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Study: Folinic acid beneficial to 81% of CFS patients...plus biomarker?

Lotus97

Senior Member
Messages
2,041
Location
United States
Why do you think folinic acid blocks methylfolate? In 81% at least it appeared to not. If all goes well folinic acid is buffered and converted to methylfolate. Folinic acid is not only for nucletoides. It is storage form in the cell for folatea. Would expect much of it goes to methylfolate IF all is working well and no MTHFS defect. The really high dose are for cns penetration and saturation. Just like the r eally high doses if methylfolate used by some in these forums.
I thought for the people who can't process folinic acid the folinic acid builds up and blocks methylfolate. The reason I was asking about people who could normally process it was because I thought maybe since the dose of folinic acid was so high that even they wouldn't be able to process it quickly enough. Also, I thought you said something about folinic acid staying in the system a long time and you considered even 800 mcg kind of high. I don't have time to reread this thread right now (but I do intend to) so I'm sorry if I'm misstating what you said.

I've heard people talking about CNS before in the methylation forums, but I don't know what they mean (other than it being short for central nervous system). Actually, you and Adreno were talking about that in relation to neurotransmitters recently in that other thread. Do I remember correctly? I read through so much information in such a short amount of time it's hard for me to remember everything. Is that what people are referring to when they say "neurological healing"? I don't know what that means specifically. That's something independent of methylation I assume? I guess Leucovorin can be used sort of like Deplin as a treatment for depression.
http://link.springer.com/article/10.1023/A:1015271927517
Low folate is associated with poorer response to selective serotonin reuptake inhibitors (SSRIs) in majordepressive disorder (MDD). Folate supplementation in MDD has been studied in other settings with promising results. The objective of this study was to assess the efficacy of methylfolate as an adjunctive treatment among adults with MDD and inadequate response to an SSRI. Twenty-two adults (59% female; mean age 45.2 ± 11.0 years) with DSM-IV MDD, partial or nonresponse to an SSRI after at least 4 weeks of treatment, and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score ≥ 12 were enrolled in this 8-week prospective open trial. Exclusion criteria included current use of anticonvulsants or psychotropics other than an SSRI, or B12 deficiency. Leucovorin (folinic acid), which is metabolized to methylfolate, was added to SSRIs at 15–30 mg/day. Folate levels rose from 28 ± 19 ng/mL to 301 ± 203 ng/mL (p < 0.001). HAM-D-17 scores among the 16 completers decreased from 19.1 ± 3.9 to 12.8 ± 7.0 (p < 0.01). However only 31% of completers and 27% of the intent-to-treat (ITT) sample achieved response (≥50% reduction in HAM-D-17 scores), and only 19% of completers and 18% of the ITT sample achieved remission (HAM-D-17 ≤ 7). Leucovorin appears to be modestly effective as an adjunct among SSRI-refractory depressed individuals with normal folate levels. The application of leucovorin as an adjunct in the setting of refractory depression deserves further study.
 

dbkita

Senior Member
Messages
655
Yes neurological healing means in the cns past the bbb.

Sorry I don't have the wherewithal to discuss folinic acid right now. I have posted ad nausea about it in this thread. Yes I think anything above 800 mcg is high unless the goal is strong impact in the cns. But unless there is a problem processing why would it block except for obvious gi absorption competition. Like I said it does have a long halflife but for some that may be a good thing.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
The really high dose are for cns penetration and saturation. Just like the r eally high doses if methylfolate used by some in these forums. Yes neurological healing means in the cns past the bbb.
Is that the same thing as people who are taking high doses of methylcobalamin (and maybe adb12?) for neuropathy symptoms?
 

dbkita

Senior Member
Messages
655
Is that the same thing as people who are taking high doses of methylcobalamin (and maybe adb12?) for neuropathy symptoms?
Not necessarily. I think really high doses of mb12 and adb12 are two different things. Mb12 is clearly related to alleviating neuropathy but in some cases we are talking peripheral nerves not the CNS. Probably more about the pharmacokinetics of getting a high enough dose to impact the neurons in a beneficial manner. However, really high mb12 intake could also be to get around mb12 transport problems which I think are more prolific than people give them credit for.

I agree with Freddd that peak levels are more important for mb12 whereas sustained concentration gradient is more important in methylfolate. I believe the peak levels are to bypass some of the pharmacokinetic limitations of exogenous mb12 (i.e. non self sustaining production endogenously) and / or transporter problems.

Adb12 is more about mitochondrial function and other aspects.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Not necessarily. I think really high doses of mb12 and adb12 are two different things. Mb12 is clearly related to alleviating neuropathy but in some cases we are talking peripheral nerves not the CNS. Probably more about the pharmacokinetics of getting a high enough dose to impact the neurons in a beneficial manner. However, really high mb12 intake could also be to get around mb12 transport problems which I think are more prolific than people give them credit for.

I agree with Freddd that peak levels are more important for mb12 whereas sustained concentration gradient is more important in methylfolate. I believe the peak levels are to bypass some of the pharmacokinetic limitations of exogenous mb12 (i.e. non self sustaining production endogenously) and / or transporter problems.

Adb12 is more about mitochondrial function and other aspects.

Hi Dbkita,

I believe the peak levels are to bypass some of the pharmacokinetic limitations of exogenous mb12 (i.e. non self sustaining production endogenously) and / or transporter problems.

B12 is the vitamin with the by far most complicated distribution, transport and retention system. There are 3 transportation of COBALAMINs substances that protect b12 from biochemical hazard and move them around in the body. The "how" it gets to the brain and how that gets impaired is not clear. Why some people retain CSF injected MeCbl for 4 years and others can't make it last even 3 months is unknown.

The behavior of AdoCbl and MeCbl are very different. Four compartments are required to describe AdoCbl with 2 of them pretty mysterious. Then there are 2 compartments for MeCbl.

However, having 6 compartments gets rid of most of the puzzlers I am aware of about b12 serum half-life vs. body half-life and the loads of apparent contradictions. For instance both the "7 year vegetarian crash" and the "20 year vegetarian crash" can be separately seen as results in at least two separate compartments.

Then there is the "tissue penetration" issue with higher body levels of serum level and the peripheral nervous system is perhaps the most sensitive illustration in my experience over the range 100-5000 mcg absorbed.

Most CNS healing appears to need serum levels above an estimated 75,000-125,000pg/ml for some sufficient part of the day. A combination of AdoCbl and MeCbl appears to generally give the most effectiveness.
 

Radio

Senior Member
Messages
453
Dannybex,

I recall that you, like myself, was having some neuropathy issues likely autoimmune and or inflammation related after going on a methylation protocol.

How did you resolve this? Methylation supps helped me very much, but I am scared to go back on. Ever since that episode, I have been having relapsing and remitting parasthesia and fasiculations as I can literally feel my nerves attacked.

I had the same problem with neuropathy and its was ( B-6 ) Check it out, p5p recycles in the body for 15-20 days. The active form of B-6 is not water soluble and it can build up in the body , if you take it everyday. High levels of B-6 cause neuropathy. You are better off not supplement B6 and using active B-2. Riboflavin 5 phosphate makes B-6 active without over-driving methylation ( CBS ). Also, B-2 can help bypass the Mao-a gene.
 
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dannybex

Senior Member
Messages
3,561
Location
Seattle
I had the same problem with neuropathy and its was ( B-6 ) Check it out, p5p recycles in the body for 15-20 days. The active form of B-6 is not water soluble and it can build up in the body , if you take it everyday. High levels of B-6 cause neuropathy. You are better off not supplement B6 and using active B-2. Riboflavin 5 phosphate makes B-6 active without over-driving methylation ( CBS ). Also, B-2 can help bypass the Mao-a gene.

Thanks for this @Radio .

So…to clarify…are you saying that the activated form of B-2 can help lower B-6 and/or p5p toxicity levels?

And how long did it take for your neuropathy to resolve?
 

Vegas

Senior Member
Messages
577
Location
Virginia
I would look less at genetics and consider the influence of microbial production of folate. Humans are dependent upon their intestinal bacteria for production and interconversion of folates. This includes folinic acid, tetrahydrofolate, 5-MTHF, etc. Whereas LAB in the small intestine are typically net consumers of folate, those species that naturally predominate in the colon are net producers of various folates. This is, however, strain specific and environmentally influenced. The importance of a bacterial source of folate in humans is suggested by the fact that those roughly 18 strains known to produce folates (in the absence of any folate in the medium) are all strains found to reside in humans, versus animals. The most efficient producers of folate are the least tolerant to oxygen; in general, the more intolerant the strain is to oxygen, the higher capacity to produce folates. One strain might be a net producer of 5-MTHF and a net consumer of folinic acid. Capacities for different folate derivatives vary. As I recall, only B. Infantis and B. Bifidum, two human strains among those that predominate in infants, possess all genes necessary for complete interconversion of folates.
 

Radio

Senior Member
Messages
453
Thanks for this @Radio .

So…to clarify…are you saying that the activated form of B-2 can help lower B-6 and/or p5p toxicity levels?

And how long did it take for your neuropathy to resolve?

B-2 will not help p5p toxicity. Its will take a few weeks for the body to clear. The first thing you want to do is eat a low salt, low glycemic diet. Eat some fish and supplement with some GLA.

And how long did it take for your neuropathy to resolve?
It was like 3 days after i stop taking B-6 , no salt!
 
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Radio

Senior Member
Messages
453
I would look less at genetics and consider the influence of . Humans are dependent upon their intestinal bacteria for production and interconversion of folates. This includes folinic acid, tetrahydrofolate, 5-MTHF, etc. Whereas LAB in the small intestine are typically net consumers of folate, those species that naturally predominate in the colon are net producers of various folates. This is, however, strain specific and environmentally influenced. The importance of a bacterial source of folate in humans is suggested by the fact that those roughly 18 strains known to produce folates (in the absence of any folate in the medium) are all strains found to reside in humans, versus animals. The most efficient producers of folate are the least tolerant to oxygen; in general, the more intolerant the strain is to oxygen, the higher capacity to produce folates. One strain might be a net producer of 5-MTHF and a net consumer of folinic acid. Capacities for different folate derivatives vary. As I recall, only B. Infantis and B. Bifidum, two human strains among those that predominate in infants, possess all genes necessary for complete interconversion of folates.

I like the idea of eating more fermented foods. I think its a way to balance the system as long as you don't have a histamine, mast cell problem. Using microbial production of folate is like putting a band-aid on a gunshot wound. We need alot more methylation support , as they would say on duck dynasty ( that's a fact jack! ).
 
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dannybex

Senior Member
Messages
3,561
Location
Seattle
B-2 will not help p5p toxicity. Its will take a few weeks for the body to clear. The first thing you want to do is eat a low salt, low glycemic diet. Eat some fish and supplement with some GLA.

And how long did it take for your neuropathy to resolve?
It was like 3 days after i stop taking B-6 , no salt!

I appreciate your reply, but it doesn't seem to fit with your earlier post. You said you had neuropathy from b6, and that b6 builds up in the body because it's not water soluble (which is interesting). You then suggested the active form of b-2 (r5p) makes b6 active (converts it to p5p…

I agree with a general recommendation for low-glycemic foods, but don't understand the low-salt angle. Many of us need salt to keep our blood volume up -- and for the electrolytes. I don't know what salt has to do with neuropathy from b6, which several of us have from just tiny amounts of b6 or p5p.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
I would look less at genetics and consider the influence of microbial production of folate. Humans are dependent upon their intestinal bacteria for production and interconversion of folates. This includes folinic acid, tetrahydrofolate, 5-MTHF, etc. ...One strain might be a net producer of 5-MTHF and a net consumer of folinic acid. Capacities for different folate derivatives vary. As I recall, only B. Infantis and B. Bifidum, two human strains among those that predominate in infants, possess all genes necessary for complete interconversion of folates.

Makes sense Vegas, thanks. I would also add however that some folks have tested for antibodies to folates, so that might explain why they need the massive doses used in the study at the beginning of this thread. At least that's what I've read on other forums…
 

Radio

Senior Member
Messages
453
I appreciate your reply, but it doesn't seem to fit with your earlier post. You said you had neuropathy from b6, and that b6 builds up in the body because it's not water soluble (which is interesting). You then suggested the active form of b-2 (r5p) makes b6 active (converts it to p5p…

I agree with a general recommendation for low-glycemic foods, but don't understand the low-salt angle. Many of us need salt to keep our blood volume up -- and for the electrolytes. I don't know what salt has to do with neuropathy from b6, which several of us have from just tiny amounts of b6 or p5p.

OK, When you have neuropathy you have demyelination of the nerves...For me it was B12 problem MTRR....B6 can makes CBS run to fast and you can't repair the nerves...Yes we need salt but, when you are trying to heal neuropathy salt burns the nerves...I did not start healing until i cut out salt for 3 days... no salt...Now i can handle salt..It's my protocol to heal neruropathy +++ Fredds Protocol.
 
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Helen

Senior Member
Messages
2,243
OK, When you have neuropathy you have demyelination of the nerves...For me it was B12 problem MTRR....B6 can makes CBS run to fast and you can't repair the nerves...Yes we need salt but, when you are trying to heal neuropathy salt burns the nerves...I did not start healing until i cut out salt for 3 days... no salt...Now i can handle salt..It's my protocol to heal neruropathy +++ Fredds Protocol.

Interesting about B2, B6 and neuropathy. I have neuropathy and was examined with an EMG and an EeNG test.
It showed axonal damage but no demyelination. I had expected demyelination as blocked methylation could cause that kind of damage to the nerves. Just a single-case but at least we can´t be sure what is damaged when having neuropathy. This discussion should perhaps not be in this thread.but @dannybex we seem to have the same interest in neuropathy.
 

sflorence

Senior Member
Messages
134
Mehyl folate causes me depression, it seems.

Has anyone had better results with folinic acid when they don't respond well to methyl folate?
 

Lolinda

J'aime nager dans le froid style Wim Hof.. 🏊‍♀️🙃
Messages
420
Location
Geneva, Switzerland
OK, When you have neuropathy you have demyelination of the nerves...For me it was B12 problem MTRR....B6 can makes CBS run to fast and you can't repair the nerves...Yes we need salt but, when you are trying to heal neuropathy salt burns the nerves...I did not start healing until i cut out salt for 3 days... no salt...Now i can handle salt..It's my protocol to heal neruropathy +++ Fredds Protocol.
Hi @Radio are you still here around?I find this idea with the CBS and the one with the salt interesting. Where did you take these ideas from? Would you mind posting any links, papers, whatsoever? I tried to google myself but found only irrelevant stuff... :(
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Hi @Radio are you still here around?I find this idea with the CBS and the one with the salt interesting. Where did you take these ideas from? Would you mind posting any links, papers, whatsoever? I tried to google myself but found only irrelevant stuff... :(

Radio is long gone. Was banned I think, but not sure. The last I head he was over on the desserted ProHealth.com...