Hi, Tamara.
I, too, want to welcome you here. Yes, Dr. Neville is a friend of mine. I do participate here, and appreciate this forum a lot, but it is not "mine" in the sense that I had anything to do with starting it or maintaining it. Cort Johnson started it, and there is a faithful crew of administrators and moderators who keep it going, for the benefit of all of us.
Hanna gave you a link to the most recent version of the protocol I have suggested. Freddd, on this forum, has proposed a somewhat different protocol, though it has some things in common with the one I have suggested. The same protocol does not seem to work well for everyone, and we continue to try to understand how to optimize treatment for all PWMEs. We do agree on the importance of supplementing methylfolate and also using a high dosage of one or more of certain forms of B12, either sublingually or by injection, but beyond that, there are differences in the protocols, and we have not come to complete agreement on everything concerning them.
With regard to testing, Dr. Amy Yasko does offer a panel that characterizes about 30 genetic polymorphisms. It can be helpful, especially for those who follow her complete treatment program. This program involves a large number of supplements, frequent lab testing, and considerable complexity and cost. I have attempted to simplify this and lower the cost by extracting a "simplified" protocol from her overall program, because many PWMEs had difficulty following her complete treatment program.
With regard to genetic testing, some people are running the 23andme.com genotyping panel. It costs less than the Yasko panel, and has many more polymorphisms on it. However, it does not include all of those on the Yasko panel, and it requires some interpretation, which some people in this forum have been working on.
The testing that I most favor is the Health Diagnostics methylation pathways panel, which is a biochemical panel that evaluates the actual current status of the methylation cycle, the folate metabolism and glutathione, rather than genetic tendencies. This panel will tell you if methylation treatment is likely to help, and it will also give baseline data for comparison later, to evaluate the progress of the treatment. Contact information and an interpretive guide are pasted below.
Since many people have deficiencies in necessary nutrients, I also favor running a Genova Diagnostics NutrEval profile or a Metametrix ION profile. These are available through some doctors, or without a doctor's order from
www.directlabs.com. These profiles will evaluate your overall energy metabolism and indicate whether there are deficiencies in vitamins, minerals or amino acids. They will also give some information about toxic metals and the condition of the digestive system.
Some people just try the protocol without doing any testing, for reasons of cost or inability to get to a doctor or to find one who is knowledgeable and will cooperate. I don't recommend this, but sometimes it works out O.K. Other times it doesn't, because there are nutritional deficiencies or elevated toxic metals or serious intestinal dysbiosis, and then the person has to go back and try to detect and correct these problems. There have also been a small number of cases with serious adverse effects, so I recommend working with a physician while on this type of treatment. It sounds like you have had some high-level help in finding a knowledgeable physician, and that's great!
If you would like to get more detailed information about methylation treatment and the rationale behind it, you could view the video (or look at the slides, which are available by clicking on the blue print below the video) at this site:
http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/${weburl}
I am also attaching a simplified explanation of the Glutathione Depletion--Methylation Cycle Block hypothesis for ME/CFS.
I hope this helps.
Best regards,
Rich
Methylation Pathways Panel
This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.
The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead.
Available from:
Health Diagnostics and Research Institute540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879 USA
Phone: (732) 721-1234
Fax: (732) 525-3288
Email: lab@vitdiag.com
Lab Director: Elizabeth Valentine, M.D.
Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone, or you can use the interpretive guide below:
March 25, 2012
Interpretation of Results of the Methylation Pathways Panel
by
Richard A. Van Konynenburg, Ph.D.
Independent Researcher
Disclaimer: The Methylation Pathways Panel is offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA. I am not affiliated with these laboratories, but have been a user of this panel, and have written these suggestions at the request of Tapan Audhya, Ph.D., Director of Research for the Health Diagnostics lab, for the benefit of physicians who may not be familiar with this panel. My suggestions for the interpretation of results of the panel are based on my study of the biochemistry involved, on my own experience with interpreting panel results as part of the analysis of a fairly large number of cases of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) over the past four years, and on discussion of some of the issues with Dr. Audhya. I am a researcher, not a licensed physician. Treatment decisions based on the results of applying this panel and its interpretation to individual cases are the responsibility of the treating physician.
Application: In addition to being useful in analyzing cases of ME/CFS, this panel can also be usefully applied to cases of autism and other disorders that involve abnormalities in glutathione, methylation and the folate metabolism.
The panel includes measurement of two forms of glutathione (reduced and oxidized), S-adenosylmethionine (SAMe), S-adenosylhomocysteine (SAH), adenosine, and seven folate derivatives.
According to Dr. Audhya (personal communication), the reference ranges shown on the lab reports for each of these metabolites were derived from measurements on at least 120 healthy male and female volunteer medical students from ages 20 to 40, non-smoking, and with no known chronic diseases. The reference ranges extend to plus and minus two standard deviations from the mean of these measurements.
Glutathione (reduced): This is a measurement of the concentration of the
chemically reduced (active) form of glutathione (abbreviated GSH) in the blood
plasma. The reference range is 3.8 to 5.5 micromoles per liter.
Glutathione plays many important roles in the biochemistry of the body, including serving as the basis of the antioxidant enzyme system, participating in the detoxication system, and supporting the cell-mediated immune response, all of which exhibit deficits in CFS. The level of GSH in the plasma is likely to be more reflective of tissue intracellular glutathione status than the more commonly and more easily measured red blood cell or (essentially equivalent) whole blood glutathione level, which is about three orders of magnitude greater, because red blood cells are normally net producers of glutathione. Also, knowledge of the level of the reduced form, as distinguished from total (reduced plus oxidized) glutathione, which is more commonly measured, is more diagnostic of the status of glutathione function.
In order to be able to approximate the in vivo level of reduced glutathione when blood samples must be shipped to a lab, it is necessary to include special enzyme inhibitors in the sample vials, and these are included in the test kit supplied by these two laboratories.
Most people with chronic fatigue syndrome (PWCs), but not all, are found to have values of GSH that are below the reference range*. This means that they are suffering from glutathione depletion. As they undergo treatment to lift the partial methylation cycle block, this value usually rises into the normal range over a period of a few months. I believe that this is very important, because
glutathione normally participates in the intracellular metabolism of vitamin B12, and if it is low, a functional deficiency of vitamin B12 results, and insufficient methylcobalamin is produced to support methionine synthase in the methylation cycle. In my view, this is the mechanism that causes the onset of ME/CFS. This functional deficiency is not detected in a conventional serum B12 test, but will produce elevated methylmalonate in a urine organic acids test. In my opinion, many of the abnormalities and symptoms in ME/CFS can be traced directly to glutathione depletion.
Anecdotal evidence suggests that PWCs who do not have glutathione depletion do have abnormalities in the function of one or more of the enzymes that make use of glutathione, i.e. the glutathione peroxidases and/or glutathione transferases. This may be due to genetic polymorphisms or DNA adducts on the genes that code for these enzymes, or in the case of some of the glutathione peroxidases, to a low selenium status.
Glutathione (oxidized): This is a measurement of the concentration
of the oxidized form of glutathione (abbreviated GSSG) in the blood
plasma. The reference range is 0.16 to 0.50 micromoles per liter.
Normally, oxidized glutathione in the cells is recycled back to reduced glutathione by glutathione reductase, an enzyme that requires vitamin B2 and NADPH. If this reaction is overwhelmed by oxidative stress, the cells export excess GSSG to the plasma. In some (but not all) PWCs, GSSG is elevated above the normal
range, and this represents oxidative stress. It is more common in CFS to see this level in the high-normal range. This value may increase slightly under initial treatment of a partial methylation cycle block.*
Ratio of Glutatione (reduced) to Glutathione (oxidized): This is not shown explicitly on the panel results, but can be calculated from them. It is a measure of the redox potential in the plasma, and reflects the state of the antioxidant system in the cells. The normal mean value is 14. PWCs often have a value slightly more than half this amount, indicating a state of glutathione depletion and oxidative stress. This ratio has been found to increase during treatment of a partial methylation cycle block, but other types of treatment may be necessary to bring it to normal.*
S-adenosymethionine (RBC): This is a measure of the concentration of S-adenosylmethionine (SAMe) in the red blood cells. The reference range is 221 to 256 micromoles per deciliter.
SAMe is produced in the methylation cycle and is the main supplier of methyl (CH3) groups for a large number of methylation reactions in the body, including the methylation of DNA and the biosynthesis of creatine, carnitine, phosphatidylcholine, coenzyme Q10, melatonin and epinephrine. This measurement is made in the red blood cells because the level there reflects an average over a longer time and is less vulnerable to fluctuations than is the plasma level of SAMe.
Most PWCs have values below the reference range, and treatment raises the value.* A low value for SAMe represents a low methylation capacity, and
in CFS, it usually appears to result from an inhibition or partial block of the enzyme methionine synthase in the methylation cycle. Many of the abnormalities in CFS can be tied to lack of sufficient methylation capacity.
S-adenosylhomocysteine (RBC): This is a measure of the
concentration of S-adenosylhomocysteine (SAH) in the red blood cells. The reference range is 38.0 to 49.0 micromoles per deciliter.
SAH is the product of the many methyltransferase reactions that utilize SAMe as a source of methyl groups. In CFS, its value ranges from below the reference range to above the reference range. Values appear to converge toward the reference range with treatment.
Sum of SAM and SAH: When the sum of SAM and SAH is below about 268
micromoles per deciliter, it appears to suggest the presence of
upregulating polymorphisms in the cystathionine beta synthase (CBS)
enzyme, though this may not be true in every case. For those considering following the Yasko treatment program, this may be useful information.
Ratio of SAM to SAH: A ratio less than about 4.5 represents low
methylation capacity. Both the concentration of SAM and the ratio of
concentrations of SAM to SAH are important in determining the
methylation capacity, because they affect the rates of the methyltransferase reactions.
Adenosine: This is a measure of the concentration of adenosine in the
blood plasma. The reference range is 16.8 to 21.4 x 10(-8) molar.
Adenosine is a product of the reaction that converts SAH to homocysteine. It is also exported to the plasma when mitochondria develop a low energy charge, so that ATP drops down to ADP, AMP, and eventually, adenosine. Adenosine in the plasma is normally broken down to inosine by the enzyme adenosine deaminase.
In some PWCs adenosine is found to be high, in some it is low, and in some it is in the reference range. I don't yet understand what controls the adenosine level in these patients, and I suspect that there is more than one factor involved. In most PWCs who started with abnormal values, the adenosine level appears to be moving into the reference range with methylation cycle treatment, but more data are needed.
5-CH3-THF: This is a measure of the concentration of 5L-methyl
tetrahydrofolate in the blood plasma. The reference range is 8.4 to 72.6 nanomoles per liter.
This form of folate is present in natural foods, and is normally the most abundant form of folate in the blood plasma. It is the form that serves as a reactant for the enzyme methionine synthase, and is thus the important form for the methylation cycle. It is also the only form of folate that normally can enter the brain. Its only known reactions are the methionine synthase reaction and reaction with the oxidant peroxynitrite.
When there is a partial block in methionine synthase, the other forms of folate continue to be converted to 5L-CH3-THF by the so-called “methyl trap” mechanism. Some of the 5L-CH3-THF is broken down by reaction with peroxynitrite, which results from the condition of oxidative stress that is usually concomitant with glutathione depletion.
Many PWCs have a low value of 5L-CH3-THF, consistent with a partial block in the methylation cycle. Most methylation treatment protocols include supplementation with 5L-CH3-THF, which is sold over-the-counter as Metafolin, FolaPro, or MethylMate B (trademarks), as well as the newer Quatrefolic (trademark) and in the prescription “medical foods” supplied by PamLab, including Deplin, CerefolinNAC and Metanx. There are some others on the market that include both racemic forms (5L and 5R) of this folate.
When methylation treatment is used, the level of 5-CH3-THF rises in nearly every PWC. If the concentration of 5-CH3-THF is within the reference range, but either SAM or the ratio of SAM to SAH is below the reference values, it suggests that there is a partial methylation cycle block and that it is caused by inavailability of sufficient bioactive B12, rather than inavailability of sufficient folate. A urine organic acids panel will show elevated methylmalonate if there is a functional deficiency of B12. I have seen this combination frequently, and I think it demonstrates that the functional deficiency of B12 is the immediate root cause of most cases of partial methylation cycle block. Usually glutathione is low in these cases, which is consistent with such a functional deficiency. As the activity of the methylation cycle becomes more normal, the demand for 5-CH3-THF will likely increase, so including it in the treatment protocol, even if not initially low, will likely be beneficial.
10-Formyl-THF: This is a measure of the concentration of 10-formyl
tetrahydrofolate in the blood plasma. The reference range is 1.5 to 8.2 nanomoles per liter.
This form of folate is involved in reactions to form purines, which form part of RNA and DNA as well as ATP. It is usually on the low side in PWCs, likely as a result of the methyl trap mechanism mentioned above. This deficiency is likely the reason for some elevation of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) often seen in PWCs. This deficit may also impact replacement of cells lining the gut, as well as white blood cells.
Rarely, 10-formyl-THF is found to be much higher than the normal reference range. If this is found, the patient should be examined for cancer, since cancer cells upregulate this form of folate in order to make purines more rapidly to support their rapid cell division.
5-Formyl-THF: This is a measure of the concentration of 5-formyl
tetrahydrofolate (also called folinic acid) in the blood plasma. The reference range is 1.2 to 11.7 nanomoles per liter.
This form is not used directly as a substrate in one-carbon transfer reactions, but it can be converted into other forms of folate, and may serve as a buffer form of folate. Most but not all PWCs have a value on the low side. It is one of the
supplements in some methylation protocols. It can be converted to 5L-CH3-THF in the body by a series of three reactions, one of which requires NADPH, and it may also help to supply other forms of folate to the cells until the methionine synthase reaction comes up to more normal activity.
THF: This is a measure of the concentration of tetrahydrofolate in
the blood plasma. The reference range is 0.6 to 6.8 nanomoles per liter.
This is the fundamental chemically reduced form of folate from which several other reduced folate forms are synthesized, and thus serves as the “hub” of the folate metabolism. THF is also a product of the methionine synthase reaction, and participates in the reaction that converts formiminoglutamate (figlu) into glutamate in the metabolism of histidine. If figlu is found to be elevated in a urine organic acids panel, it usually indicates that THF is low. In PWCs it is lower than the mean normal value of 3.7 nanomoles per liter in most but not all PWCs.
Folic acid: This is a measure of the concentration of folic acid in
the blood plasma. The reference range is 8.9 to 24.6 nanomoles per liter.
Folic acid is a synthetic form of folate, not found in nature. It is added to food grains in the U.S. and some other countries in order to lower the incidence of neural tube birth defects, including spina bifida. It is the oxidized form of folate, and therefore has a long shelf life and is the most common commercial folate supplement. It is normally converted into THF by two sequential reactions catalyzed by dihydrofolate reductase (DHFR), using NADPH as the reductant. However, some people are not able to carry out this reaction well for genetic reasons, and PWCs may be depleted in NADPH, so folic acid is not the best supplemental form of folate for these people.
Low values suggest folic acid deficiency in the current diet. High values, especially in the presence of low values for THF, may be associated with inability to convert folic acid into reduced folate readily, such as because of a genetic polymorphism in the DHFR enzyme. They may also be due to high supplementation of folic acid.
Folinic acid (WB): This is a measure of the concentration of folinic acid in the whole blood. The reference range is 9.0 to 35.5 nanomoles per liter.
See comments on 5-formyl-THF above. Whole blood folinic acid usually tracks with the plasma 5-formyl-THF concentration. They are the same substance.
Folic acid (RBC): This is a measure of the concentration of folic acid in the red blood cells. The reference range is 400 to 1500 nanomoles per liter.
The red blood cells import folic acid when they are initially being formed, but during most of their lifetime, they do not normally import, export, or use it. They simply serve as reservoirs for it, giving it up when they are broken down.
Many PWCs have low values of this parameter. This can be caused by a low folic acid status in the diet over the previous few months, since the population of RBCs at any time has ages ranging from zero to about four months. However, in CFS it can also be caused by oxidative damage to the cell membranes, which allows folic acid to leak out of the cells. Dr. Audhya reports that treatment with omega-3 fatty acids has been found to raise this value over time in one cohort.
If anyone finds errors in the above suggestions, I would appreciate being notified at richvank@aol.com.
* Nathan, N., and Van Konynenburg, R.A., Treatment Study of Methylation Cycle Support in Patients with Chronic Fatigue Syndrome and Fibromyalgia, poster paper, 9th International IACFS/ME Conference, Reno, Nevada, March 12-15, 2009. (http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf)
Simpler explanation of GD-MCB hypothesis for ME/CFS
1. To get an isolated case of ME/CFS (I'm not talking here about the epidemics or clusters), you have to have inherited some genetic variations from your parents. These are called polymorphisms or single-nucleotide polymorphisms. We know what some of the important ones are, but we don't know all of them yet. I think it’s likely that at least some make it difficult for a person to maintain a normal level of glutathione. This is a topic that needs more research.
2. You also have to have some things happen in your life that place demands on your supply of glutathione. Glutathione is like a very small protein, and there is some in every cell of your body, and in your blood. It protects your body from quite a few things that can cause problems, including chemicals that are toxic, and oxidizing free radicals. It also helps the immune system to fight bugs (bacteria, viruses, fungi) so that you are protected from infections by them.
3. Oxidizing free radicals are molecules that have an odd number of electrons, and are very chemically reactive. They are normally formed as part of the metabolism in the body, but if they rise to high levels and are not eliminated by glutathione and the rest of the antioxidant system, they will react with things they shouldn't, and cause problems. This situation is called oxidative stress, and it is probably the best-proven biochemical aspect of chronic fatigue syndrome. One of the important oxidizing free radicals is peroxynitrite.
4. There are a variety of things in your life that can place demands on your glutathione. These include physical injuries or surgery to your body, exposure to toxic chemicals such as pesticides, solvents, or heavy metals like mercury, arsenic or lead, exposure to infectious agents such as viruses or bacteria, or vaccinations, or emotional stress that causes secretion of a lot of cortisol and adrenaline, especially if it continues over a long time. Just about anything that "stresses" your body or your mind will place a demand on glutathione. All people experience a variety of stressors all the time, and a healthy person's body is able to keep up with the demands for glutathione by recycling used glutathione molecules and by making new ones as needed. However, if a person's body cannot keep up, either because of extra-high demands or inherited genetic polymorphisms that interfere with recycling or making glutathione, or both, the levels of glutathione in the cells can go too low. When glutathione is properly measured in most people with ME/CFS (such as in the Health Diagnostics methylation pathways panel), it is found to be below normal.
5. One of the jobs that glutathione normally does is to help your cells to convert incoming vitamin B12 to the right amounts of the two forms of B12 that they use. If there is not enough glutathione, this won’t happen. This is called a “functional deficiency” of vitamin B12. A conventional blood test for vitamin B12 will not reveal this problem. In fact, many people with ME/CFS appear to have elevated levels of B12 in their blood, while their bodies are not able to use it properly. The best test to reveal this is a urine organic acids test that includes methylmalonic acid. It will be high if the B12 is being sidetracked, and this is commonly seen in people with ME/CFS.
6. When your glutathione level goes too low, your B12 also becomes naked and vulnerable, and is hijacked by toxins. Also, the levels of toxins rise in the body when there isn't enough glutathione to take them out, so there are two unfortunate things that work together to sabotage your B12 when glutathione goes too low.
7. The most important form of B12 in the body is methylcobalamin, which is one of the two active forms of B12. This form is needed by the enzyme methionine synthase, to do its job. An enzyme is a substance that catalyzes, or encourages, a certain biochemical reaction.
8. When there isn't enough methylcobalamin, methionine synthase has to slow down its reaction. Its reaction lies at the junction of the methylation cycle and the folate cycle, so when this reaction slows down, it affects both these cycles.
9. The methylation cycle is found in all the cells of the body (not counting the red blood cells, which are unusual in a lot of ways). The methylation cycle has some important jobs to do. First, together with the folate metabolism, it acts as a little factory to supply methyl (CH3) groups to a large number of reactions in the body. Some of these reactions make things like creatine, carnitine, coenzyme Q10, phosphatidylcholine, melatonin, and lots of other important substances for the body. It is not a coincidence that these substances are found to be low in ME/CFS, so that people try taking them as supplements. Not enough of them is being made because of the partial block in the methylation cycle. The methylation cycle also supplies methyl groups to be attached to DNA molecules, and this helps to determine whether the blueprints in the DNA will be used to make certain proteins according to their patterns. This "reading" of DNA is referred to as "gene expression." Methyl groups prevent or "silence" gene expression. Overexpression of genes has been observed in CFS patients, and I suspect this is at least partly due to lack of sufficient methylation to silence gene expression.
10. Another thing that the methylation cycle does is to regulate the overall use of sulfur in the body. Sulfur comes in from the diet in the form of amino acids in protein (methionine and cysteine) and as taurine and some as sulfate. The methylation cycle regulates the production of the various substances that contain sulfur that are needed by the body. The levels of various sulfur metabolites are often found to be abnormal in people with ME/CFS.
11. One of the most important sulfur-containing substances in the body is glutathione, so now you can see how this is starting to look like a dog chasing its tail! The thing that causes chronic fatigue syndrome to be chronic, and keeps people ill for years and years, is this interaction between glutathione, vitamin B12, and the methylation cycle. When glutathione goes too low, the effect on vitamin B12 slows down the methylation cycle too much. The sulfur metabolites are then dumped into the transsulfuration pathway (which is connected to the methylation cycle) too much and are eventually converted to thiosulfate and sulfate and are excreted in the urine. This lowers the production of glutathione, which requires cysteine, and now there is a vicious circle mechanism that preserves this malfunction and keeps you sick.
12. Meanwhile, the folate metabolism in the cells becomes depleted, because other forms of folate are converted to methylfolate, and peroxynitrite, the free radical, breaks down methylfolate.
13. That's the basic biochemical mechanism of ME/CFS. I believe that everything else flows from this. As you know, there are many symptoms in ME/CFS. I won't discuss all of them in detail here, but here's how I believe the fatigue occurs: The cells have little powerplants in them, called mitochondria. Their job is to use food as fuel to produce ATP (adenosine triphosphate). ATP acts as a source of energy to drive a very large number of reactions in the cells. For examples, it drives the contraction of the muscle fibers, and it provides the energy to send nerve impulses. It also supplies the energy to make stomach acid and digestive enzymes to digest our food, and many, many other things.
When glutathione goes too low in the muscle cells, the levels of oxidizing free radicals rise, and these react with parts of the "machinery" in the little powerplants, lowering their output of ATP. So the muscle cells then experience an energy crisis, and that's what causes the fatigue. Over time, because of the lack of enough glutathione, more problems accumulate in the mitochondria, including toxins, viral DNA, and mineral imbalances. These have been observed in the ATP Profiles and Translocator Protein test panels offered by Acumen Lab in the UK.
14. There are explanations that flow from this basic mechanism for other aspects of ME/CFS. I haven't figured out explanations for all of the aspects of ME/CFS, but I do think I understand a large number of them in some detail, and I've been able to explain enough of them that I believe this mechanism will account for the rest as well, if we can figure out the underlying biochemistry. My 2007 IACFS conference poster paper presented outlines of many of these explanations.
15. The involvement of infections by bacteria, viruses and fungi appears to have three aspects in ME/CFS. First, as mentioned above, infectious agents can act as one of the stressors that initially bring down the level of glutathione and produce the onset of isolated cases of ME/CFS in people who are genetically susceptible. I suspect that the clusters or epidemic occurrences of ME/CFS (such as at InclineVillage in the mid-80s) were caused by particularly virulent infectious agents, such as powerful viruses, and the genetic factor is less important in these cases.
16. Second, when a person's glutathione, methylation cycle, and folate cycle are not operating normally because of the vicious circle described above, the immune system does not function properly. In this case, viruses and bacteria that reside inside our cells and that are always in the body in their dormant, resting states are able to reactivate and produce infections, which the immune system is not able to totally put down. This accounts for the observation that most of the viral and intracellular bacterial infections seen in CFS patients are caused by pathogens that most of the population is carrying around in their dormant states.
17. Third, when the immune system's defenses are down, a person can catch new infections from others or from the environment, and the immune system is not able to defeat them, so they accumulate over time. Dr. Garth Nicolson has found that the longer a person has been ill, the more infections they have, on the average.
18. Other things that accumulate over time are various types of toxins, because the detox system depends to a large extent on the sulfur metabolism, and it will not be operating properly as long as the person has ME/CFS. The body stores much of these toxins in fat, but as the levels get higher, they begin cause problems throughout the biochemistry of the cells. Many people with ME/CFS have been tested for toxins (most commonly the heavy metal toxins, which are the most easily tested) and they are commonly found to be elevated.
19. The longer a person is chronically ill with ME/CFS, the more toxins and infections accumulate in their body, and the more symptoms they experience. This explains why the disorder changes over time, and why some people become extremely debilitated after being ill for many years.
20. The main key to turning this process around is to help the methionine synthase enzyme to operate more normally, so that the partial block in the methylation cycle and the folate cycle are lifted, and glutathione is brought back up to normal. That is what the simplified methylation protocol is designed to do, and so far, the evidence is that it does do these things in most people who have ME/CFS. I recommend that people with ME/CFS have the Health Diagnostics methylation pathways panel run to find out if they do in fact have a partial methylation cycle block and glutathione depletion before deciding, with their doctors, whether to try this treatment. This also provides a baseline so that progress can be judged later on by repeating it every few months during the treatment. Symptoms may not be a good guide to judge progress during treatment, because detoxing and die-off can make the symptoms worse, while in fact they are exactly what is needed to move the person toward recovery.
21. The main question I'm working on now is what else needs to be done to bring people to recovery? I don't have complete answers to this question yet. A few people recover from this treatment alone, but most require additional treatments. It does appear that people who suffer from illness due to toxic molds do need to remove themselves from environments where these are present. People who have Lyme disease will need to have that treated, also. Certain viral infections may also need to be treated. If the load of toxic metals is very high, they may need to be removed first. If the digestive system is in bad condition, it needs to be helped before the methylation cycle can be restored. If there are major deficiencies in important essential nutrients, they need to be restored before methylation can be corrected. We still have a lot to learn, but I'm convinced that the mechanism I have described above is the core of the abnormal biochemistry in CFS, and correcting it needs to be a cornerstone of the treatment.
