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Measuring Cardiac Output (Cheney / Peckerman research)

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by Searching, Mar 28, 2012.

  1. Searching

    Searching

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    Hello everyone,

    I am currently being evaluated by a cardiologist who has had no idea what is causing my cardiac symptoms.

    I found this article: http://www.dfwcfids.org/medical/cheney/hrt04lng.htm and strongly believe this is my situation. That is, that my cardiac output is severely limited upon standing/exertion.


    My question is: What test should I ask my cardiologist for, and how specifically should it be done?



    The article linked above states that an Impedence Cardiograph test should be done, and it should be done both lying down and upright (and if permitted, on a tilt-table at angles in-between horizontal and vertical)

    It also states they used a specific formula (thoracic algorithm) to calculate, one that was developed by the university of Minnesota. To quote directly from the above link:

    "The University of Minnesota algorithm has been approved by the FDA as a valid measurement of Q. The point is that Medicare pays for this. It's been clinically validated by a government agency and is not considered experimental or researchas long as you use this algorithm. That's important, because whenever this test result filters back to a cardiologist, the first thing many say is, well, but, you know, that's not accurate. And indeed, it may not be accurate, depending on the machine and the algorithm it uses."



    So can anyone please weigh in on this? I feel that this can truly be a huge step forward for me if it is done properly.

    I've searched this forum and have found that other names / terms being used for this test can be:

    - Idiopathic Cardiomyopathy test
    - Impedance plethysmography
    - "BioZ," for biologic impedance

    as per this thread: http://forums.phoenixrising.me/showthread.php?340-cheney-heart-test-name-!




    So how do I ask my cardiologist for it, and how do I specify the proper algorithm / patient positioning, etc. ?


    Any and all help is very appreciated. I would consider it a huge bonus if anyone has had this test done and can share their expertise with me, but I'll take any reply I can get. Thank you in advance.
  2. anciendaze

    anciendaze Senior Member

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    I have to warn you that referencing Dr. Cheney may not help you with Medicare. He has good evidence for his beliefs, but he is still written off as a nut by far too many officials. The research by Peckerman and Natelson has been out there for years without great impact.

    You may have luck with the approach you have outlined, but it will not be easy. Another avenue is echocardiography. The problem to look for is diastolic dysfunction in the left ventricle. Most likely, you have a type 1 diastolic dysfunction, not actual heart failure. Generally there are no visible structural changes in the left ventricle, though if the problem has persisted there may be remodeling of the atrium. What is apparent, when careful measurements are done, is that injection fraction is reduced, while ejection fraction is not. Either will lead to reduced cardiac output, Q. Another observation indicating a problem is E:A reversal.

    There are authoritative papers on the seriousness of diastolic dysfunction in NEJM, here's an example. Beyond immediate consequences of cardiac insufficiency there may be later problems like atrial fibrillation or mitral valve anomalies.

    It is important to emphasize that this is not classic systolic heart failure, and not associated with typical risk factors like hypertension and diabetes. Published papers indicate that this may kill you, where the important word for officials is "may". There is strong resistance to admitting the existence of any problem which costs more. I have the impression of dealing with people who would prefer that I push myself into collapse so statistics could be published in some journal of idiopathic mortality while they ponder a decision.

    Note: I am not a doctor, and cannot give authoritative personal medical advice.
  3. Searching

    Searching

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    Hi Anciendaze,

    I really appreciate your reply. You have so much knowledge, I will be reading the links right away, trying to get it all to sink in.

    I wanted to write back to explain my situation a little better, so that maybe you could guide me in the right direction.

    First off, I should have said that I'm in Canada, so no need to worry re: Medicare.

    My situation is as follows:

    I had an Echo done, then a 2 week loop monitor.
    I did the loop, got a phone call telling me to go in for a 48 hour holter.
    Then, I got a call telling me to do another 2 week loop.
    Then, I was called for a follow-up

    Was told there was something going on, but they didn't know what to do. So I got a beta blocker, with instructions to visit again in 2 months.

    So I was reading up on what I could find, and found Cheney's interview that I posted above, and thought I might finally have some sort of validation of my condition.

    As it is, my heart rate sitting is 115-140, standing is 145-185 beats per minute. I've got really bad OI/POTS symptoms. Tons of palps daily. Lots of drops and rises in blood pressure, and significant narrowing as well. No diagnosis has been made. My hands and feet also get terribly hot, red, inflamed (for no reason, and really quickly), requiring cold compresses. I also get nausea, dizziness, vision trouble, etc. I also get this odd metallic taste in the back of my mouth/sinuses when I feel worn out, like I'm about to pass out. I assume it's all related to the heart?

    I would just like to see a test show that if I do indeed have inadequate cardiac output, that maybe I can be treated with something like Enhanced External Counterpulsation.

    I'm not looking to prove anything to anyone, I just want to get to the bottom of what is wrong with my heart, and hopefully be able to do something, anything, to help myself out of this situation.
    I've read from multiple sources that my best chances of recovery are within 2 years of onset of symptoms, so I am going to go all out on this to give myself a fighting chance.

    Any advice would be greatly appreciated. Thank you (and sorry about the lengthy posts.)
  4. richvank

    richvank Senior Member

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    Hi, Searching.

    I think that Anciendaze gave you good information. Several years ago Dr. Cheney (based on the work of Peckerman) was promoting the use of impedance cardiography. I saw several results that people with ME/CFS sent me, and that method did seem to give accurate results. Later on, Dr. Cheney got a state-of-the-art echocardiograph machine, and he has focused on using that rather than impedance cardiography in recent years. Using a doppler technique, he focuses on measuring the IVRT, which stands for isovolumetric relaxation time. The IVRT is an interval in the cardiac cycle that extends from the time of the closing of the aortic valve to the opening of the mitral valve. In a normal, healthy person, the IVRT is about 70 milliseconds or so. If a person has diastolic dysfunction, which Dr. Cheney reports that he finds in nearly all his patients, the IVRT becomes significantly longer. The reason for this is that during this time interval, the heart muscle around the left ventricle (the main pumping chamber of the heart) is relaxing, so that the left ventricle can expand and take in a new batch of blood. The rate at which this muscle can relax is limited by the supply of ATP from the mitochondria of the heart muscle cells. So if there is mitochondrial dysfunction, and the rate of supply is low, then the heart muscle will relax more slowly than normal, and the IVRT will be longer than normal. The result is that the left ventricle is not able to fill completely during the time interval available before the next contraction, which is set by the internal cardiac pacemaker. The result is that the stroke volume, and hence the cardiac output (blood pumped out per minute by the heart) is lower than normal.

    In the GD-MCB hypothesis that I have proposed, the mito dysfunction results from glutathione depletion and a partial methylation cycle block. This is so far an unproven hypothesis, and Dr. Cheney has different views about the cause of the mito dysfunction.

    Another part of the problem in ME/CFS is that the total blood volume in the body is often quite a lot lower than normal. This results from central diabetes insipidus (not to be confused with diabetes mellitis, which involves blood sugar and insulin). Central diabetes insipidus is caused by insufficient secretion of antidiuretic hormone (also called vasopressin) by the hypothalamus/pituitary. The result is that the kidneys excrete too much water from the blood into the urine, and the daily urine volume may be much larger than the normal average of 1.5 liters per day. The person experiences constant thirst, and drinks more fluids than normal, but is unable to keep up with the loss into the urine, so the total blood volume remains lower than normal, and the person has hypovolemia. This causes the flow of blood back to the heart (venous return) to be lower than normal. Since the heart can only pump out as much blood as it receives, this is another factor in ME/CFS that causes the cardiac output to be lower than normal.

    In the GD-MCB hypothesis, the low secretion of antidiuretic hormone is caused by glutathione depletion in the hypothalamus and pituitary. This is so far an unproven hypothesis.

    There is also one more factor that impacts the circulation in ME/CFS, and that is the dysfunction of the HPA axis. Normally, the HPA axis plays a role in regulating the blood pressure. When it becomes dysfunctional, as in ME/CFS, the blood pressure usually drops lower than normal. When this is coupled with the low total blood volume and the diastolic dysfunction, as described above, this combination makes it difficult to deliver normal blood flow to the various parts of the body, and especially the brain when the person is upright.

    In the GD-MCB hypothesis, so far unproven, the HPA axis dysfunction in ME/CFS is also due to glutathione depletion in the hypothalamus and pituitary.

    Finally, in many cases of ME/CFS, there is a deficiency of intracellular magnesium or potassium or both. These two minerals are important for maintaining a steady heartbeat (sinus rhythm). If one or the other becomes deficient, arrhythmias or palpitations can occur..

    In the GD-MCB hypothesis, the low intracellular magnesium and potassium result from insufficient ATP supply to the membrane ion pumps, which in turn is caused by mito dysfunction, stemming as noted above from glutathione depletion and a partial block in the methylation cycle. This is so far unproven.

    All of this leads to a variety of unpleasant symptoms: orthostatic hypotension (OH), postural orthostatic tachycardia (POTS) due to efforts by the sympathetic nervous system to increase the cardiac output in the face of a low stroke volume, lack of normal blood flow to the skin, fainting in a warm shower because blood flow is diverted to the skin for cooling and less is available to the brain, pooling of blood in the legs, and palpitations.

    While some short-term measures can help to some extent with these problems, in my opinion the ultimate remedy is to lift the partial methylation cycle block using a methylation protocol, which has been shown to allow glutathione to come up to normal in most PWMEs who have been tested. This should ultimately correct all three of the above problems. While measurements have not been made to confirm improvements in the heart and circulatory system, we did observe major improvement in symptoms from this treatment, which implies improvement in the function of the heart and the circulatory system.

    Short-term measures that some people have used are (1) to supplement magnesium and/or potassium in an attempt to raise the intracellular levels of these minerals, (2) to increase the intake of water and salt, or (3) to get an IV infusion of saline, or (4) to take Florinef (fludrocortisone) together with salt, to raise the total blood volume on a temporary basis. Others have tried (5) boosting cortisol by injecting hydrocortisone (Cortef), which can raise the blood pressure, but unfortunately the adrenals tend to compensate by lowering their cortisol output if more is added exogenously, and the person ends up hooked on exogenous cortisol. Perhaps the EECP would help some, but again, this would just be a temporary measure that does not get at the core issues. In my opinion, the partial methylation cycle block must be addressed to bring long-term improvement in these problems as well as many others in ME/CFS.

    I hope this is helpful.

    Best regards,

    Rich
    Merry, ahimsa and justy like this.
  5. Searching

    Searching

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    Rich, thank you SO much for your amazingly detailed, yet very understandable answer!

    I guess my best option then would be to ask the cardiologist to test my stroke volume and cardiac output, and let him choose the way it is tested? As long as it is done with the patient vertical, is that right? Or can it show up on tests while laying down?

    This protocol you're explaining seems miraculous, but a quick Google search seems to have many different "recipes" for the treatment. Can you point me toward some reliable ones? I'll try anything I can at this point.

    I've dealth with chronic illness all my life, but have never been taken down so swiftly and severely as I have been by these cardiac symptoms. If I could improve them, my life would change drastically.

    I feel so frustrated... the doctors all tell me there is no cause nor remedy for my symptoms, yet you fantastic people on this board are clearly proving otherwise

    The think that I am most curious about is: has anyone that you know of been able to recover enough to be able to do aerobic exercise? I miss doing aquafit at the city pool, and it is my biggest dream at the moment, to go back.

    Thank you very much, I am so very lucky to have found this site and everyone here. Thank you!!!
  6. richvank

    richvank Senior Member

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    ***Hi, Searching.

    Rich, thank you SO much for your amazingly detailed, yet very understandable answer!

    ***You're welcome.

    I guess my best option then would be to ask the cardiologist to test my stroke volume and cardiac output, and let him choose the way it is tested?

    ***That would probably be helpful.

    As long as it is done with the patient vertical, is that right? Or can it show up on tests while laying down?

    ***It depends on how serious it is. Some people cannot tolerate being upright for very long. If you can tolerate having it measured both supine and upright, you would have more information. In ME/CFS, the cardiac output drops more than in a normal, healthy person when they become upright.

    This protocol you're explaining seems miraculous, but a quick Google search seems to have many different "recipes" for the treatment. Can you point me toward some reliable ones? I'll try anything I can at this point.

    ***It really isn't miraculous, but it has helped quite a few people. I'll post the most recent version of the simplified methylation protocol that I have suggested below.

    I've dealth with chronic illness all my life, but have never been taken down so swiftly and severely as I have been by these cardiac symptoms. If I could improve them, my life would change drastically.

    ***I'm sure that's true.

    I feel so frustrated... the doctors all tell me there is no cause nor remedy for my symptoms, yet you fantastic people on this board are clearly proving otherwise

    ***It's unfortunate that the conventional medical community for the most part is not aware of what needs to be done in ME/CFS. I hope that will change soon.

    The think that I am most curious about is: has anyone that you know of been able to recover enough to be able to do aerobic exercise? I miss doing aquafit at the city pool, and it is my biggest dream at the moment, to go back.

    ***I have known of a small number of people who appear to have recovered completely after doing this treatment. However, most report significant improvement, but not total recovery. This treatment appears to deal with the core of the pathophysiology of ME/CFS, but not with the etiologies (root causes). Additional treatments appear to be needed for them, and they appear to vary from one person to another. So far, I think they include Lyme disease, biotoxin illness, deeply entrenched viral infections, serious intestinal bacterial dysbiosis, serious deficiencies in essential nutrients (vitamins, essential minerals, essential amino acids, especially), or high body burdens of toxic elements, such as mercury. It appears that those who experienced complete recovery after methylation treatment had done other types of treatment prior to that, and they may have dealt with their particular etiologies, so that the methylation treatment was the last piece they needed.

    Thank you very much, I am so very lucky to have found this site and everyone here. Thank you!!!

    ***You're very welcome, and I hope that things will work out well for you.

    ***Best regards,

    ***Rich

    March 30. 2011

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

    SUPPLEMENTS

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

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

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

    anciendaze Senior Member

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    Searching, I think you have a serious problem, based on what you have said. My immediate concern would center on hypovolemia and dehydration. If you are as badly hypovolemic as I suspect dehydration could kill you quickly. Physicians typically assume patients will maintain adequate hydration by drinking when they are thirsty. This problem is outside the range of normal. I would also caution you to avoid diuretics. You don't need to excrete any more water than you already do. Whether or not you meet criteria for a clinical diagnosis of diabetes insipidus I simply don't know.

    You have been through three stages of dealing with cardiologists: the problem doesn't exist; it exists but it isn't important; it's important, but we can't do anything about it. You are fortunate that you have been monitored while active. Far too much measurement is done while a patient is lying down, without checking what happens when they do anything else. (This might explain the number of people who end up unable to do anything except lie down.) The numbers you quote are well into the range for POTS. The upper heart rate, coupled with evidence of hypovolemia, is very troubling. It suggests your heart is operating in a range where increasing rate causes no increase in output. Frankly, in my unprofessional opinion, this is dangerous.

    If cardiologists can't do anything for you you need to concentrate on what you can do yourself, as with my advice on hydration, and find doctors who can do something about underlying causes of other aspects. Every intervention should be considered an experiment. You have to keep careful track of what is done and what results. (In the past, I've kept a journal.) If an intervention does not work don't continue it beyond a reasonable trial period. Always avoid pushing yourself beyond your limits. I find heart rate recovery time after exercise (even things others don't consider exercise) a sensitive measure of how well I am doing. When this gets better so do many other things. When it gets worse I know something is wrong.

    Best Wishes!
    Merry and ahimsa like this.
  8. Searching

    Searching

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    Hello again Rich and Anciendaze,

    Rich, I'm embarassed to say that I had no knowledge of your amazing work until your reply! I had no idea that anyone other than patients would be active on this board. It is, quite frankly, awesome. I am absolutely astonished that you would take the time to read, much less comment on my situation. It means the world to me (and to my family who will directly benefit from any improvement to my health). Thank you.

    I have printed out the supplements' ingredient lists, and will take them to my pharmacy this afternoon to make sure there is no chance of interaction with any of my current medications. I will also make an appointment with my family doctor to make sure I am properly supervised.

    I would like (to satisfy personal curiosity) to have testing done before I start the supplements in order to see just how low my levels are. I am hoping you might be able to tell me what to have checked so that I can ask my doctor for it.


    Anciendaze, I will work on staying hydrated. I have never heard of diabetes insipidus! I think you're really on to something here. I had trouble with a weird white film forming in my vision, and my optometrist said that it was my eyes drying out and that I had to use gel eye drops to keep them hydrated. I was thankful at the time that it wasn't anything more serious, but I'm now starting to review symptoms in my head, and what you posted is bringing it all together. My skin is also much more dry (especially with winter time and lots of hand washing), but it has never been as bad as it is now.

    I will work on tracking everything more closely from now on, and I'll speak with my doctor about it. I am unfortunately past the point of really "exercising" so I can't do much in terms of heart rate yet. I'm having a lot of trouble just standing and walking around the house. Any effort such as standing starts "the taste" (that metallic, out of breath, wheezing feeling). I know that within about a minute of "the taste" starting, if I don't sit down right away my vision will start to blur and palpitations will start, etc, etc. Fingers crossed, I'd love to start walking if/when I start feeling better! I've got a polar heart rate monitor I was using a few years ago - I can't wait to use it again!

    I am so grateful for your help, thanks very much!
  9. anciendaze

    anciendaze Senior Member

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    Rich was the one who brought that into the discussion explicitly.

    If an optometrist thought your eyes were conspicuously dry you might check with a medical professional about Sjgren's syndrome. (Optometrists do not have full medical training. Their expertise is restricted to eyes and glasses.)
    Your heart rate recovery time from that "non-exercise" would be a good measure to watch for changes during treatment. Think of it this way, you don't have to go to all the trouble others do to have a workout.

    Best Regards,

    anciendaze
  10. richvank

    richvank Senior Member

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    ***Hi, Searching.

    Rich, I'm embarassed to say that I had no knowledge of your amazing work until your reply! I had no idea that anyone other than patients would be active on this board. It is, quite frankly, awesome. I am absolutely astonished that you would take the time to read, much less comment on my situation. It means the world to me (and to my family who will directly benefit from any improvement to my health). Thank you.

    ***You're welcome. I hope it helps.

    I have printed out the supplements' ingredient lists, and will take them to my pharmacy this afternoon to make sure there is no chance of interaction with any of my current medications. I will also make an appointment with my family doctor to make sure I am properly supervised.

    ***O.K. Sounds good.

    I would like (to satisfy personal curiosity) to have testing done before I start the supplements in order to see just how low my levels are. I am hoping you might be able to tell me what to have checked so that I can ask my doctor for it.

    ***If it's feasible for you to do so, here's what I would suggest:

    1. Run the Health Diagnostics and Research Institute methylation pathways panel. It costs US$295 and requires an order from a physician or a chiropractor. I know of quite a few people in Canada who have run this test. I'll paste the contact information for the lab below. This panel evaluates the status of the methylation cycle, the folate metabolism, and glutathione. It will give evidence of a partial methylation cycle block and the associated vicious circle mechanism, and will also provide baseline data for comparison later, if you do the treatment. This is helpful to gauge progress, because symptoms can fluctuate, and are not always a reliable guide.

    2. Run one of the combination metabolic panels, such as the Metametrix ION panel with 40 amino acids, available from some physicians or without a physician's order from
    https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx, or the Genova Diagnostics NutrEval panel, also available from some physicians or without a
    physician's order from https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default. These panels will reveal deficiencies in essential nutrients as well as giving
    a variety of information about the metabolism. In order for the methylation treatment to be successful, it is necessary that the body have adequate levels of several of the essential
    nutrients.

    3. If there are problems with the digestive system, then I also recommend running a comprehensive stool test. There are several available. One of the most comprehensive is the
    Diagnos-techs Expanded G.I. Health profile, which uses culturing methods, and samples saliva as well as stools. It requires an order from a physician. The Metametrix G.I. Function
    profile uses DNA analysis to identify bacteria, yeasts, and parasites. It is available from some physicians or from directlabs.com. There are also other comprehensive stool tests
    offered by Genova Diagnostics and Doctor's Data Lab, also available from directlabs.com If the digestive system is not doing well, this usually needs to be dealt with in order for the
    methylation treatment to be successful.


    Best regards,

    Rich


    Methylation Pathways Panel

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

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


    Available from:

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

    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, or you can use the following interpretive guide:


    March 25, 2012


    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, 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)
  11. Andrew

    Andrew Senior Member

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    Los Angeles, USA
    Here's the Peckerman protocol and research (attached)

    Attached Files:

  12. SanDiego#1

    SanDiego#1 SanDiego#1

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    SouthEast USA
    Well this Post really made my day. I was diagnosed recently by Cheney as having Diastolic
    Dysfunction. With Cardiac out put of 1.5- The lowest in his practice. He did not know how I was walking around. I have started on his protocal and am feeling some better already.He did use his new Echo machine. I have been having symptoms with heart since 2007. Kept going to Conventional MD-Cardiologist and they said they could not find anything. I was having Angina and Tacycardia. Last Sept 2011 I started having shortness of breath. I had a Calcium score done and have score of 236-blokage in left Ventricle. Cardio Dr. said not enough for a stent. My blood pressure is very low and I refused to go on a Beta Blocker or Statin. They did a Heart Cath and said everything was OK. I also have POTS??? Not sure if that is it or Cardiac. I am staying hydrated now with Electrolyte solution , which really helps. On low acid diet (from Cheney). I have been on Immune Globulin for 18 years IM weekly. Now on Magnesium/Taurine shots and neutraceuticals from Cheney. Alll of this info sound feasible but confusing as my symptoms are different but also some the same.
    Also Hydroxycoblamine sub-Q.
  13. anciendaze

    anciendaze Senior Member

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    It's frightening to realize how long advice posted here can influence people. I've just checked my posts above, and decided that, fortunately, I would not alter them if I posted today. This isn't always the case. I really hope to have new ideas and new advice in the future. Most of us badly need something new.
  14. SanDiego#1

    SanDiego#1 SanDiego#1

    Messages:
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    SouthEast USA
    Better get some new ones quick for me-I don't want to go down with the MEDICINE SHIP!!!Have researched everything I can on this and no one knows anything-FOR SURE!!!! Thanks however for your interest and interesting info.Please keep me posted on anything new-even if it is about my Diagnostician!!
  15. SanDiego#1

    SanDiego#1 SanDiego#1

    Messages:
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    SouthEast USA
    BE BRAVE-
    IF YOU CAN'T BE BRAVE-
    PRETEND TO BE-
    NO ONE WILL KNOW THE DIFFERENCE.!!!!!!
    ahimsa likes this.

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