This is topic Got my initial MTHFR results. It says homozygous (got genes from both parents) in forum Medical Questions at LymeNet Flash.


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Posted by Tammy N. (Member # 26835) on :
 
At long last it explains why I have all of my issues with sulphur, among other things. And why I crash when taking anything with sulphur (chlorella, garlic, NAC, MSM, NAC, Alpha-lipoic acid. All the wonderful things that work magic in folks who don't have sulphur issues).

Need to educate myself more. The doctor I went to was not good. I felt very uncomfortable during my appointment. Gone was the friendly doctor I met 2 weeks ago.... today she was rather cold and almost condescending. She did not understand most of what I was saying regarding Lyme, parasites, Gilbert's, my symptoms, my bulging veins, inflammation, my dehydration, etc.

She just kept saying well your blood looks good. And my Lipoprotein genotype was very good. I was blessed to get 2 good detoxing genes from my parents, so I was detoxing well (hello?????). And with the MTHFR I just need to take a good multi with methylfolate. Oh, and fish oil. That's it.

I asked which genes I had, and she looked at me like dah, there is only one test for MTHFR. I said there were like 30 different mutations. She knew nothing about it and made it seem like I didn't know what I was talking about. Ok, why bother??

When I asked about why my body has issues with B vitamins, she referred me to a liver specialist. When I addressed my lyme symptoms (Bart has especially flared since a cat scratch this summer), she referred me back to my lyme doc. As far as she could see, everything looked good. Alrighty then......

I'm not happy about this MTHFR thing, but at least it explains an awful lot to me. Explains why my body cannot process a lot of different, simple treatments.

I wish more doctors were educated in this area. The genes we have are fixed and need to be respected. And our doctors need to help us figure out how to create detours in our body to get things working again.

This is a big piece of the puzzle for me.
 
Posted by sk8ter (Member # 8671) on :
 
please go to MTHFR.net ..that is an amazing site from a ND who has it as well as his whole family....there are two main genes that not all labs tests for...
 
Posted by pme (Member # 31621) on :
 
Could you tell me what you mean by your body has issues with b vitamins?
 
Posted by Tammy N. (Member # 26835) on :
 
Sk8ter - I was just looking at the site now. Thank you. Very helpful site. Wow, so much makes so much sense.

pme - it's hard for me to explain, but I get various different reactions. Often after injections or an IV, I get a heated, swollen, unwell feeling. Tingling sensations (more than my usual). I feel woozy and not right.

For instance, I would often go to my doc for a magnesium chloride IV, which often has me feeling better right on the table. Last time I was there, I was feeling bazaar and couldn't figure out what the heck was going on. I felt sick, warm, tingling, odd. Then I found out she had added B complex because I was so exhausted and wiped out. She muscle tested me afterwards and my arm went right down. I felt ill for the rest of the night.

When I went to my dentist for ozone injections, he first injects procaine and folic acid. I immediately get a warm buzzing sensations that shoots down my arms and into my hands. I feel drugged and odd and not well.

I have heard that a lot of the B vitamins have sulphur. I have issues with sulphur, so maybe that's it. Also I have elevated bilirubin (Gilbert's) and I've been reading that some people have issues processing things (sulphur, etc.) in their livers because of this. B vitamins have a long half-life in the liver (according to the pharmacist I called last week after an unpleasant reaction to Methyl B-12 injection).

I've been getting odd reactions to B vitamins for some time and it"s only becoming more clear to me now. Sometimes we take so many different things and don't know what is causing what. I'm getting very clear now as to what is triggering what reaction.
 
Posted by jlp38 (Member # 27221) on :
 
Very interesting. Sorry for the bad genes. At least now you know what they are so you can deal with them. Science is now showing through the study of epigenetics that genes aren't everything and we can really overcome them (look up Biology of Belief by Bruce Lipton if you're interested).

Where did you get your testing done?
 
Posted by Tammy N. (Member # 26835) on :
 
jlp - I believe the same thing. (And I will check out the book, thanks.) I don't believe that our genes determined a completely fixed outcome. I believe that our bodies, having highly sophisticated capabilities, can create the detours we need to achieve good health. Sometimes we just need to help it along a bit.

My lab results are from Health Diagnostic Laboratory, Inc.
 
Posted by Tincup (Member # 5829) on :
 
Tammy!

Glad you finally have some answers! Now you can begin to address the problems and know you aren't, like I always thought I was, a big sissy-baby cause I couldn't "do" what others could. What a relief, huh?

You said.... "When I asked about why my body has issues with B vitamins, she referred me to a liver specialist."

I've had problems with a number of vitamins over the years too. I have found ONE brand of B-vitamins that doesn't cause me problems, finally.

Maybe it has/doesn't have whatever is the problem? I don't know to be honest, and at this point my theory is "if it feels good, do it."

I've been using Nature's Bounty B with B-12 Complex. It is a liquid sublingual. The only problem with it is if I sublingual, and all doesn't absorb and it gets in my "EMPTY" belly it can give me indigestion, so you may want to use if after eating a full meal.

I also believe B vitamin problems could be the higher doses found in a lot of supplements, as is the problem with some other things we take?

Anyhow, hope this helps in some way.

Feel free to check out the MTHFR info at this link. Be sure to scroll to the bottom for more info links.

https://sites.google.com/site/marylandlyme/mthfr

[Big Grin]
 
Posted by tickled1 (Member # 14257) on :
 
Tammy, Thanks so much for posting about this! I've had 2 very horrible serious reactions to chlorella so maybe this is part of my problem too. I also have supposed Gilbert's, elevated bilirubin anyway.

I'm so confused though about MTHFR. I thought those with it needed B vitamins and Glutathione but like you said you can't tolerate B-vitamins and I think Glutathione has suphur in it. I didn't know Chorella did! That's great info for me to have. However, my LLMD never mentioned that my horrible reaction could be b/c of sulphur in Chlorella so I don't know how much he knows about MTHFR. I would have thought he would know that. He seemed baffled by my reaction but I went online and saw that many people have that kind of reaction to chlorella.

Can anyone please clarify for me about the B-vitamin and glutathione/sulphur thing? Why some with MTHFR need it and others can't tolerate it. What do those that can't tolerate sulphur do for treatment?
 
Posted by tickled1 (Member # 14257) on :
 
I did check out the MTHFR website but still couldn't find those answers. I will check again.
 
Posted by tickled1 (Member # 14257) on :
 
Sorry, I'm an idiot. I'm finding the info now. (kind of) [lol]
 
Posted by feelfit (Member # 12770) on :
 
tickled, the reason could be because of other mutations that you may have too. B-12 and folic acid is a remedy for one mutation.

you may have others, like Tammy N , for instance sulfur - that causes problems. Some people cannot do the methyl B but do well on hydro B. etc, etc.

Try reading the link that I posted the other day to the genomic web- this explains everything...and quite clearly.

MTHFR is only ONE gene/mutation in the Methyl Geonomic Cycle. Look at this link AND it highlights all of the other mutations and problems that they cause. http://www.heartfixer.com/AMRI-Nutrigenomics.htm
 
Posted by tickled1 (Member # 14257) on :
 
Thanks feelfit! I will check that out!
 
Posted by TerryK (Member # 8552) on :
 
If you have problems with sulfur you may have another methylation issue which is called a CBS upregulation and/or another one called SUOX. If you have the CBS upregulation, you will need to get it treated so that supplementation for the MTHFR issues don't cause you to make more toxins. I don't have the SUOX problem so I don't know if this applies to that one or not.

There are 2 main MTHFR genes that are typically tested.
MTHFR C677T and MTHFR 1298C

If you have them there are various and numerous effects. As far as B vitamins difficulty - folic acid cannot be converted effeciently to the form our body needs so we supplement with the active form of folic acid. It is hypothesized that the result of these mutations is that one makes less glutathione.

There are a slew of other methylation genes that Dr. Yasko tests for.

Genes may not be fixed. Check into epigenetics.
http://www.pbs.org/wgbh/nova/body/epigenetics.html
http://en.wikipedia.org/wiki/Epigenetics

The hearfixer site is a great site but there are many other links if you search the archives at lymenet.

Well I've procrastinated long enough. Back to taxes. ugh!

Terry

[ 03-16-2012, 08:03 PM: Message edited by: TerryK ]
 
Posted by nefferdun (Member # 20157) on :
 
Which one are you homozygous for? C677T or A1298C. Look at Ben's site for the differences.

I just got my pack for the 30 mutations test.
 
Posted by tickled1 (Member # 14257) on :
 
Wow, that PBS article is amazing. A real eye-opener!
 
Posted by Tammy N. (Member # 26835) on :
 
Terry - I didn't realize that there was a chance that if you treat MTHFR with methylated folic acid that you could produce more toxins if you have those other possible issues you listed.

What does CBS up regulation mean? And how does that one get treated. Just curious. (Do you have this one? If yes, what are you doing that works?)

neff - I have no idea which ones I am homozygous for. Doc was not very knowledgeable at all about any of this. She said there was just one test (MTHFR) and I was homozygous. That's all that my lab report shows.

I wonder -- are there tried and true treatments for each of the possible gene mutations within this spectrum of testing??
 
Posted by TerryK (Member # 8552) on :
 
Tammy asked:
I wonder -- are there tried and true treatments for each of the possible gene mutations within this spectrum of testing??

Dr. Yasko has developed treatments for each mutation. She treats mostly autistic kids but there are many adults that frequent her forum. She lists all the mutations and what is used for each on to treat but one mutation can alter treatment for another.

Best to sign up on her forums to learn. It is free as is the yahoo group.
http://www.ch3nutrigenomics.com/phpBB2/index.php?sid=6ddb9f1180ebc6eeaebc66541c1d3f04

Here is another good discussion group.
http://health.groups.yahoo.com/group/CFS_Yasko/

Tammy wrote:
I have no idea which ones I am homozygous for. Doc was not very knowledgeable at all about any of this

Ask the doctor for a copy of your test results. You may have to sign a release form but you shoul be able to get it. Most States have laws that allow patients to get a copy of tests etc..

CBS = Cystathionine Beta Synthase

If you have this defect you will make too much ammonia, use up BH-4 are more likely to have heavy metal toxicity, can't tolerate sulfur drugs, supplements foods and there is much more that goes wrong if you have this defect. Best to go to the heartfixer site and Yasko's forum to learn.

There is a protocol whereby you limit eating sulfur foods and meat and you take supplements to help purge your body. All of this info is on Yasko's site. I've posted it on this forum before so you could look in the archives for more info.

Hope this helps.

Terry

[ 03-17-2012, 04:53 AM: Message edited by: TerryK ]
 
Posted by TerryK (Member # 8552) on :
 
CBS info from the heartfixer site - there is much more there but this is a start.

"Biochemistry � The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate, which stimulate the stress/cortisol �fight or flight� response), excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia), hydrogen sulfide (producing �brain fog�), and alpha-keto glutarate (leading to �excitotoxicity�). The G6PDH enzyme system may be affected, leading to abnormalities in sugar control. Methylation intermediates will �fall through this drain�, so the entire system suffers; our defenses against viral invasion and toxicity suffer. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy."

There is a simplified protocol that ppl can use if they have not been tested for all the mutations.

There should be a link to it here plus info on glutathione depletion and methylation.

http://www.lymeinfo.net/methylationblock.html
 
Posted by RC1 (Member # 31923) on :
 
Terry, are you saying that if you have the CBS up regulation or SOUX that if you supplement with the methylfolate one would make their situation worse?
Those things are also a different test than the MTHRFR test?
Thanks.
R
 
Posted by TerryK (Member # 8552) on :
 
RC1 wrote -
Terry, are you saying that if you have the CBS up regulation or SOUX that if you supplement with the methylfolate one would make their situation worse?

I am quoting from the doctor's info on the heartfixer site regarding the CBS upregulation. Yasko also states the same thing. As I mentioned previously, I don't know if the SUOX mutation causes the same issues.

RF1 wrote:
Those things are also a different test than the MTHRFR test?

Yes, they are different genes in the methylation cycle.

I have the CBS upregulation and cannot tolerate sulfur food, supplements or drugs very well. I'm OK up to a point but eventually reach saturation and can't tolerate anymore. The threshold has been lowered considerably since I started methylation supplements in 2008. I find that I burn all over including the muscles when I use MSM, alpha lipoic acid, eat too much meat etc etc.... It also seems to disrupt my sleep but then many things do. I've had blood sugar issues for decades and despite a mainly low sugar, low carb diet I developed diabetes last year. My sulfur issues have been worse since I developed diabetes but I'm not sure if the sulfur issues got worse first and contributed to the development of diabetes or if the diabetes causes worse sulfur issues.

I use nutrimedix sparga as a sulfur detox which seems to help quite a bit. I also take bh4 and molybdenum. Yucca too sometimes. I use the charcoal flushes when I feel I need them. I limit sulfur supplements and foods.

My doctor put me on alpha ketogluterate to help get rid of ammonia and that caused no end of difficulty. If you have the CBS upregulation you will make too much alpha ketogluterate already.

There is a computer programmer named Mark London who disputes the CBS upregulation theory. You can search for his paper via google. He wrote a paper on another issue and while I found it interesting it was not entirely accurate and a bit misleading so I haven't bothered to read his thoughts on the CBS upregulation.

If you are really interested in methylation issues the 2 groups I gave links to a few posts up will be most useful.

This might be useful for some basics
http://www.vsan.org/rok-az/methylation/Methylation.pdf

Terry
 
Posted by RC1 (Member # 31923) on :
 
Thanks for that Terry, I have started having new symptoms since starting the methylfolate, mainly bone pain. It makes me wonder if it's a sulfur thing for me too, I have also had low blood sugar my whole life.

I'm going to have to take some time to learn more about this, thanks a lot for the links. I hope it's not sulfur because I already can't eat gluten period. I live off meat and veg.
 
Posted by tickled1 (Member # 14257) on :
 
If there's a possible 30 variations and everyone's response to treatment will be different it seems like an impossible thing to figure out and get control of.

If Yasko offers the testing and then it's a do-it-yourself of figuring out treatment after getting the results do people really have success with this? Does anyone know the statistics of how many are able to effectively treat their condition?
 
Posted by canefan17 (Member # 22149) on :
 
BioRay Liver Life is designed to balance the Phase 1 and 2 detox pathways.

Something to look in to
 
Posted by tickled1 (Member # 14257) on :
 
canefan,

Would the BioRay Liver Life help no matter what is messing with the pathways?

Does anyone know if I can draw any conclusions as to whether or not I have MTHFR and if so what kind from what my Metametrix tests indicated?

The tests shows that I have:

- high succinate (CoQ10 recommended)

- high hydroxymethglutarate (CoQ10 recommended)

- very high B-hydroxyisovalerate (Biotin, B2 recommended)

- high 5-Hydroxyindoleacetate ---

- high p-Hydroxyphenyllactate (Vitamin C,E recommended)

- 8-Hydroxy-2-deoxyguanosine (Vitamin C, E recommended)

- high Pyroglutamate (N-acetylcysteine, Glutathione, other sulfur containing a.a. recommended)

- high Phenylacetate (probiotics recommended)

- high D-lactate (Non D. Lactate forming probiotics recommended)

- low Lysine (L-lycine HCI recommended)

- low Isoleucine (L-Isoleucine recommended)

- low Leucine (L-Leucine recommended)

- low Valine (L-Valine recommended)

- high Tryptophan/LNAA

- high H. Pylori (I just finished Prev-Pac for this)

- high (+3) yeast/fungi (taxonomy unavailable)-"A taxonomy unavailable finding may indicate ingested mold. The higher the number, the greater the indication for treatment, particularly when accompanied by clincal symptoms." (range +1 - +4)

- positive for aacA, aphD drug resistance gene

- low Acetate %

- high Propionate %

Additional supps. recommended:

L-Phenylalanine

Taurine
L-Threonine
Glycine
Other Antioxidants strongly needed
Selenium

Showed Delayed allergy to:

Casein
Eggs
Lamb
Milk
Wheat


Input anyone? [Smile] I'd love to hear it!

I also just posted my results on my MTHFR thread if anyone would like to reply to this there. I don't want to hijack your post!
 
Posted by sparkle7 (Member # 10397) on :
 
What did your doctor say about your Metametrix test, tickled1?

I'm just starting out with all of this. I tried the Simplified Protocol & got pretty ill. I think I "provoked a response" for sure. This indictaes to me that I have more work in this area. So, I'm going to have to do the testing & concentrate on it further...

Dr. van Konynenburg has a section of a forum where he's kind enough to answer querries -

http://forums.phoenixrising.me/forumdisplay.php?49-Detox-Methylation-B12-Glutathione-Chelation

He recommended the test that Tammy N. did -

FYI -

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

Email: [email protected]

Lab Director: Elizabeth Valentine, M.D.

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

---

Anyway, there was a study with people with Fibro & this defect. I believe about 70% reported improvement. It is pretty significant.

RC1- I had the "bone pain" you mentioned.

Tammy N. & jlp38 - Yes, I believe that the genes are subject to change, too. With the study that was done with Fibro people, it sort of proves it...

http://www.endfatigue.com/health_articles_c/CFS_FM-methylation_protocol_byneil_nathan.html
 
Posted by sparkle7 (Member # 10397) on :
 
Canefan - I don't think this is a question of detox with herbs so much. It's about a genetic defect that can be corrected with proper supplementation - mainly particular B vitamins...

You can try the "Simplified Protocol" to address it but if you have issues with that it's good to get the genetic testing done & find out what you have to address. It's unique to each person...

Thanks for the info Terry - you've been on to this longer than most of us here.
 
Posted by TerryK (Member # 8552) on :
 
Glad you found something that may be useful for you sparkle. [Smile]

Many of the methylation issues cause one to generate less glutathione. Glutathione is a major detoxifier. Once you start unblocking the methylation issues you will start to detox. This can make one pretty sick.

Many ppl start releasing heavy metals and many other toxins according to Dr. Yasko's urine testing. Best to have detox agents on board.

tickled1 - I would go to the yahoo group (link I provided in a previous post in this thread) and ask your question there.

I thought Yasko's test was very comprehensive and no guess work is required. She gives a good analysis with a list of herbs and supplements for each mutation.

Depending on which genes are affected you could also start killing viruses and parasites and possibly other pathogens. I find the Yasko main site is very very helpful when learning but the heartfixer site is the best place to start reading in my opinion.

I have found the methylation supplements (especially the folic acid) to help me stay asleep. VERY HELPFUL. I don't have to deal with nearly the level of depression that I used to have. My problem is that it is hard to pin point exactly what is helping because I've been in lyme treatment at the same time. I can say without a doubt that sleep improved considerably and I credit the supplements with getting the depression that I used to have off my back.

The CBS upregulation issues are noticible to me as well, especially the burning muscles and all over body burning (including my nostrils!) when I get too much sulfur.

I don't get blue feet and hands anymore which I'm guessing in part is due to heavy metal detoxing via better methylation and lipophos EDTA.

Terry
 
Posted by TerryK (Member # 8552) on :
 
Ticked - I haven't checked recently but you used to be able to get on-going guidance and urine testing from Yasko. This will help guide you in knowing what to focus on and also in what you are excreting.

Of course it is not free!

Terry
 
Posted by tickled1 (Member # 14257) on :
 
I don't see my LLMD again until May. I am waiting for him to get back to me on a game plan hopefully next week soon. He was waiting for me to finish my Prev-Pac first. Sounded like he wanted to maybe address the mystery yeast next.

I have another chronic illness doc that told me to do 2 IV glutathione infusion per week. I can only afford it (barely) once per week at $75 each.
 
Posted by sparkle7 (Member # 10397) on :
 
Thanks Terry. I'm not sure which is best - doing the Yasko test or the one Rich Van K suggested...

He suggested the Methylation Pathways Panel by Health Diagnostics and Research Institute. I would need to find a doctor or chiropractor to help. He also posted this to help to understand the results -

(kind of long...)

Interpretation of Results of the Methylation Pathways Panel


by
Richard A. Van Konynenburg, Ph.D.
Independent Researcher
([email protected])


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 [email protected].

* 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/ww...ethylStudy.pdf)

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It was really nice that he took the time to reply to my questions on another message board!

I'm not sure which is better...? The Yasko test or the one Rich Van K mentions. The test Rich Van K lists is about $325 but I would need an MD or chiro. Maybe it's better to have some medical support while going through this. It's pretty complicated...

I got pretty ill from doing the simplified protocol for about 2-3 weeks! I could tell this may be a big piece of the puzzle. I already did alot of the parasite detox work. I never tested high for mercury but I have been exposed to other metals. I used to do sculpture with bronze & aluminum. I've also been exposed to other toxic stuff.

Makes alot of sense that my ill health may be do to insufficient detox genetics. I never really felt it was Lyme but I don't really know. I don't want to waste alot of money on tests to see if my doctor was wrong.

Better to just go forward. I've been dreading having to deal with a metal detox. Most of the other stuff I could handle on my own but I don't think I can do this step without some kind of medical help...

Methylation & metal detox are quite complicated. It seems like you are pretty much on your own after getting the Yasko test evaluated. It's kind of up to you to get the suggested supplements. How about any residual mop-up of toxins? Does she give any suggestions?

I'm glad I am up in the north again. I would never find any help with this down south where I was living...
 
Posted by sparkle7 (Member # 10397) on :
 
PS - tickled1 - Have you tried liposomal glutathionine? You can actually make it yourself with an ultrasonic blender. I made liposomal vit. C & it worked great! I'm about to make another batch. I haven't tried some of the other things you can make liposomally like curcumin, resveratrol, ubicquinol, etc.

My significant other got rid of a cold in 24 hours by taking the vit. C I made.
 
Posted by tickled1 (Member # 14257) on :
 
Sparkle, Thanks for that info! I skimmed through it briefly and will read it in detail when I have a little more time. I'm sure it will give me a better level of understanding with all this.

I haven't tried liposomal glutathione and I don't really know what it is. I'll look it up. I was under the impression that we couldn't absorb any glutathione taken orally.
 
Posted by sparkle7 (Member # 10397) on :
 
fyi-

http://www.liposomalglutathione.com/

STRUCTURE

A liposome, often called a vesicle, is an extremely small bubble. It is invisible to us, at about 1/2 the width of a human hair, but we have magnified one 50,000 times. Liposomes have a fat-soluble exterior and an interior that is watery. This watery interior can combine with water soluble materials such as glutathione. Our liposomes are multi-layered, as you can see in the diagram to the right.

Liposomes are made from the same type of material as our cell membranes, phospholipids. The phospholipids in our liposomes are derived from lecithin, which comes from oil extracted from soy, not soy protein.

The unique structure of liposomes allows them to encapsulate biologically active ingredients. In this case the liposomes keep glutathione in its �reduced�, or biologically active state. The liposomes in our product are very stable, which allows use in an oral drink.

HOW THEY WORK

Because they are made of the same type of material as our cell membranes, liposomes penetrate mucosal tissues allowing for rapid release into the blood stream. Nutrients that are not in liposomes have to pass through the stomach to reach the liver where they are metabolized and released into the bloodstream. Some nutrients are destroyed or compromised by stomach acids. Liposomes avoid the digestive system by penetrating the mucosal tissue.

A scientific article published in 1965 in the Journal of Molecular Biology (Bangham, A.D.et al) described these vesicles for the first time and explained their similarity to human membranes. Since that time liposomes have been the subject of great interest and study. Because of their adaptability, liposomes have a wide range of applications � from delivering anti-cancer drugs to providing gene therapy and skin care. To date, more than 35,000 articles have been published in scientific journals regarding liposomes.
 


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