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Low Folate Symptoms/Paradoxical Folate Deficiency

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by arx, Aug 25, 2012.

  1. arx

    arx Senior Member

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    I have two questions:

    1.How does one know that he/she is low on folate, and similarly he/she has a paradoxical folate deficiency?

    2.Now,considering one is consuming both, l-methylfolate(deplin/metafolin) as well as folic acid. If folic acid is blocking metafolin from being absorbed, will increasing the amount of metafolin help?

    Thanks!
  2. Skyline

    Skyline Senior Member

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    I am researching the answer to this - will add to my thread if I find it.
    The main tests seem to be:
    A) Methylation panel
    B) Titrated or large dose of Metafolin - if symptoms are relieved there was folate deficiency (are there any downsides to this/ risks? looking into it)
  3. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    I don't think it is always as simple as this because when you get the methylation cycle working better, other things will change that may not bring a clear and straightforward improvement in symptoms. Sort of a 2 steps forward and one back.

    Sushi
  4. Crux

    Crux Senior Member

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    Hi Y'all;
    I feel I should caution you about increasing folate. Over the last couple of months, I've been increasing methylfolate-again.
    I was up to 3mgs. daily for about 2 wks. Energy was improving, but sleep was getting worse... not by much.
    Then, about 5 days ago, I developed a skull cracking migraine. I used to have this type years ago before starting methylcobalamin.( mb12 helps my migraines)

    Even though I quickly realized the headache was from too much methylfolate, it has taken these 5 days for the headache to recede. ( It's mild today.) I stopped folate 5 days ago.

    So, I want to bring this up as a symptom of excess folate, in hopes that other folks will titrate very slowly. Even a mild headache may be a warning from the body.
    adreno and Phred like this.
  5. Skyline

    Skyline Senior Member

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    Sushi/ Crux, thanks for these data points.

    Crux, if your energy levels are an issue, perhaps adenosylcobalamin would help? I don't really have energy issues at this point, but I felt an almost too high energy boost when taking the adenosylcobalamin for a few days - included having difficulty sleeping because of it, but I'd sit up reading most of night no problem.

    Sushi, I think I've seen references on these forums where others have tried to set apart 'startup symptoms' vs. symptoms relief etc. I'll see what I can find today - see if there are any patterns.
  6. Phred

    Phred Senior Member

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    Crux,
    Thank you, thank you, thank you!! I doubled the amount of mb12 I take, so I subsequently increased my methylfolate as well. I have been suffering some severe headaches. I thought maybe it was from low potassium, but increasing that didn't seem to help. I've also had some wicked digestive issues. So again, thank you for posting this. I was suspecting this and did lower my amount of folate earlier today. I will stay at a lower rate and see if the headaches go away.
  7. Crux

    Crux Senior Member

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    Hi Y'all;
    You're most very welcome, Phred. The headaches were so bad at first, I had to take an extra 5mgs of cortisol, and some clonazepam. They really help, but I wouldn't want to do that long term. Today, I had a big mug of green tea. I've read that it may lower folate a bit. Of course, I think the caffeine helped too. I also had 2 tsps. of turmeric in water. It may have helped...not sure yet.

    Skyline, thanks for the suggestion about adenosylcobalamin. I'm very slowly adding it...again. It really does help fatigue, but in a rock'em, sock'em way. I'm so greedy for sleep, I have to be measured about supplements.

    I did get hopped-up from the green tea---wonder how sleep will go.
  8. adreno

    adreno 3% neanderthal

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    I don't believe in "paradoxical folate deficiency". It seems more likely to me that you need something else. In my case, when I increase MB12 and methylfolate, I vastly increase my need for B2, zinc and potassium. Same like Crux, I felt wonderful for a few days, then suddenly felt terrible. After I added in more B2 I felt better again.

    But yeah, synthetic folic acid can block methylfolate. It's not good for anything, so just get rid of it.
  9. Skyline

    Skyline Senior Member

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    I think this is all 'paradoxical folate deficiency' is supposed to mean. It really is "Active Folate Deficiency" - since the folic acid is crowding out the active folate, and not able to be used. Most of us probably agree with this statement when it's phrased like this and doesn't include 'folinic acid'.

    The bigger question that you are answering is if things aren't moving forward do you:
    1. Increase Methylfolate
    2. Look for cofactors
    3. Look for issues in lifestyle: Possibly over-exertion? or not enough sleep?

    I'm hoping that by using some good quality multis (B complex, minerals etc) and with a really solid paleo diet with a lot of variety it gets round the #2. This should be our foundation to start with before we attempt methylation in general and #3.
  10. adreno

    adreno 3% neanderthal

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    Well, that's not how I understand it. The "paradoxical" part implies a paradox - that taking folate leads to a deficiency state by triggering "more healing than the present level of folate can sustain". If it's not paradoxical, it's just a deficiency. But really this is a term invented by Freddd, so he should be able to clarify if he chimes in.
  11. Crux

    Crux Senior Member

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    Hi;
    The reason I increased mfolate again, was because, from what I've read about it, folate is predominately active with healing tissues. Methylcobalamin is reputed to be most active with healing nerves. But, I've also read that there is a crossover, and that each performs on both nerves and tissues.

    One of the nagging symptoms I've had is canker sores. Since many people have healed theirs with extra folate, I decided to increase for that reason, in part. ( I tend to think that if I have lesions in the mouth, I may also have lesions elsewhere.)

    In the past, I've tried increasing B2, zinc, lysine, herbs, and so on, because they also help with healing lesions of sorts. My cankers persisted.

    I've also had to increase cortisol when they've become debilitating.

    Now, it looks like methylcobalamin is the most effective substance for these lesions, in my case.

    So, I believe it's really hard to separate the activity of each B vitamin.
    But, when I took B complexes and individual B's for years without the sublingual methy-B12, none performed at all.
    I did find that when I was taking such high dosages of methylfolate, I became hyper-sensitive to any extra folates, whether in supplements, or foods, naturally occurring, or fortified.

    I've concluded that I was over-dosing Folate, in total, and my body had to give me a good slap to indicate as such.
    In my case, I don't believe it was a paradox; it was a dire warning. " This is too too much."
  12. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Crux

    I used to be plagued with canker sores. Since taking GcMAF and Nexavir I have had none--not one! So, for me, it is looking like a pathogen issue.

    Sushi
    Crux likes this.
  13. Crux

    Crux Senior Member

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    Thanks Sushi;
    An Internist told me that cankers could be autoimmune or viral. My father's were found to be autoimmune, so I suspected mine were, because autoimmune conditions are heritable. All of his children and grandchildren have had them to varying degrees. ( I didn't have mine tested...should have.)

    But mine have improved to such a degree, that they remain small with little pain.
    I've read that with B12/ Folate deficiency, there can be an autoimmune tendency.
    Although it's too late for me now, ( I'm stuck with having to take hydrocortisone for life), I wonder if a B12 deficiency, inherited, may have made myself and others vulnerable to immune dysfunction, and infections?

    Sorry, I'm wandering way off topic here ....
  14. caledonia

    caledonia

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    1. Take the HDRI methylation panel. It measures folates, glutathione and other important things in the methylation cycle. This is a functional test of how your methylation cycle is working. In other words, the SNPs show potentials, which may or may not be activated. The methylation panel will tell you exactly what's going on. If methylation is not working correctly the cell membranes will be compromised and folates will leak from the cells.

    2. "Folic acid" is a synthetic vitamin. If you have MTHFR you won't be able to convert it to the active forms very well. In addition it will also deplete the active folates - a double whammy. Avoid it as much as you can.

    3. Methylation requires the presence of both folates and B12 - they work together to form methyl groups. So they have to be in the correct balance.

    Methyl trapping - if you take too much methylfolate and not enough B12, it will stop methylation - not what you want. Folate supplementation should be around 800mcg. The prescription folates contain way too much, and doctors often prescribe them without doing anything about B12. This clearly shows that they have no understanding of how the methylation cycle works - they are actually making the situation worse!!!
  15. Skyline

    Skyline Senior Member

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    I think was the "donut hole theory". But as you said Freddd invented it and could clarify.
  16. Critterina

    Critterina Senior Member

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    I didn't have the folate deficiency symptoms that Freddd describes - angular chelitis, acne-like lesions, and overt gut issues - until I started taking folate. So, showing symptoms of deficiency after you start taking it, seems like a paradox to me!

    I also notice that no where else are folate deficiency symptoms defined to include angular chelitis and acne-like lesions. I've looked at several medical websites. I'm afraid if I go tell my healthcare professional that these are folate deficiency symptoms that she'll contradict me, and I have no evidence except Freddd's opinion. Any help here?
  17. Critterina

    Critterina Senior Member

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    I have to ask - I've been looking at the biochemical pathways and I can't figure it out - HOW does folic acid deplete the active folate? Doesn't make sense to me! I can't see any mechanism for it. What equation am I missing?

    Also, my problem in converting folic acid to methylfolate is not MTHFR. My A1298C is +/- but my C677T is normal. If I can get to folinic acid, I can make methyl folate. But I'm SHMT +/+ so I pretty much don't get to folinic acid.

    See if I understand this right: There's a first slow step that converts folic acid to tetrahydrofolate (THF). Then SHMT catalyzes the conversion of THF to 5,10-methyleneTHF, and then acts a second time, on the 5,10-methyleneTHF to make folinic acid (a.k.a. 5-formylTHF). MTHFR is just the fourth step (that I know of), that converts folinic acid to MTHF. So a double SHMT mutation is probably very similar in effect to a MTHFR C677T mutation, except that the SHMT can be circumvented by supplementing with folinic acid, and that wouldn't really help a C677T mutation.

    I also read that folinic acid occurs naturally in plant life. Perhaps that's why I have always thought that no meal is complete without something green! Intuitively making up for my genetics.
  18. Valentijn

    Valentijn Activity Level: 3

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    I think the debate about folic acid is due to it using the same (transportation?) mechanisms that folate does, hence blocking them? I don't recall exactly, but there are definitely studies showing that folic acid supplementation does not help some people with folate deficiency issues: about 10%, if I recall correctly. I think the theory about folic acid interfering with folate, however, is much more hypothetical.
    From what I've read, SHMT has only been shown to worsen the effects of problems caused by MTHFR C677T, and that's only when the SHMT is +/+ (AA). Hence it probably has little or no effect on its own. Though I haven't had a complete re-read of the research yet, so it's possible I missed something the first time around.
    Critterina likes this.
  19. Critterina

    Critterina Senior Member

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    Thanks, Valentijn. I am stitching my understanding together, and having you correct me is great - either verifying or correcting my understanding. So this is still a "?". I will also go back to my biochemistry textbook to see whether there are alternate pathways to get to folinic acid. I've been trying to reconcile my lab results with my mutations, and finding alternate pathways has helped me understand why an amino acid can be high, when the mutation I know about makes me think it should be low.

    I was just now looking for a thread that I believe you posted in, talking about COMT +/+ individuals who didn't seem to be overmethylators. I couldn't find it. Do you remember where it is?
  20. Valentijn

    Valentijn Activity Level: 3

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    The SHMT is a bit of a "?", but since it has been studied and the increased risk only shown when combined with another SNP, it's pretty unlikely that it does anything on its own. Plus it is a "synonymous substitution", which means the + version doesn't result in a structural change to the protein created by the gene - which means it would be very hard for this SNP to have much of an impact.

    I'm not sure about the COMT discussion. Maybe you mean http://forums.phoenixrising.me/index.php?threads/interesting-comt-variations.24672/ where I have other COMT variations listed? It's possible that the additional COMT variations are having an additional impact to the ones listed by Yasko and GeneticGenie.

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