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How to Titrate to Get Out of Donut Hole Insufficiency

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, Apr 2, 2013.

  1. Freddd

    Freddd Senior Member

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    The nature of paradoxical folate deficiency/insufficiency, donut hole type, appears to have a specific characteristic; the dose required to end insufficiency appears to keeps changing. Let’s look at how that happens.


    Let’s say a person starts with a 200mcg dose of Metafolin with sufficient MeCbl-AdoCbl to start healing. In about three days frequently occur low potassium and/or donut hole folate insufficiency as a set of symptoms often called “detox”. The folate insufficiency symptoms can be relieved by taking enough Metafolin. If a person titrates at 200mcg per day they likely will not resolve the symptoms. That is because the additional folate generates additional need and plenty of time to start even more healing.


    So the question comes up, what does it take to actually get out of Donut Hole Folate Insufficiency whether from Folinic Acid or l-methylfolate.


    IF a person starts at 200mcg and gets donut hole folate insufficiency started in 3 days THEN IF they drop to 100mcg the symptoms get worse or stay the same

    ELSE IF they raise by 200mcg daily increase once per week THEN the donut hole folate insufficiency stays about the same or may worsen.

    ELSE IF they raise the methylfolate dose to 800mcg to 1600mcg each dose (4-8x previous dose) THEN

    The folate insufficiency symptoms may reduce or go may away for some days to weeks or more until the amount of healing catches up to and exceeds the new dose available. Then insufficiency comes back.

    The key to stopping folate insufficiency is to get ahead of the healing that gets started. Often several doses of 4x the size of the current dose each 3 hours will generally make a noticeable difference in one day. Several successive doses of 8x as much will make a more definite difference quicker, often in one dose. Inflammation that takes weeks to get going doesn’t heal right away but will subside over a number of days of adequate dose and the difference can often be felt in hours.


    Methylfolate Bands of Sufficiency

    1. 800mcg with no healing startup apparent, no donut hole insufficiency symptoms

    2. 2400-4800mcg , healing startup with perhaps no folic or folinic or veggie folate difficulties and only donut hole insufficiency

    3. 6000- 9000mcg, healing startup, some kind of relatively simple paradoxical folate insufficiency

    4. 12,000- 24,000mcg, healing startup with moderate paradoxical folate deficiency

    5. 28,000- 50,000mcg, healing startup, most severe paradoxical folate insufficiency

    These bands are determined pragmatically by the results people report.

    One of the things that has become very clear about l-methylfolate, is the seeming paradoxical effects. What one notices is the presence of deficiency or insuffiency symptoms. The results are symptoms that are inversely proportional to dose. The smaller the dose the more likely insufficiency symptoms are to be present as side effects, once at least one layer of healing is triggered. The larger the dose of L-methylfolate the less likely that folate insufficiency symptoms will appear. It appears that a person will have insufficiency symptoms all the way up to whatever their top of range is each time the dose goes up more slowly than healing increases.
    Laurel6123 likes this.
  2. pela

    pela

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    I am taking Solgar methylfolate 800 mcg tablets. I started at 1 tablet 11 months ago and now I am up to 14 tablets a day and still have mild deficiency symptoms. A few weeks ago at 11 tablets I was having bouts of insomnia. The additional 3 tablets literally put me to sleep at night.
  3. Lou

    Lou Senior Member

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    Hi Fredd,

    Excellent post, but please address adequate b12 dose range to accommodate trying these higher Metafolin amounts. Both you and someone else posted warnings of central nervous system damage if too much methyl folates not accompanied with enough b12. Thanks.
  4. Xara

    Xara Senior Member

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    Last week I upped my mfolate from 800 to 1200 mcg. Since all's going well I had been thinking about how much I should titrate on Friday - then I want to up mfolate again.
    Freddd, thanks for posting this, and posting this right now :) , now I have some idea how to handle this.
    Thanks pela too, it's interesting to learn that even at high doses extra intake can make a significant difference. I would not have thought of taking extra methylfolate when having sleep probs. I'll remember that.
    I am looking forward to continue to up my methylfolate, it's very exciting.
  5. Xara

    Xara Senior Member

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    That someone else might probably be me. :) Enough B12 is very important indeed.
    In case anyone is interested, after having read about my mfolate intake nowadays: I am taking 2 x 8 mg mb12 a day at the moment and 2 x 5 mg ab12. I am planning on upping those two as well.

    And I'd like to second your request, Lou: some b12 dose range might be nice.
    Better too much than too little of course, and although taking too much B12 does not bother me, peeing the excess of b12 in the toilet is a waiste of money...
  6. triffid113

    triffid113 Day of the Square Peg

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    I am not playing with mfolate. I take the solgar 800 mcg/day and whatever is in 2 Thorne Basic B and I will not take more. When I take more I feel unstable and I need to up my mB12 and my P5P and potassium and potentially my TMG, and I have great difficulty getting the ratios right in addition to ripping through copious amounts of vitamins. Enough! It does not feel safe to me. I rely on taking a wide varienty of supplements to avoid deficiency and lots of antioxidants.
    Lotus97 and jeffrez like this.
  7. jeffrez

    jeffrez Senior Member

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    Wow, those are such huge doses of methylfolate. Whatever works for you, but it just seems like a lot. Are the people taking up to 14 tablets a day noticing any definite ME/CFS improvements?
  8. pela

    pela

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    14 Sogar tablets contain less than the prescription dose of Deplin at 15 mg. I would like to be able to get by on a lot less mfolate, because it is expensive. I am taking 20 mg Mb12 and 10 mg ADB12 daily. In February I bought a bottle of Webber methylB12 5000 mcg. I have had to start taking potassium again and had to increase folate from around 8-9 tablets a day to 14. The Webber brand has been a major kick in the butt for me. I took it for a week then switched back to AOR for a week. I feel nothing on AOR. After 6 weeks or so on Webber, I still feel it almost every time I put one in my mouth. I am taking 15 mg Webber and 5 mg Enzymatic Therapy.

    As far as improvements, it comes and goes. A month ago I started jogging again. Right now I am in the middle of gut issues and fatigue that I'll happily blame on houseguests.

    Webber is sold on Amazon and at Costco if anyone else wants to try it. I would love some feedback on it:

    http://www.amazon.com/Naturals-Methycobalamin-Natural-Flavored-Microlozenges/dp/B005TP2NA6/ref=sr_1_1?s=hpc&ie=UTF8&qid=1364928256&sr=1-1&keywords=webber naturals b12
  9. jeffrez

    jeffrez Senior Member

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    That's amazing that you're jogging again. What was your level of activity/PEM before the protocol?

    What do you think of Solgar in comparison to the Webber, btw? If you've taken Solgar. Thx for the info.
  10. lnester7

    lnester7 Seven

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    Fredd what can we do when we don't pee the excess??? When I am on on b12, I feel better but my levels go up way too fast, so Doctor ask me to stop (and I astart getting angina and eye pain).
  11. pela

    pela

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    Without going into lots of detail, I was exercise intolerant but exercising anyway. My exercise tolerance has greatly improved.

    I have tried Solgar Mb12. For what it's worth I thought it better than AOR or the new unimproved Jarrow, but a total waste of money compared to Enzy or Webber. I have also tried Blue Bonnet mb12 and Swansons mb12 and thought both were useless. I am not an expert at judging MB12, I'd love to hear other opinions on these brands.
  12. jeffrez

    jeffrez Senior Member

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    Ok, good info, thanks. :)
  13. Freddd

    Freddd Senior Member

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    Hi Jeffrez,

    These doses are all determined pragmatically by people finding what they need to stop the paradoxical donut hole folate insufficiency symptoms. I suspect that it is more of a distribution problem in some way than an amount that is actually getting used. The clarity of the multi modal banding sure is suggestive. With a serum halflife of 3 hours how many dollars goes down the drain unused? WHY is so much necessary for it to be available for the needed reactions? I do know that if I eat a sizable salad plus cooked veggies with dinner symptoms can start within 12 hours. If I preload with Metafolin I don't get the symptoms. There is clearly so kind of competition there. Between the b12s and Metafolin I take it is more than $10/day. I wish it was under a dollar. The actual amount a person needs for healing otherwise looks to be that lowest band with healing turned on, maybe 2400-4000mcg, and even that is probably only 800mcg 3 or 4 times a day. The halflife is a problem. The Deplin study for depression found that the larger doses, 15mg and 30mg daily were far more effective. Maybe we are seeing a similar problem of getting the folate into the CNS. Something is clearly happening that they hadn't intended in the studies. It is noted in at least a couple of things I've read that the Metafolin had extraordinary CNS effects in a few people. So far, in looking at it several years down the road, the people who have the folate symptoms from childhood appear to be most likely to need the larger amounts and to have serious CNS involvement leading to SACD an it's first cousin MS. I could be wrong on that as data is still very thin. The Deplin study was for people with CNS mood changes, depression. So as it is CNS I'm not surprised the doses were higher. I remember my surprise at reading that. When I first got the first vitamin Metafolin (Source Naturals, one batch) It was already discontinued and I ordered all the bottles I could find to carry me over until the problems with the vitamin form got worked out. I limped along on 400mcg a day which made a huge difference and made the donut hole insufficiency symptoms far worse than none at all. I also had to use 1200mcg more potassium. 800mcg decreased donut hole insufficiency for a couple of weeks and increased potassium need. As the level goes higher the severity of symptoms has reduced and don't happen as often. There has been a lot of learning with timing and what not to take it with. I might try a little sublingual to see what happens, if that improves it.
  14. triffid113

    triffid113 Day of the Square Peg

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    That's interesting. I get eye pain and I have observed it is associated with hypothyroid. TSH should be < 2.0, however I do not get eye pain at TSH 2.3, but only TSH >2.3. These are all within the so-called normal range, but that range is not based on science. Studies have shown cholesterol rises if TSH >=2.0.

    I am beginning to think I get angina too. Well there are times when my bp is so high I can feel every artery in my chest and it's pain. But short of that I feel a kind of indigestion and I have low stom,ach acid so I wonder if it is angina..,.but putting something like water in my stomach helps blunt it so maybe that's not angina. I guess I don't know what angina feels like but I am starting to think I get it. And it has to do with high bp and high cholesterol (that means hypothyroid TSH >2.3). I get that in the winter at low humidity due to allergies...it goes away as the wearther warms up and humidity rises. But this year my arteries got so clogged, that my bp is being stubborn about lowering so I am going to try high dose MK4.

    So in short I have the above symptoms and they tie to hypothyroid for me. I know the thyroid uses mB12, but those who take thyroid hormone say that taking mB12 did not allow them to lower their hormone intake so I wonder if the thyroid does not need very much mB12.
  15. jeffrez

    jeffrez Senior Member

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    Do you take Deplin, Fred, or have you ever taken it? What do you think the chances a doc would prescribe it for you? An alt doc might, if you explained all this to them, do you think?
  16. Freddd

    Freddd Senior Member

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    Hi Pela,

    So Webber is pretty good then? One thing I have seen over and over is that the same brands generally are on top for most folks who try comparisons. And again, in some theories they should all be the same but pragmatically the difference is night and day between brands. I believe the exercise tolerance is tied to the ability to make more mitochondria among other things. For me that required all 4 of the Deadlock Quartet.
  17. Freddd

    Freddd Senior Member

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    Hi Jeffrez,

    I have talked to my doc, an internist, and he is agreeable. However, right now it is more expensive than the Solgar when I put in a large enough order for Solgar. At first until I demonstrated the effect he wouldn't and now that it is a blazing success he will. Nothing succeeds like success After all, there was no reason to since it was as an adjunctive treatment for depression and post MeCbl I wasn't depressed and wasn't taking SSRI mas a primary antidepressant.

    The thing about Metafolin is that the contract for vitamin licensing requires the product to meet the same standards as the pharmaceutical product. Merck wanted all Metafolin to be the same quality. I applaud that. Metafolin is Metafolin whoever it is from. At first quantity was limited and they were only able to make it available in kilos. Now it is clearly mass produced.
  18. Freddd

    Freddd Senior Member

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    Hi Triffid,

    Your doctor doesn't understand the pharmacodynamics of B12. 1mcg temporarily raises the serum level 200pg/ml. Anybody supplementing is going to have an above average serum level which is ONLY a statistical aberration. It doesn't mean asymptomatic. It means that 97.5% of tested people have a lower level. MeCbl produces higher serum levels for a given dose as more of it is absorbed. Are you taking CoQ10? That can cause high blood pressure during a period of healing. Also, with AdoCbl and LCF the mitochondria can proliferate and perhaps give your heart and other muscles better oxygen handling and energy generation.

    The thyroid appears largely unaffected by MeCbl and AdoCbl except when still in the active phase of Hashimoto's and then sometimes function is more normalized, by observation of a lot of us with hypothyroid. It's never made any difference for me.

    Low stomach acid has symptoms very similar to high acid. For a lot of people it seems to normalize in some months on the MeCbl, AdoCbl and Mfolate. "Rabbit pellets" feces appears to relate to low acid and some people find Betain HCL helpful.
    cph13 likes this.
  19. Freddd

    Freddd Senior Member

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    Hi Inester,

    There is no such thing as high serum level in a pragmatic sense. The question is how high for what healing. For those of us with CNS problems it requires a serum level above 100,000pg/ml or so for half the day to get enough into the CNS for healing. For healing peripheral nerves it would appear that 25,000pg/ml for at least part of the day is needed. For most other body healing it appears that 15,000+pg/ml at least part of the day does the trick. 100mcg absorbed is an instantaneous 20,000mcg/ml for a few minutes before it goes down. A top level of 900-1100pg/ml isn't even out of the continuing damage range. Everybody pees the excess. It takes about 24 hours to pee out 98-99% of a given dose. So if 10mcg is retained to the next day, the serum level could be 2000pg/ml. Unless you are taking injections of over 5mg you are unlikely to see it in the urine. Above about 10,000-15,000pg/ml the kidneys make fast work of b12. Below that the kidney action falls off and the liver and excretion in the bile takes over. I would keep it going because I think that is ignorance on the doc's part based on 50 years of research on inactive vitamins. The ONLY definitive test as to whether b12 will benefit a person is doing a trial. There is not any test or combination that can say "no benefit". They don't test of type of cobalamin, just total including junk cobalamins. A person can be fully adequate on MeCbl and low on AdoCbl as well as low CNS AdoCbl and low CNS MeCbl. Because of the research done on inactive cobalamins they don't know what it takes to heal and they don't know what real b12 healing looks like.
    lnester7 likes this.
  20. Freddd

    Freddd Senior Member

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    Webber is sold ... at Costco

    I haven't seen it out here. Is it a new product?

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