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Progressive fatigue

Discussion in 'Post-Exertional Malaise, Fatigue, and Crashes' started by Faoiseamh, Sep 16, 2012.

  1. Faoiseamh

    Faoiseamh

    Messages:
    8
    Likes:
    1
    Detroit, MI
    I was diagnosed with CFS as a child after getting mono and never recovering. I am now twenty two. I was able to live a semi-normal life until recently (not "normal" for "normal" people, but pretty normal for a lot of the people here). My fatigue has been progressing slowly in severity for at least two years now and shows no signs of stopping. Since starting school three weeks ago, it has progressed drastically. I can sleep anywhere from 16 to 20 hours a day and have to drag myself out of bed even after 18 hours of sleep. I live in a perpetual fog. I study languages and cannot retain new information any longer. My muscles and limbs feel weak and heavy. Each day is noticeably worse than the one before. I am terrified and at the end of my rope.

    Does it ever stop progressing? Do I need to quit school to stop the progression? Has anyone else dealt with this progressive fatigue and if so, when did it stop for you?
     
  2. richvank

    richvank Senior Member

    Messages:
    2,717
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    Hi, Faoiseamh.

    I'm very sorry to hear about what you have gone through over the past few years and what you are going through now.

    I would suggest that you consider getting the Health Diagnostics methylation pathways panel run, and if it shows that you have a partial block in your methylation cycle and glutathione depletion, which I suspect are likely, then I would suggest that, together with your physician, you consider trying the simplified methylation protocol. Information on these is pasted below:

    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 clinician’s letterhead.


    Available from:

    Health Diagnostics and Research Institute540 Bordentown Avenue, Suite 2300
    South Amboy, NJ 08879 USA
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Email: lab@vitdiag.com

    Lab Director: Elizabeth Valentine, M.D.

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



    March 25, 2012
    Interpretation of Results of the Methylation Pathways Panel
    by
    Richard A. Van Konynenburg, Ph.D.
    Independent Researcher


    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, but other types of treatment may be necessary to bring it to normal.*

    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, phosphatidylcholine, 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 converge 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, the other forms of folate continue to be converted to 5L-CH3-THF by the so-called “methyl trap” mechanism. Some of the 5L-CH3-THF is broken down by reaction with peroxynitrite, which results from the condition of oxidative stress that is usually concomitant with glutathione depletion.

    Many PWCs have a low value of 5L-CH3-THF, consistent with a partial block in the methylation cycle. Most methylation treatment protocols include supplementation with 5L-CH3-THF, which is sold over-the-counter as Metafolin, FolaPro, or MethylMate B (trademarks), as well as the newer Quatrefolic (trademark) 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.

    Rarely, 10-formyl-THF is found to be much higher than the normal reference range. If this is found, the patient should be examined for cancer, since cancer cells upregulate this form of folate in order to make purines more rapidly to support their rapid cell division.

    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 to the cells 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. They are the same substance.

    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)


    Hi, all.

    Various versions of the Simplified Methylation Protocol have been in use now for about five and a half years, and we have gained considerable experience with it. It is currently being used by clinicians and people with ME/CFS (PWMEs) in several other countries in addition to the U.S. Most who try it report benefit from it. A few have reported complete recovery, but most will need additional types of treatment to achieve complete recovery, and this is an area of ongoing research.

    On May 30, 2012, I posted a request for input on possible changes to the Simplified Methylation Protocol (SMP) on the Phoenix Rising ME/CFS forum and to the Yahoo cfs_yahoo group. Quite a few people tried supplements that I was considering and posted comments about their experiences. Several offered advice. Thank you to all who responded.

    As expected, different people had different experiences, and not all the comments were in agreement with each other. This is inherent, given that each person is unique, though we all share the same basic biochemical scheme, and it makes the formulation of a “one-size-for-all” protocol very challenging.

    I have reached conclusions about what I will recommend for now. There may be additional changes in the future, as more experience is gained and we learn more about how to treat ME/CFS. I will present the “bottom line” first, and then discuss the rationale behind the choices, together with some additional options, for those who are interested.

    Here is the revised Simplified Methylation Protocol as of today, August 25, 2012:

    (AS ALWAYS, I RECOMMEND THAT ANYONE ON THIS TYPE OF TREATMENT BE UNDER THE CARE OF A LICENSED PHYSICIAN. Even though this protocol consists only of nutritional supplements, a small number of people have reported experiencing serious adverse effects while on it. If this occurs, the protocol should be discontinued.)

    1. Neurological Health Formula (Holistic Health, Inc.) (Multivitamin-multimineral, plus
    additional nutrients): Swallow one-quarter tablet and increase to 2 tablets daily. Go
    up to 6 tablets daily if tolerated.
    2. Activated B12 Guard (Perque) (2,000-microgram lozenge of hydroxocobalamin):
    Take one lozenge per day, sublingually.
    3. FolaPro (Metagenics) (800-microgram tablet of 5L-methyltetrahydrofolate): Swallow
    one-quarter tablet daily, which amounts to 200 micrograms per day.
    4. Folinic acid (800 micrograms of 5-formyltetrahydrofolate): Swallow one-quarter
    tablet or one-quarter of the contents of a capsule daily, which amounts to 200
    micrograms per day.
    5. Lecithin (1200-milligram softgel): Swallow one softgel per day, which amounts to
    1200 milligrams of lecithin. If finances permit, instead of lecithin, drink a 2-ounce
    bottle of Smart Youthful Energy (NT-Factor)(Pure liposomal glycophospholipids)
    daily.

    All these supplements except Smart Youthful Energy can be obtained from www.holisticheal.com, or all but the first one can be obtained from other sources. I do not have a financial interest in any of these supplements. A pill splitter (available from drugstores) will be needed to split tablets. These supplements can be taken with or without food. Different times of the day work better for different people, in regard to effects on sleep. It is best to start with lower dosages than those suggested above and to work up slowly, to check for tolerance. Some people have found that they are very sensitive to these supplements, and can take only much smaller dosages. Others find that they need somewhat larger dosages than those suggested. For those who wish to start the supplements one at a time, I suggest starting with the Neurological Health Formula first, then adding the lecithin, then the B12, and finally the folates, with FolaPro last.


    In making this revision, I have been guided by the following goals:

    1. To provide effective treatment to correct the vicious circle mechanism that I believe to be the core of the pathophysiology of ME/CFS, involving glutathione depletion, a functional B12 deficiency, a partial block of the methylation cycle, and loss of folates from the cells. This vicious circle mechanism is described by the Glutathione Depletion—Methylation Cycle Block hypothesis for the etiologies, pathogenesis and pathophysiology of ME/CFS. This hypothesis cannot be regarded as scientifically proven, but as far as I know, it is consistent with the current body of published research on ME/CFS.

    2. To use only nonprescription nutritional supplements that are available via the internet.

    3. To use supplements that are available from a single source, where possible.

    4. To keep the protocol simple, with a minimum number of supplements, while preserving its effectiveness.

    5. To keep the cost low while preserving effectiveness.

    6. To improve the effectiveness of the protocol over that of the previous version, and in particular to increase its likelihood of being effective for more of the ME/CFS population.

    7. To preserve the ability of individuals to adjust dosages of individual supplements to match their tolerances and needs.

    8. To preserve the relevance of the clinical study of an earlier version of the protocol by Dr. Neil Nathan, M.D., and myself, to the degree possible.

    With those goals in mind, I will discuss each of the supplements in the revised protocol.

    1. Neurological Health Formula: I have decided to continue recommending this multi for a variety of reasons. First, we have a track record with it that shows that it is helpful to most PWMEs. It contains the vitamins and essential minerals to cover possible nutritional deficiencies, as well as several supplements to support the methylation cycle and related pathways that are not in other multis. Use of this multi allows the active folates to be given separately, so that people can adjust their dosages separately from that of the multi. The cost is reasonable.

    This formula does have some disadvantages as well, in my opinion. It lacks copper and iron, which are essential nutrients, and which are deficient in some PWMEs, but which are also capable of promoting oxidative stress if present in excess as free ions. This formula is also rather low in some of the other essential nutrients. Thus, it would be wise to test for levels of vitamins and essential minerals and add appropriate supplements if some are low (see below).

    This formula includes some folic acid and some cyanocobalamin, which I do not prefer.
    Folic acid is not utilized well by some people, and it competes for absorption and transport with the active forms of folate. Cyanocobalamin contains cyanide, but the amount in this multi should be well dealt with, especially since so much more hydroxocobalamin will enter the blood with this protocol.

    The fact that this formula includes several extra nutrients can be a disadvantage for some PWMEs who have sensitivities to one or more of the ingredients, and thus are not able to
    take the formula. These people will need to explore other alternatives for covering possible deficiencies in vitamins and essential minerals, and they may also need some of the additional nutrients that are in this formula.

    I had considered use of the Thorne Basic V supplement, and some people tried it and reported that they did well with it. However, others did not respond well to it, and use of it does not allow separate adjustment of dosages for the active folates, which some PWMEs must limit to very small amounts because they react very strongly to it. Also, this multi does not include some of the helpful nutrients that are in the Neuro Health Formula.

    2. Activated B12 Guard: This was used in earlier versions of the protocol to supply the high dosage of B12 that is needed to overcome the functional B12 deficiency. In the previous version of the SMP, I changed the recommendation to Hydroxy B12 Megadrops taken under the tongue. Several people have reported that this has not been as effective as the Perque Activated B12 Guard, so I am now changing back to that. Perhaps the length of time that the liquid drops are in contact with the mucosa is just too short to allow enough absorption sublingually.

    I had also considered changing the form of B12 to methylcobalamin. Some PWMEs do need to use this form, particularly if their glutathione and/or S-adenosylmethionine are very low. However, use of hydroxocobalamin is a “gentler” approach to lifting the partial methylation cycle block, and many PWMEs need such an approach. Use of hydroxocobalamin also keeps the cells in control of the rate of the methylation cycle, preventing it from being overdriven, which slows the rise of glutathione. So I have decided to stay with hydroxocobalamin as the first form of B12 to try. For people who do not get a response from the SMP within a couple of months, switching to methylcobalamin would be an option to try. Another option would be to try adding some adenosylcobalamin (dibencozide). However, I do not favor raising the overall dosage of B12 very much above 2,000 micrograms per day, and especially not when it is combined with dosages of methyfolate that are much above the RDA range of 400 to 800 micrograms per day. This combination can overdrive the methylation cycle and hinder the rise of glutathione.

    3. FolaPro: This was also used in earlier versions. In the previous version, I changed the recommendation to the liquid MethylMate B, on the basis of convenience, not having to split tablets. However, I have received reports that some PWMEs have a sensitivity to something in MethylMate B. Therefore, I am now changing back to FolaPro. Solgar Metafolin could be used instead, and it is probably less expensive, but it also contains additional additives, including mannitol and magnesium stearate, which may cause sensitivity problems for some people. The function of this supplement in the protocol is to replenish the form of folate directly needed by the methionine synthase reaction, which is partially blocked. This form has been depleted by reactions with peroxynitrite (as pointed out by Professor Martin Pall), and some people are not able to convert other forms of folate into methylfolate readily.

    4. Folinic acid: This is a buffer form of folate that most people can readily convert to other active forms of folate. Its role in the protocol is to supply these other forms while the methionine synthase reaction has still not come up to normal. This is particularly important for making new DNA and RNA for replacing cells. In the early versions of the protocol, Actifolate was used to supply folinic acid. However, it also contains some folic acid, which I would prefer to minimize. Folinic acid can be obtained either in tablet or capsule form.

    5. Lecithin: The role of lecithin is to help with repair of cell membranes, especially mitochondrial membranes, which have been damaged by oxidative stress. I suspect that the damaged mito membranes are one of the main reasons why many PWMEs have found that recovering their energy status is one of the slowest aspects of recovery from ME/CFS. In early versions of the SMP, I recommended phosphatidylserine complex to fill this role. However, the phosphatidylserine component tends to lower cortisol initially, and most PWMEs already have below-normal cortisol. Most lecithin is derived from soy, but for those who do not tolerate soy, lecithin is also available that is derived from sunflower, canola or eggs.

    I have also recommended that if finances permit, it would be preferable to use Smart Youthful Energy rather than lecithin. This is more costly, but I think it would be worth it, for those who can afford it. Smart Youthful Energy is composed of a liposomal form of pure glycophospholipids of the types needed by the cell membranes, including the mitochondrial membranes. This product has the capability to deliver these lipids to where they are needed, unchanged. Unlike other NT Factor products, there are no additional supplements besides the lipids in this product. It is derived from soy, but it does not contain soy protein, and should not provoke any reactions. Use of these lipids constitutes what has been called “Lipid Replacement Therapy,” a trademarked name.
    This approach has been tested by Dr. Garth Nicolson and others, and has been found to be very beneficial in conditions that involve fatigue, including ME/CFS.

    6. Amino acids supplementation: I considered adding this to the protocol, because I have found that some PWCs are depleted in amino acids, but issues were raised by commenters, including the possibilities that this would provoke yeast growth or increased excitotoxicity or ammonia generation. Since I don’t have much experience with supplementation with free amino acids, I have decided not to add this now. Hopefully PWMEs can consume enough protein in their diets to supply the amino acids they need.
    Those who are able to do lab testing will be able to determine their amino acids levels and correct them if necessary.


    I want to add that I have written the above keeping in mind that many PWMEs are not able to do much if any lab testing, largely for financial reasons. However, I do want to note that my preference would be for people to do lab testing before entering upon this protocol, as well as other additional treatments that may be needed, as indicated by the results of testing.

    I particularly favor running the methylation pathways panel that is offered by the Health Diagnostics and Research Institute in New Jersey, USA, and the European Laboratory of Nutrients (ELN) in the Netherlands. This panel will identify whether there is glutathione depletion, a partial methylation cycle block and folate depletion, and thus whether methylation treatment is likely to help. It will also provide baseline data
    for comparison later, to gauge the progress of the treatment.

    If there are problems with the digestive system, I favor running comprehensive stool analyses to identify them so that they can be treated. I particularly like the Metametrix G.I. Function Profile and the Diagnos-Techs Expanded G.I. Panel. If finances permit running both of them, I think it would be worthwhile. If not, I think I would choose the Metametrix panel. It is important to have the digestive system operating fairly well in order for the methylation protocol to work properly, because it is necessary to have sufficient absorption of nutrients and sufficient ability to excrete toxins, rather than recirculating them. Friendly bacteria produce some of the vitamins needed by the body. Also, correcting a “leaky gut” will take a major load off the immune system, which is dysfunctional in ME/CFS.

    I also believe it is helpful to test for deficiencies in the vitamins, minerals and amino acids and augment those that are low. They can either be measured directly, as in the vitamin,minerals and amino acids panels offered by Health Diagnostics or the ELN, or by metabolic-type testing, such as with the Metametrix ION Profile or the Genova Diagnostics NutrEval Profile.

    For people who suspect high body burdens of toxic metals, tests involving feces, urine and hair are available. High levels of some toxic metals can block enzymes in the methylation cycle and related pathways. Chelation treatment may be necessary to lower the levels enough to permit normal operation of this part of the metabolism.

    People who are sensitive to biotoxins and are being exposed to them in their homes will need to correct this situation in order for the methylation protocol to be helpful to them.
    I would particularly refer you to Dr. Ritchie Shoemaker’s website www.survivingmold.com.

    I also want to note that increased excitotoxicity (causing anxiety, insomnia, nervousness and a “wired” feeling) has been reported by many people on the SMP. I believe that this is caused by an initial further drop in glutathione in the brain when this protocol is started. I have suggested that supplementing with L-cystine (not the same as L-cysteine) may help with this. However, people who have a high mercury body burden should not do this, because L-cystine has the potential to move mercury into the brain.

    Best regards,

    Rich Van Konynenburg

















     
  3. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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    Welcome to the Forum. It sounds like you have it worse than me, but I had a flare up of symptoms 3 years ago, and was at my worst ever. Been ill 9 years now. Now I am doing better than ever. Have any of virus(es) tested still active/high? You might want to try to some mild Immune modulating drugs. Vitamin D is cheap and readily available, you might also want to research Low Dose Naltrexone (LDN). I have been on both, and a high dose of Vitamin D for the last 3 years!

    GG

    PS My illness started with Mono also.
     
  4. taniaaust1

    taniaaust1 Senior Member

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    Sorry to hear that you have been not well since a child. With an unusual for you worsening, it may be good idea to have a good doctors check up with blood tests to make sure you havent developed any other issues which you may be currently dealing with eg anemia.

    Sounds that currently that is too much for your body... your ability sounds like it has declined while you were away and now the school stuff is OVER DOING IT. If this is the case trying to do the same level of activity as you are doing right now WILL keep this illness progressing till you have no option but to quit entirely. You need to start to adjust your pacing to what your body is like right now.

    You may need a week in bed or a couple of weeks holiday to allow your body to like catch up with things, if you have been pushing yourself... and then start those studies at a lower amount eg drop 25% of your subjects.
     
  5. August59

    August59 Daughters High School Graduation

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    Have you testing to see if the EBV is active or not and , if so, how active. If you caught mono 15 or so years ago and never recovered I think someone would want to know if infection is in fact still active. Especially since you never recovered because I believe Dr. Lerner has had some patients that came down with mono and defintely felt like they never recovered from the initial bout of mono and several years later were still producing IgM subclass antibodies which is definitely not suppose to be happening.

    They good thing I believe was that they resonded very well to Valtrex (I believe).

    Welcome to the forum and I assure you that you are in good company in finding support will this dreaded disease.

    P. S. - I just noticed that you are from Detroit, MI and Dr. Lerner is in Beverly Hills, MI which is only 25 - 30 miles from where you are. Being that close I would at least encourage you to call the office and sort of interview them. The one good thing for sure that could come out of a visit is getting a proper diagnosis which can be very valuable. Here is the link to his website: http://www.treatmentcenterforcfs.com/index.html
     
    heapsreal and taniaaust1 like this.
  6. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    I am sorry to be welcoming someone so young to the board. You will find a lot of good information here.

    Are you familiar with the subject of pacing - alternating periods of activity with periods of rest? If not, that would be a good thing to learn more about while you are awaiting the methylation pathways panel results.
     
  7. hurtingallthetimet

    hurtingallthetimet Senior Member

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    hello welcome to baord lots of wonderful people : )

    my fatigue gets worse and worse as time goes by...everyone is different though
    take carea nad again welcome
     
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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  9. Faoiseamh

    Faoiseamh

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    Richvank, thank you for the information. I will bring it up with my doctor and hopefully she will run the panel.

    ggingues, I am glad to hear that you are doing better now. :) I am not sure about the viruses, I've had so much bloodwork done and they can't find much. I will look into the Vitamin D.

    Tania, I have to agree with you, I think I am overdoing it. Today I feel a bit better than I have, but I think it's because I did nothing but rest for four days. Otherwise, school exhausts me. I am afraid that I will have to drop two out of my three classes in order to get back to where I was. I'm not sure why I'm worsening... but I'm going to get more bloodwork done this week.

    August59, I called Dr. Lerner's office today but their call line was closed for the day. I am going to call back tomorrow. I believe the last time I was tested the EBV virus was active, but that was a long time ago.

    Little Bluestem, I am not familiar with it, but it sounds like a good idea. I will look into it more. I think that it would be good to pace my school work.

    Hurtingallthetime, I'm sorry that your fatigue is getting worse like mine. I hope it stabilizes soon.

    Heapsreal, thanks for the link. I have most of the symptoms but am hoping still (after all these years) that I do not have CFS. I really hope that I don't and that it's a misdiagnosis.

    Thank you so much for all of your help :hug: This post gave me a lot of great ideas and things to bring up with my doctor.
     
  10. SOC

    SOC Moderator and Senior Member

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    College is very energy intensive. It's not just the walking from class to class -- all the mental energy needed can take a big toll. Also, if you have any form of OI (and many of us do), being upright all day can be problematic. Fortunately, your GP might be able to give you some help with OI issues, if you have them.

    If you haven't read this page (here at PR) about OI, I suggest you give it a look. It might give you some ideas on how to get a relatively quick improvement in some difficult symptoms. http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/problems-standing
     
  11. rlc

    rlc Senior Member

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    Hi Faoiseamh, welcome to the forum, sorry to hear things have been getting worse for you. You say that you have had a lot of tests and they haven’t found much, if you get copies of your test results and post them on the forum there are a lot of knowledgeable people here who may be able to spot some tests that haven’t been done or some important results that have been overlooked. There is a big difference in quality between doctors and a lot of them are very out of date, also a lot of reference ranges for tests have been proven to be wrong and yet the labs have not updated the ranges to the new information, if your doctor isn’t aware of these issues which most aren’t possibly treatable things get overlooked.

    If you haven’t had it done recently I recommended that you get your vitamin D3 levels tested, if you have been sleeping so much you can’t have been getting much sun which is where people get vitamin D3 from. And Detroit is quite far north which means that it has a long vitamin D winter during this time the sun rays are too weak for people to produce vitamin D. Vitamin D deficiency causes fatigue, muscle weakness and pain, brain fog, a weakened immune system and a whole host of other problems.

    I would also recommend that you get your doctor to retest you for all the other things that can cause fatigue, your worsening symptoms may not be your original condition worsening, it may be something new happening that could be very treatable.

    Having the symptoms attributed to CFS doesn’t confirm that you have it because these symptoms are found in so many other common illnesses, so there is still hope that your original diagnosis was wrong. So like I say if you can get copies of your test results from your doctor some of the people here may be able to point you in the direction of other tests that need doing or better doctors to see, which may help you

    Hope this helps

    All the best
     
    August59 and SOC like this.
  12. August59

    August59 Daughters High School Graduation

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    Hey rlc - Wanted to run my reply to her progressive fatigue problem by you as you may know the doctor better than I do. She lives only about 25 miles from Dr. Martin Lerners clinic and felt like that would be an awfully good option for her since she came down with mono and never seemingly recovered. Dr. Lerners main focus is the EBV and he has pretty good record in treating younger, newer patients.

    What I don't know about him is if he does a broad panel blood test to help support his typical diagnosis and if it doesn't support his usual diagnosis, does he look at different approaches to at list get properly diagnosed as CFS if in fact that is what she has?

    Just looking for some feedback because as much as I have heard about Dr. Lerner I still don't feel like I know that much about him.

    Thanks
     
  13. Faoiseamh

    Faoiseamh

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    Thank you, SOC. I am unsure if I have OI, I feel better when sitting down but don't most people? (I don't know...) I will have to look into this. I have noticed that I feel better while sitting down or laying a lot lately, but I think that is due to my overall muscle weakness that has come on for whatever reason.

    rlc, I didn't know that about Vitamin D deficiency. I will have to write all of this down and bring it in to my doctor. I also agree that I need all of the common causes of fatigue retested, I haven't had them done in about two years and I have worsened significantly since then. I am hoping dearly that this isn't CFS. I don't have some of the symptoms, like pain, so that makes me hopeful.

    I have so many lab results that I don't know where to begin, but I will look through them and post some here if I get a chance.
     
  14. Crux

    Crux Senior Member

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    Hi Faoiseamh;

    I think the Methylation Protocol is worth some consideration, because it emphasizes B12 and Folate---very helpful for fatigue and cognitive function, memory, etc. ( I wish I would have taken it when I was in school....).
     
  15. SOC

    SOC Moderator and Senior Member

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    I second the vitamin D. I feel much better when my vitamin D levels are at the high end of normal. It's easy enough to get vitamin D levels checked and bring them up if needed.
     
  16. rlc

    rlc Senior Member

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    Hi August59, I not sure how extensive Dr lerners testing for other diseases is, I think there are some of his patients on the forum, maybe they could advise on this. I not aware of him ever saying anything about finding very high misdiagnosis rates that some of the other Doctors like Dr Hyde find, so it does make me wonder how extensive his testing is. I have seen the testing that is done by some of the other CFS doctors to rule out other diseases and been very unimpressed with them.

    My feeling is that it looks like Faoiseamh,s doctors hasn’t even tested for the most common cause of fatigue in western countries vitamin D deficiency and there is probably some other things that should have been tested for that haven’t been. So my opinion would be to start with looking at what testing they have had done, and see what has been missed and if there is anything that has been missed by relying on out of date reference ranges first.

    If that doesn’t turn up anything useful then Doctor Lerner would probably be a good next step to see if there is some kind of persistent viral infection going on that may respond to treatment. But it is also possible that the stress of the previous EBV infection has triggered some other underlying health problem and EBV is no longer a problem.

    I gather he is very expensive so I feel it would be best and cheaper to get a normal doctor to run all the basic tests first, and then see Dr Lerner if nothing is found.

    Sorry I don’t really have the answers on Dr Lerner’s testing protocol, but I’m sure there are some of his patients on the forum who could provide the information you want.

    All the best
     
  17. rlc

    rlc Senior Member

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    Hi Faoiseamh, Vitamin D deficiency is very common and can be extremely debilitating, it was wrongly named a vitamin way back, but it is actually a hormone, and if you have been sleeping a lot and not been in the sun you are very likely deficient.

    When you see your doctor ask them if they will do these tests, they will show up the most common causes of the kind of fatigue you are experiencing.

    Vitamin D3 (has to be the D3 test the other test for D2 is of no use for testing vitamin D levels)
    B12
    Folate
    Full iron studies
    TSH, T4, T3,
    Celiac test, ( you have to be eating gluten containing foods for at least a month before doing this test or it may give a false negative)
    Morning Cortisol
    Glucose Fasting
    ANA
    CBC (complete blood count)
    CMP (comprehensive metabolic panel) this contains a whole lot of tests see http://en.wikipedia.org/wiki/Comprehensive_metabolic_panel including tests for liver and kidney problems and it tests for calcium which is important to have tested if you have to take vitamin D, because it will show if you have any of the diseases that you can’t take vitamin D with.
    Cholesterol
    Triglycerides

    Phosphate
    Urine analysis
    Homocysteine
    Oestrogen
    Progesterone
    Testosterone
    FSH (follicle stimulating hormone)
    LH (luteinizing hormone)

    ESR
    CRP

    CK (Creatine Kinase)
    C reactive protein
    IgA, IgG, IgM (these tests will show up hidden inflammation, allergies or infection)

    It would be a good idea to retests EBV and test for other common infections like CMV, if you have had possible exposure to lyme disease get that tested, or possible exposure to the likes of Hep C and hep B, HIV get them tested.

    These tests will pick up most of the common causes of Fatigue, or lead to further tests to find the cause, it may seem a lot but if your doctor is taking you seriously they should be happy to do them maybe not all at once, but over a couple of appointments if nothing shows up on the first round of tests. The reference ranges used by most labs for TSH, B12 Glucose and vitamin D are wrong so post your results and people will help you with that.

    On this page is the new ME primer that contains information on other additional tests that can be done to rule out other disease, and what other possible diseases that can cause these symptoms are, if you have a doctor who doesn’t seem to know what they are doing get them to read it see http://www.iacfsme.org/Portals/0/PDF/PrimerFinal3.pdf

    I would advise making a double appointment with your doctor and make sure that they give you a full physical. It’s very easy when feeling sick and tired to go to the doctors and either forget what it was you wanted to talk to the doctor about, or get distracted by what they’re saying, so it helps to prepare before you go, write down all your symptoms and rate them on a scale of one to ten if you can, and times when they get worse or if there is anything that makes them worse, write down your family history of illnesses going back as far as you can, write down any overseas travel that you have had in case you have a foreign illness that the doctor won’t think of unless you tell them where you have been, any possible exposure to infections or environmental poisons you may have had e.g. heavy metals, toxic chemicals, mould etc and any medications or supplements you are on. And really tell them how terrible you are feeling and how badly it is affecting your life, if you don't make a fuss they are likely to ignore you. If your doctor hasn’t been overly helpful in the past take a support person with you, doctors behave better when they know someone else is watching them, and take pen a paper to write things down the doctor tells you so you don’t forget. If you don’t feel that your doctor is very good or helpful just get another one there is a vast variance in the quality of doctors.

    If these tests and any others that the doctor orders don’t find a cause for your suffering, then it may be worth going to doctor Lerner he from my understanding will do a lot of tests for different viruses, but I gather he is very expensive, so personally I think there is no point in spending a large amount of money to see him until you have more basic testing done which you can get a lot cheaper from a normal doctor. And which may diagnoses your condition.

    Like I say when you have the time if you want to post previous test results there are a lot of kind, knowledgeable people here who will do their best to help you.

    Hope this helps

    All the best
     
  18. Faoiseamh

    Faoiseamh

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    rlc, I have had those tests done in the past (most if not all, I'll have to look through my old tests), but not in the past year and a half or so. I am thinking of having them redone just because my symptoms have been worsening, thank you for making a list for me. I went to the Cleveland Clinic a year and a half ago and they pretty much examined me from head to toe and couldn't find anything. Because of this, I am disheartened, but it makes sense to have them redone as my symptoms are getting worse.

    Thank you for your post, it's really helpful. I will definitely bring my mom along to the doctor's as I'm not always the best dealing with doctors. I also didn't know that about the reference ranges, I'll post my test results.

    I'm hoping they'll find something this time around. That would be great.
     
  19. August59

    August59 Daughters High School Graduation

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    The Mayo Clinic in Rochester, MN treats potential CFS people the exact same way. 2 weeks of serious testing and then don't tell you a thing. I'm sorry you had to experience that too. I think all the big clinics treat CFS that way.
     
  20. redrachel76

    redrachel76 Senior Member

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    My biggest mistake was not resting when I first got mononucleosis at age 15 and just carrying on. I had a remission after a big rest of 6 weeks and then went back to school and it came back at age 16. I remember at 17 and 18 feeling bad and resting seemed to help more than it does now but I stupidly chose not to rest and to carry on and study. Every doctor always told me to carry on or just rest a week.

    If I were in your shoes I would pack up college for a very long time - even months, rest a lot and sort out my health until I got into in a proper long remission. People and doctors are often scared to give the advice of stopping college/work for a very long time in this illness. Maybe they do not want the resposibillity but that is what I wish I had done.
     

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