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Methylation, what it is, and how many CFS patients have problems?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by redo, Jun 28, 2011.

  1. redo

    redo Senior Member

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    Does anyone have a quick and easy explanation of what methylation is? I tried reading the wiki but my brain is too foggy now.

    And, does anyone have a link to a study indicating prevalence of methylation problems with CFS patients?
     
  2. Sushi

    Sushi Moderator and Senior Member Albuquerque

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  3. Freddd

    Freddd Senior Member

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    HI Redo,

    100% of CFS and FMS symptoms are b12 and folate with cofactor deficiency symptoms. Approximately 1/3 of the b12/folate deficiencies symptoms are methylation shutdown related including all the cell reproduction failure and breakdown of epithelial, endothelial, muscle and neurological tissues.
     
  4. anniekim

    anniekim Senior Member

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    Fredd, in your opinion, what are the other two thirds? Thank you
     
  5. xchocoholic

    xchocoholic Senior Member

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    Hi Freddd,

    While I appreciate your efforts here, I have a problem with this statement. And I'm sure most of us old timers do. As someone who's been on the boards for years now, I've seen that many of our ME/CFS symptoms respond to dietary changes or nutritional support that have nothing to do with B12 or Folate or methylation. ME/CFS is definitely a combo of immune system problems not just methylation.

    Many / most of us have food intolerances that are responsible for creating cytokines that are causing CFS symptoms. Food and chemical allergies, which are different from food intolerances, are playing a large role in some of our CFS symptoms too.

    In fact, many of my CFS symptoms simply vanished after going on the elimination diet WHILE many of my nutrient levels were still very low ... these included B12 (< 300), Iron (needed IV), pregnenolone (level = 70 year old), chromium and I can't remember what else right now. As far as I know my folate wasn't checked until after I'd been on it for awhile and then it came up higher than recommended.

    AND my B12 is over 1600 right now and I still have fatigue, OI and PEM. I realize that you think these tests are unreliable but seeing as how I took sublingual Country Life ADB12 and Enzymatic MB12 for several months and that's what drove this up, I think there is a connection. My B12 was only at 700, before taking ADB12 and MB12.

    The symptoms that vanished included ataxia with leg weakness and foot dragging, a constant buzzing, narcolepsy, IBS, etc, etc At this point, if I am exposed to any gluten whatsoever, I get nocturnal myoclonus (jerking) and horrible insomnia. Theanine (specifically for the jerking - also an alternative for Klonopin), melatonin and 5HTP take care of these symptoms within a hour for me everytime without fail. NOT B12 or folate.

    Thanks for all your help here, but I hate to see people get sucked into doing only ONE protocal when CFS is a mixed bag ... I'd still be very sick if I'd only tried either of the methylation protocals ...

    The gut bacteria are playing a role here too but as far as I can tell, not as much as KDM thinks .... According to my latest CDSA my gut bacteria is still off (no lactobaccillus) but all of my CFS neurological problems are under control. Like I said before though, all of my neurological problems appear to be from gluten intolerance. I'm a DQ2 and a celiac. (Small rant ... now how hard would it have been to look for that 20 years ago ?) Others have similiar reactions to dairy, soy, corn, dyes, etc etc ...

    FWIW ... When I first took ADB12 and MB12, I noticed an improvement. The ADB12 seemed to eliminate what I call sudden muscle weakness where I had muscle strength for a minute or so but then my muscles would give out. (FWIW. This appears to return if I've been exposed to gluten) ... And the MB12 helped my energy leveles. After about 3 months taking ADB12 or MB12 both of these kept me awake all night. Solgar P5P did the same thing ... I had to take 9 mg of melatonin, 300 mg of theanine and 300 mg of 5HTP to sleep at all. Within 24 hours of stopping ADB12, MB12 or P5P, I could sleep without any supplements again.

    Again thanks for your efforts here but PWCs, especially the newbies, need to realize that ME/CFS is a mixed bag not just the result of a screwed up methylation cycle ... tc ... x
     
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Because we are still treating symptoms and test abnormalities even b12/folates, until we find the actual cause we will be chasing our tail. But treating defiencies and symptoms has to help us in someway, maybe keeping us as healthy as we can with cfs/me until the time comes that theres a definative test and treatment. This just shows that once again we all react differently to most treatments.

    cheers!!!
     
  7. xchocoholic

    xchocoholic Senior Member

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    Hi Heaps,

    Sadly at this point, ME/CFS IS just a group syptoms so knowing any PWCs root cause is going to be something a good doctor or the patient has to figure out.

    And because our medical profession hasn't taken this illness seriously and looked for root causes, I've seen repeatedly how someone diagnosed with ME/CFS recovered who actually had candida, a nutritional deficiency, food intolerance or something else that was causing their symptoms. Or in my case, All of the above plus a few other diagnosises ... :mask:

    The NIH stated over 5 years ago that celiac disease is being misdiagnosed as CFS but that didn't seem to get anyone's attention. Not that we're all celiacs but if the NIH noticed this, then I wonder how many times it happens and what else are they are seeing diagnosed as CFS that was actually something else. :confused:

    FWIW. I think I was only gluten intolerant and not a celiac for the first 15 years of this illness. ONLY being the understatement of the year ... :eek:

    Thanks to forums like this we've come a long way in the last few years in helping PWCs live better lives. The reason I posted here is that I don't want the idea that the methylation treatments are THE ANSWER to stop the progress we're making in determing to the root cause of ME/CFS ... IMHO, Dr. Myhill has come the closest to coming getting to her patients root causes. She takes a multi dimensional approach that recognizes how each of us is different ...

    tc ... x
     
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    After so many posts we should recieve a cfs doctorate from pheonix rising, lol. we mostly treat ourselves with a good doc who will write us scripts and do some testing.
     
  9. redo

    redo Senior Member

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    Freddd. I've used Sterop (such as this), which is really high dose B12, over a long time, and it did nothing to me. Not worse, not better.

    Sushi. I tried to read the stuff in the link, but I am none the wiser. Guess I have too much brain fog to comprehend.

    Anyone who can sum up what methylation is in a sentence or two?
    Does it have anything to do with detoxification? Is it something the bacteria in the gut do? Or the liver? What is it?
     
  10. richvank

    richvank Senior Member

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    Hi, redo.

    Methylation is a biochemical reaction in which a methyl group (a CH3 group) is attached to a molecule.

    Yes, the methylation cycle controls the sulfur metabolism, which is a major contributor to the body's detoxication system.

    It happens in every cell of the body, but the liver is the main producer of SAMe, which is the principal methyl donor in the body.

    Rich
     
  11. aprilk1869

    aprilk1869 Senior Member

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    This is a fairly nice description of methylation...

     
  12. redo

    redo Senior Member

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    Are there any test which can show if one have methylation problems?
    And which drugs would one take if one had methylation problems?
     
  13. richvank

    richvank Senior Member

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    Hi, redo.

    Yes. In my opinion, the best is the methylation pathways panel offered by the Health Diagnostics and Research Institute in New Jersey. It is a blood test, requires an order from a physician or a chiropracter, and costs $295, including the shipper to send the samples to the lab. Contact info and comments on interpreting the results are pasted below. This panel gives direct information about the status of the methylation cycle, the folate metabolism, and glutathione.

    In my opinion, the next best is a urine organic acids panel that includes figlu, methylmalonate, pyroglutamate and the citric acid cycle metabolites. I am most familiar with the Genova Diagnostics Metabolic Analysis Profile. This is available through some physicians, or may be ordered directly from www.directlabs.com for $299 without a physician's order:
    https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx

    The urine sample may be collected at home and sent directly to the lab in the mailer provided. Results will come back to you directly by email (or postal mail, if you request it). This panel will give you indirect information about the status of the methylation cycle, folate metabolism, and glutathione, as well as information on other aspects of the overall metabolism. However, it requires some interpretation, and is most useful if combined with some other panels.

    Incidentally, I followed some of your comments on the gut issue in ME/CFS. My current view is that there are numerous interactions between the partial methylation cycle block in ME/CFS and the gut problems, and that treatment will be most effective if they are tackled together.

    Best regards,

    Rich


    Methylation Pathways Panel

    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinicians letterhead.


    Available from:

    Health Diagnostics and Research Institute
    540 Bordentown Avenue, Suite 2300
    South Amboy, NJ 08879
    USA
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Lab Director: Elizabeth Valentine, M.D.

    Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.




    May 19, 2011


    Interpretation of Results of the Methylation Pathways Panel

    by
    Richard A. Van Konynenburg, Ph.D.
    Independent Researcher
    (richvank@aol.com)


    Disclaimer: The Methylation Pathways Panel is offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA. I am not affiliated with these laboratories, but have been a user of this panel, and have written these suggestions at the request of Tapan Audhya, Ph.D., Director of Research for the Health Diagnostics lab, for the benefit of physicians who may not be familiar with this panel. My suggestions for the interpretation of results of the panel are based on my study of the biochemistry involved, on my own experience with interpreting panel results as part of the analysis of a fairly large number of cases of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) over the past four years, and on discussion of some of the issues with Dr. Audhya. I am a researcher, not a licensed physician. Treatment decisions based on the results of applying this panel and its interpretation to individual cases are the responsibility of the treating physician.

    Application: In addition to being useful in analyzing cases of ME/CFS, this panel can also be usefully applied to cases of autism and other disorders that involve abnormalities in glutathione, methylation and the folate metabolism.

    The panel includes measurement of two forms of glutathione (reduced and oxidized), S-adenosylmethionine (SAMe), S-adenosylhomocysteine (SAH), adenosine, and seven folate derivatives.

    According to Dr. Audhya (personal communication), the reference ranges shown on the lab reports for each of these metabolites were derived from measurements on at least 120 healthy male and female volunteer medical students from ages 20 to 40, non-smoking, and with no known chronic diseases. The reference ranges extend to plus and minus two standard deviations from the mean of these measurements.

    Glutathione (reduced): This is a measurement of the concentration of the
    chemically reduced (active) form of glutathione (abbreviated GSH) in the blood
    plasma. The reference range is 3.8 to 5.5 micromoles per liter.

    Glutathione plays many important roles in the biochemistry of the body, including serving as the basis of the antioxidant enzyme system, participating in the detoxication system, and supporting the cell-mediated immune response, all of which exhibit deficits in CFS. The level of GSH in the plasma is likely to be more reflective of tissue intracellular glutathione status than the more commonly and more easily measured red blood cell or (essentially equivalent) whole blood glutathione level, which is about three orders of magnitude greater, because red blood cells are normally net producers of glutathione. Also, knowledge of the level of the reduced form, as distinguished from total (reduced plus oxidized) glutathione, which is more commonly measured, is more diagnostic of the status of glutathione function.

    In order to be able to approximate the in vivo level of reduced glutathione when blood samples must be shipped to a lab, it is necessary to include special enzyme inhibitors in the sample vials, and these are included in the test kit supplied by these two laboratories.

    Most people with chronic fatigue syndrome (PWCs), but not all, are found to have values of GSH that are below the reference range*. This means that they are suffering from glutathione depletion. As they undergo treatment to lift the partial methylation cycle block, this value usually rises into the normal range over a period of a few months. I believe that this is very important, because
    glutathione normally participates in the intracellular metabolism of vitamin B12, and if it is low, a functional deficiency of vitamin B12 results, and insufficient methylcobalamin is produced to support methionine synthase in the methylation cycle. In my view, this is the mechanism that causes the onset of ME/CFS. This functional deficiency is not detected in a conventional serum B12 test, but will produce elevated methylmalonate in a urine organic acids test. In my opinion, many of the abnormalities and symptoms in ME/CFS can be traced directly to glutathione depletion.

    Anecdotal evidence suggests that PWCs who do not have glutathione depletion do have abnormalities in the function of one or more of the enzymes that make use of glutathione, i.e. the glutathione peroxidases and/or glutathione transferases. This may be due to genetic polymorphisms or DNA adducts on the genes that code for these enzymes, or in the case of some of the glutathione peroxidases, to a low selenium status.

    Glutathione (oxidized): This is a measurement of the concentration
    of the oxidized form of glutathione (abbreviated GSSG) in the blood
    plasma. The reference range is 0.16 to 0.50 micromoles per liter.

    Normally, oxidized glutathione in the cells is recycled back to reduced glutathione by glutathione reductase, an enzyme that requires vitamin B2 and NADPH. If this reaction is overwhelmed by oxidative stress, the cells export excess GSSG to the plasma. In some (but not all) PWCs, GSSG is elevated above the normal
    range, and this represents oxidative stress. It is more common in CFS to see this level in the high-normal range. This value may increase slightly under initial treatment of a partial methylation cycle block.*

    Ratio of Glutatione (reduced) to Glutathione (oxidized): This is not shown explicitly on the panel results, but can be calculated from them. It is a measure of the redox potential in the plasma, and reflects the state of the antioxidant system in the cells. The normal mean value is 14. PWCs often have a value slightly more than half this amount, indicating a state of glutathione depletion and oxidative stress. This ratio has been found to increase during treatment of a partial methylation cycle block.*

    S-adenosymethionine (RBC): This is a measure of the concentration of S-adenosylmethionine (SAMe) in the red blood cells. The reference range is 221 to 256 micromoles per deciliter.

    SAMe is produced in the methylation cycle and is the main supplier of methyl (CH3) groups for a large number of methylation reactions in the body, including the methylation of DNA and the biosynthesis of creatine, carnitine, coenzyme Q10, melatonin and epinephrine. This measurement is made in the red blood cells because the level there reflects an average over a longer time and is less vulnerable to fluctuations than is the plasma level of SAMe.

    Most PWCs have values below the reference range, and treatment raises the value.* A low value for SAMe represents a low methylation capacity, and
    in CFS, it usually appears to result from an inhibition or partial block of the enzyme methionine synthase in the methylation cycle. Many of the abnormalities in CFS can be tied to lack of sufficient methylation capacity.

    S-adenosylhomocysteine (RBC): This is a measure of the
    concentration of S-adenosylhomocysteine (SAH) in the red blood cells. The reference range is 38.0 to 49.0 micromoles per deciliter.

    SAH is the product of the many methyltransferase reactions that utilize SAMe as a source of methyl groups. In CFS, its value ranges from below the reference range to above the reference range. Values appear to be converging toward the reference range with treatment.

    Sum of SAM and SAH: When the sum of SAM and SAH is below about 268
    micromoles per deciliter, it appears to suggest the presence of
    upregulating polymorphisms in the cystathionine beta synthase (CBS)
    enzyme, though this may not be true in every case. For those considering following the Yasko treatment program, this may be useful information.

    Ratio of SAM to SAH: A ratio less than about 4.5 represents low
    methylation capacity. Both the concentration of SAM and the ratio of
    concentrations of SAM to SAH are important in determining the
    methylation capacity, because they affect the rates of the methyltransferase reactions.

    Adenosine: This is a measure of the concentration of adenosine in the
    blood plasma. The reference range is 16.8 to 21.4 x 10(-8) molar.

    Adenosine is a product of the reaction that converts SAH to homocysteine. It is also exported to the plasma when mitochondria develop a low energy charge, so that ATP drops down to ADP, AMP, and eventually, adenosine. Adenosine in the plasma is normally broken down to inosine by the enzyme adenosine deaminase.

    In some PWCs adenosine is found to be high, in some it is low, and in some it is in the reference range. I don't yet understand what controls the adenosine level in these patients, and I suspect that there is more than one factor involved. In most PWCs who started with abnormal values, the adenosine level appears to be moving into the reference range with methylation cycle treatment, but more data are needed.

    5-CH3-THF: This is a measure of the concentration of 5L-methyl
    tetrahydrofolate in the blood plasma. The reference range is 8.4 to 72.6 nanomoles per liter.

    This form of folate is present in natural foods, and is normally the most abundant form of folate in the blood plasma. It is the form that serves as a reactant for the enzyme methionine synthase, and is thus the important form for the methylation cycle. It is also the only form of folate that normally can enter the brain. Its only known reactions are the methionine synthase reaction and reaction with the oxidant peroxynitrite.

    When there is a partial block in methionine synthase, 5L-CH3-THF drains from the cells into the blood plasma by the so-called methyl trap mechanism. As other forms of folate are converted to 5L-CH3-MTF, this mechanism depletes the cells of folates in general.

    Many PWCs have a low value of 5L-CH3-MTF, consistent with a partial block in the methylation cycle. Most methylation treatment protocols include supplementation with 5L-CH3-MTF, which is sold over-the-counter as Metafolin, FolaPro, or MethylMate B (trademarks), and in the prescription medical foods supplied by PamLab, including Deplin, CerefolinNAC and Metanx. There are some others on the market that include both racemic forms (5L and 5R) of this folate.

    When methylation treatment is used, the level of 5-CH3-THF rises in nearly every PWC. If the concentration of 5-CH3-THF is within the reference range, but either SAM or the ratio of SAM to SAH is below the reference values, it suggests that there is a partial methylation cycle block and that it is caused by inavailability of sufficient bioactive B12, rather than inavailability of sufficient folate. A urine organic acids panel will show elevated methylmalonate if there is a functional deficiency of B12. I have seen this combination frequently, and I think it demonstrates that the functional deficiency of B12 is the immediate root cause of most cases of partial methylation cycle block. Usually glutathione is low in these cases, which is consistent with such a functional deficiency. As the activity of the methylation cycle becomes more normal, the demand for 5-CH3-THF will likely increase, so including it in the treatment protocol, even if not initially low, will likely be beneficial.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. The reference range is 1.5 to 8.2 nanomoles per liter.

    This form of folate is involved in reactions to form purines, which form part of RNA and DNA as well as ATP. It is usually on the low side in PWCs, likely as a result of the methyl trap mechanism mentioned above. This deficiency is likely the reason for some elevation of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) often seen in PWCs. This deficit may also impact replacement of cells lining the gut, as well as white blood cells.

    5-Formyl-THF: This is a measure of the concentration of 5-formyl
    tetrahydrofolate (also called folinic acid) in the blood plasma. The reference range is 1.2 to 11.7 nanomoles per liter.

    This form is not used directly as a substrate in one-carbon transfer reactions, but it can be converted into other forms of folate, and may serve as a buffer form of folate. Most but not all PWCs have a value on the low side. It is one of the
    supplements in some methylation protocols. It can be converted to 5L-CH3-THF in the body by a series of three reactions, one of which requires NADPH, and it may also help to supply other forms of folate until the methionine synthase reaction comes up to more normal activity.

    THF: This is a measure of the concentration of tetrahydrofolate in
    the blood plasma. The reference range is 0.6 to 6.8 nanomoles per liter.

    This is the fundamental chemically reduced form of folate from which several other reduced folate forms are synthesized, and thus serves as the hub of the folate metabolism. THF is also a product of the methionine synthase reaction, and participates in the reaction that converts formiminoglutamate (figlu) into glutamate in the metabolism of histidine. If figlu is found to be elevated in a urine organic acids panel, it usually indicates that THF is low. In PWCs it is lower than the mean normal value of 3.7 nanomoles per liter in most but not all PWCs.

    Folic acid: This is a measure of the concentration of folic acid in
    the blood plasma. The reference range is 8.9 to 24.6 nanomoles per liter.

    Folic acid is a synthetic form of folate, not found in nature. It is added to food grains in the U.S. and some other countries in order to lower the incidence of neural tube birth defects, including spina bifida. It is the oxidized form of folate, and therefore has a long shelf life and is the most common commercial folate supplement. It is normally converted into THF by two sequential reactions catalyzed by dihydrofolate reductase (DHFR), using NADPH as the reductant. However, some people are not able to carry out this reaction well for genetic reasons, and PWCs may be depleted in NADPH, so folic acid is not the best supplemental form of folate for these people.

    Low values suggest folic acid deficiency in the current diet. High values, especially in the presence of low values for THF, may be associated with inability to convert folic acid into reduced folate readily, such as because of a genetic polymorphism in the DHFR enzyme. They may also be due to high supplementation of folic acid.

    Folinic acid (WB): This is a measure of the concentration of folinic acid in the whole blood. The reference range is 9.0 to 35.5 nanomoles per liter.

    See comments on 5-formyl-THF above. Whole blood folinic acid usually tracks with the plasma 5-formyl-THF concentration.

    Folic acid (RBC): This is a measure of the concentration of folic acid in the red blood cells. The reference range is 400 to 1500 nanomoles per liter.

    The red blood cells import folic acid when they are initially being formed, but during most of their lifetime, they do not normally import, export, or use it. They simply serve as reservoirs for it, giving it up when they are broken down.

    Many PWCs have low values of this parameter. This can be caused by a low folic acid status in the diet over the previous few months, since the population of RBCs at any time has ages ranging from zero to about four months. However, in CFS it can also be caused by oxidative damage to the cell membranes, which allows folic acid to leak out of the cells. Dr. Audhya reports that treatment with omega-3 fatty acids has been found to raise this value over time in one cohort.

    If anyone finds errors in the above suggestions, I would appreciate being notified at richvank@aol.com.

    * Nathan, N., and Van Konynenburg, R.A., Treatment Study of Methylation Cycle Support in Patients with Chronic Fatigue Syndrome and Fibromyalgia, poster paper, 9th International IACFS/ME Conference, Reno, Nevada, March 12-15, 2009. (http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf)
     
  14. richvank

    richvank Senior Member

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    Hi, redo.

    Drugs are not helpful for methylation problems, but orthomolecular treatment has been found to be helpful. There are several orthomolecular methylation treatments in use now. All of them have in common that they contain a form or forms of folate (most containing chemically reduced forms rather than folic acid), and high dosage of a form or forms of vitamin B12, taken sublingually or by injection. Most also include other supporting nutrients needed by this part of the metabolism.

    Which particular treatment is most helpful seems to vary among people, probably at least in part for genomic reasons. There has not been a controlled clinical comparison of the various methylation treatments.

    The most recent version of the protocol I have suggested is pasted below.

    Best regards,

    Rich


    March 30. 2011

    SIMPLIFIED TREATMENT APPROACH
    FOR LIFTING THE METHYLATION CYCLE BLOCK
    IN CHRONIC FATIGUE SYNDROMEMarch 30, 2011 Revision
    Rich Van Konynenburg. Ph.D.
    (Based on the full treatment program
    developed by Amy Yasko, Ph.D., N.D.
    which is used primarily in treating autism [1])

    SUPPLEMENTS

    1. General Vitamin Neurological Health Formula [2]: Start with tablet and increase dosage as tolerated to 2 tablets daily
    2. Hydroxy B12 Mega Drops [3]: 2 drops under the tongue daily
    3. MethylMate B [4]: 3 drops under the tongue daily
    4. Folinic acid [5]: capsule daily
    5. Phosphatidyl Serine Complex [6]: 1 softgel capsule daily (or lecithin, see below)

    All these supplements can be obtained from http://www.holisticheal.com.
    The fourth supplement comes in capsules that contain 800 mcg. It will be necessary to open the capsules, dump the powder onto a flat surface, and separate it into quarters using a knife to obtain the daily dose. The powder can be taken orally with water, with or without food.
    These supplements can make some patients sleepy, so in those cases they take them at bedtime. In general, they can be taken at any time of day, with or without food.
    Phosphatidyl serine can lower cortisol levels. Patients who already have low evening cortisol levels may wish to substitute lecithin [7] (at one softgel daily) for supplement number 5 above. Lecithin is also available from http://www.holisticheal.com.
    For those allergic to soy, lecithin from other sources is available.
    GO SLOWLY. As the methylation cycle block is lifted, toxins are mobilized and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
    Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.

    [1] Yasko, Amy, Autism, Pathways to Recovery, Neurological Research Institute, 2009, available from http://www.holisticheal.com or Amazon.
    [2] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
    [3] Hydroxy B12 Mega Drops is a liquid form of hydroxocobalamin (B12), supplied by Holistic Health Consultants. 2 drops is a dosage of 2,000 mcg.
    [4] MethylMate B is a liquid form of (6s)-methyltetrahydrofolate supplied by Holistic Health Consultants, based on Extrafolate S, a trademark of Gnosis S.P.A. 3 drops is a dosage of 210 mcg.
    [5] Folinic acid is 5-formyltetrahydrofolate. capsule is a dosage of 200 mcg.
    [5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center. 1 softgel is a dosage of 500 mg.
    [7] Lecithin is a combination of phospholipids without phosphatidylserine. One softgel is a dosage of 1,200 mg.
     
  15. Sing

    Sing Senior Member

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    New England
    Awesome, Rich!

    Thank you for taking the time to put all this together for us--again, it might be--but many are just coming to this as a possible avenue for improvement.

    (For preservation purposes, anyone wanting to email this thread to yourself or another can click on Thread Tools on upper right. I believe you have to be signed in.)
     
  16. redo

    redo Senior Member

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    Thanks for a thorough answer Rich.

    Do you know if this is mainstream enough that a random doctor would accept the results if I took a test and it came back showing many irregularities?
     
  17. richvank

    richvank Senior Member

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    Hi, redo.

    Unfortunately, most of the mainstream physicians are not aware of methylation and the importance of methylation in various disorders. They are generally familiar only with lab tests offered by the major conventional medical labs that are covered by Medicare and the insurance companies, which the methylation pathways panel is not. The reason I wrote the comments on interpretation is to assist physicians in using this panel, which is not familiar to the vast majority of them. Methylation is not taught in medical schools, as far as I know. Some physicians have heard of DNA methylation, but that's about as far as it goes.

    If a drug rep from PamLab has visited a physician, the physician probably will have heard of methylation, because PamLab produces "medical foods" that address the methylation cycle. They include CerefolinNAC, Metanx and Deplin. They contain only nutritional supplements, not drugs, but are given only by prescription and thus fit the "M.O." that physicians have been trained to be comfortable with. These medical foods are recommended for other disorders (high homocysteine, pre-Alzheimer's and depression), but some physicians have been giving them "off-label" for CFS. If you check out the survey results on the CureTogether.com site, you can see that CerefolinNAC is in the top half of treatments rated by average effectiveness by PWCs. However, it is not optimized for treating CFS: http://curetogether.com/chronic-fatigue-syndrome/treatments/ The "methylation treatments" are rated quite a bit higher, and they are the orthomolecular treatments, such as the one I have suggested.

    After med school. I think most physicians obtain a great deal of their new information from drug reps who visit them and give them free samples of new drugs. If some information is not useful for promoting a drug, or particularly if it would tend to decrease use of a drug, it is not likely to be conveyed to physicians by drug reps. The problem with methylation in this regard is that improving it by use of orthomolecular treatment could very well cut into sales of some drugs, such as antidepressants, because the metabolism of the neurotransmitters, which these drugs address, depends to a large degree on methylation.

    The physicians who are most likely to be aware of methylation are the naturopaths (N.D.s), the osteopaths (D.O.s), the integrative physicians, those who practice functional medicine, those in environmental medicine, and those who are involved in the DAN! (Defeat Autism Now!) project. We are continuing to try to increase the number of physicians who understand the methylation issue and are able to treat it, but this is slow going, because patented drugs are not involved, so there isn't a financial incentive to promote it. The fact is that not much happens in the medical system unless somebody is able to make considerable amounts of money from it. The internet is very helpful in getting information out about other options, which are often better, from the standpoint of the patient.

    Best regards,

    Rich
     
  18. Dreambirdie

    Dreambirdie work in progress

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    N. California
    This is the sad, and sometimes horrible, truth.

    So glad you are here on the internet with us! Thanks for RE-explaining methylation. AGAIN.
     
  19. Freddd

    Freddd Senior Member

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    Salt Lake City
    For a lot of people the shutdown of methylation results in impaired cell reproduction. So, in the epidermis we see all sorts of irritations and breakdown; skin rashes, acne, skin falling apart on finger tips and around nails, dandruff, nausea, angular cheilitis around mouth, IBS, inflamed lungs, inflamed stomach, canker sores, burning beef-red tongue, burning bladder, elevated MCV>92, elevated MCH, decreased platelet count, increased multisegmented nutraphils, inflamed arteries and veins, nervous system - CNS and peripheral breaking down. These are the very obvious effects of methylation failure. Basic looking at your skin can tell you a lot. How your epithelial and endothelial tissues feel can tell a lot. These all can turn on and off together. These are many of the more obvious symptoms of methylfolate deficiency and methylb12 deficieincy. Lack of either one can shut down methylation. Also glutathione, whey and NAC via "methyl trap" and folic acid, folinic acid and vegetable source food folate via paradoxical folate deficiency can all shut down methylation.
     

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