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Anyone else have methylfolate "wear off" after ~6 hours?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by bigmillz, Apr 22, 2017.

  1. bigmillz

    bigmillz Senior Member

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    After a very successful week stretch at 10mg daily, I'm starting to notice that about 6 hours after dosing, I get really tired, and the most obvious benefits seem to wear off.

    I've tried going above 10mg, but it's just too much at this time. I get brutal headaches, start sweating, and get really agitated. 8-10mg gets by okay.

    Is this just due to the half life of methylfolate? Should I break the 10mg into multiple 2mg doses every few hours? Will that feel as effective?
     
  2. Mary

    Mary Senior Member

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    You might be experiencing low potassium which can be induced when taking folate and/or B12. This is because cells will start to divide more rapidly when remedying a deficiency of folate and B12, increasing the need for potassium and thus inducing a deficiency. If you haven't already done so, I urge you to read about low potassium and methylation - there are several threads on this board about it, here's one: http://forums.phoenixrising.me/inde...tant-info-re-low-potassium.49540/#post-818100
     
  3. bigmillz

    bigmillz Senior Member

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    Thanks @Mary

    Ive considered this but it never seemed to resolve the problem. I will give it another shot though this week. I was out of town and didn't have potassium on me (just bananas and avocados).

    If it is potassium, does it make sense that roughly another 6 hours later (12 hours after dosing) that I would start to bounce back? Mind you this usually means after dinner. Which one day included French fries. Hmm!
     
  4. Mary

    Mary Senior Member

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    I don't know. It does sound a little odd. When my potassium tanked, I was hit with severe fatigue which would have lasted at least a couple of days I think if I hadn't been aware of the low potassium issue.

    A couple of other things struck me - that's a high dose of folate - how did you arrive at it? I do well with 1600 - 2400 mcg. Are you taking B12 with it? Taking folate alone can mask a B12 deficiency.

    In any event, I would divide the folate into 3 doses. Any supplement I have to take in high doses, I generally divide into 3 doses, breakfast, lunch and dinner.
     
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  5. bigmillz

    bigmillz Senior Member

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    I started at 400mcg and kept working up everytime I felt deficiency symptoms. @Freddd was right - roughly 3x the original dose would do the trick.

    Finally when I got over 8mg these deficiency symptoms seemed to dissipate completely. Then I just went a little higher because it felt better. I used to take 6mg daily in 3 doses and had this tiredness problem too, as well as a lot of irritability. That's been remedied with B2 - thanks @Sherpa

    I take 5mg of mB12 and 1.5mg of adB12 daily. I've tried going higher on the mB12 but it didn't work out so well.
     
  6. Creachur

    Creachur

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    Isn't 10mg a day a bit high? I'm new to this forum and I haven't followed the protocols or advice here but found for myself that 2 to 3 mg a day was good. I kind of felt I was pushing the dose a bit too high. I'm sure Google can find examples of people taking extreme amounts but what is a typical beneficial dose for those who need methylfolate?

    How can you afford to buy such an amount? Out of interest, what brand are you using?


    As the B vitamins are water soluble, I personally would dose any given B vitamin several times a day. That's not terribly scientific way of predicting things because (1) some of the B vitamins might accumulate or (2) the B vitamin may start off a beneficial effect which runs for longer than the B vitamin is actually present.

    I'm no expert whatsoever about folate but there seems to be possible points along its metabolic path where it could accumulate (I'm thinking MTHFR defects and folic acid and guess there may be other similar points where pooling could occur).

    I take 800mcg doses of methylfolate (as Metafolin) and find I need re-dosing 6 to 8 hours later which may reflect too low a dose to start with to see me through a longer period of time. If I wake in the night I might take 400mcg methylfolate. However maybe the need to re-dose is due to a rebound effect of the body overshooting when trying to re-assert it's normal balance. In other words, maybe it's a sort of withdrawal symptom than a true need.

    I wonder if smaller doses may be better even with the same 6 to 8 hour time interval between doses. Unfortunately I find the 6 to 8 hours period I mentioned sometimes simply doesn't always apply and I guess this may be due to various other processes, maybe B12, interacting with the methylfolate.

    I suppose the best we have to go on is seems to work in practice. I would be very interested to hear what frequency of dosing other people use for methylfolate.



     
    Last edited: Apr 23, 2017
  7. stridor

    stridor Senior Member

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    I have a hard time absorbing mfolate and have to open capsules and pour into the buccal pouch. I gave up at 9 mg a day swallowed as I just couldn´t afford it. When I was the sickest, I was taking 3-4 mg a day s.l. and dosing around every 3 hours. Now I am around 1-1.5 mg a day.

    Some people here that are taking high doses of folate will not be absorbing well either and might want to try going sublingual.
     
  8. bigmillz

    bigmillz Senior Member

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    I'm thinking this week (after taking today off) I'll restart at a lower dose. When I used to take 2mg, it was too low. I was becoming absolutely miserable. 1mg was even worse - far worse than none at all.

    I buy Jarrow, and I'm trying Solgar too, but there's a few high dose brands on Amazon now at more reasonable costs. Still not cheap. But if the benefit is there...

    I'm having issues with mood swings the past few days, so I suspect I've pushed it to high, and that it just took a few days to catch up to me. It's really hard to describe, but it's not pleasant. A lot of anxiety and stuff like that.

    Sounds like spacing it out is the way to go regardless.
     
  9. alicec

    alicec Senior Member

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    The half life is about 4 hours so it could be. Try divided doses (3-4 spread over the whole day).
     
  10. caledonia

    caledonia

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    I take methylcobalamin, adenosylcobalamin, and electrolytes (potassium, magnesium and sodium) all 4 times a day.

    I can take more if I do it that way, and it absorbs better.
     
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  11. bigmillz

    bigmillz Senior Member

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    Hey everyone, wanted to give an update here to hopefully help some others.

    Splitting the dose up did the trick. No extra potassium required. Currently taking a dose with breakfast, lunch, and dinner.
     
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  12. Kathevans

    Kathevans Senior Member

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    I do best taking folate four times a day. Though I'm taking about 10mg a day, I wake up routinely around 4-6 a.m. and need another dose. Then after a couple of hours I go back to sleep again. And when I take it during the day, I notice folate deficiency symptoms after about 2 1/2 or 3 hours--runny nose, IBS, tiredness, pain. I keep thinking that I haven't reached the right dose for my body, or as Fred says, I'm so deficient ( a life of folate block because I wasn't taking enough B12, and was taking folic acid) that I'm working on refeeding syndrome. Even Greg, the B-12 Oils guy says that I most likely need to 'fill my tanks'. How high I might have to go, or for how long, I'm not sure. But at this dosage, my ears are ringing and I may just take it slow and wait it out. As @stridor says, the expense also becomes prohibitive. And another question for you, Stridor: I don't recall the timing of your story, but do you think getting the mercury out has lowered your need for folate? (Something that is still ahead of me over the next couple of years--lots of work to go) Or only that you managed to fill up, so to speak, and your needs dropped?
     
    Last edited: May 1, 2017
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  13. stridor

    stridor Senior Member

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    @Kathevans That is a tough question to answer. If I had to try to quantify things I would say that there was a gradual decrease in use starting towards the end of chelation with a sizable dip when I treated the mycoplasma infection.

    Mycoplasma likes mucous membranes and a gut affected by mycoplasma looks a lot like the that of celiac with flattened villi. It may be that after treating this that I started to absorb better (?)

    The whole methylation and mercury question is something that I have thought about but really don't know. Can someone chelate mercury well if their methylation system is compromised....and can someone restore the methylation pathway well if mercury is present?

    The whole thing smacks of a Catch 22. Hard to fix methylation until mercury is gone but you can not chelate well until the methylation system is optimized. Maybe that is the best we can do in the end. Tackle both problems but expect a longer road to recovery as these two issues slowly resolve.

    Cutler is not big on people pursuing methylation. Don't even mention MTHFR to him - he gets quite snarky about the whole business. He recommends that people take B vitamins and thinks that there is no benefit to mfolate and mB12.

    The guy saved my life but we did not always agree on things.

    So, while I am using much less now I am not able to state with any confidence why that is.
     
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  14. caledonia

    caledonia

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    @stridor @Kathevans
    Regarding methylation and mercury. I've made an extensive study of methylation, and now in the past year or so, mercury.

    The link is that mercury (and lead and possibly aluminum) inhibit the methylation cycle at methionine synthase. Some cycle diagrams show this. This is right where B12 is the co-factor for methylfolate to create methionine and eventually SAMe.

    So it's a very important step in the methylation cycle.

    So you can either have genetics or epigenetics inhibiting the methylation cycle (or both). So you can have genetic mutations in MTHFR and MTR inhibiting things or you can have toxic metals inhibiting things (or both).

    I've seen a lot of people's genetics on here, and most have some form of MTHFR - a lot greater than you would see in the general population. If they don't have that, they have GST (glutathione) mutations. I've only seen a few people who have neither. I've seen a lot of people who have symptoms of metal toxicity.

    In my opinion, people with methylation mutations are the "canaries in the coalmine" - they're already not detoxifying well, so when they accumulate metals, they're more likely to get sick than someone without mutations. Then once you've accumulated some metals, your ability to detoxify gets even worse. So you can see how it can become a vicious downward spiral. Of course, it's possible to have no methylation or glutathione mutations, and still have enough toxic metal exposure to become very sick.

    We've seen on here that it's possible for some people to take enough folate and B12 to compensate for genetics and even mercury inhibiting the cycle. However, they need to continue to take high dose supplementation, and they may also continue to have various health issues.

    There are also people who have chelated out mercury and other metals and get significantly better.

    If you had a total block of methylation you would be dead. So there is still some methylation going on even with both the mutations and the metals inhibiting things.

    I agree with Stridor about trying to tackle both to the extent that your body allows. Even if it's just a little bit of B12 and folate, or very low doses of a chelator. Both strategies are accomplishing the same thing, which is increasing your methylation capacity. If you're maxed out on how much B12 and folate you can take and you still have issues, it's time to look at metals. Things should get better as the metals come out.

    Of course, you can't change your genetics. But, in general, if you didn't have the metals adding an additional burden, you should be able to be healthy with 1, 2 or even 3 MTHFR mutations. Those with 4 mutations (extremely rare) are very sick. Most were never born to begin with.
     
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  15. stridor

    stridor Senior Member

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    @caledonia
    My sense of things is that pretty much everyone who has methylation issues should be tested for metal. Even if as you say, they are able to some degree bolster the pathway with mfolate/mB12 etc, that is still potentially leaving mercury trapped behind the BBB.

    During your reading did you come across the idea that mercury that is warehoused in the astrocytes comprising the BBB corrupts the B12 molecule as it crosses into the brain?

    My last attempt to decrease the B12 failed and I would like to get down to one needle a day. I hope that there is something to this idea and that my next attempt will succeed.
     
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  16. Kathevans

    Kathevans Senior Member

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    Well, @stridor and @caledonia, thank you. It seems many here have come to this pass. It's been a slow and rocky path for me with methylation--a bit of both Fred's and Greg's protocols--which is to say a lot of focus on getting B2 functional, which seems to have been a stumbling block for me. And now, as Fred's refeeding theories go, I'm working on Folate, but because of my snps, always with plenty of B12. Amazingly, I have found Adeno B12 to be a tricky one, too, though one that my body clearly needs. I've never injected B12, but have worked my way up to one squirt of the Methyl Oil and one per day of the Adeno/Methyl combo. My body seems to need still more Adeno and more folate. For me these two seem to work in concert.

    The mercury is something that has given me the chills along the way, but that I've avoided because it seemed so overwhelming. Now, after nearly two years of working with methylation, with no clear resolution of symptoms, I'm staring at my teeth. A mouth full of crowns and several root canals. The expense is exhorbitent, but my symptoms are disturbing and though Greg says there are no problems with mercury, I think it's like Cutler poo-pooing methylation. Both are important. I have all sorts of tingling in my head, ears, face, and while it goes away occasionally, I haven't managed to get rid of it for more than portions of a day. Same with my tangling fascia, particularly Dupytrens contracture and two trigger fingers which I can actually feel getting worse or better depending on my last dose of folate.

    And of course, the gut. Stridor, I remember your thread on mycoplasma and will have to refer to it again as I move forward. Only in the past two months have I begun to take digestive enzymes, to use a bit of l-glutamine, do a bit of oil pulling. I bought some Betaine HCL and am hoping I can tolerate it now. In the past it destroyed my fragile sleep.

    I feel as if I'm inching forward, every day some sort of challenge, every night the same. But there's no other choice, not if you still hold tight to a dream or two for your life...which I do. Not least of which is a good night's sleep, one good enough to wake feeling rested and full of energy.

    To see your progress, Stridor, gives me hope. And many of us, I'm sure. Thank you for continuing to spread your wisdom, even as functional as you now are. It's a generous gift.

    A bike! I didn't ride mine at all last year! Maybe this...
     
  17. stridor

    stridor Senior Member

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    @Kathevans
    To be clear about Cutler's position. He thinks that methylation is important but the last time I checked, which was 2 years ago, his position was that chelation would restore function in this pathway. And he is likely right for the majority of people - remove the poison, free-up enzyme function and things are going to improve.

    The problem is that the methylation pathway is a series of enzymes and some SNPs function better than others. All of this will be on a continuum with complete recovery on one end and on the other those like us who will need life-long methylation supports because our genetics stink and likely have an epigenetic component as well.

    Some of us find ourselves in deep holes with all of this and a bit of folic acid and cyanocobalamin is not going to help us get out. Cutler is not against mfolate or mB12 per se, but he thinks that they are an unnecessary expense.

    Following his ideas on methylation kept me sick for 18 months longer than necessary. My discussions with him on this ended with me being designated an "unusual case". That is that my genetics might indicate that I would need to pay attention to my B12 and folate status beyond taking B50 tabs.

    Chelation was super-tough until I took mB12 and found a "rung in my ladder".

    B2 was a real problem for me as well. If you know my story then you know that I had symptoms consistent with "running dry" even though I was supplementing. Greg was kind enough to look at my SNPs even though I am not a customer. The guy is a saint. Anyway, he encouraged me to increase my B2 intake further and to add back more folate, which I try to remember to do.

    You never know who will read these posts in the future so I will embed this message. If you are someone who is chelating mercury and you do not improve significantly after the dump phase, put methylation issues at the top of the list.
     
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  18. caledonia

    caledonia

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    I hadn't really gotten down to that level, so I did a quick google search on your keywords.

    Check out this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406448/
    - the last paragraph before the conclusion:

     
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  19. Kathevans

    Kathevans Senior Member

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    Well, guys, thanks again! I'm going to put a reference to this thread someplace where I hope I'll remember it when I need it about a year or so from now. Meanwhile, I've got a headache for some reason and am gearing up for the lower left quadrant of my mouth to be mercury-free after tomorrow. Are there any mercury-specific threads here or just the random mention in many? I know for example that both @garyfritz and @Johnmac have dealt with or are dealing with mercury issues. I've read about them largely on the Transdermal B-12 threads.

    I've also become a member of the Facebook Cutler Chelation site, but I still have to get and read the book--I've just become aware of the dueling protocols where the Cutler folks have nothing good to say about, say Quicksilver Sceintific's Mercury Tri-Test, as opposed to the Doctor's Data one for metals. Opinions? I've only had NutrEval and other very standard blood work by my primary care physician, this latest in blood work only, which I understand doesn't have to do with past exposure. Still, given I eat almost no fish, the results were a bit dismaying: Blood Mercury: 5 ng/mL (in a range of: 0 - 9 ng/mL).

    @caledonia The link you provide is terrific in many ways and confirms not only higher doses of both B-12 and folate, but also those who showed the best results were in the Methyl B-12 category (that is, opposed to Hydroxy B-12). It's nice to see confirmation...
     
    Last edited: May 3, 2017
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  20. stridor

    stridor Senior Member

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    @Kathevans There is much work to be done. It might help if you steer clear of as much of the politics as you can. I had to bite my tongue a few times. There are facts and there is speculation and conjecture. The facts are that thousands of people have recovered using Cutler's Protocol. A few like me, made it but we had to adopt other important stratagies.

    Very few people can not handle ALA...it happens, but not often. There are those people who have (+) Melisa tests for metal allergies. They are just going to have to dig in and accept that it will take longer. Speaking of which I did 300 rounds which is more than most.

    I blame faulty methylation but really, who knows?

    ALA works and it is something that your body needs and uses. It has the spin-off of recycling glutathione. It is very important that our treatment does not add to our oxidation burden. When you put this on the back burner in your mind, put a big Vitamin C sign beside it :)

    @caledonia
    Great article. My personal story could be partially explained by this. It provided an explanation of why someone might end up being hypothyroid in the brain (my theory of what is going on with Mad-as-a-Hatter disease) while peripheral T4/TSH levels are fine.

    It also provides a possible explanation for why I seem to be stuck at 2 needles a day of mB12. Good work and thanks.
     
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