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Help with Genes, Intolerant of Methyl-B12/SAM-e, Freddd

Discussion in 'Genetic Testing and SNPs' started by JCastro, Oct 11, 2016.

  1. JCastro

    JCastro

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    Freddd's protocol helped me for a while with many things.

    I did high dose methylcobalamin, methylfolate, and adenosylcobalamin with co-factors. Eventually one day, I went into a severe agitation/rage/excitotoxic state after taking 30mg b12+30mg folate, 10mg adeno and 200mg of SAM-e. I was hospitalized from this and only benzos relieved the distress. This indicates that high glutamate and excitotoxicity is causing this, as RichVanK said. I also lost my appetite completely.

    Months later, if I take even 1mg of Methyl-B12 these symptoms come back.

    It seems that I do need to fix my methylation, as when I discontinue everything I develop major depression and become non-functional. I have multiple chemical sensitivities, anxiety, and brain fog as well.

    Can someone please help me with this? Will hydroxocobalamin be good for me; will it cause agitation in me?

    Gene SNPs

    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    MAO A R297R rs6323 T +/+
    MTHFR C677T rs1801133 AA +/+


    VDR Bsm rs1544410 CT +/-
    VDR Taq rs731236 AG +/-
    MTRR K350A rs162036 AG +/-
    MTRR A664A rs1802059 AG +/-
    BHMT-02 rs567754 CT +/-
    AHCY-01 rs819147 CT +/-
    AHCY-19 rs819171 CT +/-


    Detox Profile
    CYP1B1 L432V rs1056836 GG +/+
    GSTP1 I105V rs1695 GG +/+
    GSTP1 A114V rs1138272 TT +/+
    SOD2 A16V rs4880 GG +/+

    CYP1A2 164A>C rs762551 AC +/-
    CYP1B1 N453S rs1800440 CT +/-
    CYP1B1 R48G rs10012 CG +/-
    CYP2C19*17 rs12248560 CT +/-
    CYP2D6 S486T rs1135840 CG +/-
    CYP2D6 2850C>T rs16947 AG +/-
    CYP3A4*1B rs2740574 CT +/-
    NAT2 R197Q rs1799930 AG +/-
     
    Last edited: Oct 11, 2016
  2. caledonia

    caledonia

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    Hi J,

    According to Yasko's simplified roadmap, you have pretty sensitive SNPs due to COMT and VDR taq mutations. She suggests Hydroxy B12 and Adenosyl B12.

    Plus your experience with methyl supplements also shows that you're sensitive. The amounts you were taking (30mg each MB12 and Mfolate) were extremely high mega doses. Same with the adenosyl. The SAMe was within the range of a normal dose.

    Unfortunately, there's no way of telling until you try the supplements. You could potentially use self muscle testing - I haven't had luck with supplements such as B vitamins that take a long time to really kick in.

    If you want to retry B vitamins, my suggestion would be to follow my document Start Low and Go Slow in my signature link. It has several tips on how to divide doses very small, use niacin if you starting having trouble, etc.

    As an example, I take 20mcg of methylcobalamin, 4 mcg of adenosyl, daily and 1mcg of methylfolate twice a week. That's micrograms, not milligrams. That's small. There's another person on here doing 1 mcg of methylcobalamin.

    If you're not tolerating hydroxycobalamin, another option is to use methylcobalamin cushioned with a bit of niacin.

    Ben Lynch also has tips for people having trouble with methylfolate. I assume the same tips would help with methylcobalamin.

    http://mthfr.net/methylfolate-side-effects/2012/03/01/
    http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

    Also if you have chemical sensitivities, consider that you may have mercury + arsenic toxicity. I have this. Mercury inhibits the methylation cycle. Mercury and arsenic inhibit the Kreb's energy cycle.

    Mercury can cause the GABA/glutamate imbalance that causes anxiety. I've had this too. It's improved since I got my mercury fillings out. I'm working on Cutler frequent dose chelation.

    Mercury can also cause depression and brain fog. I've had these too.

    So basically you can support your methylation cycle, and it may help a little or a lot, but if you have these toxic metals, the ultimate fix is to chelate them out.

    See my signature link for Cutler chelation for the proper testing and interpretation. This is the only protocol I trust for this. I've gotten worse with other protocols, now I know why.
     
  3. alicec

    alicec Senior Member

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    The fact that you once tolerated and got benefit from these high doses indicates that your problem has nothing to do with the form of the vitamins (eg methyl sensitivity) or with your SNPs.

    These things are the same now when you are having problems as they were when you were tolerating the supplements.

    There is no evidence that COMT +/+ (the first SNP does cause some slowing of the enzyme, the second does nothing) means methyl sensitivity. It is a theory and plenty of people who are COMT +/+ (including myself) tolerate methyl groups just fine.

    Your VDR SNPs actually do nothing. In any case you had these SNPs when you were tolerating the supplements - they haven't changed! Nor have they suddenly started "expressing" themselves and causing you problems. They are part of the gene structure and are expressed whenever the gene is expressed. This does not change from birth to death.

    I have had a similar experience to you, though not nearly as extreme. I once tolerated and got a lot of benefit from quite high doses of all four members of the DQ. Then I started getting agitation, feeling hyped up, irritation, sleep disturbance etc.

    I stopped all B12/folate/carnitine and felt much worse. Eventually I found a balance where I could tolerate moderate amounts of methylfolate and methyl B12. This certainly made me feel better, though I still tend to overreact if I go too far. I have spent the last almost 12 months trying to get to the bottom of what is going on.

    It does seem that trace mineral depletion is at least partially responsible (and in my case, a certain amount of macromineral depletion in the form of calcium was also an issue).

    Freddd has described this in terms of refeeding syndrome, which seems to be a reasonable explanation.

    You will need to experiment to find out which minerals are an issue for you. Before I read that thread I was persuaded to try boron. It had an almost magical effect for a while. Later I found that I needed some calcium as well as the boron. After reading Freddd's post, I bought every mineral in individual preparations and have been experimenting further. Several things have been helpful, but I haven't yet gotten back to where I was before the agitation started.

    There may be other things involved, but mineral balance is an important part of it.

    On a slightly different matter, if you don't already take large amounts of magnesium, do try it. It can be very helpful for glutamate excitotoxicity since it antagonises the NMDA receptor.
     
  4. JCastro

    JCastro

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    @caledonia,
    I am definitely going to keep it low for now, titrating up as I can.

    I have spent much of today reading over Freddd's posts and I am torn between the excitotoxic hypothesis vs. the neurological brightening hypothesis. One thing is for sure: I need the supplements, because since I was hospitalized in June and stopped the Freddd protocol, I regressed to the point of almost being catatonic.

    I am most definitely mercury toxic and have completed over 20 rounds of the Cutler Protocol. Currently chelating as we speak. Like you, I was damaged by chelation with DMPS IV.

    @alicec
    Yes, this seems true. I was able to tolerate high doses for two months before this happened, so I imagine Freddd's theory that things really get going once you have the DQ in place is valid.

    I have a Doctor's Data Hair Mineral Analysis coming back soon, awesome!

    Things that apparently balance GABA/glutamate seem to help with the agitation, such as taurine, theanine, niacin, and magnesium.

    I can tolerate L-Carnitine Fumarate (855mg) and Adenosylcobalamin (10mg) just fine. Well, AdCb gives me a headache. It seems to be mostly B12 and slightly Folate that ignites rage.

    Thank you both.
     
  5. alicec

    alicec Senior Member

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    I know just what you mean. I wasn't that bad but did have difficulty getting out of bed. It was a serious decline.

    I am the opposite - even tiny amounts of carnitine and aodB12 cause trouble. Eventually I decided to try to stabilise with the two that I did tolerate and which did make a big difference - namely methyl folate and methylB12. I thought I would revisit the carnitine and ado later but haven't reached that point yet.

    Determining mineral status can be difficult and you might not get any clear answers. Of course Cultler claims that mercury causes deranged mineral transport and thus that essential element values on a hair test can't be taken at face value if mercury is an issue. But let's set that to one side for the moment.

    In my own case I had as many mineral tests as possible (plasma, RBC, urine and hair) to try to get some insight and none of them made it obvious that I should try the trace minerals that I found helpful. At best, the hair test showed that boron, molybdenum and manganese were lowish (but not abnormally so) and these were minerals that made a difference - especially boron.

    The only sign of had of compromised calcium status was a highish ratio of 1,25 diOH vit D to 25 OH D (which did normalise when I introduced moderate amounts of calcium).

    Determining true copper status seems almost impossible. In the end I found that increasing zinc seemed to do the opposite for various copper measures from what might be expected so I finally decided to bite the bullet and try copper supplements. This was in the face of no obvious copper deficiency symptoms (such as Freddd clearly had) and blood tests which possibly suggested too much copper.

    I have just started the copper experiment but it seems to be helping.

    So unfortunately determining empirical response might be the main way to go.

    I still feel I am missing something but so far have no clues as to what that might be. Still the minerals have taken me a long way.
     
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  6. caledonia

    caledonia

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    Glad to hear you're already doing Cutler chelation.

    I forgot to mention that SAMe also creates methyl groups, so adding that to the methylcobalamin and methylfolate is like doubling up.

    My suggestion would be to do either MB12 + folate, or MB12 + SAMe, and not both.

    Some people do better with their mental health on SAMe instead of folate. This is part of William Walsh's protocol.
     
  7. Athene*

    Athene* Senior Member

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    @alicec Your posts here on minerals are very helpful, thanks. Can you say how much of boron and copper you take? Or which kind of copper? I began copper 2mg (standard bottle of 'copper bisglycinate chelate' from health food shop) last week. I noticed a huge increase in demand for potassium, but nothing else. Boron 2 x 3mg seems to be helping - started a few days ago. It stopped the constant peeing and thirst and muscle aches I had from taking 1,000iu of vitamin D for a few days (every time I try vitamin D, I get hypercalcemia symptoms, but the boron so far has helped that). I use zinc 11mg daily. I use manganese and molybdenum also. Tons of potassium required, as always, since I increased 5MTHF.

    If you read this brief article on copper:

    http://www.globalhealingcenter.com/natural-health/copper-deficient/

    There's a comment below the article by 'Lenny' about the dangers of supplementing with copper if one has 'biounavailable' copper:

    'This article is somewhat misleading. The body is not always able to excrete copper as needed through normal bowel and urinary movement. Nor does excess copper always show up in serum. A lot of free unbound copper can become stored in the body's tissues and organs, and rather this is the area into which the medical community at large has not looked at sufficiently and in which silence remains. In fact, it is this excess unbound stored copper that simultaneously creates a copper deficiency condition and symptoms.'

    And 'Josh' comments:
    'I have high biounavailability and when I used to take supplements with copper or ones that affect copper I'd get a rush of creative energy, which made me think I was healing.'

    What do you make of this? I have no knowledge about any of this. What is one supposed to do/take to use this 'biounavailable' copper?
     
  8. alicec

    alicec Senior Member

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    Currently I am taking 3 x 3 mg boron daily in addition to about 0.7 mg from a trace mineral combo (more on this below). When I first discovered the beneficial response to boron and seemed to have a near bottomless need for it I took 3 times that amount for several months.

    As for copper, I have experimented with 3 mg (as bisglycinate) daily. There did seem to be a slight favourable response at first but this quickly petered out.

    Some similar happened with manganese and molybdenum.

    Then I got the impression that the additional trace minerals were perhaps making me feel worse. I'm not sure about this - maybe I was just worrying too much that some of these minerals can be toxic in too high a dose.

    So currently I am in a bit of a dilemma and can't really decide what to do about ongoing supplementation of trace minerals.

    For some years I have taken a trace mineral preparation (without copper) from Thorne - I continue to take this daily, plus the additional boron (and additional selenium), but fluctuate on whether to add copper and more manganese and molybdenum.

    I have read the stuff about biounavailable copper and while I don't reject it entirely, I am sceptical - it seems to be something of a self-fulfilling cult. I couldn't find any really convincing evidence, just the same stuff endlessly repeated.

    I can't give any clear answers I'm afraid.

    I still haven't really solved the changing basis of my B12/folate response - the mineral stuff has only taken me so far, but has definitely helped.
     
  9. Athene*

    Athene* Senior Member

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    Many thanks @alicec
    Will check out Thorne. That's interesting re the 'cult' observation. Lot of those about. I've read in a few places tonight that if thyroid and adrenals and liver aren't working properly (none of mine are) then copper will build up in tissues (I guess this is more of the 'biounavailable' thing?). And that you need bile to excrete excess copper. Don't know about the veracity of all that. But I am hypothyroid, hypothyroid and PEMT ++ and still can't make bile even though I've been using sunflower lecithin for a couple of months to try to improve liver/bile function.

    Do you happen to know if ox bile would be a good idea to use? I worry about BSE since the UK scare in the 80s. Or anything else to do about PEMT? I was feeling 'cured' the first week on lecithin, then collapsed after trying to do some part-time hours. Still haven't recovered.

    I wanted to increase Boron because of the calcium regulating effect, but after only a few days of Boron 3mg x 2, I'm now noticing breast pain/tenderness about an hour after taking it (though it does wear off) like I had years ago, so it's definitely raising oestrogen for me - old familiar sign. Not sure what to do about that.

    Do you use zinc as well as the copper? The internet seems to be full of warning about needing to use both even if deficient in only one...?
     
  10. alicec

    alicec Senior Member

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    Not sure about the first part though it sounds plausible. Certainly the normal route for copper excretion is via the faeces, so low bile production could affect that.

    For years I took ox bile with every meal (along with pancreatic enzymes). I was mainly interested in improving digestion, which these certainly did and at that stage wasn't following what was happening with minerals. It's certainly worth trying ox bile supplementation.

    Long term supplementation with high levels of zinc can certainly induce copper deficiency. The kind of figure quoted is maybe more than 75 mg/day. Below that it depends on many things I guess.

    I had always thought that copper was plentiful and getting enough zinc was more likely to be a problem, plus was concerned with potential toxicity of copper, so chose the Thorne trace minerals without copper. It contains 15 mg zinc.

    I have taken that preparation for a long time. A couple of years ago I started having various tests for mineral status.
    One of these was a provoked urine which seemed to indicate some build up of copper, so I added another 25 mg zinc.

    Later I followed plasma zinc, copper and ceruloplasmin. All were a little below mid-range but the copper zinc ratio was a little high and the non-ceruloplasmin copper (NCC; ie the potentially damaging copper) was considerably higher than is apparently desirable. This didn't seem to improve with the additional zinc so I decided to add more zinc. Next tests certainly showed a better copper zinc ratio but the NCC was worse. This suggested to me that increasing zinc was not a good idea and I have stopped all additional zinc apart from what is in the Thorne prep.

    At this point I decided I would try adding copper, something I had never been willing to do previously because of the provoked urine and NCC results..

    I haven't done it consistently for any length of time and I'm still not sure whether it is a good idea or not.

    I plan on having more blood tests soon and another hair mineral analysis (copper on that has been mid range) but it seems very difficult to gauge true copper status or indeed true mineral status in general.
     
  11. Athene*

    Athene* Senior Member

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    Thanks for that, @alicec Very helpful to know.
    You have some useful testing available to you! Doctor here refuses/says she can't test for copper or zinc, 'lab won't do them'. I found a private lab that tests copper (on its own) for €200, so I really will have to go by empirical results as you mention elsewhere. It really is tricky. I'm scared of copper too. Isn't there a link for women between copper and oestrogen. My oestrogen is dropping now and I think I read somewhere that low oestrogen can cause copper deficiency? If it's true that oestrogen raises copper then boron might help raise copper too (Boron certainly raises my oestrogen)? But what I've just said is likely very simplified and not accurate at all...

    And thanks re ox bile & pancreatic enzymes. I wonder if you can remember which ones you used?
     
  12. alicec

    alicec Senior Member

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    Yes I can easily get plasma and RBC copper and zinc done and plasma ceruloplasmin, though results haven't been terribly enlightening. I am quite interested to see what happens after marked reduction in zinc supplementation and a little copper addition. If anything useful shows I'll let you know.

    Nutricology ox bile, 500 mg per meal.

    The pancreatic enzyme preparation I used was Creon 40,000. At my worst, when I appeared to produce almost nil pancreatic enzymes (as measured by pancreatic elastase on a CDSA), I was taking 7 capsules per meal. This is a huge dose, almost as high as that used in cystic fibrosis which the high dose preparations were developed to help. Over several years I was able to gradually reduce this considerably and still take some from time to time (25,000 per meal).

    In Australia at least, Creon is mainly available on prescription and is subsidised on our pharmaceutical benefits scheme - otherwise the high dose stuff would be prohibitively expensive.

    I believe the low dose versions - Creon 5 or 10 may be available without prescription.

    There are of course other pancreatic enzyme preparations available at places like iherb but Creon has two advantages. It is the only one I know of which comes in high strengths and it is formulated into many tiny enteric microspheres which are able to mix more thoroughly with food in the gut.

    To work out the equivalent strength for other preparations, you need to know that the numbers refer to lipase units in the preparation. So Creon 40,000 contains 40,000 lipase units per capsule.

    I think the stuff at iherb is around 5- 10,000 units. This is probably a reasonable place to start if you just want to help digestion along a bit but if you have serious problems, Creon in higher strengths is the way to go.
     
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  13. Athene*

    Athene* Senior Member

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    That's so good of you @alicec Many thanks for this invaluable information. I'll get on to it asap. I've been meaning to address the bile issue but didn't know where to start, which supplements were best, and doctor isn't really interested - 3 family members have had their gallbladders removed and I'ld like to keep mine if possible...

    Yes, please do let me know how you get on with the tests after your reduction in zinc and addition of small dose copper. I hope it works out well for you.
     
    matt3n likes this.
  14. alicec

    alicec Senior Member

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    I have made a post here that may be of interest.

    As I noted above, minerals have been important in restoring at least in part the beneficial effects of B12/folate but have only taken me so far.

    Recently I found that biotin had become the major limiting factor. Adding large amounts opened the floodgates, greatly improving my response to B12/folate, and opening up need for more minerals.

    I'm still working my way through this.

    Appreciating the general principle behind these reactions might be helpful for other people who run into similar problems but unfortunately the detail is likely to vary greatly.

    Essentially, as I note in that post,

     
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  15. Athene*

    Athene* Senior Member

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    Glad you found something to move things along @alicec Will check out the post you mention, thanks
     
  16. Athene*

    Athene* Senior Member

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    I just tried increasing Biotin this morning. Instead of my usual 300ug x 3 I took one of Jarrow's 5000mcg. I was able to do more today (washing up, unpacking a few boxes). Not able for much more, but since I had a bad crash from over doing Ubiquinol a few weeks ago this is the best day I've had (though it doesn't sound much, I've been barely able to lift my arms until today). Is it possible to change things so quickly with Biotin @alicec or is it perhaps coincidence or some placebo like effect, do you think?
    Also, I have a thyroid blood test coming up next Wednesday and I found an article that says Biotin can interfere with the lab assay. Do you think this is reliable information, and if it's water soluble as article says, would it leave enough time if I drop it for a couple of days before test? Thanks for all the info you've posted, by the way. It's really very helpful.
     
  17. alicec

    alicec Senior Member

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    Well it could be coincidence or placebo but you could probably work that out stopping and starting a few times and seeing if you get the same effect with it and lose the effect without.

    Biotin is a cofactor for a number of enzymes involved in energy pathways so if it has become limiting it is conceivable that adding it back could result in improved energy responses.

    With me it seemed to be that it was enabling B12/folate to work better.

    Great find. Yes that makes a lot of sense. Dropping biotin for a couple of days before a test should be sufficient.

    Interestingly I've just had a whole lot of blood tests and have been taking massive doses of biotin. It will be interesting to see if some are odd.

    I was waiting till I got results (some are for minerals) before posting again about some recent experiences.
     
  18. Athene*

    Athene* Senior Member

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    Thanks @alicec It was a stroke of luck finding the article.

    It does seem like Biotin could be a limiting factor for me. And as if it was enabling b12 & folate - especially helping the low folate symptoms of achiness, weakness and hair shedding (handfuls every day since last crash and hardly any today. It's odd, I lose it if I move around much at all, and if I walk, I get drenching sweats & tons of hair comes out later with the general flu-like collapse. Keeps growing fast though. But today, hardly any fell out even with exertion) and the buzzing and tingling in my feet that I had when I first began b12 was there again today which I took as a good sign.

    I look forward to your next post. I wouldn't have thought of raising Biotin if I hadn't read your update. Calcium, D3 & Boron were a disaster for me (hypercalcemia within days) though I know you had success with calcium & boron.
    Can I ask do you take D3?
     
  19. alicec

    alicec Senior Member

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    Yes. Currently 4,000 IU daily. Am waiting for blood tests to see if this is a reasonable dose. In the past I managed to overdose on D and stopped taking it for some time. It took a long time for stores to be depleted. Eventually blood levels became too low.

    It takes a long time to stabilise on a given dose so still not sure if this is the right one.
     
  20. Athene*

    Athene* Senior Member

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    Interesting @alicec. My last D3 was 100nmol/L (in winter without sun or supplementation). Calcium within normal range. But I seem to need higher serum level than 100nmol/L to feel better, because I always feel much better after sunbathing in summer and gradually feel worse as winter goes on. I can't tolerate oral or transdermal D. I'm considering buying a UVB lamp - apparently it acts like sunshine on the skin and so the body self-regulates the D? You may be interested in this discussion on it here, but sounds like you're fine with supplements.

    Another much better day today on Biotin - 15,000mcg. Happy to have managed a long hot shower without needing the plastic garden chair I've been having to use. I might try these high doses for a while and keep an eye on the minerals like you've mentioned here. My other separate B doses are similar to yours.

    Can I ask should I increase Thiamin (should it be a particular kind?) if I'm taking high-dose Biotin (I only use 15mg Thiamin in a B-Complex)? And one more question, if you don't mind - will Biotin increase need for potassium? (I'm already on potassium gluconate 3,600mg daily)...
     

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