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New to the simplified protocol... pretty severe reaction - Can anyone help?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by treefrog, Mar 15, 2012.

  1. treefrog

    treefrog

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    NJ, USA
    Hello all-

    Yes, I've been dealing with chronic illness for many years... (over 10 under 20 years) Also known as CFS, Fibromyalgia, Lyme, what have you.

    Anyway, I tried to study as much as I can but I'm not a scientist. I tried many things over the years. I heard some good things about the methylation protocol & decided to try it.

    At first, I did the new protocol every other day. After about 2 weeks, I upped it to every day & by about the 3rd week I was floored. The symptoms were increased back pain & general pain - mostly in my ribs, shoulders & lower back, malaise, fatigue, insomnia, & a bad migraine like headache.

    I don't know if there are many doctors in my area (northern NJ - USA) but I have been doctor-less for at least the past 3 years.

    I feel like this is definitely hitting something & I'd like to explore it further but I don't want to become totally incapacitated or make myself worse. It's kind of scary doing this stuff on my own so I can use any help or suggestions. I would be open to trying a doctor who understands the methylation approach. I just don't know how to find one.

    I haven't had any recent testing done so, I can't reference that. Is this important at this point since it seems that I have "provoked a response"?

    I did visit the Fibromyalgia & Fatigue Center about 5 or 6 years ago - so, I do have some ideas of what is happening. They didn't get into methylation back then & I ultimately felt my time & lots of money there was a waste. That's when I sort of took matters into my own hands.

    It just seems that if I got this big effect from 3 weeks of the new simplified protocol - I must be on to something. How should I proceed?

    Best wishes to all of you!
     
  2. illsince1977

    illsince1977 A shadow of my former self

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    Sorry I have nothing to help. Just wanted to say welcome!
     
  3. chilove

    chilove Senior Member

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    HI there,

    Are you taking extra potassium? Read the threads here about that.. that could be your problem if you aren't taking enough.

    It would be helpful if you listed out everything you are taking.

    Best to you!

    Audrey
     
  4. richvank

    richvank Senior Member

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    Hi, treefrog.

    It does sound as though the simplified methylation treatment is interacting with your illness. I would suggest taking it a little more slowly, such as by skipping days or taking smaller dosages. One way to find a physician familiar with this is to contact the Health Diagnostics and Research Institute, also in New Jersey, and ask them for names of physicians near you who order the methylation pathways panel. I think it's best to be monitored by a physician when on this type of treatment. I hope this treatment ends up helping you.

    Best regards,

    Rich
     
  5. merylg

    merylg Senior Member

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    Hi treefrog,

    I also get some pretty severe reactions on the Methylation protocols (both the SMP & Freddd's). After many months of trying to work out what was making me feel so ill ...and it's not low potassium as I have had that tested at least twice close to the symptoms manifesting...

    I have worked out that I react to Methyl B12 and Methylfolate (Solgar Metafolin) ...singly or together.
    I am not sure if it is an intolerance reaction, allergic reaction or toxic reaction.

    I DO know that I eventually built up huge levels of serum B12, serum folate & red cell folate. Not sure how these levels relate to continuing on a methylation protocol.

    Maybe it has something to do with some problems I am having with my liver??? Not sure.
    I have played around with lowering doses but I still get the same reaction, usually overnight, worse by morning ; nausea, malaise, dehydration, toxic feeling, shortness of breath, un-refreshing sleep.

    Another possibility is that I need to remove myself from a toxic environment first! :eek:
     
  6. treefrog

    treefrog

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    Thank you for your replies!

    This is what I was taking:

    Neurological Health Formula - 1/4 pill

    Megafolinic (Source Naturals) - 1/4 pill (200 mcg)

    Molybdenum - 250 mg

    Phosphatidylserine Complex (Country Life) - 1 pill

    Neuro-PS (phospholipid complex from soy lecithin) (standardized at 20% phosphatidylserine equal to 100 mg)
    which typically provides: 500 mg *
    Phosphatidic Acid *
    Phosphatidylinositol *
    Soy Phospholipids & Glycosides *
    Phosphatidylcholine *
    Phosphatidylethanolamine

    MegaDrops - Hydroxy B12 - 2 drops

    MethylMate B - 3 drops

    ----

    I also take some other supplements like Olive Leaf Extract, Oil of Oregano, diflucan (on occasion), etc. (for yeast), homemade liposomal vit. C, chlorella... None of these things gave me a strong reaction. I have taken them for a while prior to the simplified protocol (SMP).

    I also treated for parasites for about 2 years prior to going on the SMP. I have also tried treating Lyme with antibiotics for about 9 months & the non-salicilic acid protocol for Fibro (many years ago). These didn't have much of an effect either way. The anti-parasite herbs & drugs did have a big effect but it hasn't been a cure.

    I tried alot of other treatments, physical therapy, biofeedback, etc. over the years. I try to stay away from drugs like anti-depressants but pain meds have been quite helpful. They are not easy to get these days even though they can be quite effective - so, I'd like to get rid of the pain if at all possible. I don't like taking mind altering drugs if I can avoid it.

    I'be been trying to loosely follow Dr. Klinghardt's protocol but I have not tested KPU/HPU. I read that it was suggested to do that prior to the methylation protocol. Any advice regarding that issue? Would it be better to start with KPU first?

    Thanks for the info about the research group in NJ. I will look into it! It's just that I spent alot of time & money on doctors & got nowhere. I started studying this on my own & I feel I made some progress. The methylation protocol is quite complicated - so, I think I need help. Especially, since it seems to be activating something...

    The other issue is that I had tests done for mercury & they were quite low - to my suprise. I feel I may have a metal toxicity, though. I studied sculpture & was exposed to aluminum & bronze. I've also had jobs workng with pesticides, printing inks/solvents, & darkroom chemicals. So - even tough I tried to have a good diet, I was exposed to alot of toxic stuff in the past.

    ----

    Any suggestions will be appreciated! I will look into them.

    Have any of you tried any energetic testing for this protocol? Has it helped?
     
  7. treefrog

    treefrog

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    PS - re: Another possibility is that I need to remove myself from a toxic environment first!

    Yes, this is very significant! I recently moved into a place that I think has high EMFs. I have gotten worse since I have been here. I can't move again right now - so, I'm trying to deal with it as best as I can.

    Any suggestions about how to mediate for EMF exposure would be appreciated. I have tried "earthing" with a ground wire but I'm not sure if it helps.
     
  8. treefrog

    treefrog

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    Not to be obnoxious but I found this info...

    http://www.prohealth.com/library/showarticle.cfm?libid=16138

    3. The best methylation test (the one we used in our study) is simply called a "methylation panel" from Vitamin Diagnostics Lab in New Jersey. [Now Health Diagnostics and Research Institute, phone 732 721-1234]. It runs about $325 for 11 measures of methylation chemistry, so it would be cheaper to just start the protocol, which is what I advise. I don't typically order the panel unless the patient is not responding to it adequately, so we can figure out what they are missing.

    -----

    Does anyone know if this includes suggestions of what to take like I read that the Yasko panel does. I probably need some professional advice but I haven't gotten to calling around about all of this yet.
     
  9. richvank

    richvank Senior Member

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    Hi, treefrog.

    No, it doesn't, but here is a guide for interpreting it:

    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-THF, this mechanism depletes the cells of folates in general.

    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), 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)

    Best regards,

    Rich
     
  10. treefrog

    treefrog

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    Great! Thank you. I like trying to understand this stuff on my own - if possble. I'll look it over tomorrow. It saves some money over the Yasko testing. I'm not sure if I need a doctor's recommendation to get the test. I'll check into it on Monday.

    Thanks!
     
  11. richvank

    richvank Senior Member

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    Hi, treefrog.

    Yes, you need an order from a physician or a chiropracter, and the test can't be ordered from New York state. Here's the contact information:

    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

    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.

    Rich
     
  12. treefrog

    treefrog

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    Thanks, again. I'll have to give them a call on Monday to see if they can recommend someone to work with on this. Judging from my reaction - it seems like it is something that may help me to address it further. I've done some reading on it but I didn't want to attempt it due to lack of money... It may really help, though. I'm tired of being ill.
     
  13. Hanna

    Hanna Senior Member

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    Jerusalem, Israel
    Hi Rich,
    Sorry if the question was asked before, but I'de like to know if it is advised to stop all methylation supplements before testing, and for how long. (I've been taking methylation supps for a year now but didn't test for partial methylation block),
    best
    Hanna
     
  14. richvank

    richvank Senior Member

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    Hi, Hanna.

    It's O.K. to stay on the supplements. In the clinical study that Dr. Nathan and I carried out, the patients continued to take the supplements as they reran the panel every 3 months, and the results we got were well-behaved in terms of how they varied over the nine months, and how well they reflected the condition of the patients. The important parameters on the panel are not sensitive to whether supplements are taken at the time of testing.

    Best regards,

    Rich
     
  15. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    In general, the people I've seen who've not been able to tolerate Rich's protocol are all living in quite moldy environments.

    Toxic mold seems to be a much more problematic factor in this disease than EMF's, from what I can tell.
     
  16. treefrog

    treefrog

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    Sometimes I wonder which came first - sensitivity to mold or inability to detox properly...?

    I felt better down south where it's actually drier than in NJ... (I lived there for a few years) It's quite damp here. If it's a mold issue, I'd probably have to move to a place where its dry & there are different types of plants & trees. I don't think the house where I'm living has a mold problem - it could be leaf mold outside.
     
  17. treefrog

    treefrog

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    PS - Dr. Klinghardt feels EMFs are a large part of illness. There was a study of yeast growth in high EMF environments - it really flourishes in high EMF exposure. I'm sure it's the case with other pathogens. Combined with inability to detox properly - I'm sure it makes sensitive people ill. There have been correlations between cancer & yeast... Not to mention cell phone use & brain cancer.
     
  18. treefrog

    treefrog

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    Another question...

    I feel like this is working! I'm really happy about that even though I got kind of ill. Is it really necessary to kow the specifics of what I may need to address by testing? Does it help to know all the specifics or can I just continue with the SMP?
     
  19. treefrog

    treefrog

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    I did some checking around & it will cost about $1000 to get the test done & have the doctor evaluate it. They charge $400 an hour + the state makes everyone get a physical for $175. Then, they charge $75 for the blood draw... sheesh. A bit much, isn't it?

    Does this test cover the kind of genetic things that the Yasko test evaluates for? I'm not real familiar with them but some people have to do different combinations of things to treat things like excess sulfur or ammonia or deficient potassium which some people are mentioning.

    I'm pretty tapped out financially. Everything is so expensive... I know the doctors like to give you these huge lists of expensive supplements to take. If it does turn out to be metals - I'll have to deal with that, as well. Not to be complaining.... I'd like to get well but how does one afford all of this? I'm too ill to work but they wouldn't give me a disability, either. It's not easy.

    Thanks to everyone for your help!
     

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