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Methylb12 and adrenal fatigue?

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

  1. Anteah

    Anteah Senior Member

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    Hi, I just started on MethylB12 Jarrow lozenges and feeling as though my adrenal fatigue symptoms are coming back. Does mb12 stimulate the adrenals? Does it mean I need a smaller dosage? I would hate to overstimulate my adrenals, because I've been doing better lately on avoiding all forms of stress as much as possible and wouldn't want to go back and undo that. ANy advice would be greatly appreciated!
  2. xrunner

    xrunner Senior Member

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    There was a time when methylb12 made me feel overstimulated, cause insomnia e subsequently crash. At the time I found hydroxyb12 more relaxing and helpful.
  3. Anteah

    Anteah Senior Member

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    OK, I see, so I probably should cut the dose pretty dramatically then, and see how that works for me. Thanks for much for clearing it up for me, it helped a lot. Do you also know if Methylfolate stresses the adrenals as well or is it relatifvely safe in large dose amounts?
  4. Ema

    Ema Senior Member

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    The B vitamins, particularly methyl B12 and methylfolate, are vital for proper adrenal functioning. Many doctors would recommend a good B complex as well as extra B12 in particular to treat flagging adrenals. I certainly don't see those nutrients as counterproductive. In fact, increased methylation should only help with adrenal function.

    Have you had a saliva cortisol test? Are you taking anything to support your adrenals now?

    Freddd writes often about start up effects with the B12 protocol. You might want to go back and read through those threads. What dose did you start on?
  5. Anteah

    Anteah Senior Member

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    Hi, Ema! Thanks for responding. No unfortunately I have not ever had any tests, I am uninsured and sort of poking in a dark, going by feel so to say. I honestly can say that I feel as though I have high cortisol levels most of the time since when I take Phosphodylserine, which is an ACTH damepner I feel much, much better, minus the slight depression it brings me, but as far as anxiety is is a true miracle.

    I take Michael's Lab Adrenal Support, and has been doing well on that, but find anything over 3 pills a day overstimulating, even though 3-4 per day is a serving size. I did read Freddd's posts about the start up reactions and quite frankly i was really scared as to what mine may be, but besides some muscle pain (nothing serious i can still work) and extreme energy increase (overstimulation) I have not experienced much.

    I took 1000mcg yesterday and woke up today feeling "adrenal symptoms" as if I pushed myself way too hard the day before. Same feeling I get when I'd eat casein containing products, which i am severely intolerant of. So not sure, what's going on, but thinking to slow down to a 1/4 of a pill and see how i do on that. It makes sense that B vitamins are important for healthy adrenals, but mine are faaaar from healthy, i am thinking even that I was probably born with weak ones, so chances are that I got to start much slower then some other folks.

    Anyway, thanks for your suggestions. I'll keep seeing how it goes, and like you said will go and delve into the B12 threads some more.
  6. jeffrez

    jeffrez Senior Member

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    I feel that way from mb12 often, too. I thought I read somewhere that b12 can tax adrenals, but many ppl have told me that they don't believe that's the case.

    Lowering the dosage would obviously be something to try, as well as switching forms to hydroxy b12 as xrunner suggested. If you suspect adrenal/hpaa/cortisol problems, a salivary cortisol test would be a really good investment, imho. It can really show what's going on not only with cortisol, but with DHEA, too, and possibly even pregnenolone (not sure all labs test that).
  7. biophile

    biophile Places I'd rather be.

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    In the beginning I found that methyl-B12 (Jarrow) may have a mild stimulant effect. But I was able to build up a tolerance. It is the methylfolate and folinic acid that I have more trouble tolerating. Re the HolisticHeal drops, I had the hydroxy-B12 drops last year, and when I applied them daily sub-lingually, an ulcer eventually formed on the area where the drops were landing (probably the additives), so I just switched to diluting them in liquid which seemed to avoid that problem.
  8. adreno

    adreno 3% neanderthal

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    MB12 or MF won't overtax your adrenals. Many people do feel wired on high doses of it, though. Just reduce the dose until it's tolerable.
  9. iacyi

    iacyi

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    Taking hydroxo and particularly methyl B12 (Enzymatic brand) I started experiencing worse fatigue, sleeping more in the day and struggling to get back up, feeling woozy. Switching from Enzymatic to Jarrow seemed to make things slightly better, but I've since read Jarrow may now be weaker.

    Recently I switched back to Enzymatic at 2mg a day and started crashing hard again. Upping methylfolate to ~5-6mg per day has taken the edge off (I react badly to folinic). Also I've just dropped the mB12 to 1mg which seems to have helped.

    The fatigue, drowsiness, nausea etc. seem to fit with 'adrenal fatigue' based on past experience with hydrocortisone. Though I also experienced some unsteadiness and clumsiness, which seem to be alleviated by taking mfolate. Still figuring it all out...

    Edit: I started having back pain on the day I made this post. I'm concerned it could be spinal inflammation from not dropping my folate with the B12... Don't want to give anybody any bad ideas.
  10. Ema

    Ema Senior Member

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    The good news is that you can order a saliva test yourself through ZRT/Canary Club for about $125. Most insurances won't cover saliva testing anyway so that may not be a huge impediment. I would highly suggest saliva testing because high and low cortisol have a lot of overlap in symptoms (anxiety can also come from low cortisol) and it is really hard to know what is going on without it. Just make sure to stop the PS and adrenal supplement for two weeks or so if you want a good clean baseline.

    I just looked up this product and it contains licorice which will potentiate the effects of cortisol in your system by keeping it from breaking down as quickly. The other ingredients are adaptogens - ginseng is generally stimulating to adrenals and ashwagandha can help with either high or low cortisol. It's kind of a kitchen sink formula but certainly not the worst of the ones that are out there. But it does seem more skewed towards low cortisol than high.

    Certainly some people have to start with crumbs of the B12...hopefully Freddd's threads can help you figure out your dosing. I am still working through all that myself trying to figure out optimal doses...
  11. Anteah

    Anteah Senior Member

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    It looks like everyone responds so different to Methyl-donors. Perhaps those of us with weaker adrenals to begin with get the grunt of it as far as the adrenal symptoms go when starting? It sure is confusing. I am hoping to be able to start doing some testing, but I am working with such a minimal amounts of money that I have to pick my battles. Have been saving for Yasko test for a while, which is pretty pricey, but I feel like I have to know what all I am dealing with, because I've been taking this and that supplement and dropping and adding different foods for almost 10 years now with a very slow progress, so maybe it is a somewhat naive thinking, but I really hope that her test will explain what all that's going on in my body. Have you guys done that test or considered doing it? Do you think it's worth it?
  12. richvank

    richvank Senior Member

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    Hi, Anteah.

    If money is limited, I would suggest first running the Health Diagnostics and Research Institute methylation pathways panel to find out if you have glutathione depletion and a partial methylation cycle block. If these are present, a methylation-type treatment (including forms of B12 and folate) are likely to help you. This panel costs $295 and requires an order from a physician or a chiropractor. It is a blood test, so it also requires going to a lab to have your blood drawn.
    Here is the contact information for this panel:


    In the U.S., the panel is 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, or you can use the interpretive guide below:


    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)
  13. jeffrez

    jeffrez Senior Member

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    With all due respect to Yasko & richvank, when money's an issue I wouldn't bother with the methylation panels, tbh. Yes, they might provide some info to you, but then what? Then you just do the methylation protocol or a variation anyway, usually based on symptoms.

    I think esp. in a case where money's an issue and you suspect HPAA problems, the salivary cortisol testing is a *much* better and more useful option. You can really make good ground knowing what your cortisol patterns are doing, whereas - again - w/the methylation panel results you'll basically just be doing the same methylation protocol steps as you likely would w/out the test - and would be saving a whole lot of money.

    If someone had unlimited funds, I would say definitely go for the methylation panels. The more info the better, of course. Treatment is likely to be the same regardless, though, so why not save money that could be put to much better practical use on ASI panel & actual treatments. JMHO.
  14. Anteah

    Anteah Senior Member

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    Everyone, thanks for your suggestions! I will try to stick to mb12 and folate and see how i do. Not sure why i got so stuck on thinking i need to do Yasko test, but from reading their forum it just seemed as though the treatments they are doing vary greatly (in detail) one to another based on their knowledge of their genetics. Not sure if they have had better results with those treatments or not though.
  15. madietodd

    madietodd Senior Member

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    I did both methylation tests, and also adrenal saliva testing. Both methylation tests showed that I had a not-severe methylation block. I've done methylation protocols for over a year, switching out supplements and types of B12, and have seen no results.

    It would be much cheaper to just do Rich's protocol for 3 months and see what happens, than to test. You need a doctor, natropath, or chiropractor to order the New Jersey test, and Yasko can't send her test to certain states (mine is one of them).

    The saliva testing showed that my cortisol is at the top of normal at night, but nobody has ideas about how to bring that down. So far, I haven't figured out a way to use that information to improve my sleep.

    If you get the saliva testing, I advise doing the $179 test, where you provide 4 samples, so you see your cortisol curve through the day.

    Madie
    jeffrez likes this.
  16. Ema

    Ema Senior Member

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    Have you tried melatonin, phosphatidyl serine, holy basil, schisandra or the like for the high cortisol at night?
  17. Anteah

    Anteah Senior Member

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    Tried GABA and 5-HTP (not Melatonin). Also tried PS, works pretty good, but gives depression at higher doses and causes that weird left front ventrical headache kind of pain and depressed breathing. Never tried the other 2, probably should, but unless they are in some sort of one label concoction I just cant afford getting that many separate supplements, that's my biggest issue, unfortunately, and that's why I guess I thought that if I get genetic test it can tell me what all that I should use as far as supplements and what is counterproductive. Probably just wishful thinking, because I see people on their forum struggle just as much trying to find the answers and protocol that is right for them. No shortcuts in CF world i guess :).
  18. roxie60

    roxie60 Senior Member

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    I'm on MB12 sublingual and feel nothing, been on it since April and B+ vitamins. I wsa hoping it was going to be my silver bullet. My cortisol is way to low in the AM and a little too high evening (falls with in range betwen 12N and 6PM which is th time frame I can function).
  19. biophile

    biophile Places I'd rather be.

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    A long time ago I had a RBC Zn test to rule out zinc deficiency causing bizarre symptoms after 20 sessions of IV CaEDTA treatment. However, I was already taking 40-80mg Zn (elemental) per day for about 6 weeks before the test but after cessation of said chelation treatments. The result was within normal range so I stopped taking zinc. Do you think I took enough zinc to interfere with the test? I still sometimes wonder if I have a zinc deficiency, unfortunately I seem to have developed a sensitivity to zinc even in relatively low doses.
  20. jeffrez

    jeffrez Senior Member

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    P5P, the active form of B6, can lower cortisol. P5P also won't be likely to have the long-term HPAA effects that PS can have.

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