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Bouncing off the walls with folinic acid

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Creekee, Mar 15, 2013.

  1. Lotus97

    Lotus97 Senior Member

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    I can't really say for sure if that dose is right for you. Sometimes you'll feel ok at first, but then the effects will stack up after a couple of days or longer and then you realize you've gone too far. Again, I don't know if that dose is the right dose. I'm just saying that if it is too high you might not notice it right away. It also depends on your overall health. If I had done methylation last year after having made a recovery I might have had an easier time, but after having a relapse before starting methylation my body wasn't able to handle it and now I'm taking a very low dose for now. I know my body needs rest now more than anything including more methylation supplements.

    My best guess why Rich only recommends 200 mcg of folinic acid is that there certain SNPs or polymorphisms that prevent certain people from processing folinic acid in which case it would build up and block methylfolate, but it seems you don't have one of those based on your reaction. If you are converting folinic acid to methylfolate then you could run into the same problems that occur from taking too much methylfolate. That would be another reason why Rich kept the dose at 200 mcg (for a seemingly opposite issue).

    With B12, Rich recommends starting with hydroxocobalamin and only switch to methylcobalamin and/or adenosylcobalamin if you don't improve, but as with the folinic acid which you seem to be doing good on a higher dose than Rich recommends you're of course free to do whatever you like regardless of what Rich or Freddd recommend. It's impossible to design a perfect protocol that works for everyone, but here's what Rich says regarding which B12 to take:
    I had also considered changing the form of B12 to methylcobalamin. Some PWMEs do need to use this form, particularly if their glutathione and/or S-adenosylmethionine are very low. However, use of hydroxocobalamin is a “gentler” approach to lifting the partial methylation cycle block, and many PWMEs need such an approach. Use of hydroxocobalamin also keeps the cells in control of the rate of the methylation cycle, preventing it from being overdriven, which slows the rise of glutathione. So I have decided to stay with hydroxocobalamin as the first form of B12 to try. For people who do not get a response from the SMP within a couple of months, switching to methylcobalamin would be an option to try. Another option would be to try adding some adenosylcobalamin (dibencozide). However, I do not favor raising the overall dosage of B12 very much above 2,000 micrograms per day, and especially not when it is combined with dosages of methyfolate that are much above the RDA range of 400 to 800 micrograms per day. This combination can overdrive the methylation cycle and hinder the rise of glutathione.

    Best regards,

    Rich Van Konynenburg
     
  2. Freddd

    Freddd Senior Member

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    Hi Creeke,

    In this case feeling good is a great aiming point. You will be healing with that. Really. Keep it going as long and strong as you can. When it stops you will miss it.
     
  3. Lotus97

    Lotus97 Senior Member

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    50 mcg? That's it? I know Quatrefolic is supposed to be more potent than other forms of methylfolate (except maybe Metafolin), but I was taking 2 capsules of B right (for a total of 100 mcg methylfolate) with no B12 for 5 weeks and that caused a crash in me. Recently, I was taking a Thorne b complex that also had 100 mcg of methylfolate (with some B12 this time) and I don't think it did much, but I think most days I was taking it with potassium and vitamin C so I probably cancelled out the methylfolate. The other day I tried increasing my dose of hydroxocobalamin from 1000 mcg to 1500 and added about 200 mcg folinic acid and that was too much so I took the next day off. I should mention that I was also taking a lot of TMG (in the form of betaine hcl) so that could partially explain my reaction.
     
  4. Lotus97

    Lotus97 Senior Member

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    Victronix
    If someone is experiencing adverse symptoms from methylation then taking more methylfolate is almost always going cause more symptoms (not less). Many of those symptoms in group 3 could be from a lot of different things. Some of your symptoms might be from low potassium so I'd recommend supplementing with that if you're not already doings, but if that doesn't fully alleviate your symptoms I'd recommend lowering your dose or even stopping for a day or two if things are really bad
     
  5. Lotus97

    Lotus97 Senior Member

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    Hi Creekee

    I see you're following Rich's Simplified Methylation Protocol (SMP). There's nothing wrong with getting some advice from Freddd, but keep in mind that there are several key disagreements between Freddd and Rich. Much of the advice Freddd has been giving to you and others who are following Rich's protocol is in direct conflict with what Rich has said. Rich was very deliberate in designing his protocol the way he did. It's important to adapt whichever protocol you are on to your own needs, but I would recommend staying within the guidelines. For example, if you do decide to take more folinic acid (800 mcg rather than 200 mcg) then you might want to hold off on adding methylfolate since it seems that you're already converting the folinic acid into methylfolate based on the effects your describing. If you take more than 200 mcg, I'd recommend dividing up your dose and spread it out throughout the day. This would be good for all B vitamins actually.

    Also, I would recommend staying with hydroxocobalamin for now. Most people are able to convert a hydroxocobalamin into enough adenosylcobalamin and methylcobalamin so you wouldn't need to take those in addition to hydroxocobalamin. One thing I'd recommend with B12 is to hold the tablet between your upper lip and gum rather than under your tongue. You'll aborb more B12 that way since the tablet will dissolve slower. Another thing is to split up your B12 into 2-3 doses as with the rest of your b vitamins. I found that an X-Acto/Exacto knife works best for cutting up sublinguals. Dividing up your b12 dosage will be especially useful in the early stages of methylation since SAMe, glutathione, and folate are needed to recycle B12 and those are all low at the beginning of methylation.
     
  6. Freddd

    Freddd Senior Member

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    Hi Victronix,

    One of the very confusing thing about methylfolate is that it causes the most intense symptoms when it is low. It allows a little but of healing to start but not enough to continue. Then the body starts complaining that it is being starved to death of l-methylfolate with really intense insufficiency symptoms. Then as that starvation is reduced by increasing l-methylfolate the insufficiency symptoms go away. Then some people get confused because low potassium can happen at the same time as insufficiency because healing on one layer can create potassium need at the same time another layer is complaining of insufficiency via insufficiency symptoms.

    L-methylfolate has no known side effects different from placebo from the Deplin study. It does start healing frequently and when there isn't enough to maintain healing there is a huge outburst of insufficiency symptoms. This gets confused because folinic acid can do the same thing or just plain block methylfolate in some people so one never knows what is happening there. Folinic acid response does not predict l-methylfolate response. A mix of the two does not predict the single item.
     
  7. Creekee

    Creekee Senior Member

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    Lotus97,

    Thanks so much for all the info and explanation. Yes, I know Freddd and Rich have different approaches. Not sure where all they vary, but I'm trying to get on top of it. o_O Really appreciate the info about doses and timing; thank you. You're probably saving me from myself. So far I'm staying at the low doses of everything. And sticking with the hydroxoB12. Things are going really well; not eager to rock the methylation boat. Before starting the protocol, I'd been taking methylB12 injections but had B12 deficiency symptoms with a high (2,000) serum level. Haven't taken time to research if some people don't do well with the methylB12 (?). I'll have 23andMe results soon, so hoping for a little more direction there.

    Meanwhile, I continue to be surprisingly functional. Yippeee! Day three with a headache, but sounds like that's not too unusual at this point.

    Very grateful to have your input!
     
  8. Lotus97

    Lotus97 Senior Member

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    For my first two attempts the dosage was too high and my health got worse as a result. Now I'm taking it very slowly due my poor health health right now. It's important to find a baseline where you feel relatively ok. That way if you increase your dose and then realize it's too high, you know where to go back to. Also, when you do increase your dose you might feel ok at first, but then after a few days realize it's too high. And when you do lower your dose it might take a few days before the effects of overmethylation wear off.

    I think I remember Freddd saying something about the B12 in injections not always being good quality so maybe you got a bad batch (?) Enzymatic Therapy is the best brand for methyl B12 sublinguals. Jarrow is no longer a good brand. Some people tend to be overmethylators which is why Rich recommends starting with hydroxocobalamin, but if you don't experience any improvement then he gives instructions in his revised protocol thread about switching to methylcobalamin and adenosylcobalamin and also raising methylfolate dosage. For anyone who is planning to switch from hb12 to mb12 and raise methylfolate I would recommend switching to the b12 first and establish a dosage before also raising methylfolate. It's usually a good idea to limit the number of variables you're dealing with.
     
  9. Creekee

    Creekee Senior Member

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    Major body pain the last couple of days. Ick ick ick. I'm at week six and have not increased any supps.
     
  10. Lotus97

    Lotus97 Senior Member

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    Methylation can increase inflammation. Also toxins are mobilized during methylation. It could be either of those or both. These will happen even if you're not overmethylating, but higher doses can make things worse.
     
  11. Lotus97

    Lotus97 Senior Member

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    Creekee

    A few things I forgot to mention in my last post. It could also be from low potassium, but since you didn't increase your dosages it's more likely what I mentioned before. It would still be a good idea to supplement with potassium just to make sure.

    Also, many people when they start methylation get extra energy. If their bodies aren't able to handle the increase in activity then that's going to catch up with them eventually. For me, it was my adrenals that got burned out. It's possible that your pain is from going beyond your limit of activities.
     
  12. Creekee

    Creekee Senior Member

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    Thanks, Lotus. I got hold of some potassium and added it to the mix. This pain thing is a recurring theme for me. And I keep thinking if I understood what's going on, I'd have a much better idea of what my core problem is. Had this same dramatic increase in pain all three times I started low dose naltrexone. Presumably naltrexone and SMP are improving immune function. Improved immune function causes big pain. So...inflammation or toxins?

    I don't think I overdid. Although that's always a mysterious line in the sand. Even though I was feeling hugely more energetic, I was trying to be careful.

    Today the pain seems a tiny bit better but energy is rather like someone let the air out of the balloon.

    So appreciate your input, Lotus!
     
  13. Victronix

    Victronix Senior Member

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    Thanks, that's good info for me. I'm starting up the methylfolate again, at a very low dose, < 50 mcg (Douglas Labs B-complex, which has 400 methylfolate as Metfolin).

    Interestingly, I'm getting a constellation of symptoms but they do not seem to be potassium symptoms, so I'm wondering if the folate receptor antibodies issue is what might be going on for me, since the methylfolate start-up symptoms feel like a flu -- hot, like I have a fever, tired, a few aching joints and minor muscle aches, but not the potassium symptoms that I get like my feet cramping and waking up at night. If so, the person who originally posted on here about folate receptor antibiodies said her doctor described it as a resistance, presumably that would need to be pushed through.

    In any case, I will be continuing on this course. I know from my previous trials that the fever feeling goes away. I'm taking about 7000 mcg methyl B12 and a question has been whether the lopsided ratio may be playing a role in making things harder, but I'm not going to worry about that at this point and focus on slowly and carefully increasing the methylfolate. Definately the need for methyl B12 decreases when I'm taking methylfolate, so I will experiment with decreasing that a little if it feels right, to keep things from escalating too fast.

    I don't think I overdid. Although that's always a mysterious line in the sand.

    Very well put! Hope your pain decreases.
     
  14. Lotus97

    Lotus97 Senior Member

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    Those sound like symptoms from methylation itself rather than specifically from methylfolate. If you're taking that much methylcobalamin then even a tiny bit of methylfolate is going to kick things into high gear for most people.
     
  15. Lotus97

    Lotus97 Senior Member

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    There was a thread where people were talking about side effects from low dose Naltrexone. Someone had recommended LDN to me since I have Lyme, but I haven't decided whether I want to try it yet. I take it LDN is reactivating your immune system then? Rich said methylation could do the same thing. This quote is kind of long, but it might be useful in explaining everything that's going on during methylation including the relationship between inflammation and the immune system. And also possible toxins released during the process.
    =================================​
    One physician I know gives all his patients the methylation treatment, and then watches the response. If they experience some symptoms that appear to be caused by detox, but they are able to tolerate them, he continues with this treatment. If they have intolerable symptoms that appear to be related to mobilization of toxins, then he stops the methylation treatment and works on improving the status of the gut. When that is working better, he moves on to supporting the liver. His thinking is that the toxins that were being mobilized were being reabsorbed by the gut and sent back to the liver. In order to properly process and excrete the toxins, the gut and liver must both be functioning well enough to handle them.

    My guess is that when there is an inflammation response to methylation cycle treatment, there is an infection. If the inflammation continues without resolution, then my guess is that the immune system has been reactivated, but is not capable of defeating an existing infection. In such cases, I think that treating to support the immune system would be one approach. Another would be to test to determine what pathogen is causing the infection, and then treating it with an antibiotic, antiviral or antifungal, depending on the pathogen.

    I think it's important to note that a healthy person would not have any reaction to the supplements used in the methylation protocols, because their methylation cycle, detox system and immune system would already be functioning normally. So the fact that there is a response, even though it may seem to be deleterious, means that the methylation cycle was partially blocked and that these supplements were needed. However, the way one should proceed from that point on probably depends on the type of response that the individual person has.

    So far, I'm pretty sure that if the following are present, they will need specific treatment, in addition to treating the methylation cycle partial block: biotoxin (including mold) illness, Lyme disease and its coinfections, well-entrenched viral infections, and high body burdens of toxic heavy metals, such as mercury. There may be others of which I'm not aware, but there is some experience with these, at least, which people have reported

    I believe that the partial methylation cycle block is the pivotal abnormality in the pathogenesis and pathophysiology. With respect to the root cause or causes (etiology) of ME/CFS, I have suggested that this disorder arises from a combination of a genetic predisposition and some combination of a variety of stressors, which can be physical. chemical, biological, or psychological/emotional. I've suggested that this combination leads to glutathione depletion, which leaves B12 unprotected, which causes a decreased production of methylacobalamin, which inhibits methionine synthase, which forms a vicious circle with glutathione depletion, making ME/CFS a chronic condition. The retroviruses would fit within the biological stressors in my hypothesis, and certainly could be a root cause. If effective treatment of the retroviruses ends up bringing about recovery from ME/CFS, that will be very convincing as to its role as an etiologic agent. I hope that turns out to be the case for at least some of the PWMEs/PWCs. It may not be true for all of them, though, because this population seems to be very heterogeneous.

    The reason I have included the variety of stressors as etiologic agents is that I have studied the published "risk factor" studies, and have also queried quite a few PWMEs/PWCs as to the events that preceded their onset, and I've found a variety of precursors. The common factor seems to be that they are all things that would be dealt with by the body's nonspecific stress response systems, and these in turn are known to place demands on glutathione.

    In addition to this, there are now many PWMEs/PWCs who have taken the Health Diagnostics methylation pathways panel, and nearly all of them show evidence of a partial methylation cycle block or glutathione depletion, and usually both.

    And when treatment was given in our clinical study that is directed toward lifting the partial methylation cycle block, we observed by testing that this does in fact occur, and that glutathione also comes up automatically. This was accompanied by improvement in symptoms in at least two-thirds of those who were treated.

    Putting all of this together, I think the GD-MCB hypothesis is consistent with the observations and with known biochemistry and physiology. That doesn't mean that I believe that it is scientifically proven, which is a very high standard to meet, and requires considerable investment in time, money and effort, but that it is a valid working hypothesis. I'm hoping to interest researchers and fundors in this model so that it can be more thoroughly tested.

    The methylation cycle is at the beginning of the sulfur metabolism. It is fed by methionine, which comes in as part of protein in the diet. Homocysteine is produced from methionine (via SAMe and SAH) in the methylation cycle, and then methionine synthase "decides" how much should be converted back to methionine, to stay in the methylation cycle. In the liver and kidneys, the BHMT reaction also converts some homocysteine back to methionine. The rest of the homocysteine enters the transsulfuration pathway, which is downstream.

    The way that methionine synthase does its "deciding" is that the cobalt ion in the cobalamin that is its cofactor gets oxidized at a rate that depends on the state of oxidative stress in the cells. The more oxidizing this state is, the more often the cobalt ion gets oxidized, and that temporarily shuts down the methionine synthase reaction and diverts the homocysteine flow into the transsulfuration pathway, which helps to make more glutathione, which counters the oxidative stress. Unfortunately, in ME/CFS this delicate mechanism gets overwhelmed, and the oxidative stress becomes more severe, so that glutathione doesn't recover and get control of it. The result is that methionine synthase becomes partially blocked, and the sulfur metabolites drain down the transsulfuration pathway, into sulfoxidation, and get excreted too much as taurine and sulfate, which depletes methionine. The whole sulfur metabolism becomes dysfunctional, and that takes down the cell-mediated immune response as well as the detoxication system. As well, everything that depends on methylation reactions is affected, including gene expression, synthesis of several needed substances, and the neurotransmitter metabolism. Also, this drains the folates from the cells via the methyl trap mechanism, and that affects things that depend on folate, such as synthesis of new RNA and DNA. The latter is what cause the red blood cells to be too big and too few in number.

    The methylation cycle is so fundamental to so many parts of the body's biochemistry that when it becomes dysfunctional, it causes a host of problems, and this is why people experience so many symptoms, involving so many body systems and organs, in this disorder.
     
  16. Victronix

    Victronix Senior Member

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    I had a tiny bit of fever feelings when I first started B-12, but also a lot of other sensations which were fairly intense and related to nerves healing. Most of the methylfolate symptoms for me are very different from B-12, and certainly the effects over time are quite different (symptoms increase on day 2 and it can take 4 days to return to 'normal' after stopping with methylfolate, whereas the effects of B-12 were more shorter, for me). Currently I'm not having any of the B-12 methylation symptoms, like feeling hyper, agitated, anxious, heart palps, etc., probably because of the very low dosage. I feel calm, just hot and a little flu-like. I've been at this same B-12 dosage for awhile (and on the Jarrow before that for over 3 yrs) and in general when I increase it I get some energy, may feel slightly nauseated for 1 morning, but nothing significant.

    Interestingly, with the similarly small amount of folinic acid the dominate symptom was dry eyes, which was awful.
     
  17. Lotus97

    Lotus97 Senior Member

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    Currently I'm not having any of the B-12 methylation symptoms, like feeling hyper, agitated, anxious, heart palps, etc.,
    Those are symptoms usually related to overmethylation (and it's good you're not experiencing them), but the flu-like symptoms can sometimes happen even if you're taking a relatively low methylation dose. When I restarted methylation a few months ago, I began feeling malaise and flu-like symptoms on and off even though the dose I was taken was even lower than what Rich recommends and I wasn't overmethylating.
     
  18. Victronix

    Victronix Senior Member

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    Those are symptoms usually related to overmethylation (and it's good you're not experiencing them)

    The symptoms of agitation/stimulation are usually referred to as 'start-up symptoms' in the B-12 community because (like everyone on the B-12 forum said at that time), they reliably dissipate in about 2 weeks. I was severely B-12 deficient at the time and basically the mB12 stimulated raw and damaged nerves. It was expected that that would happen.

    At the time, I had a minor injury to my right hand that seemed to be increasingly worse over time. I had simply banged it on a shelf by accident, no broken bones, no swelling. It hadn't healed in months and doctors could not figure out what the problem was. But it was bad enough, hurting enough, that I was unable to use it, so could not write or do anything with my right hand. Doctors assumed there was some kind of ongoing inflammation following my very minor injury, but no anti-inflammatories seemed to make a difference. Then, within just days of starting mb12, amidst the awful start-up symptoms, my hand healed and I was able to write again. It was amazing. That really was a concrete benefit that helped me to get through the start-up symptoms and convinced me of the direct benefit I was getting.

    The B-12 was in extremely low dosages then, as now (at something like 1/10th what most were taking), but caused a lot of agitation in the process of (for example) healing my hand. But the more B-12 I took, over time, the less the agitation symptoms appeared at all when I increased dosages. The point was to get to a dosage where I no longer had numbness in my feet, muscle pains, migraines, etc. And that worked. It just took a long time.

    It's possible that the addition of the mfolate will lead to an ongoing state of agitation, in which case I would need to titrate down. But I think the point is to stop if agitation simply were to go on and on. I take a dose every other day in order to get a sense of how it will manifest, since the symptoms tend to be increased for me on day 2.
     
  19. Lotus97

    Lotus97 Senior Member

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    I've also heard of people who start taking various vitamins and minerals that they're deficient in sometimes having start-up symptoms. The key is distinguishing those from overmethylation which can have similar symptoms. It sounds like you're being cautious which is good.
     
  20. Creekee

    Creekee Senior Member

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