CONFIRMED FOLATE DEFICIENCIES - PLEASE POST HERE

[Freddd]

Sorry, HCY stands for?

Hi SJB,

Homocysteine. It's presence is associated with heart dieases, strokes, inflammation and all sorts of things. It's presence is caused by lack of mb12 and/or methylfolate and/or p5p. Prescriptions to reduce homocycteine such as Metanx (the best) contain methylb12, Metafolin and p5p. Older less effective ones contain cyanocbl, folic acid and b6.

 

[richvank]

Hi Rich,

I would like to expand on that. The MMA will detect specifically a shortage of adb12 in the mitochondria. The HCY test applies specifically to mb12 and/or methylfoalte and/or p5p. However, "normal" "in-range" levels of MMA and HCY do not show sufficiency. And that is the problem. The tests won't tell you what a trial will. The trial is needed whether the tests are run or not. They are not definitive. Somewhere on one of the threads is a listing of all the problems of relying on the tests in peer reviewd articles. They are not predictive of non-reponse and those markers don't show up until the system is extremely broken. They can tell you that you are in BAAAAD trouble but not that you would benefit. "Normal" is based on a popualtion with 50% having at least some deficiency.

Hi, Freddd.

I prefer the methylation pathways panel, which gives direct information about the status of the methylation cycle, the folate metabolism, and glutathione. For people with an ME/CFS diagnosis for whom I have results of both the methylation pathways panel and a urine MMA measurement, generally there is some elevation in MMA if the methylation pathways panel indicates a partial block in the methylation cycle. The MMA measurement is less direct than the methylation pathways panel, but I think it is still useful.

For people who have inborn errors of metabolism in their intracellular B12 processing enzymes, the situation is more complicated, because some of these mutations affect only methyl B12, not adenosyl B12, and thus MMA can be normal when there is a deficit in methyl B12, and hence a partial methylation cycle block. We need to start distinguishing which people have the various mutations, and it may be possible to do this with the 23andme.com panel. In your case, I think you have a mutation in the Cblc complementation group, and it seems to affect both your methyl B12 and your adenosyl B12, which is why supplementing both of them is helpful to you.

The homocysteine test is not as helpful in ME/CFS. If it is high or low, it does indicate that there is a problem. But if it is normal, there can still be a partial methylation cycle block. I think the reason is that the homocysteine level in this situation can be affected by the methionine status and by whether or not there are polymorphism in the CBS or AHCY genes.

Best regards,

Rich

 

[aquariusgirl]

Maybe one reason athene is not seeing any gains in spite of taking tons of B12 is that it is being oxidised by toxins.
Athene, are you on hydroxy? I injected 1ml of 25mg/ml for ages...I don't think it did a whole lot. It did do something in concert with the folates, but i suspected a lot of it was vaporised by toxins.

 

[Gloria H]

Another active folate supplement?

Freddd or anybody else ... I recently started Solgar metafolin. But Quatrefolic is the folate source in my Swanson B Complex that I started in mid Nov. In searching Phoenix forums, I didn't find any mention of Quatrefolic, a folate form made available recently. The other stuff in this B Complex looked good to me. If anybody has experience with Quatrefolic for CFS, I'd be very interested to hear of it. Here are a couple links:
http://www.gnosis-bio.com/quatrefolic.php
https://www.swansonvitamins.com/SWU533/ItemDetail

Blessing to you!

 

[readyforlife]

What is the difference between Metafolin and Folapro?

 

[richvank]

What is the difference between Metafolin and Folapro?

Hi, ready.

As far as the active ingredient is concerned, they are the same.

They both contain 5L-methyltetrahydrofolate, produced by the Merck process. FolaPro is sold by Metagenics. Metafolin is sold by Solgar. The Solgar Metafolin tablets contain mannitol, but the rest of the binders are pretty much the same as in FolaPro.

Best regards,

Rich

 

[maddietod]

From post #12, Rich:
"2. The problems with folinic acid could be due to a polymorphism in the MTHFS (not to be confused with MTHFR) enzyme. I suspect that Freddd has this mutation. This is the only enzyme that can convert folinic acid to another form of folate, from which it can be converted to yet others. If folinic acid builds up, it has been published that it will inhibit the SHMT reaction, and that will inhibit the production of 5-methyl tetrahydrofolate, which is the one needed by methionine synthase in the methylation cycle. It will also inhibit the formation of new RNA and DNA, for the production of new cells. This especially impacts the production of blood cells, cells lining the gut, and cells of the hair follicles, thus causing problems there especially."

Can I test for this polymorphism? Easily?

 

[L'engle]

I don't have anything definite yet. I've been taking 800-2000mcg metafolin with mb12 for several months. One thing I noticed when my illness got worse a few years ago is that vegetables I used to like, particularly green ones, seemed sickening to me. I would feel worse after eating them, in a general sort of way. Not stomach upset, just not quite right somehow. So I am planning to buffer vegetable intake with larger amounts of metafolin, such as 4000mcg before a meal and see if there is improvement in overall condition. I used to really like broccoli but just the sight of it now, yuck! Similar to a lesser extent for kale, spinach and green peppers, green onions, even lettuce sometimes. I still like other greens like bok choy and zuchini, but I am apt to wonder about the folate content.

I will post more if I find out anything more definite.

Some folate content of differnet vegetables, from www.whfoods.com:

broccoli: 57.33 mcg for 91g
kale: 16.90 mcg for 130 g
spinach: 262.80 mcg for 180g
bell peppers: 42.32 mcg for 92g
zucchini: 32.77 mcg for 113g
squash: 41.00 mcg for 205g
cauliflower: 60.99 mcg for 107g

Vegetables I'm ok with, like yams and cucumber, had no folate listed.

 

[richvank]

From post #12, Rich:
"2. The problems with folinic acid could be due to a polymorphism in the MTHFS (not to be confused with MTHFR) enzyme. I suspect that Freddd has this mutation. This is the only enzyme that can convert folinic acid to another form of folate, from which it can be converted to yet others. If folinic acid builds up, it has been published that it will inhibit the SHMT reaction, and that will inhibit the production of 5-methyl tetrahydrofolate, which is the one needed by methionine synthase in the methylation cycle. It will also inhibit the formation of new RNA and DNA, for the production of new cells. This especially impacts the production of blood cells, cells lining the gut, and cells of the hair follicles, thus causing problems there especially."

Can I test for this polymorphism? Easily?

Hi, Madie.

The 23andme.com polymorphisms panel characterizes several for the MTHFS gene, but I don't know which, if any of them, could be the one responsible for folinic acid intolerance.

Best regards,

Rich

 

[maddietod]

Ha ha! Yes I can test, but no I can't learn anything!

 

[richvank]

Ha ha! Yes I can test, but no I can't learn anything!

Right. Maybe not right now, but stay tuned!

Rich

 

[Rosebud Dairy]

I have had a POOR response to food intake of folic acid fortified food (the flour in my pizza) and later in the same day salad - raw leafy green vegetables.

I did not pre-load with metafolin before eating this foods, ( I am avoid like the plague any supplement with additional folic acid), and woke up the next day feeling like I'd been hit by a truck. --tired, brain fogged achy. Then I remembered, I took 5 HTP the night before to help with sleep.

These reactions are not as bad when I eat veggies that are lightly cooked -- carrots -- or leafy ones that are cooked for a long time, such as collards---even when I have fortified flour foods--I allow myself a little bit of sourdough bread. I wonder if I do better with sourdough breads, as the folic acid that starts there from forced supplementation of the flour is reduced or converted to SOMETHING more useable by my body by the fermentation process. I love fermented vegetables, and they do not cause as much of a problem - such as homemade saurkraut.

Something is going on with my foods. I just have yet to figure it out.

I do know one interested physician and one interested dietician.

So much to sort out!

Diet was careful yesterday -- feeling better today.

 

[richvank]

Hi, all.

As part of the effort to try to sort out who is intolerant to folic acid, folinic acid, glutathione and its constituents (as in NAC and whey protein), and who is not helped by forms of B2 other than methyl- and adenosyl-B12, and why, I am going to post my 23andme.com polymorphism results for three genes: DHFR, MTHFS, and MMACHC.

Here's the rationale: As far as I know, I personally do not have any of these issues, so comparing to my polymorphism results might be a place to start, though obviously N=1, with me being the 1, is not going to give statistical significance. I do think, though, that doing a comparison with the results of people who know they have one or the other of this issues might tell us whether any of the polymorphisms characterized by 23andme might be involved in producing these issues. Also, maybe some others who know that they don't have these issues will post their results, and that will help us to see which SNPs might be important. I hope you all will understand that I'm not setting myself up as the perfect genetic model, far from it! This is just a place to start. I suspect that we will find that if a person is homozygous for a certain crucial SNP, that may be what causes an intolerance of this sort. It might be a sufficiently clear result that we won't need a lot of people's data to figure it out.

Note that it is possible that the SNPs characterized by 23andme might not include the ones that are important to us in the present context, but on the other hand, they may, and this is at least a place to start.

Note also that the intolerance of folic acid may be biochemical in nature (such as having low NADPH) rather than genetic, and if so, we won't find a connection here, but I think it is worth a try.

O.K., first the folic acid intolerance. If it's genetic, I think it must involve the DHFR gene, because that one codes for an enzyme that must be used to chemically reduce folic acid before it can be used. If that reaction is slow, folic acid will build up in the blood and could hinder the transport of active folates into the cells. So here are my polymorphism results for DHFR:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
DHFR 79960547 rs7387 A or T TT
DHFR 79970592 rs1643659 C or T TT
DHFR 79972074 rs1677693 G or T GG
DHFR 79975205 rs1643649 C or T TT
DHFR 79975227 rs11951910 C or T TT
DHFR 79978113 rs865646 G or T GG
DHFR 79980489 rs13161245 A or G AA
DHFR 79980896 rs10072026 C or T TT
DHFR 79983754 rs11490741 C or T CC
DHFR 79983761 rs863215 C or T CC
DHFR 79985331 rs1478834 A or C CC
DHFR, MSH3 79986537 rs1650697 A or G GG


O.K., next is folinic acid intolerance. I think this has to involve the MTHFS gene, because it codes for the only enzyme that can convert folinic acid to another form of folate, which can then be converted to others. If this reaction is slow, folinic acid can build up, and that will inhibit the SHMT reaction, which will hinder the synthesis of 5-MTHF, needed for the methylation cycle. So here are my MTHFS results:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
MTHFS 77924615 rs8923 C or T CT
MTHFS 77925626 rs2733103 C or T CC
MTHFS 77925800 rs16971427 A or C AA
MTHFS 77929052 rs655473 A or G AA
MTHFS 77931252 rs17284990 C or T TT
MTHFS 77941626 rs16971450 A or G AA
MTHFS 77942037 rs6495446 C or T CT
MTHFS 77945097 rs7177659 A or C CC
MTHFS 77945214 rs6495449 A or G GG
MTHFS 77949320 rs17285431 A or C AC
MTHFS 77951108 rs6495451 C or T CT
MTHFS 77952423 rs2586154 A or G GG
MTHFS 77955337 rs12899781 G or T GT
MTHFS 77959026 rs16971478 A or G AA
MTHFS 77959188 rs2586153 C or T CC
MTHFS 77961443 rs2562744 A or C AA
MTHFS 77964742 rs2733106 A or G AA
MTHFS 77965338 rs12438477 A or C CC
MTHFS 77969105 rs12898642 C or T CT
MTHFS 77970821 rs2586182 A or C AA
MTHFS 77971712 rs2733088 A or G AG
MTHFS 77973395 rs12440798 C or T CC

O.K., now the combination of the other features: intolerance of glutathione, NAC, and whey protein, and inability to utilize forms of B12 other than methyl- and adenosyl-B12. There are more than one mutation that can cause this, but the most common is mutations in the MMACHC gene, which codes for the CblC complementation group. Here are my results for that one:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
MMACHC 45743033 rs12029322 C or T CC
MMACHC 45744346 rs10789465 C or T CT
MMACHC 45746515 rs2275276 A or G AG
MMACHC 45746525 i5004496 C or T CC
MMACHC 45746541 i5004494 C or T TT
MMACHC 45746588 i5004495 C or T CC
MMACHC 45747107 i5004497 A or G GG
MMACHC 45747363 rs16832550 C or T CC
MMACHC 45748734 rs882803 A or G AG

O.K., that's it. I may have opened a Pandora's box, because the comparisons may be pretty complex with all these possible polymorphisms, but maybe something helpful will come out of this.

Best regards,

Rich

 

[therron]

I haven't tried folic acid or folinic. My experiences with methylfolate tell me that my folate deficiency manifests as neuropathy. I know this because my neuropathy completely disappeared after adding a 2nd and equal dose of methylfolate to my day. Although other gains have disappeared, lack of neuropathy has remained. Hurray!

 

[maddietod]

Therron, do you notice a difference when you do or don't eat vegetables?

 

[Freddd]

Hi, all.

As part of the effort to try to sort out who is intolerant to folic acid, folinic acid, glutathione and its constituents (as in NAC and whey protein), and who is not helped by forms of B2 other than methyl- and adenosyl-B12, and why, I am going to post my 23andme.com polymorphism results for three genes: DHFR, MTHFS, and MMACHC.

Here's the rationale: As far as I know, I personally do not have any of these issues, so comparing to my polymorphism results might be a place to start, though obviously N=1, with me being the 1, is not going to give statistical significance. I do think, though, that doing a comparison with the results of people who know they have one or the other of this issues might tell us whether any of the polymorphisms characterized by 23andme might be involved in producing these issues. Also, maybe some others who know that they don't have these issues will post their results, and that will help us to see which SNPs might be important. I hope you all will understand that I'm not setting myself up as the perfect genetic model, far from it! This is just a place to start. I suspect that we will find that if a person is homozygous for a certain crucial SNP, that may be what causes an intolerance of this sort. It might be a sufficiently clear result that we won't need a lot of people's data to figure it out.

Note that it is possible that the SNPs characterized by 23andme might not include the ones that are important to us in the present context, but on the other hand, they may, and this is at least a place to start.

Note also that the intolerance of folic acid may be biochemical in nature (such as having low NADPH) rather than genetic, and if so, we won't find a connection here, but I think it is worth a try.

O.K., first the folic acid intolerance. If it's genetic, I think it must involve the DHFR gene, because that one codes for an enzyme that must be used to chemically reduce folic acid before it can be used. If that reaction is slow, folic acid will build up in the blood and could hinder the transport of active folates into the cells. So here are my polymorphism results for DHFR:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
DHFR 79960547 rs7387 A or T TT
DHFR 79970592 rs1643659 C or T TT
DHFR 79972074 rs1677693 G or T GG
DHFR 79975205 rs1643649 C or T TT
DHFR 79975227 rs11951910 C or T TT
DHFR 79978113 rs865646 G or T GG
DHFR 79980489 rs13161245 A or G AA
DHFR 79980896 rs10072026 C or T TT
DHFR 79983754 rs11490741 C or T CC
DHFR 79983761 rs863215 C or T CC
DHFR 79985331 rs1478834 A or C CC
DHFR, MSH3 79986537 rs1650697 A or G GG


O.K., next is folinic acid intolerance. I think this has to involve the MTHFS gene, because it codes for the only enzyme that can convert folinic acid to another form of folate, which can then be converted to others. If this reaction is slow, folinic acid can build up, and that will inhibit the SHMT reaction, which will hinder the synthesis of 5-MTHF, needed for the methylation cycle. So here are my MTHFS results:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
MTHFS 77924615 rs8923 C or T CT
MTHFS 77925626 rs2733103 C or T CC
MTHFS 77925800 rs16971427 A or C AA
MTHFS 77929052 rs655473 A or G AA
MTHFS 77931252 rs17284990 C or T TT
MTHFS 77941626 rs16971450 A or G AA
MTHFS 77942037 rs6495446 C or T CT
MTHFS 77945097 rs7177659 A or C CC
MTHFS 77945214 rs6495449 A or G GG
MTHFS 77949320 rs17285431 A or C AC
MTHFS 77951108 rs6495451 C or T CT
MTHFS 77952423 rs2586154 A or G GG
MTHFS 77955337 rs12899781 G or T GT
MTHFS 77959026 rs16971478 A or G AA
MTHFS 77959188 rs2586153 C or T CC
MTHFS 77961443 rs2562744 A or C AA
MTHFS 77964742 rs2733106 A or G AA
MTHFS 77965338 rs12438477 A or C CC
MTHFS 77969105 rs12898642 C or T CT
MTHFS 77970821 rs2586182 A or C AA
MTHFS 77971712 rs2733088 A or G AG
MTHFS 77973395 rs12440798 C or T CC

O.K., now the combination of the other features: intolerance of glutathione, NAC, and whey protein, and inability to utilize forms of B12 other than methyl- and adenosyl-B12. There are more than one mutation that can cause this, but the most common is mutations in the MMACHC gene, which codes for the CblC complementation group. Here are my results for that one:

Gene Position SNP Versions Richard Van Konynenburg's Genotype
MMACHC 45743033 rs12029322 C or T CC
MMACHC 45744346 rs10789465 C or T CT
MMACHC 45746515 rs2275276 A or G AG
MMACHC 45746525 i5004496 C or T CC
MMACHC 45746541 i5004494 C or T TT
MMACHC 45746588 i5004495 C or T CC
MMACHC 45747107 i5004497 A or G GG
MMACHC 45747363 rs16832550 C or T CC
MMACHC 45748734 rs882803 A or G AG

O.K., that's it. I may have opened a Pandora's box, because the comparisons may be pretty complex with all these possible polymorphisms, but maybe something helpful will come out of this.

Best regards,

Rich

Hi Rich,

The software I had shelved for a while and am getting busy on again has some proprietary things going on inside of it but suffice it to say, it collects information in the terms of "characteristics" which can include symptoms, side effects, diagnoses correct or incorrect, test results of all sorts, supplements, medications, procedures, ANYTHING at all, and then identifies patterns, large and small, and patterns of patterns. So even an incorrect diagnosis of "alcoholic" based on the pattern of blood work can be useful and significant. If I had that functioning and we had the data from 100 people or so with various paradoxical folate deficiencies and the genetic and 100 people that didn't have any form of paradoxical deficiency we could identify the genetic patterns if they were included in the tests. This gives me renewed deisre to get this done.

 

[maddietod]

They can't send this test to Maryland; I'm looking for a workaround.

 

[therron]

Therron, do you notice a difference when you do or don't eat vegetables?

I can't say that I notice any immediate differences. I can tell you that my health has continued to decline while eating the most "wholesome" diet of anyone I know. I have a huge organic garden and my own chickens. My food is much safer as far as pesticides, etc, but I do wonder if it affects my folate metabolism like Freddd. By the way, I am compound heterozygous for MTHFR 677 and 1298...............double whammy.

 

[Freddd]

I can't say that I notice any immediate differences. I can tell you that my health has continued to decline while eating the most "wholesome" diet of anyone I know. I have a huge organic garden and my own chickens. My food is much safer as far as pesticides, etc, but I do wonder if it affects my folate metabolism like Freddd. By the way, I am compound heterozygous for MTHFR 677 and 1298...............double whammy.

Hi Therron,

As another organic gardener who enjoys the fruits of my labor, it is a hell of a thing to find out that the very things I thought should be helping me, and that I enjoy, were destroying my health. I have to be very careful now how much of the veggies I eat. I find that if I take 3200mcg of Metafolin with each meal I'm less likely to have a paradoxical folate deficiency episode that causes any of the usual symptoms than if I take only 1600mcg or 2400mcg with each meal, within the same daily dose total of 12,800mcg. I'm still experimenting to see how I can keep from have paradoxical folate deficiency. I have never made it an entire month yet.

 

[Athene]

Since I stopped taking my B-complex with folic acid, I've had a headache from hell - 4 days of relentless, extreme pain. Is this likely to be connected?