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Methylation

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Cort, Aug 10, 2009.

  1. Freddd

    Freddd Senior Member

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    Methylmercury-methylcobalamin 1mg/day model

    Hi Rick,

    Based on this available information I built an Excel model including the half-life, body load at earliest toxic effects of methyl mercury and 3 potential rates of utilization of methylb12 in methylating mercury in the body. It probably needs refinement and may have bugs. If you would like a copy of the Excel spreadsheet send me your email via private message. I assumed limited body loads of 30mg and 50mg and cut off conversion after that where applicable and demonstrated falling body load and serum level as would be expected with a 76 day serum half-life. I present this as a possiblity, a hypothesis to answer the question you asked. How does it sound to you? Did I forget anything important? Am I misinterpreting something. Does this fly?


    This question about mercury came up very early in my mb12 usage, a pain doc/professor I know who edits a journal as well. He asked about mercury. Maybe now 5 yeqars later I might be on the path to giviong him an answer.


    Methylmercury - Methylcobalamin 1mg/day Model
    Version 1.0 - 08/24/09

    Just a few terms and numbers that figure into this.
    "Methylmercury" is a shorthand for "monomethylmercury", and is more correctly "monomethylmercuric cation"

    Methylcobalamin has 1344.4 grams/mol. Mercury has 200.59 grams/mol and methylmercury has 215.6247 grams/mol.

    It takes 6.70228mg of methylb12 to methylate 1mg of mercury.

    It takes .149204mg of mercury to utilize the methyl groups from 1mg of methylb12

    According to the World Health Organization (WHO, 1976), the earliest effects of methyl mercury in humans occur when blood concentrations are between 200 and 500 ng/mL. These blood concentrations correspond to body burdens of 30 to 50 mg Hg/70 kg and are equivalent to daily intakes of 3 to 7 g/kg.

    Less than 1% of the body burden of methyl mercury is excreted daily, resulting in a biological half-life of approximately 70 days (Berlin, 1983). Over a 4-day period, a human volunteer excreted only about 6% of the ingested dose of radiolabeled, protein-bound methyl mercury, the biological half-life ultimately being 76 days (Miettinen, 1973).
    http://rais.ornl.gov/tox/profiles/methyl_mercury_f_V1.shtml


    A 76 day half-life amounts to 0.0099 loss per day, just a hair under 1%.

    So the question that arises is the old woodchuck question, how much wood .? What is the efficiency of conversion of mercury to monomethylmercury.

    At 100% efficiency, all methylb12 donating methyl group to Hg it would require 201mg to 335mg of methylcobalamin to immediately convert 30-50mg of Hg to methylmercury causing the earliest effects of methyl mercury in humans.


    At 10% efficiency, 10% of all methylb12 donating methyl group to Hg it would require 2011mg to 3351mg of methylcobalamin to immediately convert 30-50mg of Hg to methylmercury causing the earliest effects of methyl mercury in humans.


    At 1% efficiency, 1% of all methylb12 donating methyl group to Hg it would require 20,107mg to 33,511mg of methylcobalamin to immediately convert 30-50mg of Hg to methylmercury causing the earliest effects of methyl mercury in humans.


    So then, what is the serum level of methylmercury contributed to by 1mg of methylb12 injected daily or equivalent in sublingual?



    One Day

    At 100% efficiency - 0.147725493mg 0.984ng/ml
    At 10% efficiency - 0.014772593mg 0.0984ng/ml
    At 1% efficiency - 0.0014772593mg 0.00984ng/ml


    One serum half-life (76 days)

    At 100% efficiency - 7.913814388mg 52.758ng/ml
    At 10% efficiency - 0.7913814388mg 5.2758ng/ml
    At 1% efficiency - 0.07913814388mg 0.52758ng/ml




    201 days cutoff at 30mg accumulated


    At 100% efficiency - 12.89302584mg 85.9533ng/ml
    At 10% efficiency 1.289302584mg 8.59533ng/ml
    At 1% efficiency - 0.1289302584mg 0.859533ng/ml




    335 days cutoff at 50mg accumulated


    At 100% efficiency - 14.3765611mg 95.8433ng/ml
    At 100% efficiency cutoff at 201 days 3.394385667mg 22.6286ng/ml
    At 10% efficiency - 1.43765611mg 9.58433ng/ml
    At 1% efficiency - 0.143765611mg 0.958433ng/ml




    Five Serum half-lives (380 days)


    At 100% efficiency - 14.56805435mg 97.12ng/ml
    At 100% efficiency cutoff at 201 days 2.168310737mg 14.4553ng/ml
    At 100% efficiency cutoff at 335 days 9.183650551mg 61.224ng/ml
    At 10% efficiency - 1.456805435mg 9.712ng/ml
    At 1% efficiency 0.1456805435mg 0.9712ng/ml


    Ten Serum half-lives (760 days)

    At 100% efficiency - 14.89901603mg 99.3266ng/ml
    At 100% efficiency cutoff at 201 days 0.049260372mg 0.3284ng/ml
    At 100% efficiency cutoff at 335 days 0.208637089mg 1.3906ng/ml
    At 10% efficiency - 1.489901603mg 9.93266ng/ml
    At 1% efficiency - 0.1489901603mg 0.993266ng/ml




    DISCUSSION

    Lets consider then that it would take about 200mg of methylb12 to convert 30mg all at once with 100% efficiency to reach the lowest toxic effects level of methylmercury. While this is on top of the unknowable existent methylmercury level, we can assume that conversion isnt 100%. Considering that even a 1000mcg dose of MB12 has substantial effects as methylb12 it is obvious most of it isnt being immediately disabled by mercury, that in fact most of it is being flushed rapidly out of the body with some small number of mcgs being utilized as b12. So perhaps a 10% conversion rate is the right order of magnitude for conversion. At 10% conversion with a 76 day serum half-life the contributed level of methylmercury never gets above 10ng/ml, 5% of the minimum needed level to cause toxic effects. So it appears most likely that the only persons affected would be ones who are already sitting at the edge of toxic effect.
  2. serg1942

    serg1942 Senior Member

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    To Fredd: a compilation of your main posts?

    Hi Fredd

    First, congratulations for your great improvement, after having suffering so much timeYou have done a really good work, and it is very generous from you to share your experience with all us, and also to try to fit the pieces of your improvement together, in order to help other sick people. Thanks for that!

    I suffer from severe CFS after a very high mercury poisoning from amalgam fillings. Of course I have not the knowledge you have on B12 metabolism and related pathways, and of course I am not a researcher as Rich is. But my main humble target in my life is: 1- to understand whats wrong with me, and 2- to reach a cure (choose the order you prefer! ;-)

    Well, like you can see my written english is poor, so is my english understanding, so It is hard for me to read a lot of English, as I have to re-read, look in the dictionary, etc. (like I use to say to an American friend, I wish all we speak the same language, even mandarin! ;-)

    Well, my purpose is to read in paper your theory in detail, and if I can, to ask you a few questions I have, as I dont agree in certain things with you (I belong to an spanish association of people affected by amalgam fillings, and my interest here is more than big). But before doing this, I need to have all the data you have written, and it is being complicated to compile all of it from the forum as it seems to be disseminated in different threads

    Could you mind to post the links to your main posts where you explain in detail your case, your hypothesis, etc, so that I (and other brainfoggers!) can compile easily all your written work, print it, and study it? It would be so much appreciated and useful

    Other possibility could be to write a paper explaining in brief the bases of your theory, like Rich did. This would be a very good way to understand and to discuss your position on the role of B12, the methylation cycle, Hg and their interactions, in ME/CFS.

    Best wishes, and again thank you for opening this fantastic discussion.
    Sergio
  3. Freddd

    Freddd Senior Member

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    Hi Sergio,

    If you click on my name at the head of any of my posts one of the options is to list all of my posts. If you do that you will see that they are concentrated in several threads with a few outside of those threads.

    As this is the first time I have closely examined any mercury issues almost everything about mercury that I have written is right here on this thread. What is your serum level of mercury that leaves you with "very high mercury poisoning"? And how do you get that very high level from amalgams? What is the mechanism? I've had amalgam fillings most of my life. Do they do things differently in Spain? Do they mix amalgams differently?

    You are certainly wlecome to sit and observe and contribute to the ongoing conversation here. Rich and I have an exchange of ideas and hypotheses going on here in a hopefully scientific manner. We hope to hash out just how methylyb12 does interact with body loads of mercury.
  4. serg1942

    serg1942 Senior Member

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    Freddd: summary of your statements?

    Hi Freddd,

    Thanks for answering. Yes, I know I can do that, I mean, to look for all your posts…I only asked you if it were possible for you to write your links to your main posts (not all of them), or maybe to write something short, where you can “capture” your main ideas in short, for me (because of the language and my big brain fog) and also for others. It would be wise to have your main ideas summarized in a paper to discuss them all together. So far I think the most relevant things you are exposing are:

    - methylB12 and adenosyl B12 are the only B12s capable of improving the symptoms of CFS (extrapolating your symptoms due to some genetic issues to the rest of PWC’s, likely without your inherit genetic problems)

    - Inactive hydroxocobalamine is countraproductive at all, as it can deplete methyl B12 stores.

    - Glutathione is also counterproductive as it also depletes the activated methyl B12.

    - The toxicity of mercury is mainly due to the lack of methyl B12 produced when it is methylated. (Not for the toxic effect of methylHg)

    - The detoxification symptoms many of us experiment while shifting the methylation cycle block, is due really to lack of methyl B12, and not because of detoxification due to a better liver phase II status.

    - The same rationale behind the fact of taking active forms of folates serves equally to defend the use of activated B12s

    - There are not accurately tests to asses B12 deficiency, but empirical try.

    I think these are your main arguments. Aren’t they?

    Well, I disagree with you in nearly all this statements, but I have not read all your posts as there are many and they are very long…it would be a very good idea if you explain the “whys” of your arguments in a shorter way, so that a discussion may be more fluid and easier.

    (I would like to understand and discuss your point of view re: these subjects, but I don’t want to do that without reading all your posts, and it is nearly impossible as they are many, and very long…)

    Re: Hg, I had 12 ppm in hair (being 1 the maximum “safe” level), and 40 micrograms/l in blood (being 10 the maximum “safe levels” for acute poisoning, not for chronic). Serum level of mercury is not a reliable test, as the half life of Hg in blood is 60 days. Afterwards it is mostly kept inside the body.

    Re: amalgams, they are the same everywhere. They release inorganic Hg in form of vapour and also impregnate the gum. Temperature, pH and galvanic currents are the main factors involved. The WHO advices of their dangerous for health since 1991, and FDA has been forced by law to advice of their dangerous for human health.

    Regards,
    Sergio
    Lotus97 likes this.
  5. jenbooks

    jenbooks Guest

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    Hi Freddd/Sergio

    Thanks Sergio for that concise list.
    I too have serious amalgam poisoning. I can't even tolerate a single pill of 50 mg DMSA without redistribution causing kidney aches.

    Freddd, just as you can't make active B12s, some of us have genetic polymorphisms that render us unable to detoxify the amount of mercury stuck in our mouths (in my case lots at once after braces were removed and lots of cavities). Then we're badly poisoned by this extremely toxic metal. Others have ability to chelate it effectively on their own and even though it surely isn't good for them, they don't get poisoned by it.

    15-20% of the population probably is vulnerable to mercury amalgams in a serious way. I take this from findings in the autistic community.
  6. Freddd

    Freddd Senior Member

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    Hi Sergio,

    You distort or misstate the main statements and then disagree with them. I'll repond point by point somewhat later when I have time.
  7. serg1942

    serg1942 Senior Member

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    Hi Fredd,

    Yes, maybe I am distorting your arguments. This is because I don’t want to discuss them, until be sure that I have understood them well.

    This is because I’ve asked you to compile your main argument of your hypothesis on CFS in a brief document, for me and many others to discuss this in a easier way.

    I don’t want you to correct my misinterpretation of your arguments. Just would like you to write your correct arguments, explaining in short the rationale behind them, in a way we can open a more easy-to-follow debate on them.

    This is just an idea, as I have not the energy to read all your posts and then reply them in a never-ending message. I, and probably others, need something more succinct to look at it, study it in detail, and then discuss the points we would like to.

    I am just concerned about PWC’s taking a lot of methyl B12, and getting sick from that, as they can methylate and redistribute Hg through the bloodstream to the rest of the body. Many following the treatment to shift the methylation cycle have experimented the down-side effect of taking methyl-B12 (not being part of the protocol recommended by Rich), in the same way Janebooks has explained for a chelation with DMSA (I also has experimented this). The point here is that we have corroborated an augment in our urine metal excretion as we improve this cycle, so we can't ignore the detoxification process, and the caution we need to have because of it.

    I do appreciate your work. I just wanted you to consider a clearer and brief explanation of your ideas/arguments/statements/theories, in the benefit of all of us. Sure the discussion will be easier.

    Thanks,
    Sergio
    Lotus97 likes this.
  8. Freddd

    Freddd Senior Member

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    Hi Sergio,

    The concise story, as concise as it's gotten so far is at http://forums.aboutmecfs.org/showthread.php?t=188 in a series of posts.

    I will attempt to make some of main statements here without much in the way of explanation or outside references.



    • There is a large list of symptoms in the above mentioned thread. These symptoms are from an international set of lists of b12 deficiency symptoms and from people as to what actually responds and heals with active b12s. Not all the things on the list will heal. Some represent damage that doesn't heal.
    • There are 4 main branches of b12 deficiencies, 1- CNS/CSF adb12, 2- CNS/CFS mb12, 3 - Body adb12, 4 - Body mb12. These further are each affected separately by methylfolate deficiencies causing 8 secondary branches. Then there are other cofactors cuasing thousands of variation in teritary branches.
    • I work from symptoms only, not diagnoses. Each diagnosis disregards many symptoms and is only an interpretation and may not be correct or may limit understanding to some small area. People often become very defensive of a specific diagnosis which limits their ability to see the larger more complete picture. Sometimes the diagnosis is totally wrong and leads one down some very strange roads of mistreatment. I would rather speak of people with symptoms set xxx or zzz than a specific diagnosis or interpretation of what is happening which is usually context limited.
    • I use peer reviewed research carefully. Some of the interpretations can get really stretched, by the researcher or by the person reading the research. I try to carefully spearate what is probably fact from interpretation and opinion. In b12 research in particular much research is terribly biased by the lab mistake of 61 years ago.
    • A small amount of research that did spinal fluid draws found that people with CFS, FMS and Alzheimer's (or who looked like they had those diagnoses) had Cerebral Spinal Fluid cobalamin levels 25-50% of the CSF cobalamin levels of the control groups in comparison to the percentage of serum cobalamin levels in the same people. This is early stage research and suggestive that these low levels may do something and be related to the diagnosed diseases. There is no level set that is defined as "deficient".
    • The tests given around b12 are strictly limited in what they can do. The serum cobalamin test doesn't tell you which active b12 you are drastically short of. The uMMA test indicates generally adb12 and the Hcy test indicates generally mb12 (or p-5-p or methylfolate) because of the breakdown it indicates. MCV, MCH and half a dozen other blood characteristic tests can also indicate certain breakdowns out of the possible 600 or so. The "active b12" test, a new one, indicates only how much active b12 is bound in HTCII. It toally ignors inactive b12s and unbound b12s. All of these tests can indicate how bad the trainwreck is generally but not if there is a trainwreck. None of them separately or together can indicate that a person has no active b12 responsive symptoms. None of them can indicate if the person has enough to actually heal and be in good health. None of them can even detect at all a CSF/CNS deficiency at any level, only body deficiencies. I can post research references for all of this if you want to follow up on it.
    • I, and a good number of others, but not even close to everybody, have response patterns to one or both active b12s, described in the 5 week trial posting, that are suggestive of CSF penetration by diffusion of the active b12s and a reasonably definite response to those after a body equiblibrium is already established. The Japanese are exploring this threshold effect with people with a variety of neurological diseases. Recently a group with diabetic neuropathies received intrathecal injections of mb12 with excellent healing responses of the neuropathies. Some remained at high CSF cobalamin levels months later and some had levels that declined rapidly. My hypothesis is that this threshold effect is the response of somebody with depressed CSF/CNS levels for unknown mechanism(s).
    • I am still in an information gathering stage and hypotheis formation and bouncing ideas around stage on mercury. When I ask you for information regarding mercury, it is for that purpose. That discussion is taking place right here on this forum. A few posts back I posted the output of my first attempt at a model which may or may not be correct or may be correct for some situations only. It concerned specifically methylmercury and the conversion of other forms to methylmercury by methylb12 and the disposition of that by the body. It's a rough draft, a work in process that needs refinement and/or corrections, nothing more. Rich and I are bouncing ideas back and forth. One of the ways I do that is build numeric models.
    • Regarding "detoxification": it's another one of those words that may mean a dozen different things to a 3 different people. In computer lingo the term is "overloadded". It has multiple meanings and which one is meant is rarely clear from context. "Detoxing" bacterial toxins is quite different than detoxing mercury for instance.
    • It is very evident that the reactions people have are partly determined by which supplements they take in what order.
    • There is some research that indicates that a variety of inactive cobalamins can bind in places preferentially to active b12s blocking them from functioning.
    • In my experience with more than 1000 people face to face with a single challange dose of 1 or both active b12s with symptoms questioning and several hundred persons in much greater detail over a period of time via the internet, that people who have taken inactive b12s, cyanocobalanmin and/or hydroxycobalamin, tend to be the ones that have relatively more extreme reactions, but are not the only ones that do. I don't know the parameters any further than that. I don't know why. I can only speculate
    • Many people with CFS/CFIDS/FMS/ME diagnoses along with MS, PA, idiopathic neuropathies, diabetic neuropathies, mysterious neurological diseases and so forth diagnosis, often have dramatic or lesser effects with both active b12s and cofactors.
    • For any inactive b12 to do ANYTHING specific to b12 in the body they must first become converted to the only two active b12s, both of which are required. A person can be drowning in mb12 and still be deficient of adb12.
    • 80% of mercury's toxic neurological effects appear identical with those of b12 deficiencies. Causality is not known. I have speculated that perhaps it is partly because mercury disables b12. One mg of mercury could disable 400-800% of the body's entire supply of methylb12 (remember, all that b12 in muscles is largely adb12 and doesn't enter into that).
    • The symptoms of b12 deficiencies occur regardless of the causes, whether poor absorbtion, poor retention, surgery, side effects of medications, toxin exposure, parasites, bacterial overgrowth, liver problems, genetic, cofactor lack causing the b12 there not to be properly utilized, aging,vegetarian, poor transfer to or retention in CSF, or probably other unknown or known causes. I had half a dozen reasons including being a vegetarian for 20 years, medications, missing cofactors, CSF, possibly retention, and genetic reasons at the very least. Any one or two of the reasons could have been fully sufficient for causing one or many subsets of symptoms. The genetic ONLY came into play because of diet, drugs, possibly aging, CSF transfer problems. Otherwise it didn't appear overly significant. The CSF/CNS problems with CFS/FMS may or may not be genetic but have nothing at all to do with the IMEs that Rick was talking about.
    • In the persons taking active b12s and having had significant response to active b12s, glutathione or glutathione producing precursors caused near immediate muscle pain, joint pain, stuffy nose, burning eyes, burning throat, chemical sensitivities, allergies, hay fever, GI tract inflamation, stuffy ears, severe muscle spasms, increased paresthesias and all these increased each week and finally it caused an return of numbness and neurological problems in feet and legs that nothing but high dose injections had caused to back off. I had to restart anti-inflammatory meds, antihistamine, valium, lorazam because of glutathione/precursors. In 6 weeks it had reversed 6 months of neurological progress and returned hay fever, chemical sensitivity, spasm and inflammatory state to that of nearly 6 years ago and rapidly returning to pre mb12 status. It didn't cause anything that I didn't used to have while in a fully b12 deficient state but it sure returned them hard and with a vengence. I am as interested in answers on this one as it is a puzzle to me. The other 8 people who tried it in various ways all had similar experiences. It was an unmitigated disaster for me; far worse than merely changing to an ineffective brand or changing back to sublingual from injectable. Most of those things hadn't been present for 5 years or more.
    • Adb12 and mb12, together with methylfolate and suitable cofactors, addeded in a suitable order produce more healing, more predictable healing and more widespread healing and quicker healing for more people than either cyanocoblamin or hydroxycobalamin.
    • It is an invalid assumption that folic acid can be converted to the active folate in sufficient amounts for all healing for everybody. This is demonstrably false in research and practice.
    • It is an invalid assumption that cyanob12 and hydroxyb12 can be converted to BOTH active b12s in sufficient quantity for all healing for everybody. This is demonstrably false in research and practice.
    • It is an invalid assumption that b6 can be converted to sufficient p-5-p for all healing for everybody. Some pharmaceutical companies are trying to get a law passed that would make p-5-p prescription only so they can have an exclusive right to supply what works at much higher prices.
    • I try to minimize the number assumptions about what "ought" to work in a statistically significant number of people compared to placebo" because in practice these many things don't work as well as the active forms.
    • When a person uses an inactive cobalamin they are limited to a very small keyhole amount that the body can convert each day to active forms if everything is working correctly. This limited amount misses all the advantages the larger amounts of unbound active b12s provide.
    • People who take inactive cobalamins often have more extreme reactions of whatever names and causality attribution if and when they switch to active b12s. This is descriptive. I experienced it too.
    So, Sergio, there is an attempt at summarization of many key points in a nutshell. I've probably missed a few nuts and shells. Mostly these are just observational and descriptive of research and/or experiential results of myself and others. There is little opinion, explanation or attempts to attribute causality.
  9. serg1942

    serg1942 Senior Member

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    Hi Freddd,

    Thank you so much for taking the time to summarize your main ideas in this post. I do think this is in benefit of many of us, that unfortunately get lost with excess of information due to the big brain fog and lack of energy. So I really appreciate that.

    I will study your comments, and of course I will follow your fantastic interaction with Rich closely as well (as far as I can!), with my only purpose of learning more about my illness and about how to cure it.

    I hope to get back to you as soon as I have enough energy, to discuss some of your arguments, if you dont mind (now that they are summarized).

    Best,
    Sergio
  10. Freddd

    Freddd Senior Member

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    Hi Sergio,

    Most of what I said can hardly be construed as arguments. They are for the most part either direct observations or reporting of some research or a combination. If you wish to take issue with the research I'll post the sources for you so you can write the researchers, if they are still alive and in business as some is recent and some has been around for a while. As far as what I have experienced and/or observed, they are what they are. Perhaps you could run some trials and post your observations of results or the research backing up your opinions. Then a jolly good time could be had by all.


    As far as the FDA and amalgams,
    The warning is not aimed at the general population, only at two groups already urged to limit mercury from another source — seafood — because too much can harm a developing brain.
    The fillings, formally known as dental amalgams, "contain mercury, which may have neurotoxic effects on the nervous systems of developing children and fetuses," reads the FDA Web posting.
    That does not mean it truly harms, and the FDA advises against removing existing fillings.
    The agency still is studying whether the small amount of mercury vapor released by chewing and brushing is enough to cause neurologic disorders or other problems in youngsters. There have been only a handful of rigorous studies comparing children given either amalgam fillings or tooth-colored resin composite fillings that are mercury-free — and those studies haven't detected any brain problems.
    http://www.usatoday.com/news/health/2008-06-12-dental-fillings_N.htm





    Specifically, the FDA recommended that the product labeling include:
    • A warning against the use of dental amalgam in patients with mercury allergy;
    • A warning that dental professionals use adequate ventilation when handling dental amalgam;
    • A statement discussing the scientific evidence on the benefits and risk of dental amalgam, including the risks of inhaled mercury vapor. The statement will help dentists and patients make informed decisions about the use of dental amalgam.
    http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm173992.htm


    FDA: Dental Amalgam Safe But Should Include Warning

    WASHINGTON, July 29 -- Dental fillings that contain mercury are safe, but have been upgraded from low-risk to moderate-risk devices, the FDA said.

    In its final rule on dental amalgam, the FDA recommended that product labeling include warnings against use in patients with mercury allergy and that dental professionals use adequate ventilation when handling the product.
    The label should also have a statement about the product's benefits and risks -- including those from inhaling mercury vapor, the agency said.

    The FDA considers dental amalgam fillings safe for adults and children age 6 and up. The agency says the amount of mercury in patients with dental amalgam fillings is well below levels associated with adverse health effects.

    http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/15287

    "and FDA has been forced by law to advice of their dangerous for human health"

    If you were to read the FDA statement it does not say "dangerous to human health". They warn against it's use in those allergic to mercury just as they would warn against anything to which a person is allergic. They also warn dental professionals who handle a lot of the stuff. You sound somewhat eager to overstate the mercury situation.

    A good theory has to account for the entire range of ocurrances, not just the preferred ones and not one's opinion. Let us apply critical thinking to all this. Have fun. Hope you feel better. Brainfog is no fun. It clouds ones thinking and is a real hinderance to clear thinking.
  11. serg1942

    serg1942 Senior Member

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    Hi Fredd,

    I’m not sure whether your tone is a bit disrespectful with me. If so, please, think this is not a fight. This is dialog between sick people. So please remind this when answering me again.

    I am the one who must say whether my brain fog prevents me for thinking crearly, not you. In fact, if I write something, I do it thinking clearly doing a great effort.

    I can’t do trials and post my observations, as I am sick and housebound (I don't know if you are joking here...). I Just study my illness like most of us here to find a solution. So I’m sorry we cannot have a jolly time like you'd like to

    RE: amalgams
    , The FDA, forced by law (and forbid my mistakes in grammar), had to write in his web what is said in this article:

    http://www.reuters.com/article/idUSN0439217520080604

    “As part of the settlement with several consumer advocacy groups, the FDA agreed to alert consumers about the potential risks on its website and to issue a more specific rule next year for fillings that contain mercury, FDA spokeswoman Peper Long said.

    Dental amalgams contain mercury, which may have neurotoxic effects on the nervous systems of developing children and fetuses," the FDA said in a notice on its Web site.

    Pregnant women and persons who may have a health condition that makes them more sensitive to mercury exposure, including individuals with existing high levels of mercury bioburden, should not avoid seeking dental care, but should discuss options with their health practitioner, the agency said”


    So yes, they agreed and did advise about the health issues of dental amalgams on health. And yes, they had by law to issue a more specific rule for amalgams with the deadline at 7/28/09.

    It seems that they again have advocated for the safety of amalgams, so I’m sure they will be pressed again.

    There's a lot of evidence on amalgam filling risks. I could give you hundreds of reports and studies on that, but the document I have prepared is in Spanish. However I can give you important evidence about the clear position against amalgams and the advocation on the use of alternative fillings materials:

    WHO:


    www.who.int/ipcs/publications/cicad/en/cicad50.pdf
    www.who.int/water_sanitation_health/medicalwaste/mercurio_es.pdf

    UNEP:

    http://www.unep.org/GC/GC22/Document/UNEP-GC22-INF3.pdf

    European Comision:

    http://ec.europa.eu/environment/chemicals/mercury/pdf/study_report2008.pdf

    European Parlament:

    http://www.europarl.europa.eu/sides...reference=A6-2008-0260&format=XML&language=EN

    You may look also at the Memoramdum of Paris Appeal:

    http://www.artac.info/images/telech...9ce93f83cff2=4632329f1a3ba310fa84e06b111ff548

    or at Luxembourg appeal:

    http://www.europaem.org/news/luxembourg appeal/English Luxembourg Appeal sign..pdf

    or to read papers from experts on the subject like:

    Report by Maths Berlin, a Professor Emeritus of Environmental Medicine, to the Swedish Minister for Health and Social Affairs:

    http://www.sweden.gov.se/content/1/c6/01/76/11/fb660706.pdf

    Or for example some studies on the subject:

    - The Effect of Dental Amalgams on Mercury Levels in Expired Air.c. W. Svare, C. Peterson, J.W.reinhardt, D. B. Boyer, C. W. Frank, D. D. Gay, and R. D. Cox. J Dent Res 60(9):1668-1671, September1981.
    - Human exposure to mercury and silver released from dental amalgam restorations. Skare I, Engqvist A. Arch Environ Health. 1994 Sep-Oct;49(5):384-94.
    - Significant mercury deposits in internal organs following the removal of dental amalgam, & development of pre-cancer on the gingiva and the sides of the tongue and their represented organs as a result of inadvertent exposure to strong curing light (used to solidify synthetic dental filling material) & effective treatment: a clinical case report, along with organ representation areas for each tooth. Omura Y, Shimotsuura Y, Fukuoka A, Fukuoka H, Nomoto T. Acupunct Electrother Res. 1996 Apr Jun;21(2):133-60.
    - Mercury in saliva and feces after removal of amalgam fillings, Bjrkman L, Sandborgh-Englund G, Ekstrand J., Toxicol Appl Pharmacol. 1997 May;144(1):156-62.
    - Mercury Concentrations in Urine and Whole Blood Associated With Amalgam Exposure in a US Military Population. A. Kingman, T. Albertini, and L.J. Brown. J Dent Res 77(3): 461-471, March, 1998.
    - Dental amalgam fillings and the amount of organic mercury in human saliva. Leistevuo J, Leistevuo T, Helenius H, Pyy L, Osterblad M, Huovinen P, Tenovuo J. Caries Res. 2001 May-Jun;35(3):163-6.
    - Dental amalgam and mercury levels in autopsy tissues: food for thought.Guzzi G, Grandi M, Cattaneo C, Calza S, Minoia C, Ronchi A, Gatti A, Severi G. Am J Forensic Med Pathol. 2006 Mar;27(1):42-5.
    - Mercury in human brain, blood, muscle and toenails in relation toexposure: an autopsy study. Lars
    - Bjrkman, Birgitte F Lundekvam, Torgils Lgreid, Bjrn I Bertelsen, Inge Morild, Peer Lilleng, Birger Lind, Brita Palm and Marie Vahter. Environmental Health 2007, 6:30 doi:10.1186/1476-069X-6-30.
    - Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. Palkovicova L, Ursinyova M, Masanova V, Yu Z, Hertz-Picciotto I. J Expo Sci Environ Epidemiol. 2008 May;18(3):326-31. Epub 2007 Sep 12.
    - Mercury release from dental amalgam restorations after magnetic resonance imaging and following mobile phone use. Mortazavi SM, Daiee E, Yazdi A, Khiabani K, Kavousi A, Vazirinejad R, Behnejad B, Ghasemi M, Mood MB. Pak J Biol Sci. 2008 Apr 15;11(8):1142-6.
    - Neurological symptoms among dental assistants: a cross-sectional study. BE Moen, BE Hollund and T Riise. Journal of Occupational Medicine and Toxicology 2008, 3:10 doi:10.1186/1745-6673-3-10.


    Finaly you can read a few books / reports on the dangerous of amalgams fillings like:

    - Amalgam Illness: Diagnosis and Treatment. What you can do to get better. Dr. Andrew Cutler, 1999, ISBN 0-9676168-0-8.
    - A Comprehensive Review of Heavy Metal Detoxification and Clinical Pearls from 30 Years of Medical Practice. Dr Dietrich Klinghardt, MD, PhD.
    - It's All in Your Head: The Link Between Mercury Amalgams and Illness. Hal A. Huggins. Avery Publishing; 1 edition (July 1, 1993). ISBN-10: 0895295504. ISBN-13: 978-0895295507.


    This is just a few bibliography on the dangerous of amalgams. Maybe it is useful for you to your ongoing study. I can give you more data in this respect. Just ask me.

    There’s a myriad of other bibliography on Hg dangerous, not only from amalgams but also from vaccinations and from food. I could give you many bibliography on this as well if you like.

    If you read all this, maybe you don’t think that I am overstating the mercury situation. Maybe it’s you who is being hasty in judging me.

    BUT, please, take into account that my only goal was just to have a summary on your main ideas in the benefit of the PWC’s, and I am not going to enter in a discussion about amalgams, or mercury toxicity. This is something clear to me that needs no discussion at all.

    Thank you again for summarizing your main ideas in a short post as I proposed to you. This is what really matters, and this will do the discussion easier.

    Best wishes,
    Sergio
  12. jenbooks

    jenbooks Guest

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    I hope we don't get into an argument about amalgam poisoning here. It's clear amalgams can cause great harm, especially to the 15-20% of the population that has trouble clearing mercury. It is banned in more ethical countries. Here there are special interests that warp honest science. Consider Bisphenol A--it has taken a huge amount of grassroots advocacy by scientists doing experiments, journalists, media, and consumers--to force the chemical industry to consider banning it. They were making a million $ an hour on it and they had the FDA in their pockets for many years. 'Nuff of that.

    I'm more interested in the honest patient reports about the different B12 experiments. Lisa, Sushi, had trouble with methylb12--while for Freddd it was a lifesaver.
  13. serg1942

    serg1942 Senior Member

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    Yes Lenbooks,

    It wasnt my intention to open a debate on amalgams dangerousness. I just felt the need to show to Freddd that people, (in this case me), when talk, can have arguments to do so. This is because I have written only a few quick references on the dangerousness of amalgams. The same happens with Bisphenol-A. It is clear it is dangerous, and will be banned in few years in the EU, the same that amalgams are banned in a few countries already. I am not going to talk about this here from now onwards. Just felt I was a bit despised, and the better form to answer to this is with evidences of what I was talking about.

    I am also, and only interested in the B12s subject, as I myself have also experimented a bad reaction to methylB12, and in the other hand, by taking hydrxoB12, my methylation cycle improved, and in the meanwhile my urine heavy metal levels raised accordingly, so it is clear for me that in my case, (like Dr. Nathan and Richs study shows), the hidroxoB12 is effective in restoring the methylation cycle, and for do that it has to be converted into methyl B12

    So please, lets focus on that subject, as taking high doses of methyl B12 may be dangerous for many of us.

    Regards,
    Sergio
  14. aquariusgirl

    aquariusgirl Senior Member

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    Bad reaction to methyl B12, but probably need it

    Hi

    Here's my 2 cents on the debate. Just my experience.

    I've been on the yasko protocol since Feb 2007. I've been supplementing hydroxy B12 since then in various forms. For the past 6-8 months or somwhere around there I've been injecting 2-3ccs of 25mg/ml every day, which I think is a lot in anyone's book.

    Progress has been slow.. although supporting my methylation cycle is the only treatment that has worked for me so far.

    Anyway, I thought I would try methyl B12 as I thought that would speed things up. I ordered some injectable stuff from a compouding pharmacy. I tried a smidge ..less than 1/10th of 1 cc.. and it messed my brain up for days. FOR DAYS. It was very unpleasant.

    Now I think I went with too high a dosage ...5mg/ml.. (and I ordered 3 bottles.. more $$$ down the drain).. But anyhow, I feel like methyl B12 needs to be approached VERY carefully.

    Fredd's theory about large dosages of methyl B12 being better than small ones is interesting, but I don't think I'll be volunteering to try this any tiime soon.

    It seems to be a case of what we really need being really potentially damaging for us.

    I have had helacious reactions to glutathione and hydroxocobalamin and Lipoflow (I think it was the glut plus Methyl B12 product).

    When I tried those 2 things I was in agony for a week. It felt like my brain was on fire.. on the one occasion.. and the only thing that helped was yasko's RNAs which are kinda expensive.

    That's all I can tell you.

    It would be nice to figure out a safe way to take methyl B12 .. maybe teeny, tiny doses??? because it just seems like otherwise we could be at this for years as Klinghardt has apparently said.

    I just don't think I can afford to lose any more brain cells.

    Cheers
    L.
    Lotus97 likes this.
  15. Freddd

    Freddd Senior Member

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    Hi Sergio2,

    Im not sure whether your tone is a bit disrespectful with me. If so, please, think this is not a fight. This is dialog between sick people. So please remind this when answering me again.

    I cant do trials and post my observations, as I am sick and housebound (I don't know if you are joking here...). I Just study my illness like most of us here to find a solution. So Im sorry we cannot have a jolly time like you'd like to


    I dont want to get caught up in an amalgam and mercury tizzy either. Rich brought up the question and we are both examining it in our respective ways. He asked specifically abpout conversion of mercury to methylmercury by taking methylb12 and I worked up a model of a hypothetical situation. What is most apparent from that model is that it takes a lot of b12 to convert very little mercury to methylb12, which might be of import to you. It does show that there is an alternate path out of the body besides the urine. However, until Rich looks this over and its revised and discussed and revised etc I wouldnt attempt anything at all based upon it. I was trying to look at the numbers behind the many assumptions which is an approach I often take.

    I'll try again. I may get off into approach and philosophy a bit. I was sick and housebound too. And I was rapidly becoming increasingly disabled. However, I'm absolutely serious about trials. Let me explain. First, you do have a captive trial subject, yourself. That would make this a longitudinal trial rather than a cross sectional. But also you have your association members and fellow sufferers in this malady. They may only be available by internet but they are still available and likely as interested as you are to find a solution. Let me say that without a way to research and exchange information I could not have done what I did. I wasn't up to spending day after day in a medical library.

    In a generic sense the problem is what I call "95% medicine". It's the application of statistics to medicine. It does not include in it's solutions those who fall outside the range, whether its a plus/minus 2 standard deviations (95%) or the 20-40% of non responders to hydroxyb12 or the xx% who are hypersensitive to mercury or anything else.

    What differentiates my experience of trying a variety of supplements based on a lot of reading is that I did it systematically in a number of ways. When I had a response to a substance I tried to maximize the response if it was small, or tone it done some if it was large but to ride it all the way until I could tell if it was a beneficial response. In all this I found a lot of things that made no difference. I found only one set of things that made a substantial detrimental difference, glutathione precursors. I didn't quit it after the first day despite immediate onset of inflammation was that the inflammation was expected with it later clearing and showing improvement. Instead it was just the opposite so I put up with all of it's misery for 6 weeks until I could tell what direction it was taking. It played 52 pickup with the symptoms and so it was difficult to tell at first. Finding pivot point symptoms became a key practice of mine. It was very easy at first. After the first few layers of symptoms were dealt with, it became more difficult to find pivot point symptoms and finding additional things that made a difference.

    I started the whole thing with 8-9 months of reading. I took on myself as the consulting client and set out to solve the problem. First I had to find out about the problem. It was clear early on that it was a b12 problem as I had figured out in 1980 with no solution besides liver at that time and 100% of researchers and medical persons telling me I was wrong.

    This time I had the internet and Google. I made contact with a lot of people with very silmilar problems to mine despite a multiplicity of causes. I looked for all the assumptions in the research. I looked for all the cracks in the definitions. I paid close attention to all those for whom the solutions didn't work; the left out 5% or whatever. On the internet I studied the folks who were similar to me, who fit some of the same patterns. I derived the patterns. In studying those folks I again found those who had excellent long term results and those who didn't and revised the patterns. They were each their own longitudinal study. I found the patterns evident. I found the system and how it worked in practice. As it matched up to the literature, when reading between the lines and eliminating assumptions and wishful thinking, of which there was waaaay to much.

    Elsewhere on the net I am engaged in a multi person dialog attempting to come to an understanding of all the contradictory statements made about the enterohepatic circulation system and the roles of TC1, TC2, TC3, HTC1, HTC2 and HTC3 and how it all fits together. One would think that there is a reasonably accurate consensus about something so studied for 60 years but there isn't. The literature is filled with contradictory interpretations, sloppy language (which may be at the heart of many of the problems), wishful thinking to justify pet theories, false assumptions based on somebody elses earlier wishful thinking and so on. This doesn't even get into more controversial areas of types of b12 and their actions. This is just supposed to be a straightforward explanation of how b12 gets into the body from food and is retained explanation. That it does so when everything is functioning normally as an end result is obvious. The devil is in the details as they say. I did not see much application of Finagles Universal Constant Variable in the numeric data. Instead I saw Fudges Wishful Implications Linguistic Principle freely applied in explaining the numeric data and what it meant.

    My advice is to apply a similar jaundiced eye to mercury and amalgam research. Watch yourself carefully. Observe what occurs. Make systematic changes and see what happens. Learn to predict what will occur from change x. Be willing to learn different interpretations.

    When I start telling you what something means, it is an interpretation or opinion, not to be confused with direct observation. So I observe X and offer an explanation and meaning Y. One of the things I saw over and over in this whole methylb12 business was that persons who had the most severe deficiencies had the fastest and most intense reactions. I also observed that many of these people were likely to interpret an intense reaction as a bad reaction and immediately stop the methylb12. If I had done that I wouldnt be here today writing this. I also observed that taking small daily doses could keep the startup reactions going almost indefinitely as it (hypothesis) never can reach a saturated equilibrium that way. I distinguish a small daily dose from a small dose at any one time. To an extent the recharge hypothesis appears correct in a way not meant by those generally using it. We dont appear to have a holding tank for b12 anywhere including the liver. The liver has a higher concentration on the way to recycling and re-refinement. The bladder also serves as a holding tank for the cobalamins going out of the body without recycling. The bulk of b12 in the body is functional b12 in the mitochondria and elsewhere, in position to do its job. Its all of these functional places being filled (hypothesis) that appears to cause noticeable reaction. When some 600 potential reactive sequences all try to fire up at once it causes a sizable disturbance.

    I observed that the intensity of reaction occurs at some relatively small level of methylb12 hitting the blood. That is to say, from Zero to some maximum quantity, intensity increases as level increases, this is observable. In my own experience with 5 star sublinguals, a 5mg dose was only slightly more intense than a 1mg dose. A 25mg (5x5) during the course of the day was no more intense than a single 5mg dose. 5mg as 5x1, was no more intense than 1mg. of 1mg was almost as intense as a 1mg. mg was almost as intense as mg. The biggest increase in intensity came with the first 1/8 tablet, approximately 10-25mcg making it to serum which saturates the HTC2 transport system. Ceiling was reached with about 2mg at a single dose. Other people were observed to have similar results.

    I observed that higher doses stopped having noticeable effects quicker than lower doses. It (hypothesis) appeared to cause a saturated equilibrium much faster.

    In observing over 1000 people face to face taking a first dose (1-5mg mb12 and/or 3mg adb12) I saw a lot of intense reactions. Most were not as intense as my own first reaction but some were. I also observed quite a few people with no applicable symptoms, or very few, having no discernable reactions at all. In longer term consumption and tracking, most everybody who continued to describe their experiences, some did not, eventually got through the startup period, some quicker than others. While the startup experiences were quite often intense and unpleasant, they generally were not damaging or dangerous. My own increase of blood pressure with CoQ10 was one of the most dangerous. I stopped CoQ10 for a year until I had healed mostly and then it was no problem. The things that consistently are associated with more intense startup reactions are methylators which I normally suggest as adding down the road after the mb12 no longer causes any startup reactions and having taken cyanob12 and/or hydroxyb12 for a while before changing to active b12s.

    If I had been taking methylfolate, SAM-e, and l-carnitine fumarate before starting mb12 and then adb12 I would have had a quadruple whammy startup all at once. Each of those had really significant startup afterwards. To have added them into the startup effects of mb12 would have been overwhelming. ORDER IS IMPORTANT! I had them as 5 separate startup effects. The one thing that can reasonably be started ahead of mb12 is adb12 as that starts an entirely different subsystem, the mitochondria and is not a methylator. It is my understanding that hydroxyb12 coverts more readily to adb12. However, again order is important because l-carnitine affects this dramatically and should be started after adb12 startup has ended to avoid a double whammy.

    Lack of SAM-e and lack of methylfolate serve to keep mb12 throttled back. Lack of methylfolate and lack of l-carnitine serve to keep adb12 throttled back.


    That anybody (hypothesis, otherwise how could you explain such as response) has any reaction at all to methylb12 and/or adb12 after a year on hydroxyb12 just indicates how poorly hydroxyb12 actually is being converted to these only two active forms of b12 and quite unable to populate all the open positions for b12. If hydroxyb12 were actually being converted adequately to either or both forms of b12 then one would expect the response of somebody without deficiency; none at all. So the question may come down to why doesnt hydroxycobalamin convert to enough active b12 to satisfy the bodys needs?

    As I havent helped folks though this kind of changeover from where they have already gotten all the methylators on board without any active b12s I dont have experience in that and havent observed folks in all of the variations. I would expect that a cessation of methylators and of l-carnitine for at least a couple of weeks before starting with crumbs of methylb12, multiple times per day, might be a way to try. And remember, intense and unpleasant usually are not dangerous or damaging. As a caution I would also stop CoQ10 and monitor my blood pressure.

    And Sergio, I dont know about this mercury thing. I would wait until this gets hashed out with Rich before running a trial with your hypersensitivity. Good luck and good health.
  16. acer2000

    acer2000 Senior Member

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    Is there any real hard evidence that suggests taking Methyl b12 in the presence of mercury really causes any problems? I mean our bodys must contain tons of other methyl donors. If its not b12, its probably something else. Anyone have a link to a study that shows that taking b12 causes mercury to "go to the brain" like people have suggested? Or is this just an urban myth.

    Note: I'm not claiming some people don't feel worse when they take methyl b12, I'm just curious what the evidence is for the proposed mechanism "it causes mercury to go the brain".
  17. Freddd

    Freddd Senior Member

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    Hi Asus,

    Honestly I have never seen any hard evidence of such. If you look at that post a few up I did, which is VERY preliminary, it shows just how weak a methylator mb12 is. SAM-e is considered the universal methylator for good reason. As I point out, if my reasoning is correct on just the molecular masses and amount of methyl groups available, assuming 10% of the methylb12 actually succeeds in methylating Hg before it's excreted then it would take 67mg of injected mb12 to methylate 1mg of HG, say 500mg of sublingual methylb12. As it then appears to be mobilized from the tissues and available for excretion in the bile at about 1% a day, it will reach an equilibrium at a safe level and decrease. Rich mentioned high dose IV mb12 a situation we likely will never see here. If this isn't right I need people to tell me why and where my errors are of any kind from math to chemistry to concept to execution. Further, adenosylb12 isn't a methylator at all and does only one thing, produce energy in the mitochondria. It should have no effect on mercury or methylation at all yet can go most of the way towards relieving the fatigue of CFS and muscle pain of FMS.
  18. Freddd

    Freddd Senior Member

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    Something I would like to clarify about order of adding supplements. I don't think that there is one order for everybody. Some people do best on one order of startup and others on a different order. I've changed by opinion over and over on this as I've seen additional information. Order of startup has become much more important within the system as I see it based on previous experience and the additional data supplied by so many here with their experiences. Titration is also important, more for some than for others. My view of this of course evolves as I receive more input. It's not a belef system. I'm really a hard core pragmatist, it has to work. The trick is in understanding what the many variations mean and how that needs to affect startup order and what the startup symptoms mean. Different theoretical constructs will assign different meanings to the startup characteristics. I thank everybody for giving their own personal stories and results. They are all important to understranding what is going on. The thing I absolutely don't want to see is peoples' lives destroyed and maintained in that condition by ignorance, faulty research and ignorant insurance company policies, many of which I helped enforce. Unfortunately I didn't get to define the rules, just write the software that enforced them. If anybody has had sucess at getting an insurance company to pay for daily mb12 or any other daily b12 injections I would appreciate finding out about it.
  19. Freddd

    Freddd Senior Member

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    Restoring the remethylation pathyway to normal activity

    Here is an interesting article on the some of the effects of methylb12 that has relevance here.

    http://ndt.oxfordjournals.org/cgi/content/abstract/17/5/916



    [SIZE=+1]Abstract[/SIZE] Background. Hyperhomocysteinaemia, which is considered to be induced by impairment of the remethylation pathway in patients with chronic renal failure (CRF), cannot be cured solely by folic acid therapy. In the present study, we investigated the additional benefit of administration of methylcobalamin, which is a co-enzyme in the remethylation pathway, on lowering total homocysteine (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose folic acid supplementation.

    ...
    Conclusion. The benefit of methylcobalamin administration on lowering plasma tHcy levels in HD patients was remarkable. Our study suggested that both supplementations of high-dose folic acid and methylcobalamin are required for the remethylation pathway to regain its normal activity. This method could be a therapeutic strategy to combat the risk associated with atherosclerosis and cardiovascular disease in patients with chronic renal failure.
  20. susan

    susan Senior Member

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    what form potassium

    Fredd,
    Thank you for your help. I have started the Methyl B12 .....1/4 of a 1000mcg ..no problems so far....ordered others. Does the Jarrow 5000mcg come from Ihereb as I could not see it on their site? Now what kind of potassium....citrate or chloride. I have adrenaline induced high Bp will that be Ok taking it.?

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