if a person has low histamin, they are OVER-Methylated(like me), and if they have excess Histamine they are UNDER-methylated. and based on that he suggests supplements. I tried his test and took(and am still taking) the supplements he suggested, and I can firmly say it improved my symptoms 70%. The interesting thing is, they started working almost immediately. Now having done his test, and now educating myself on genetic tests, I see a corrolation. People that he calls Over-Methylated would be people that would be +/+ COMT and MAO A, why? because he says people who are overmethylated have exess amounts of Dopamine and Seratonine. I think it's not a coincidence that my 23andme tests show that I am both COMT ++ and MAO A ++. That
    is the defenition of someone who is OVER-Methylated. And a person who is UnderMethylated would be ++ on the MTHFR genes (which I am only +/- on) .

    So here is where the difference in opinion between Dr. Walsh and Dr. Lynch and Yasko comes in. Dr. Walsh believes that if someone is UnderMethylated they would benefit from Folate. If they are Over-Methylated, they will benefit from Folic Acid. . This is why I am reluctant to try MethylFolate. Dr. Lynch calls Folic Acid garbage and thinks only Methyfolate has benefits

    Here is a passage from Dr. Walsh's book "Nutrient Power" (Page 46-47) on Folic Acid:
    Overmethylated patients clearly thrive on Folic Acid, where as methyl-deficient patients exhibit intolerance. In 1994, I reported this surprising finding at the Society for Neuroscience annual meeting and concluded that the methyl/folate ratio has a special significance in mental heath. Recent epigenetic research finally provided a convincing explanation for this phenomenon. Several studies have shown that reducing dietary folates can increase methylation at histone tails and DNA sites. Vanderbilt University biochemists have reported that folates enhance histone demethylation. A National institutes of Health(NIH) study reported that activation of a folic acid receptor gene can increase histone acetylation. In effect, folic acid increases genetic expression of transporters, causing reduced activity of dopamine and serotonin(WHICH IS WHAT I WANT!!) Folate and methyl produce opposite effects on neurotransmission. Folic acid is a serotonin reuptake enhancer, whereas methionine and SAMe are serotonin reuptake inhibitors. Giving folic acid to an undermethylated depression patient results in improved methyl levels (SAMe) throughout the body and brain but reduced methyl levels at key histones and CpG islands that regulate neurotransmitter activity.
    Folic Acid Supplements can either increase or decrease methylation at histone trails and CpG islands, depending on the portion of the DNA strand that is involved. With respect to mental health, Folic Acid supplements generally must be avoided for undermethylated patients and emphasized for overmethylated patients.


    This is why I am reluctant to try methylfolate. As I said, based on his test I was over-methylated. BTW, an interesting find in the book is there are much fewer overmethylated people than undermethlylated people.

    When I got my 23andme test and saw I have both COMT++ and MAO A, it blew my mind. Off course Dr. Walsh never talks about those genes in his book, but when I read what those genes do, it was a basic definition of what Dr. Walsh describes as Over-Methylation. COMT ++ produces exess dopamine and MAO A ++ produces excess seratonin, and Overmethlated person is one who has excess Dopamine, Seratonin, and Norepenephrin. Very interesting to say the least. And I don't think it's a co-incidence.
    Last edited: Aug 16, 2014
  12. caledonia

    caledonia

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    I've read Walsh's book too. He's done some great work for mental health patients. However, he hasn't adapted to the newer gene research.

    I've come to the same conclusion as you, that "overmethylation" is not true overmethylation, but is instead the action of COMT (not sure about the MAO A part).

    If you have MTHFR and MTR/MTRR mutations (folate and B12 mutations) and they are expressed, such as having mental health issues, then you are undermethylated which means not producing enough methyl groups. This will cause you not to produce neurotransmitters correctly. Some neurotransmitters may be low, while others, such as glutamate, may be high, causing anxiety.

    Folic acid has a couple of problems - people with MTHFR mutations can't convert it so it will slow down methylation, and the unmetabolized folic acid may cause cancer. So it's not a good long term solution.

    Therefore it is suggested that you avoid folic acid and take methylfolate. You can avoid problems with COMT by taking hydroxycobalamin and Starting Low and Going Slow with all methyl supplements such as methylfolate or TMG. Have niacin on hand in case you get the methylation cycle cranking too fast producing too many methyl groups (true overmethylation).

    Please see my documents starting with the SNPs Interpretation Guide, then Start Low and Go Slow, then Roadblocks to Successful Methylation (all linked in my signature below).

    If you decide to try this approach in lieu of Walsh's approach, I'd be interested in hearing how you do with it.
  13. Peyt

    Peyt

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    Hi Caledonia, any idea where I can find info on types of folate?
    I need to avoid anything with Calcium(Over-Methylators do poorly with it) and I see that for example most Folinic Acid are made from calcium folinate. And I saw a few labels on folate that had calcium. I have a bad reaction to calcium. If I were to try folate, I need to make sure it's the none calcium kind(if such thing exists) ... any suggestions? Thanks
  14. Peyt

    Peyt

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    Just wanted to put a follow up on this post. Last week, I purchased some Folic Acid and took some. I noticed, I did not get the good feeling that I was getting when I was taking this Folic Acid that I had posted earlier on this thread: http://www.amazon.com/Foods-Folic-Acid-800mcg-Tablets/dp/B0009U84Z4/ref=sr_1_1?ie=UTF8&qid=1407389411&sr=8-1&keywords=folic acid now

    The difference between the 2 Folic Acids is that the 2nd one(NOW Brand) combines the Folic Acid with 25MCG of Vitamin B12 (as cyanocobalamin).

    Also, in the last 2 days, I have been educating myself on the Detox SNPs (Thanks to Caledonia's great
    Interpretation Guide that has made my life so much easier).....
    Well, after running my Detox profile with 23andme, I found out that I am +/- on SOD2 .... and guess what supplement helps with SOD2???
    According to this study, Vitamin B12 (as cyanocobalamin) does!!
    http://www.ncbi.nlm.nih.gov/pubmed/21672628

    So now I suspect that all this time, the great feelings that I was getting from the NOW brand Folic Acid had nothing to do with the Folic Acid and more to do with the Vitamin B12 (as cyanocobalamin) which was combined with the folic acid in the formula! which was helping the SOD2 ! lol

    Just wanted to share this info and let people know that I was wrong by thinking Folic Acid was helping me feel better (less depressed) I suspect it was the Vitamin B12 (as cyanocobalamin).

    But now I am not sure if I should take Vitamin B12 (as cyanocobalamin) for my SOD 2. because based on my SNPs I should be using the Hydroxy B12.... Gosh this stuff is so confusing! lol

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