CONFIRMED FOLATE DEFICIENCIES - PLEASE POST HERE

soulfeast

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Rich,

is enada (nadh) the same as nadph?

http://www.iherb.com/Source-Naturals-ENADA-NADH-5-0-mg-30-Tablets/4855?at=0

I may experiement with the folinic vs metafolin first or add in the enada if this is correct. I think it is from my memories of yasko work but want to make sure.

Where do we find the correct tests:

https://www.23andme.com/

Thank you..



Hi, Athene.

For what it's worth, I think that the problems with folic acid, folinic acid and glutathione (including supplements that help to build glutathione, such as NAC and whey protein) that some people experience are all separate issues. While Freddd reports having all of them, I don't believe that they necessarily go together in everyone who has one or another of them.

My current working hypothesis for these is as follows:

1. The problems with folic acid could be due to a person having inherited a slow form of the DHFR enzyme, so that they are not able to convert folic acid to tetrahydrofolate at as high a rate as normal. It has been published that people vary by a factor of five (500%) in their ability to do this. If folic acid is not converted, it enters the blood stream and competes with active forms of folate for entry into the cells. This would lower the availability of 5-methyl tetrahydrofolate in the cells, which would produce a partial methylation cycle block. Another way that folic acid could cause problems is that this conversion requires NADPH, which Dr. Cheney has found to be low in many of his ME/CFS patients. If this reaction lowers NADPH further, it will not be available to support other reactions in the methylation cycle and the folate metabolism, as well as glutathione reductase. This would cause problems in all those parts of the metabolism.

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.

3. The problems with glutathione and associated substances are likely due to an inherited mutation in the CblC complementation group (coded by the MMACHC gene), which is part of the B12 processing pathway inside the cells. If certain mutations are present in this gene, the result will be that glutathione will bind B12 as glutathionylcobalamin, and the cells will not be able to make use of it. This will then cause a partial methylation cycle block and a lowering of the feeding of fuel to the Krebs cycle in the mitochondria, lowering the ATP production of the cells. I think that Freddd has this one, too. Associated with this type of mutation is also an inability to use cyanocobalamin or hydroxocobalamin as one's B12 source, because the Cblc complementation group is responsible for preparing these for conversion to the coenzyme forms of B12 (methyl B12 and adenosyl B12). People who have this type of mutation, which I think Freddd has, need to put large amounts of these two coenzyme B12 forms into their blood, either sublingually or by injection, in order to force enough of them to diffuse directly into the cells to be used without further processing inside the cells.

I should also note that if a person is particularly low in NADPH, I suspect that they will also have problems with glutathione and related substances, because they will not be able to reduce glutathione readily after it becomes oxidized. This will cause a buildup of oxidized glutathione and thus shift the redox potential in the oxidizing direction, worsening the oxidative stress and exacerbating all the associated symptoms. I suspect that this problem would show up more slowly than the problem I just described involving Cblc.

So my point is that I believe that a given person who has ME/CFS may have one of these issues without having all of them, and as far as I can tell, most of the people don't have any of them. I'm basing this on the results of the clinical study that Dr. Nathan and I carried out, in which we used folic acid, folinic acid and hydroxocobalamin, and about two-thirds of the people had significant improvement. It is certainly possible that at least some of the other third had one or more of these problems, but there was also evidence that some had biotoxin illnesses, and this could have prevented their recovery as well.

I'm glad that Freddd is attempting to get more information about how people are affected by these supplements. This could end up helping people who do not respond well to the simplified treatment protocol that I have suggested. If we can understand why, we might be able to do some relatively inexpensive genetic characterization, such as with www.23andme, and be able to determine what protocol would work best for different people.

So I hope that people will try to distinguish which of these issues they actually have, and not assume that if they have one of them, they must have all of them.

Best regards,

Rich
 

Freddd

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Ok. I am willing to give this a try. I am sorry again to say I have not been following this thread for a long time and only managed to comprehend barely. How do you start? I have solgar metafolin and jarrow b12. I take 400 mcg of folinic and metafolin and 10 mg of mb12 and the source naturals Ab12 one a day.

my kids glut is showing low on organic acid markers test.. mine mid range which though the md said the marker can reveal intracellular issues and theirs are intracellular (dont know how this marker can tell that).. what about a need for glut supplementally?

My son is showing folate issues (however the oat manages to tell that) and low b12 but his MMA was low as well.. red blood cells too large. I think my MMA is low or lowish as well and red blood cells were creeping into a good range for a while and I think back up. What would cause this?

Rich and Freddd both.. if you see this post.. what do you think of the OAT for measuring these things?

And... what's the cost of a folinic "Deficiency" that would develope form taking metafolin only?

Thank you..

I take 400 mcg of folinic

For starters, ditch that. It will take several days to wash out. Elliminate all folic acid from enriched cereals, Ensure, Instant Breakfast and similar things, whey, glutathione, NAC. Then after the couple days take 7.5-8.0 mg of Metafolin. Then take 3200mcg with each meal that has vegatable source food folate (folinic acid). Watch what symptoms go away. It takes cheilitis about 2 days to reverse direction and up to a month to heal fully. IBS can start fading after 5-6 days. Mood and personality changes can change in a couple of days. Inflammation can take up to 10 days or so to fade but start sooner. It's quite variable and that is what we are trying to identify, the mpst frequent and fastest changes going in and out.

And... what's the cost of a folinic "Deficiency" that would develope form taking metafolin only?

Healing starts if you folinic acid caused paradoxical folate deficiency, otherwise no symptoms at all of which I am aware.
 

soulfeast

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Freddd. did I ask how you deal with glutahione deficiency? I am missing one glut gene (though heard many people are.. still.. )

And yes, nerves calm down then sometimes or not an intense burning pain follows that I welcome over the frayed nerve feeling because it feels so unstable. My gait can go off during the frayed nerve feeling and the glut fixes or "fixes" that...

My legs esp become packed with what feels like toxic soup.. hard lumps and edemic feeling though not visually edemic. Sever muscle weakness right now. I usually have no salt on hand and dont know how good a potassium supp that is but have made salty lemonade with it in past with real salt and no salt. I feel to edemic though to think of a salty lemonade. Sometimes I crave them.

Thank you..

Hi Soulfeast,

We need to fire up the way forward machine and see what we can find out about induced and paradoxical folate deficiecies about 100 years from now. We ar\e only now working on being able to identify it.

lipo glut has "saved me at times from these awful feeling neuropathic? creepies and frayed nerve feelings.. nerves feel like they are buzzing and fraying, creeping and like mad. B12 has helped but does not address like the lipo gut. The lipo glut can also cause these feelings which in turn more lipo glut "cures."


Glutathione did stop some of the neurological things for me, by making the nerves less functional and in some weeks, noticably more numb and damaged. What is typically called "glutathione detox reaction" is a fast and hard folate deficiency. Initially there is a quieting of the nervous system. Then an increase in inflammational pain, increase in allergic reactivity, increased hypersensitive responses, IBS, appearance of acne, skin problems, increased nauesa, increased mallaise.

I would not make ANY assumptions about whether or not you have a problem with glutathione etc until you are on ONLY metafolin (not folic or folinic) for month or two and have substantial improvement. As glutathione's effects can go on for weeks after the last dose, and if the folage deficiency symptoms are NOT reversed with large doses of methylfolate and mb12/adb12 the negative effects of glutathione can be totally invisible because the things it causes have never gone away. It can also block up to 100% of the effectiveness mb12, Metafolin and adb12.
 

soulfeast

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I dont have the lip inflammation. And IBS is not a huge issue at least not lately. Could this still be an issue? For me, it sever muscle weakness, inflammation, and lately swelling in my face and a packed full of toxins feeling in my legs.

Has taking that much metafolin that fast (not ramping up) caused anyone to crash? (not that im not already crashed).

I want to give this a try but wondering if ramping up on he metafolin works ok. Thats 10 pills of solgar a day spread out over the day or at once? And 4 pills with meals containing folinic but staying away from high folinic (folate) foods as much as possible? no FA of course.

If ramping up is ok... then is 800mcg a day for a while then adding up 800 mcg at a time workable until I feels safe going higher faster?

I think Rich has mentioned some body processes requiring folinic and wondering how those fair without the folinic but also getting that with a folinic processing issue that maybe the body doesnt get to use it anyway??

Would a person crave mb12 if there is a metafolin defiency? Could that be a reason and not a b12 defiency? though I think that would mean borrowing the methyl group form the b12 to give to folinic which would or not be able to convert to L-5-methyltetrahydrofolate?

Thank you.

I take 400 mcg of folinic

For starters, ditch that. It will take several days to wash out. Elliminate all folic acid from enriched cereals, Ensure, Instant Breakfast and similar things, whey, glutathione, NAC. Then after the couple days take 7.5-8.0 mg of Metafolin. Then take 3200mcg with each meal that has vegatable source food folate (folinic acid). Watch what symptoms go away. It takes cheilitis about 2 days to reverse direction and up to a month to heal fully. IBS can start fading after 5-6 days. Mood and personality changes can change in a couple of days. Inflammation can take up to 10 days or so to fade but start sooner. It's quite variable and that is what we are trying to identify, the mpst frequent and fastest changes going in and out.

And... what's the cost of a folinic "Deficiency" that would develope form taking metafolin only?

Healing starts if you folinic acid caused paradoxical folate deficiency, otherwise no symptoms at all of which I am aware.
 

Freddd

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I dont have the lip inflammation. And IBS is not a huge issue at least not lately. Could this still be an issue? For me, it sever muscle weakness, inflammation, and lately swelling in my face and a packed full of toxins feeling in my legs.

Has taking that much metafolin that fast (not ramping up) caused anyone to crash? (not that im not already crashed).

I want to give this a try but wondering if ramping up on he metafolin works ok. Thats 10 pills of solgar a day spread out over the day or at once? And 4 pills with meals containing folinic but staying away from high folinic (folate) foods as much as possible? no FA of course.

If ramping up is ok... then is 800mcg a day for a while then adding up 800 mcg at a time workable until I feels safe going higher faster?

I think Rich has mentioned some body processes requiring folinic and wondering how those fair without the folinic but also getting that with a folinic processing issue that maybe the body doesnt get to use it anyway??

Would a person crave mb12 if there is a metafolin defiency? Could that be a reason and not a b12 defiency? though I think that would mean borrowing the methyl group form the b12 to give to folinic which would or not be able to convert to L-5-methyltetrahydrofolate?

Thank you.
Hi Soulfeast,

I was on up to 2400mcg daily of Metafolin for 6 months after discontinuing glutathione precursors and it didn't help. Then someone suggested ramping that up a lot. It worked. After 6 months of continued downhill, a single dose of 8mg of Metafolin multiple 10mg injections of mb12 and several 50mg doses of adb12 I finally started turning it around. I had been doing 5mg injections of mb12 before that, also without effect. It took a lot more than my normal doses to overturn the effects of glutathione.


I think Rich has mentioned some body processes requiring folinic and wondering how those fair without the folinic but also getting that with a folinic processing issue that maybe the body doesnt get to use it anyway??

All you lose is the folate deficiency symptoms of paradoxical folate deficiency. There is an alternate pathway starting with methylfolate.


caused anyone to crash?

The Deplin, 7.5mg and 15mg says "generally well tolerated and side effects similar to placebo". On the other hand the side effects of Cerefolin NAC included severe folate deficiency symptoms otherwise known as "NAC detox" and "glutathione detox".

I dont have the lip inflammation.

HUH??? Are you meaning sores at the corners of the mouth?

it sever muscle weakness, inflammation, and lately swelling in my face and

Sounds like folate deficiency.
 

soulfeast

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Cheilitis is a medical condition involving inflammation of the lip. I have never had the sores or inflammation.

I developed frozen shoulder after I used CSM for the first time along with sever POTS. Recently after my sinus surgery ( sinus disease full of fungal balls from mold illness), I crashed again. Hoping detox once that load was taken away.. but feeling like death. So tired and weak. But also my other shoulder started to freeze up.. muscles hard knots like in a continual state of contraction and now wondering if this is the paradoxical folate deficiency and or potassium not getting into cells. The POTs as well.. I also developed tachy (with the POTS) and breathlessness that would not end for weeks, now a month. and that feeling when your leg feels like it is having tiny spasms all over .. like restless legs.. this increased. What struck me was I went back to massage therapist and the sole of one of my feet started "seizing up" in a bad cramp along with the tiny insane little muscle spasms all in that leg. Wondering again.. if this is from the potassium depletion esp.

Im trying to catch up on your latests posts and explanations. Not yet understanding the paradoxical folate deficiency.

I did stop the folinic. I am away from home and only brought enough supps for the time here, so taking the 400mcg of metafolin for now and took out the nac and glut. I have also been eating protein bars with whey.

I will have to ramp up on metafolin. I am afraid of crashing. The safety notes may not be relevant to everyone esp with CFS-ME...??

I did take 600mg of potassium today, 300 this am and the extreme muscle fatigue went right away.. still there but not near as severe. I think some of the edemic feeling is gone as well.. just dont feel as "stuffed."

I think Rich has said that folinic perfoems other functions separate from methylation but I could be wrong about that. Hope so if this is an issue for me.

Thanks, Freddd.

Robin
 

adreno

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.. muscles hard knots like in a continual state of contraction and now wondering if this is the paradoxical folate deficiency and or potassium not getting into cells. The POTs as well.. I also developed tachy (with the POTS) and breathlessness that would not end for weeks, now a month. and that feeling when your leg feels like it is having tiny spasms all over .. like restless legs.. this increased.
Sounds like low potassium to me.
 

soulfeast

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The potassium has helped alot.. unbelievable and grateful for the info! Now to figure out, if I can, the paradoxical folate defiency and how glut interfers with b12. Is there a thread that explains this in detail? I am off folinic now. Does the folinic compete with the methylated form and win out in cells?
 

Freddd

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The potassium has helped alot.. unbelievable and grateful for the info! Now to figure out, if I can, the paradoxical folate defiency and how glut interfers with b12. Is there a thread that explains this in detail? I am off folinic now. Does the folinic compete with the methylated form and win out in cells?

Hi Soulfeast,

There are threads on both subjects.

Let's call the paradoxical folate deficiency from folic acid PFD1, and the paradoxical folate deficiency from folinic acid/veggie food folate as PFD2. PFD2 I would expect to also contain PFD1.

If the particular form can't be utilized by the body it builds up. The hypothesis is that it competes with the methylfolate and has a longer serum halflfe. particularly the folinic acid and hence fills up the transport system or something because it accumulates and the methylfolate is cleared rapidly.

The glutathione combines with mb12 and adb12 inti glutathionylcobalamin and is immediateky flushed froim the body by the kidneys. This is very visible if one has enough b12 in the body to be viswible in the urione. Then when there is no b12 for use as a cofactor in a cell, the methyfolate is flushed from the cell (methyltrap). In a nutshell or two there it is.
 

maddietod

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Hi Soulfeast,

There are threads on both subjects.

Let's call the paradoxical folate deficiency from folic acid PFD1, and the paradoxical folate deficiency from folinic acid/veggie food folate as PFD2. PFD2 I would expect to also contain PFD1.

If the particular form can't be utilized by the body it builds up. The hypothesis is that it competes with the methylfolate and has a longer serum halflfe. particularly the folinic acid and hence fills up the transport system or something because it accumulates and the methylfolate is cleared rapidly.

The glutathione combines with mb12 and adb12 inti glutathionylcobalamin and is immediateky flushed froim the body by the kidneys. This is very visible if one has enough b12 in the body to be viswible in the urione. Then when there is no b12 for use as a cofactor in a cell, the methyfolate is flushed from the cell (methyltrap). In a nutshell or two there it is.
Do you have any idea how long it takes for the accumulated folic/folinic acid to flush out? Is this related to how much methylfolate is taken? Assuming no intake of folates through supplements, and a very low-folate diet. I'm wondering how long it takes to re-set to a new baseline.
 

adreno

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Do you have any idea how long it takes for the accumulated folic/folinic acid to flush out? Is this related to how much methylfolate is taken? Assuming no intake of folates through supplements, and a very low-folate diet. I'm wondering how long it takes to re-set to a new baseline.
I remember Freddd mentioned two weeks somewhere; correct me if I'm wrong.
 

Freddd

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I remember Freddd mentioned two weeks somewhere; correct me if I'm wrong.
Hi Adreno,
For me the folic acid subsided enough in 12-24 hours for metafolin to make a difference and about twice that for folinic. There is no reason to wait to start metafolin, it will go to work almost right away. It akes about 2 weeks for a lot of the symtoms to go away.
 

Freddd

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Talking about paradoxes ...

Ferdinand Feghoot's wife heard a lot of carousing in the basement where he kept his time machine. Then she heard some distinctive sounds of female laughter. She went downstairs and saw her husband with a volutuous woman in 17th century French costuming on each arm. She said "Ferdinand, what's the meaning of this!"

Ferdinand looked up to her on the stairs and said "My dear, haven't you heard of the pair of doxies of time?"
 

Rosebud Dairy

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Symptom of paradoxical folate deficiency --

Reading the term "paradoxical folate deficiency" and being so brain fogged as to not know what in the heck it is!!!!
Reading this thread (while in the fog) and not understanding what is being talked about unless one were to see a list of symptoms in big red letters.
Reading the list of symptoms again (while in the fog) and not remembering having read it.
Reading the list of symptoms, for perhaps a 4th or 5th time, and finally understanding that the folic (maybe folinic) acid(s) one is taking might be having adverse health effects.

Once I get a steady state for a couple of weeks, I will test folinic also. Right now, I am just testing folic, but have to get through a probably full two week washout of neuropathy symptoms AND a k-drop to see what remains, then testing with folinic.

angry rashes that may have been attributed to other things - acne, skin sensitive to things put on it.
--The clearest my skin was actually came at a time that was doing a special diet for my stomach, which was also low folic/maybe low folinic, and my acne cleared up a TON.
 

Freddd

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Hi Rosebud,

Just stop taking folic acid and folinic acid and take Metafolin right a way. You will know soon. You are making it far too complcated. Two week washout is nonsense and not needed. You wil know in a few days most likely.
 

adreno

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I would like to test without folinic acid, which is in my B complex. I can order the Douglas Labs, but it might take up to a month for the shipping. So my question is: can I do without the B complex for now? Or is it better to continue and preload with methylfolate?
 

Freddd

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I would like to test without folinic acid, which is in my B complex. I can order the Douglas Labs, but it might take up to a month for the shipping. So my question is: can I do without the B complex for now? Or is it better to continue and preload with methylfolate?
Go to a drug store and buy a cheap minimal b-complex with folate of b12.
 

Rosebud Dairy

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Freddd,
When I say testing folic or folinic, I am talking about doing what you mentioned -- just dietary. I ditched supplemental folic/folinic back in December if not longer ago, but I am trying to see how much blocking I can get if I take at least 3200 methylfolate before a meal, but I am somewhat deathly afraid of the leafy greens I love so dearly, and I don't want to start eating them again for a bit, at least until I am remembering to take the methylfolate before each meal. Tonight, we went out, I forgot my dose before the meal, but took a rescue dose of probably 9 mg sublingually as soon as I got home.

I am seriously considering getting the compounding pharmacist to work up a 24 hour time release methylfolate of at least 15 mg, maybe 20. The docs and I are talking about it. I hate to have a two day set back just because I forgot my dose.

another symptom of PFD-- The mouth sores that many people get at start up I got again after my bad folic acid week after they had been gone a couple of weeks. It was notable. I did not have neuropathy on the bottoms of my feet after hyperbarics today, which was good.
 

Rosebud Dairy

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confirmed folate deficiency ---
possible symptom -

An even meal was had without pre-loading, and the next morning was rough....headache, catching a cold, mucous was thicker, and sinuses were starting up. from just one exposure to folic fortified foods. -- maybe