Transsulfuration pathway - help with interpretation required

[BiancaS]

Hi, I received yesterday my amino acid urine panel back and would really appreciate some help with the interpretation. For clarification, this amino acid panel was taken just before the switch from HDXCBL and Folate to MTHCBL/ADCBL and 5-MTHF.

As far as I can see, there did not seem to be much of an issue with Folate. However, given that I had positive MMA on another test, I think that switching to the active forms of B12 was a good idea.

From serine/cystathinine levels, I guess there is a problem with the transsulfuration process (high serine/low cystathionine). I was deficient on Molyb, so that might be a cause. What is puzzeling though is the high level of Glycine and the fact that my intracellular glutathione levels have gone up significantlly. Since I used to supplment with iv Glutathione, I am not sure if this actally means that my methylition cycle is now producin glutathione, or if these are inflated results due to supplementation. My ATP level is still low, which means there is still a problem somewhere in the chain.

I am borderline KPU/HPU positive and it looks like I might have a heavy metal issue (aluminium, cadmium and plumb). Since detox is important, I am wondering if chelation is possible with DMPS or DMSA when there is an issue wh the transsulfuration pathway.

Thanks foryour help!

GABA 7 (5-12)
Alanin 97 (95-277)
Asparagin 83 (25-71) +
Cystein 47 (35-81)
Cystathionin 6 (<196)
Glutaminc acid 16 (1-14) +
Glutamin 402 (252-614)
Glycin 2839 (388-1179)+
Taurin 400.8 (90-800)
Histidin 481 (121-541)
Lysin 121 (36-96) +
Laucin 40 (18-39) +
Methionin 27 (3-38)
1-Methyl Histidin 150 (104-263)
3-Methyl Histidin 294 (<1022)
Phenylalanin 36 (9-42)
Serin 516 (124-246) +
Threonin 87 (37-114)
Tyrosin 61 (59-132)
Valin 31 (13-34)
Cirtullin 1,9 (<2,9)

 

[richvank]

Hi, I received yesterday my amino acid urine panel back and would really appreciate some help with the interpretation. For clarification, this amino acid panel was taken just before the switch from HDXCBL and Folate to MTHCBL/ADCBL and 5-MTHF.

As far as I can see, there did not seem to be much of an issue with Folate. However, given that I had positive MMA on another test, I think that switching to the active forms of B12 was a good idea.

From serine/cystathinine levels, I guess there is a problem with the transsulfuration process (high serine/low cystathionine). I was deficient on Molyb, so that might be a cause. What is puzzeling though is the high level of Glycine and the fact that my intracellular glutathione levels have gone up significantlly. Since I used to supplment with iv Glutathione, I am not sure if this actally means that my methylition cycle is now producin glutathione, or if these are inflated results due to supplementation. My ATP level is still low, which means there is still a problem somewhere in the chain.

I am borderline KPU/HPU positive and it looks like I might have a heavy metal issue (aluminium, cadmium and plumb). Since detox is important, I am wondering if chelation is possible with DMPS or DMSA when there is an issue wh the transsulfuration pathway.

Thanks foryour help!

GABA 7 (5-12)
Alanin 97 (95-277)
Asparagin 83 (25-71) +
Cystein 47 (35-81)
Cystathionin 6 (<196)
Glutaminc acid 16 (1-14) +
Glutamin 402 (252-614)
Glycin 2839 (388-1179)+
Taurin 400.8 (90-800)
Histidin 481 (121-541)
Lysin 121 (36-96) +
Laucin 40 (18-39) +
Methionin 27 (3-38)
1-Methyl Histidin 150 (104-263)
3-Methyl Histidin 294 (<1022)
Phenylalanin 36 (9-42)
Serin 516 (124-246) +
Threonin 87 (37-114)
Tyrosin 61 (59-132)
Valin 31 (13-34)
Cirtullin 1,9 (<2,9)

Hi, Bianca.

I've looked over your test results and your earlier posts. It looks as though you had some good testing done. I can't say that I understand all the results, though. The broad supplementation you have had makes it difficult to interpret your test results, because some things that might be expected to be low have been raised artificially by supplementation.

Since your recent results showed elevated MMA and leucine, I think that you must have low adenosyl B12, even though your blood serum B12 was high. Usually when adenosyl B12 is low, methyl B12 is also low. However, your results of normal methionine, SAMe, and homocysteine suggest that your methionine synthase reaction is operating normally, which suggests that there is enough methyl B12. However, your high MCV and low erythrocyte count indicate that the erythropoietic cells in the bone marrow do not have enough active folate. That would suggest that your reduced folate is low, which in turn would suggest that your methionine synthase reaction is not running at up to a normal rate. So this is puzzling to me. You also have a high ratio of phenylalanine to tyrosine, and that suggests low tetrahydrobiopterin (BH4), which also suggests that there might be a problem in the folate metabolism, since the biopterin cycle is linked to the folate metabolism.

You do appear to have low flow in your transsulfuration pathway, based on the high serine and low cystathionine, as you suggested. I realize that you are supplementing B6 and magnesium, and that B6 has tested normal, but there may still be insufficient B6 (or its active form, P5P, which requires B2 for its formation).

I suspect that you might be a person who has inherited a slow version of the DHFR enzyme, which converts folic acid to tetrahydrofolate, and also completes the thymidine synthesis pathway by converting dihydrofolate to tetrahydrofolate. It is also involved in the biopterin cycle. I think that could explain some of your results. Now that you have switched from folic acid to 5MTHF, that should help with the folate issues (high MCV, low erythrocyte count), and maybe the BH4 deficiency, also. (I think that the Thorne product is a racemic mixture of the active and inactive forms of methylfolate, so your effective dosage will be half of the nominal dosage of the supplement. Merck in Switzerlad and Germany have a patent on making Metafolin, which is the pure active form, but I don't know if it is sold there.) By taking adenosyl B12 directly, you should experience a lowering of the MMA level.

You initially had some indicators of low glutathione (measured low in immune cells, Hashimoto's hypothyroidism, poor cell-mediated immunity, buildup of toxic metals), but it seems that that has been corrected by the I.V.s and the oral acetyl glutathione.

It sounds as though the heavy antibiotics have knocked out the friendly flora in your gut, and these will need to be built back up with probiotics.

You appear to have mitochondrial dysfunction, based on the low ATP and the fatigue. It may be caused by toxin buildup.

As I say, I don't completely understand all your results. I guess these are all the comments I can make. So I guess you still have not found the prince. I hope that your switch to the different forms of B12 and folate will help you.

Best regards,

Rich

 

[BiancaS]

Hi RIch,

Thanks so much for taking the time to reply.

I am expecting my BH4 levels today, but I would also suspect them to be rather low. Am also waiting for the Yasko test to check for polymorphisms and NutrEVal should bring me further towards understanding the problem. How many day before taking the NutrEval would you suggest stopping all supplements to get realistic results?

Doctors suspect that my low erythrocyte count is due to intracellular pathogens (Bartonella), so that might be an explanation. I am taking 100mg a day of the active B6, but given that I have KPU, I am not sure this is enough. I think I might also be low on B2, so will add additional supplement of the active B2, plus moly. Have to check in Germany if the Merck 5-MTHF is sold here.

Until all test results are back, my main priority seems to be detox and pathogen killing ;-) Detox does not seem to be that simple. I had 2 months worth of iv ALA and Glutathione, which should have helped with Detox, but it doe not seem to do the trick. Maybe it's because I have a Val105 polymorphism in my GST-P1 enzyme. Therefore, I am looking into either DMSA or DMPS, but not sure if this can be taken if there is an issue with sulfuration? As an alternative, I am considering Apherese (plasma washing) that is used here to clean the plasma of toxins, pathogens, etc.

As far as I understand, as long as the methyliation cycle is not fully restored, it is very likely my glutathione will be depleted quickly if supplementation is stopped, so I guess the new intracellular levels do not relect actual glutathione production of the body, but reflect supplementation only?

Thanks again!

 

[richvank]

Hi RIch,

***Hi, Bianca.

Thanks so much for taking the time to reply.

***You're welcome.

I am expecting my BH4 levels today, but I would also suspect them to be rather low. Am also waiting for the Yasko test to check for polymorphisms and NutrEVal should bring me further towards understanding the problem.

***That sounds very good. I continue to be impressed at the comprehensive testing that you are doing. I've analyzed quite a few cases over the past few years, some of them very well documented, but I think yours takes the prize for the most thorough lab testing. Hopefully this will pay off for you.

How many day before taking the NutrEval would you suggest stopping all supplements to get realistic results.

***I think they send instructions about that with the test kit, and I would suggest just following them, if you can tolerate being off your supplements for the time they recommend. Nevertheless, I think it will be important to anyone attempting to understand the results that they have a knowledge of your detailed supplementation history.

Doctors suspect that my low erythrocyte count is due to intracellular pathogens (Bartonella), so that might be an explanation.

***O.K. I haven't had much experience with Bartonella.

I am taking 100mg a day of the active B6, but given that I have KPU, I am not sure this is enough.

***I don't know, either. I think Dr. Klinghardt recommends 4 x 75 mg = 300 mg per day of B6 plus P5P, using his "Core" supplement for KPU (HPU):
http://www.biopureeurope.com/core-mineral.html

I think I might also be low on B2, so will add additional supplement of the active B2, plus moly. Have to check in Germany if the Merck 5-MTHF is sold here.

***O.K.

Until all test results are back, my main priority seems to be detox and pathogen killing ;-) Detox does not seem to be that simple. I had 2 months worth of iv ALA and Glutathione, which should have helped with Detox, but it doe not seem to do the trick. Maybe it's because I have a Val105 polymorphism in my GST-P1 enzyme.

***I agree that that can interfere with the glutathionation Phase II detox pathway.

Therefore, I am looking into either DMSA or DMPS, but not sure if this can be taken if there is an issue with sulfuration?

***Some people do have difficulty tolerating these sulfur-containing chelators. I don't know how well you would tolerate them. You might also consider some of the other detoxifiers that Dr. Klinghardt uses, also shown on the above-mentioned website. In particular, he has reported good results with MicroSilica.

As an alternative, I am considering Apherese (plasma washing) that is used here to clean the plasma of toxins, pathogens, etc.

***I'm guessing that this is what is called hemoperfusion in the U.S. Does it involve passing the blood over a bed of activated charcoal? I understand that this is used by toxicologists in some poison control centers in the U.S., but I don't think its use is very widespread here. It sounds to me like a very powerful technique, and one that may be necessary when the detox system is not able to deal with the toxins, such as for genomic reasons, as you have mentioned. I have suggested it to two people because of their particular toxicity issues. The first was not able to do it, and unfortunately died. She had a high body burden of polybrominated biphenyl flame retardant, due to its being accidentally put into cattle feed in Michigan in the 1970s. I don't know whether the second has followed up on my suggestion or not. I would like to know more about the outcomes of this type of treatment.

As far as I understand, as long as the methyliation cycle is not fully restored, it is very likely my glutathione will be depleted quickly if supplementation is stopped, so I guess the new intracellular levels do not relect actual glutathione production of the body, but reflect supplementation only?

***I think that is true, though it sounds as though you have been able to raise your glutathione pretty well by supplementation. One concern I have is whether the body is able to recycle the added glutathione when it becomes oxidized. This requires the glutathione reductase reaction, which needs B2 and B3. B1 in the form of benfotiamine would probably also be helpful, because it stimulates transketolase, which helps to move glucose into the pentose phosphate shunt on the glycolysis pathway. This is the pathway that makes NADPH (containing niacin or B3), and NADPH is the form of B3 needed by the glutathione reductase reaction. In the long run, it does appear to be necessary to lift the partial methylation cycle block in order to keep glutathione up in a sustained way.

***I don't know if you have had the methylation pathways panel (offered in Europe by the European Laboratory of Nutrients in the Netherlands). If not, and if it is feasible for you to do so, I think this panel would give some useful information about your methylation, folate, and glutathione status.

Thanks again!

***You're welcome.

***Best regards,

***Rich

 

[aquariusgirl]

hi bianca
if you go ahead with the apharesis...could you please post about it here?
thanks!

 

[BiancaS]

Hi,

Will do. It's called cellabsorptionapheresis or so. They are running your plasma through specialised filters, depending on what they re treating for (apheresis is indicated in various conditions), but in the case of lyme, cfs, mcs, I understand they are using a filter called Cellsorption if I am not wrong. They are following the guidelines of international apheresis organisation (not the german one - thank god). He also said that after the apheresis, you get ivs with mitochondiral support, liver support, etc and they are also tesing what would be the best therapeutical way to balance out Th1/Th2. The doctor running the center is an environmental doctor, who specialises in immunology and immunotoxicology.
After your first session, they remove your sludge and will do an indepth analysis of what is going on in your body, based on what they have found there. Sessions are done with 14 days inbetween and th number you need depends on what they find in your blood after your fist session. OK, that's the theory, let me see how it works in practice.

Rich, I will be looking at the methylation pathway panel in Europe and will run that as well. I tested positive for slight oxidative stress, so there might be an issue with theredused vs oxidated glutathione. I currently take 150 mg of benfotiamine and 100mg of thiamine. B3 is 100mg per day. B2 is certainly my current weak spot and will get the active form as soon as possible.

 

[richvank]

Hi,

Will do. It's called cellabsorptionapheresis or so. They are running your plasma through specialised filters, depending on what they re treating for (apheresis is indicated in various conditions), but in the case of lyme, cfs, mcs, I understand they are using a filter called Cellsorption if I am not wrong. They are following the guidelines of international apheresis organisation (not the german one - thank god). He also said that after the apheresis, you get ivs with mitochondiral support, liver support, etc and they are also tesing what would be the best therapeutical way to balance out Th1/Th2. The doctor running the center is an environmental doctor, who specialises in immunology and immunotoxicology.
After your first session, they remove your sludge and will do an indepth analysis of what is going on in your body, based on what they have found there. Sessions are done with 14 days inbetween and th number you need depends on what they find in your blood after your fist session. OK, that's the theory, let me see how it works in practice.

Rich, I will be looking at the methylation pathway panel in Europe and will run that as well. I tested positive for slight oxidative stress, so there might be an issue with theredused vs oxidated glutathione. I currently take 150 mg of benfotiamine and 100mg of thiamine. B3 is 100mg per day. B2 is certainly my current weak spot and will get the active form as soon as possible.

Hi, Bianca.

This all sounds really good: the apheresis, the methylation pathways panel, and the B vitamins.

This use of apheresis sounds really innovative. I wonder if they have published any results on this approach. I'll have to look in PubMed. It sounds as though it could be helpful to many people, especially those whose immune system and detox system are not able to clear toxins from the blood adequately.

Best regards,

Rich

 

[BiancaS]

I looked at their website and the mention something about collecting data on what they find in the plasma and publishing it. The website is unfortunately in German. http://www.inus-world.de/de/privates-apherese-und-dialysezentrum Will ask the doctor if they have their material in English as well, as I would think this might be interesting for people outside of Germany as well. Will keep you posted.

 

[lucyhem]

Help with interpretatin of Methylation Panel

Hi all
I am up and running with the protocol and the Health Diagnostic's test.
I would like some help with interpretation.


Glutathione (oxidised) .54 [/B] (.16-.500)
Glutathione (reduced) 3.0 (3.8-5.5)
S-Adenosylmethionine (RBC) 239 (221-256)
S-adenosylhomocysteine (RBC) 56.6 (38-49)

FOLIC ACID DERIVIATIVES
5-CH3-THF 9.0 (8.4-72.6)
10 Formyl-THF 1.2 (1.5-8.2)
5-Formyl-THF 1.9 (1.2-11.7)
THF 1.04 (.60-6.80)
Folic Acid 10.2 (8.9-24.6)
Folinic Acid (WB) 9.7 (9-35.5)
Folic Acid (RBC) 312 (400-1500)

Adenosine 24.9 (16.8-21.4)

These are the preliminary results faxed to my doctor. I don't know if the final results will be more detailed or complete.

I am happy to find a test the finally confirms some of what i have been experiencing!
How often do people retest to track progress?
My doctor who treats autistic children had some recommendations based on his experience. I would like some feedback on that.
He suggested raising Glutathione w NAC.
He also recommended B6, TMG and DMG.

I am up to almost a full dose of the Simplified Methylation Protocol for about a week. I am still not on a full dose of the neurological health formula but I am with the methylmate, folinic acid and B12. Have not got the Lecithin yet but will soon. I am not having any significant NEW reactions, but i have constant fluctuations of symptoms so it is a little hard to track. My first day on the almost full protocol I had one of those I Feel-Like-MySelf-Again days, preceded by a full uneventful, restful nights sleep, which is rare. But that has not occurred again.

My sense about the methylfolate is that my body loves it. But I am not sure about the B12. I am know there is talk about trying other forms of B12 and I will look back at Fredd's posts. Any thoughts about the welcomed.

Thank you for your help,

Lucy H.

 

[lucyhem]

PS I have the double 677T gene variant. That is the only one I have tested.

 

[richvank]

***Hi, Lucy.

Hi all
I am up and running with the protocol and the Health Diagnostic's test.

***Sounds good!

I would like some help with interpretation.

***O.K.

Glutathione (oxidised) .54 [/B] (.16-.500)
Glutathione (reduced) 3.0 (3.8-5.5)

***This combination means that you are suffering from glutathione depletion and oxidative stress.

S-Adenosylmethionine (RBC) 239 (221-256)
S-adenosylhomocysteine (RBC) 56.6 (38-49)

***This combination means that you have a partial block in your methylation cycle. Your SAMe level is at the mean of the normal reference range, but your SAH level is high. The ratio of SAMe to SAH affects the rates of most of the methylation reactions in the body, and yours will be slowed because of the high SAH level.

FOLIC ACID DERIVIATIVES
5-CH3-THF 9.0 (8.4-72.6)

***This is methylfolate, and your level is pretty low. You've reported that you have SNPs in the MTHFR enzyme, which makes this form of folate, and that will contribute to your low level. There would clearly be a benefit to you to supplement methylfolate.

10 Formyl-THF 1.2 (1.5-8.2)

***This form of folate is below the reference range. It is used to make purines, which are necessary for making RNA and DNA. The low value will affect your body's ability to make new cells, and this will likely show up first with the blood cells and the cells lining the gut. Supplementing folinic acid will likely help to raise this level (I realize that you will get conflicting advice from Freddd about folinic acid, and I'm sorry about that, but I think it will help here.). Note below that your whole blood folinic acid level is low normal, as is the level in your blood plasma (as shown by the 5-Formyl-THF value, which means the same as folinic acid. These are the same substance, just measured in different blood compartments).

5-Formyl-THF 1.9 (1.2-11.7)
THF 1.04 (.60-6.80)
Folic Acid 10.2 (8.9-24.6)
Folinic Acid (WB) 9.7 (9-35.5)

***These forms of folate are all low-normal. This is evidence that folate has drained from your cells via the "methyl trap" mechanism, which is a consequence of the partial block of methionine synthase in the methylation cycle.

Folic Acid (RBC) 312 (400-1500)

***This is further evidence of oxidative stress. The cell membranes have been damaged by oxidative stress and are leaky. The phosphatidylserine complex or lecithin in the protocol should help to repair them.

Adenosine 24.9 (16.8-21.4)

***I don't have an interpretation of this one. Several factors seem to influence the level of adenosine.

These are the preliminary results faxed to my doctor. I don't know if the final results will be more detailed or complete.

***No, you received the complete report that the lab sends out.

I am happy to find a test the finally confirms some of what i have been experiencing!

***Well, I guess that is a cause for rejoicing, though we have kind of a twisted view of things! These results do show that you suffer from the combination of glutathione depletion, partial methylation cycle block, and folate draining from the cells. This also implies that you have a functional B12 deficiency, though that is not evaluated directly in this test panel. The best measure of that would be a high methylmalonate value on a urine organic acids test, such as the Genova Diagnostics Metabolic Analysis Profile.
I believe that these results also mean that the Glutathione Depletion--Methylation Cycle Block hypothesis does fit your case, and that you should benefit from treatment to lift the partial methylation cycle block.

How often do people retest to track progress?

***I suggest every 3 months. This is the interval we used in our clinical study. It gives time for significant changes, and there is a data set with which to compare, from the clinical study.

My doctor who treats autistic children had some recommendations based on his experience. I would like some feedback on that.
He suggested raising Glutathione w NAC.

***I prefer to raise glutathione automatically by lifting the partial methylation cycle block. Some people benefit from NAC, and some do not tolerate it well. Freddd is one who does not tolerate it, and found that it set him back. If NAC is used in a person who may have a high body burden of inorganic mercury, it is best to limit the daily dosage to 300 mg, because NAC has been shown to move mercury into the brain in rat studies by Aposhian et al.

He also recommended B6, TMG and DMG.

***I think B6 would be a good idea in your case, because you have a normal value for SAMe and a high value for SAH, together with glutathione depletion. This suggests that you would benefit by draining more homocysteine into the transsulfuration pathway. B6 will help this. Make sure you have enough B2, also, because it is needed to convert B6 into its active form, P5P, in the cells. Magnesium will also support the transsulfuration pathway enzymes.

***There is some TMG in the multi that is part of the protocol. The benefit of this is that it will stimulate the BHMT pathway in the liver and kidneys, which will help to make SAMe. Your SAMe level already looks pretty good, so you may not need more TMG.

***DMG slows the BHMT pathway. Since you have been supplementing B12 and the folates for some time now, I think it would be O.K. to add some DMG. This will shunt more of the homocysteine from the BHMT pathway to the methionine synthase pathway, which is the one that is partially blocked.

I am up to almost a full dose of the Simplified Methylation Protocol for about a week. I am still not on a full dose of the neurological health formula but I am with the methylmate, folinic acid and B12. Have not got the Lecithin yet but will soon. I am not having any significant NEW reactions, but i have constant fluctuations of symptoms so it is a little hard to track. My first day on the almost full protocol I had one of those I Feel-Like-MySelf-Again days, preceded by a full uneventful, restful nights sleep, which is rare. But that has not occurred again.

***Things are likely to bounce around at first, but if you hang in for 3 months on this protocol, it should be clear whether it is helping or not.

My sense about the methylfolate is that my body loves it.

***Your sense is supported by your low-normal methylfolate level in the lab panel and by your known SNPs in the MTHFR enzyme.

But I am not sure about the B12. I am know there is talk about trying other forms of B12 and I will look back at Fredd's posts. Any thoughts about the welcomed.

***Yes, Freddd feels strongly that hydroxocobalamin is not the form of B12 to use, based on his experience and the experiences of some others. However, in our clinical study, in which we did repeated lab measurements, we found that over two-thirds of the patients received significant benefit with hydroxocobalamin in the protocol. It is of course up to you to choose your course of action, but I would suggest staying with hydroxocobalamin for 3 months before deciding which way to go after that. This issue seems to depend on the individual genetic makeup of each person.

Thank you for your help,

***You're welcome.

***Rich

Lucy H.

 

[richvank]

I looked at their website and the mention something about collecting data on what they find in the plasma and publishing it. The website is unfortunately in German. http://www.inus-world.de/de/privates-apherese-und-dialysezentrum Will ask the doctor if they have their material in English as well, as I would think this might be interesting for people outside of Germany as well. Will keep you posted.

Thanks, Bianca. I see that there are some published papers on this. Looks like most of them are involved with using this technique to lower cholesterol. I think that analyzing what is pulled out of the blood by this method is a very good idea.

Best regards,

Rich

 

[lucyhem]

a few more questions

Rich
Thank you so much for your quick and thorough response. A few more questions.
Do you recommend a dosage and kind of B6 and B2? Is it P5P plus B6 or just P5P? I can buy supplements wholesale as I am a healthcare provider. The B6 seems to come in 50 mg capsules.

I think think that the folinic acid is fine for me. Does one ever raise that dose?

Re B12, I can get the injectable. Do you think it would be worth trying injecting again now that i have the methylfolate, which I did not last time I tried the injections. IF so, what dosage do you recommend?

What is the BMHT pathway? I am a bit confused by the last bit about stimulating and also slowing the BMHT pathway.

You refer to a study already completed. Are there published results from that?
Have people had the experience of feeling more symptoms at first, then better, on this protocol?

 

[richvank]

***Hi, Lucy.

Rich
Thank you so much for your quick and thorough response.

***You're welcome.

A few more questions.
Do you recommend a dosage and kind of B6 and B2? Is it P5P plus B6 or just P5P? I can buy supplements wholesale as I am a healthcare provider. The B6 seems to come in 50 mg capsules.

***I don't have a recommendation on dosage, except that going really high on B6 can cause neuropathy. That takes of the order of a gram a day, though, and it is reversible by stopping the B6. You might have to experiment with dosage, but 50 mg is a good place to start. People with KPU (HPU) have to use bigger dosages, because B6 is one of the nutrients that are lost in this disorder. P5P probably doesn't do much good over plain B6, if taken orally, because an enzyme in the gut removes the phosphate group before it is absorbed. (Then the phosphate group is put back on by the liver before the P5P is put into the bloodstream. Then the phosphate group is removed yet again before transport into the cells. Inside the cells, the phosphate group is put back on again, to make the active form and to keep it in the cells.)

I think that the folinic acid is fine for me. Does one ever raise that dose?

***Yes, people do all sorts of things! -) There is a competition for absorption beween the folate forms, and the most important one to get into the cells is the methylfolate, because it is needed by methionine synthase, the enzyme that is partially blocked in M.E. When this enzyme gets going at a normal rate, it will produce tetrahydrofolate, which is the "hub" of the folate metabolism, and can be converted into other folate forms. So I guess I think it's best not to push folinic acid too high, relative to methylfolate. The problem should eventually take care of itself.

Re B12, I can get the injectable. Do you think it would be worth trying injecting again now that i have the methylfolate, which I did not last time I tried the injections. IF so, what dosage do you recommend?

***I think that injecting is a very good way to get it into the blood, more efficiently than sublingual application. I would suggest starting low, at about 1 milligram per day, and working up as tolerated.

What is the BMHT pathway? I am a bit confused by the last bit about stimulating and also slowing the BMHT pathway.

***The BHMT pathway is an alternative pathway that converts homocysteine to methionine, found only in the liver and kidneys. BHMT stands for the enzyme betaine homocysteine methyltransferase. Its reactants are homocysteine and betaine (also called TMG or trimethylglycine). Its products are methionine and DMG (dimethylglycine). If a person is very low in SAMe, this reaction can be used to promote production of SAMe initially by taking TMG, and then it can be inhibited later (by product inhibition of the reaction) by taking DMG. The SAMe is helpful for recycling cobalamin for the methionine synthase reaction, which is the one we really want to stimulate in M.E., but the BHMT pathway can take homocysteine away from the methionine synthase reaction. By encouraging the BHMT reaction at first, and the inhibiting it later, after the B12 and methylfolate has been raised in the body, one can get the benefit of the SAMe production while avoiding the competition for homocysteine. It is important to get the methionine synthase reaction going, because it involves the folate metabolism as well, and also because it regulates the rest of the sulfur metabolism.

You refer to a study already completed. Are there published results from that?

***You can find the report here:

http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf

Have people had the experience of feeling more symptoms at first, then better, on this protocol?

***Yes, most do have that experience. I think it is due to mobilization of toxins, as the improving function of the sulfur metabolism brings the detox system and the immune system back up to more normal operation. They go to work on the backlog of toxins and pathogens that have accumulated during the illness.

***Best regards,

***Rich

 

[rydra_wong]

***Hi, Lucy.



***Yes, most do have that experience. I think it is due to mobilization of toxins, as the improving function of the sulfur metabolism brings the detox system and the immune system back up to more normal operation. They go to work on the backlog of toxins and pathogens that have accumulated during the illness.

***Best regards,

***Rich

TMG protects against postprandial (after meal) homocysteine (neurotoxin) surges. So your average SAMe/homocysteine may be normal, but after meals homocysteine can go high causing damage still. The people who get the highest doses of TMG by diet get 2g/day. Unless you eat a lot of fruits and veggies you probably dont get that much. Keeping homocysteine low is an important key to longevity.

P5P protects the kidneys from glycation by blood suagr, whereas B6 does not. This has been proven. Also B6 in a dose as low as 100mg can cause neuropathy, whereas P5P does not. P5P is the active form. I dont know about how it is digested, only the study results from its consumption vs B6.

I did not know that P5P was important in PKU...that is BH4 deficiency, is it not? (Which I have). I cant pin it down for sure but I seem to need an extra 50mg P5P tablet besides what is in my Thorne Basic B. I did verify that for my genes, there is no difference in homocysteine between 50mg and 200mg P5P. This may be because I take 1g TMG and that route runs faster than any other route for homocysteine as it involves only 1 enzyme. Or it may have something to do with my AHCY genes slowing down the cycle in som eway (idk what the AHCY defects do to me, actually). I have a problem becomeing anemic post menopause...it seems like if I run out of my extra P5P pill I am gasping for air. But I cant tell for sure because times when I've tested I have been found to be low ferritin (but not low hemoglobin) and iron fixes it.

Very interesting. Thanks!
Rydra

 

[greenshots]

I can't say why exactly but I know that Yasko always recommends NADH with any glutathione since it often becomes oxidized & somehow drains a critical area, the MTR/MTRR. If the MTR goes down, you get into big trouble and don't make methyl B 12 or recycle it properly.

I also remember that just the leucine being elevated can mean clostridia but its been years since I understand that whole pathway and the results.

Angela