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Genetic mutations and recent abnormal VitD discovery

Discussion in 'General ME/CFS Discussion' started by enduin, Apr 14, 2015.

  1. enduin

    enduin

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    Hi all,
    I hope this is the right section where to post is, if it isn't feel free to move it, or I'll edit/delete.

    I've been having issues with autoimmune disorders (psoriasis and prostatic arthritis) and lower energy since 2007, but it's been since late 2011 that things started to get really bad, starting with fatigue, depression, in 2012 the fatigue got quite extreme, then in 2013 IBS, and in 2014 I also started having panic attacks, nausea, headaches, got diagnosed with pre-diabetes, vasovagal issues (fluctuation of BP, dizziness, BP drops when I try to work out) worsening of memory, brain fog, very frequent urination (no matter how much I drink I'm dehydrated in the morning because I pee during the night, even during the day as soon as I drink I start peeling like crazy like my body doesn't want to retain water).

    Over the last four years I tried so many things, too many to write in a post, but theone thing they all have in common is that nothing worked, or if they worked, they worked for a brief period of time, just to go back to normal afterwards.

    Since the beginning of the year I've been focusing on methylation and genetic mutations, and since Nov 2014 I've been eating a low carb/high(good)fat/high protein diet to help with the pre-diabetes, which seemed to have reduced the frequency of panic attacks (I though it was because wild fluctuations of glucose were linked to release of adrenaline case of reactive hypoglycemia).

    My genetic test shows that I'm homozygous for
    - MTHFR A1298C, MTRR A66G, MAO A R297R

    And heterozygous for
    - CBS A360A, COMT V158M, COMT H62H, VDR Bsm, VDR TAQ, BHMT 08

    I've been reading like crazy and tried to make sense of all this, and I decided that I would start with the Yasko simplified protocol to address glutamate/GABA imbalance and the CBS mutation, then support the shortcut methylation through the BHMT, then switch to Ben Lynch's protocol for the methylation proper.
    I also run a bunch of tests, as much as my finances would allow, before starting the protocol:
    - CMP doesn't show anything out of the ordinary
    - homocysteine (tested properly) is 8 so normal
    - ammonia is 19, normal
    - the essential elements test showed low levels of trace minerals, especially lithium (started supplementing trace minerals and lithium right after)
    - the amino acids urine test showed everything low but I'm pretty sure it's biased, because I was very dehydrated so the creatinine ration is not normal

    I started with cutting down sulphur and possible glutamate sources from my diet in January, then in Febrary I started the phase 1 from Yasko protocol (can post which supplements if necessary) and after a week I started feeling better, had more energy, doing work was not as excruciating as usual, mood was better, libido was higher, etc. Usually when I feel better from something I try it only lasts a day or two, but this lasted a whole month. On the other hand I was peeing more than usual, especially at night, so my sleep was even worse than usual.
    After a month of that, I started feeling a bit worse, my knee arthritis flared up, had less energy, but I thought it was just a temporary bump on the road. Shortly after that I started the phase 2, with the phosphatidylserine, etc, to stimulate the shortcut methylation through the BHMT. After starting this, I started having panic attacks again, and low BP issues, which prevents me from working out at the gym (if it's already low, when I work out it gets even lower and I get dizzy and then get a panic attack. I've seen a cardiologist and nothing is wrong with my hearth, he thinks it's a vagal nerve issue). I then stopped the BHMT protocol, since I read it can result in higher adrenaline/dopamine ratio, and having a COMT mutation I'm probably more sensitive to that; after a few days I started the Ben Lynch protocol.

    So now it's been 3 weeks that I've been doing the Ben Lynch protocol. I started with just methyl B12, started really low and worked my way up to 4000 mcg. I stopped all the other supplements for the first week, then I reintroduced the trace minerals, milk thistle, magnesium and potassium and adenosyl B12.
    Besides the first day with adenosyl B12 I haven't noticed any improvement whatsoever and I'm pretty much at the same point I was before I started the Yasko phase 1 in February: I have some really bad days with extreme fatigue, nausea, headaches, diarrhea, anxiety and panic attacks. Then other days I'm more functional, but I'm still always quite tired and I get exhausted from doing small things. My BP is still fairly low, and I have a hard time working out even a little (which I really need to keep my pre-diabetes in check). The panic attacks come and go.
    Now I'm at the point where I think I loaded up with enough methyl B12 that I can switch to the B12 with methylfolate, again starting very low and working my way up.

    One thing though I discovered in the past few weeks is that the Vitamin D test I performed came up with abnormal results: my Vitamin D 25-hydroxy is 20 (very low) and my Vitamin D 1,25-dihydroxy is 75 (too high). The interesting thing is that I haven't mentioned that my wife suffers from symptoms very similar to mine (she also has mutations and she's going through the same tests and protocols I'm doing), and she also has the Vit D 25 low and Vit 1,25 high.
    This could explain why we both had some elevated calcium in the past few years, but normal PTH. Also Yasko's phase1 supplements contained some Vit D, and we stopped peeing so much after stopping the supplements, so I wonder if it was related.
    The only thing I could find aboUt this Vit D anomaly is that shows inflammation and is not uncommon in autoimmune patients. As far as the cause I read it can be caused by chronic infections, like sarcoidosis, but also possibly by Lyme and other less known chronic viral/bacterial infections.
    I'm planning to get to optimal levels of methyl B12 and methylfolate, since the methylation is connected to the immune system, but then I have no idea what to do, especially since it seems like it's not making me feel any better and there is probably some other underlying problem.
    I would be really really grateful if anybody with experience with this, could give me some advise on how to proceed, because after all these years of researching, reading, and trying things, I feel like I'm more confused than ever...
    Thanks!!!
     
  2. Valentijn

    Valentijn Senior Member

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    @enduin - VDR Bsm/Taq +/- aren't having an impact. Nor is the CBS A360A +/-. Nor BHMT 08 +/-. Based on the data you've provided for those SNPs, there's no need to "treat" them.
     
  3. Sidereal

    Sidereal Senior Member

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    This problem is commonly reported by ME/CFS patients. We don't know what causes it. It's very unlikely to be those Yasko SNPs since they are very common in the general population.
     
  4. enduin

    enduin

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    Thank you for your answers!

    I don't think the VitD anomaly is caused by the SNPs, but I read of some people whose VitD levels normalized after they did an antibiotic protocol for Lyme or other chronic infections. I wanted to know if anybody could shine some light on this.

    Also @Valentijn may I as why you say that the CBS, VDR and BHMT don't have any impact? Is it because they are heterozygous?

    Thanks again!
     
    Valentijn likes this.
  5. Valentijn

    Valentijn Senior Member

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    Those VDR and BHMT SNPs have little impact when homozygous, and very little or none when heterozygous. Certainly not enough to have a noticeable effect on gene function.

    The CBS SNP has no known effect when homozygous or heterozygous.
     
  6. xks201

    xks201 Senior Member

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    "
    Vitamin D is rapidly metabolized in the liver to form 25-hydroxy (OH) vitamin D. Additional hydroxylation of 25-OH vitamin D takes place in the kidney by 1-alpha hydroxylase, under the control of parathyroid hormone, to yield 1,25-dihydroxy vitamin D.



    1,25-Dihydroxy vitamin D is the most potent vitamin D metabolite. It stimulates calcium absorption in the intestine and its production is tightly regulated through concentrations of serum calcium, phosphorus, and parathyroid hormone.



    1,25-Dihydroxy vitamin D levels may be high in primary hyperparathyroidism and in physiologic hyperparathyroidism secondary to low calcium or vitamin D intake. Some patients with granulomatous diseases (eg, sarcoidosis) and malignancies containing nonregulated 1-alpha hydroxylase in the lesion may have elevated 1,25-dihydroxy vitamin D levels and hypercalcemia."
     
  7. Gondwanaland

    Gondwanaland Senior Member

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    My 2¢: get your minerals balanced first, otherwise the adrenal burden will only increase. The link in my signature "Balancing nutrients" has been helping me immensely. I suggest focusing on sodium and magnesium first.
     
  8. enduin

    enduin

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    In all the reading I've been doing I never encountered this notion, do you have some links to the studies that support this to share? I would love to be able to read them since there is so much conflicting info about SNPs.

    I had my parathyroid hormone tested more than once because on a few occasions my blood calcium level was a bit high and my endo was suspecting that it could be a parathyroid issue and abnormal calcium levels that could explain my fatigue and other symptoms. I also developed small kidney stones. The problem is: my parathyroid hormone tested 100% normal every time, so it's not the parathyroid. That's why I'm thinking about sarcoidosis and chronic infection.

    Thank you for the info. I have been trying to fix my mineral balance, had been taking magnesium on and off for a while (helped with occasional arrhythmias) and after the urine essential element test I started supplementing lithium, potassium and trace minerals. Magnesium tested normal but I still take it. I will read the article in your sig, thanks!
     
  9. Sidereal

    Sidereal Senior Member

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    It is possible to have hyperparathyroidism despite normal PTH levels.
     
  10. Valentijn

    Valentijn Senior Member

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    Generally I read the full research papers linked to each SNP at dbSNP. Summaries by Yasko or anyone basing their sites off of her misinformation are not trustworthy.
     
  11. xks201

    xks201 Senior Member

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    Pth itself has such a short half life that in my opinion by itself it means nothing
     
  12. enduin

    enduin

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    The problem is that according to my doc nothing in the panel I had done supports parathyroidsim. Not only the parathyroid hormone is normal, but the calcium and ionized calcium are not consistently high, they were high on two occasions, then they were normal both times I tested them recently with the parathyroid panel.
     
  13. enduin

    enduin

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    Thank you, I will check that out!
    i know my wife (who also has chronic fatigue) is homozygous for CBS699t and she has abnormally low homocysteine, but then there are other things she tested that don't fit the CBS theory, so it's still a big question mark..,
     
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  14. Valentijn

    Valentijn Senior Member

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    Yes, CBS C699T +/+ would only have a small impact. I'd be surprised if it caused homocysteine results to fall outside of the normal range. Regarding Yasko's bizarre claims about it, we have a thread at http://forums.phoenixrising.me/index.php?threads/couple-of-questions.22718/

    Basically it looks like Yasko equates a common variation in that SNP with the effects of half of the gene being lopped off in a lab yeast, or with having three copies of the entire gene. There's simply no sane basis for the claims about CBS C699T causing a huge up-regulation in the gene function.
     
  15. enduin

    enduin

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    Thank you for the link!!! In all my reading that one clearly slipped through the cracks. It does somehow reinforce what we were thinking, that there are big holes in Yasko's theory. The only things that matched were that my wife's homocysteine is low and that she can't tolerate wine or cider with sulfites. On the other hand everything else didn't match, ammonia was fine and we don't react to any sulphur containing food that is not wine or cider with added sulfites.

    We are doing methylfolate and methyl/adenosyl b12 supplementation at the moment with no good results. I'm also taking potassium but not sure if I'm taking enough. Will probably get it tested soon to check.

    I'm really wondering if most of our symptoms could be traced back to the calcium fluctuations due to high VitD 1,25. I read of people normalizing their VitD levels after an antibiotic protocol. Has anybody ever been able to address the VitD issue in any other way? I'm a bit concerned about being on antibiotics for several months.
     
    Valentijn likes this.
  16. Sea

    Sea Senior Member

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    NSW Australia
    @enduin this is slightly off topic but thought I'd mention, sulphites are not the only substance in wines and cider that are likely to cause intolerance.
    Amines are another big trigger for some folks
     
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  17. Gondwanaland

    Gondwanaland Senior Member

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    Tyramine is a big issue for +/+MAO-A
     
    merylg likes this.
  18. enduin

    enduin

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    Amines might be a problem for me, since for a period of time everything fermented was giving me diarrhea. Now I don't get that anymore, but beer seems to make panic attacks from likely, while distilled spirits don't.

    On the other hand for my wife it's definitely the sulphites, because she doesn't react to beer, and she doesn't react to sulphite-free wines and ciders...
     
  19. Violeta

    Violeta Senior Member

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    I know someone with this set of test results, she had a calcification of one of her parathyroids. Removal doesn't get to the cause of the calcification of the parathyroid, I understand that, but it does give a clue to what is possibly going on. She did say, though, that she has VDR bsm mutation, and that causes too much conversion of inactive D to active D.

    Have you read the Marshall Protocol information? I don't think he has the answer, but he does say that the VDR can be infected. He has a protocol that involved avoiding all Vitamin D and then using antibiotics to deal with it. Several years after reading his information a thought came into my head that vitamin K2 might actually be a much easier way to accomplish the same thing.

    I am interested in this because I have a lot of the symptoms, I don't get testing done, though.

    Have you been tested for any viruses?

    Also, may I ask if you have read about boron deficiency related to the possible calcium dysregualtion?

    Do you have signs of incorrect usage of calcium? I always think of soft tissue calcification when I think of calcium dysregulation, but I am wondering if the calcium can also mess up vagus nerve receptors. I also think of some sort of pathogen when I think of calcium misplacement, and recently looking into viruses and how they love the nerves, I am wondering if the vagus nerve receptors has something to do with that in conjunction with the calcium.

    I was consistently taking a good K2 for a couple of weeks and saw improvement. I had started focusing on other things and wasn't as careful, and may have had a backslide.

    May I ask if you have noticed any worsening of vasovagal symptoms from eating fruit?
     
    Last edited: Jun 20, 2015
  20. Violeta

    Violeta Senior Member

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    One more question, have you ever eaten potatoes and had a negative reaction? I have been looking at acetylcholine receptors, (vagus nerve having acetylcholine receptors), and antagonists. Atropine, a constituent of potatoes, is an acetylcholine receptor antagonist, and can cause symptoms. But they also contain something that messes with calcium uptake, which could raise calcium blood levels without the necessary rise in parathyroid hormone.
     

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