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

Victronix

Senior Member
Messages
418
Location
California
Q: Should I presume that vitamin C affects folinic acid the way it affects methylfolate in the gut? I guess unless someone knows otherwise I should separate them out from each other in time.
 

Victronix

Senior Member
Messages
418
Location
California
I think the Quatrefolic methylfolate might be more potent because I tried Thorne's b complex with methylfolate more recently and it didn't seem to have the same effects.

Another variable is that I noticed that the start-up effects really changed over time even within the same type of methylfolate -- some of the effects that I had at the start, like temperature dysregulation and exhaustion, went away almost totally over time, even as other symptoms remained or got worse.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I think the Quatrefolic methylfolate might be more potent because I tried Thorne's b complex with methylfolate more recently and it didn't seem to have the same effects.

Another variable is that I noticed that the start-up effects really changed over time even within the same type of methylfolate -- some of the effects that I had at the start, like temperature dysregulation and exhaustion, went away almost totally over time, even as other symptoms remained or got worse.

Hi Victronix,

When one get's healing started the symptoms change constantly. In following through the next step is to see what is most obviously missing based on the remaining or worsening symptoms. Without knowing the details it's hard to say what is going on. In the active b12 protocol all these symptoms would be expected to change and go away pretty quickly, if it is kept going. If this does reflect results of healing to me that would indicate that you could finish up a lot of healing in the next year or so.

I think it is important for people who have healing working solidly to try an A_B with Quatrefolic vs. Metafolin, directly back and forth to see if there are any changes say, at least 2 or 3 cycles through until it is clear what the differences are, or are not.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Folinic acid is not polyglutamated. It is monoglutamated like many folates. He may have crossed that up with the dietary natural folates I described above. I see no reason directly that folinic acid would raise glutamate. That form is stable. It does not get broken down to cross membranes. The only possible indirect link is that really high TH4 levels can lead to over-processing of histidine into a glutamate derivative (this is the same reason that histamine levels are low in high methylation states). But how much that actually impacts excitotoxicity is not clear to me.

Also I am sorry but that idea that the amount of glutamate in supplemental folates (remember they all get reduced to monoglutamate form in the intestinal lumen) is a significant impact on someone is unlikely to say the least. The reason is simple. The amounts. If you take 800 mcg of folic acid or folinic acid, you get about 1/3 of that as glutamic acid. You get a ton more glutamate in simple protein foods. Even if you take 3200 mcg of folic or folinic acid you get like 1 gram. 1/4 lb of ground hamburger has 3.3 grams or so.
I probably should have posted the quote. What I meant is that he said folinic acid would lower glutamate because it's polyglutamated (or at least he thought it was at one time). I didn't want to post it here because like I said I wasn't sure if it was accurate since he only mentioned it once in 2010 (even though he talked about glutamate induced excitotoxicity many times since then). This is what he said:
"Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin."
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Q: Should I presume that vitamin C affects folinic acid the way it affects methylfolate in the gut? I guess unless someone knows otherwise I should separate them out from each other in time.
I asked that earlier and I don't think anyone knew the answer. Since methylfolate is also in Rich's protocol, it's hard to what it's effect is. Although Rich thought folinic acid's ability to create nucleotides which are important for making new DNA and RNA for new cells, and also for making ATP was significant, it might be hard to quantify its effect if you're taking other supplements.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Just to clarify, in that thread I was actually trying to make it clear that most dietary folates are NOT folinic acid.
I guess I did not make that clear enough.

Here is what I posted in the thread you linked:

"Folinic acid is a 5-formyl derivative of THF. The folates in vegetables are not folinic or folic acid (a fully oxidized synthetic folate, i.e. pteroylmonoglutamic acid). This is a notorious misconception in the research community. The folates in food are metabolites of THF packed within polyglutamates. In the intestinal lumen these polyglutmate dietary forms are broken down into monoglutamate variants which can then be converted to DHF and then THF by their respective enzymes. The DHFR enzyme is not present in humans for the synthetic folic acid it is present for processing dietary folates. Folinic acid is readily converted to 5,10 methylene THF without use of DHFR. That being said dietary folates parallel more with folic acid than with folinic acid with one crucial difference ... they can be processed in the intestinal lumen and the liver. Folic acid (I am pretty sure) being fully oxidized must be converted in the liver.

I don't think this changes the fact that high dietary folates could be an issue for some people who can not make use of them, have intestinal wall damage, or critical needs for 5mthf but let's be honest while maybe garden feasts are not a good idea, it is not wise probably to eschew vegetables entirely as a general rule."

Technically that was a little strong in the sense that animal and plant cells will have folinic acid in them. Just like TH4, L5mthf (say in liver), or 5,10 methylene THF, etc. But the dominant form that is ingested as dietary folates is the natural, non-oxidized folate (folic acid is the oxidized, synthetic version that can only be processed in the liver). Again this is cleaved of most glutamates in the intestine and further reduced to DHF in the intestines or liver. From there DHFR takes it to THF.
Thanks for clarifying this. Even though I still don't understand it, I at least have a starting point (and I don't want to start with a faulty premise). So plant folate isn't folinic acid, but is meat methylfolate? And just for the record, I studied theater, English, art, and photography in college so science isn't exactly my cup of tea...anyway. So what is going on with Freddd and veggies then since they're not folinic acid?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thanks for clarifying this. Even though I still don't understand it, I at least have a starting point (and I don't want to start with a faulty premise). So plant folate isn't folinic acid, but is meat methylfolate? And just for the record, I studied theater, English, art, and photography in college so science isn't exactly my cup of tea...anyway. So what is going on with Freddd and veggies then since they're not folinic acid?

Hi Lotus,

So what is going on with Freddd and veggies then since they're not folinic acid?

I wish I knew. You see I like veggies and eat lots of them. They don't hit nearly as hard as folinic acid but they can make a very rapid noticeable difference.

One short period in my life, when I was on the ski patrol at Sugarloaf, I ate about 1.5 pounds of meat in 5000 calories daily while skiing 25,000-40,000 feet of vertical a day in cold or very cold weather and relatively few veggies, I didn't have angular cheilitis. I healed from 3 months of resistant strep and pneumonia. It was the healthiest time of my life until recently.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I was taking -- from time to time -- off and on for years -- folic acid, when I thought there was only 'one' folic acid.

It came as part of a sublingual b12/folic acid combo. Did seem to help, but I think it was most definitely the ad-b12 in it, and not the folic acid. Country Life brand...think it was 400mcgs folic and 500 mcgs ad-b12.

p.s. I personally don't think folinic blocks methylfolate. Not sure, but believe it slowly converts to methylfolate if you don't have various genetic issues others have mentioned.
Right, but they do compete for absorption which is different than blocking. I don't think it's really an issue unless you need a massive amount of methylfolate. When I was referring to folic acid or folinic acid blocking methylfolate though, I just meant for the people who can't convert it. Since you said you can't convert folic acid, I was wondering if you had taken methylfolate at the same time since when I took folic acid and methylfolate at the same time I felt the effects of the methylfolate even though I was taking 15 times as much folic acid as methylfolate.
 

Victronix

Senior Member
Messages
418
Location
California
I've found that my response to a tiny dose of folinic is nearly identical to the response to methylfolate (this is after having stopped any folic acid in my supplements at all now for at least 2 weeks, and in my diet for months, having gone gluten-free and eating mostly at home) and the symptoms mimic folate deficiency. Having had enriched wheat products for decades, it's possible that getting folic acid out of the liver could take many weeks or months (I know when my thyroid when hyper, it took about 6 months to 'use up' all the excess thyroixine that can be stored all over the body). But so far I have no real info to verify any of that. Alternately, it's possible there is no role of folic and it's just how I respond to folinic or methylfolate regardless of folic.

I've never had any bad response to vegetables that I'm aware of.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I've found that my response to a tiny dose of folinic is nearly identical to the response to methylfolate (this is after having stopped any folic acid in my supplements at all now for at least 2 weeks, and in my diet for months, having gone gluten-free and eating mostly at home) and the symptoms mimic folate deficiency. Having had enriched wheat products for decades, it's possible that getting folic acid out of the liver could take many weeks or months (I know when my thyroid when hyper, it took about 6 months to 'use up' all the excess thyroixine that can be stored all over the body). But so far I have no real info to verify any of that. Alternately, it's possible there is no role of folic and it's just how I respond to folinic or methylfolate regardless of folic.

I've never had any bad response to vegetables that I'm aware of.
I've gone from 1600+ folic acid last year down to around 200 mcg now. My health is too poor to play around with methylfolate right now. Taking it before contributed to a major relapse. Hopefully my body is processing the folate from my food. I'm not taking much folinic acid or B12 either right now. Even if methylation doesn't make me wired to the point where it's uncomfortable, I still end up spending all day at the computer which does make my other symptoms worse.
I think the Quatrefolic methylfolate might be more potent because I tried Thorne's b complex with methylfolate more recently and it didn't seem to have the same effects.

Another variable is that I noticed that the start-up effects really changed over time even within the same type of methylfolate -- some of the effects that I had at the start, like temperature dysregulation and exhaustion, went away almost totally over time, even as other symptoms remained or got worse.
I'm not sure if I forgot to mention it, but most days I was taking the Thorne with vitamin C and/or potassium so that could explain it. I hope someone will try out Quatrefolic methylfolate because I'm curious if it really is that much more potent or if I'm just sensitive. I do seem to react to too much B12 also so it's probably a combination of both. Swanson's is having a buy one get one free offer on Quatrefolic if anyone's interested (both 400 and 800 mcg)
http://www.swansonvitamins.com/swanson-ultra-folate-5-methyltetrahydrofolic-acid-400-mcg-30-veg-caps
http://www.swansonvitamins.com/swanson-ultra-folate-5-methyltetrahydrofolic-acid-800-mcg-30-veg-caps
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Hi Lotus,

So what is going on with Freddd and veggies then since they're not folinic acid?

I wish I knew. You see I like veggies and eat lots of them. They don't hit nearly as hard as folinic acid but they can make a very rapid noticeable difference.

Could it be something else in the veggies...oxalates...phenols/salicylates...or ???
 

greenshots

Senior Member
Messages
399
Location
California
Thats a really good point danny, if he has the CBS it could be phenols and if he has the ACAT it could be oxalates. It would be really hard to pinpoint it to folate when there are so many variables.
 

dbkita

Senior Member
Messages
655
I probably should have posted the quote. What I meant is that he said folinic acid would lower glutamate because it's polyglutamated (or at least he thought it was at one time). I didn't want to post it here because like I said I wasn't sure if it was accurate since he only mentioned it once in 2010 (even though he talked about glutamate induced excitotoxicity many times since then). This is what he said:
"Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin."
While glutamate is certainly related to excitotoxicity I am not sure about the connection with folinic acid. Dietary folates are generally polyglutamates and turned into monoglutamate form in the interstinal lumen or the liver. I do not know if there is a capability to turn them into monoglutamate form inside of cells. So not sure what Rich meant back in his 2010 post.
 

dbkita

Senior Member
Messages
655
Thanks for clarifying this. Even though I still don't understand it, I at least have a starting point (and I don't want to start with a faulty premise). So plant folate isn't folinic acid, but is meat methylfolate? And just for the record, I studied theater, English, art, and photography in college so science isn't exactly my cup of tea...anyway. So what is going on with Freddd and veggies then since they're not folinic acid?

So plant folate isn't folinic acid, but is meat methylfolate?

Dietary folates are technically any folate derivative. But the majority ingested from plants is not THF, not folinic acid, and not l5mtthf. They are simply folate (the natural non oxidized polyglutamated form of folic acid). It is pretty clear if you look at the diagram in the link I put in my post. So no plant folates is NOT meat methylfolate. I never said that sorry.

The distribution in animal cells is probably different. More slanted towards THF, methylfolate and folinic acid. Sorry I don't know the exact distribution. Folates taken in by animals are converted in the intestinal lumen and the liver primarily. So I don't think there should be a lot of simple folate (i.e. the guy who gets reduced to DHF who in turn gets converted into THF) if you are eat muscle meat. Organ meat may be a different matter. Liver is very high relatively speaking in methylfolate. But folinic is stored as a intracellular buffer in all animal cells. I am not familiar enough with plant physiology to reliably telly you the concentrations in plants. That being said, most of the folate you ingest from foods like grains and vegetables I believe is the dietary folate I keep trying to describe. The picture in the link I posted is worth a 1000 of my words. Again there is a reason why mankind has the DHFR enzyme (not to be confused with DHPR).
 

dbkita

Senior Member
Messages
655
Hi Lotus,

So what is going on with Freddd and veggies then since they're not folinic acid?

I wish I knew. You see I like veggies and eat lots of them. They don't hit nearly as hard as folinic acid but they can make a very rapid noticeable difference.

One short period in my life, when I was on the ski patrol at Sugarloaf, I ate about 1.5 pounds of meat in 5000 calories daily while skiing 25,000-40,000 feet of vertical a day in cold or very cold weather and relatively few veggies, I didn't have angular cheilitis. I healed from 3 months of resistant strep and pneumonia. It was the healthiest time of my life until recently.
Meat will have l5mthf, folinic acid and THF along with other forms. Plant sources may have more slant towards the simpler folates that need to be reduced once or twice to get into the folate cycle to begin with. Most meat is muscle meat. Liver and organ meats, etc. will have more l5mthf.

But for comparison, 82 grams of hamburger (essentially a small patty) has only 7 mcg of folate period of ALL forms. So if you ate 1.5 lbs of hamburger that is like ~60 mcg of all folates. On the other hand a 1/4 cup of walnuts has 28 mcg already. An avocado 163 mcg! A 100 gram turkey leg only 9 mcg. Asparagus, a 1/2 cup of only six spears has 134 mcg!

You see a pattern, right? Note technically a plant source may have MORE folinic acid than a meat source in absolute number, but will be lower relative to the other folate forms in the plant. Is that clear?

Animal flesh and plants have not only different amounts of folates but MUST have different distributions of folate concentrations. Hence like I said I think the majority of plant folates are not folinic acid, not methylfolate, not THF, but the non-reduced forms (folate and DHF). But again since plant sources are much higher than animal ones generally in total folates, they may very well have a higher absolute amount of folinic acid per serving.

Hope that helps.
 

dbkita

Senior Member
Messages
655
I've gone from 1600+ folic acid last year down to around 200 mcg now. My health is too poor to play around with methylfolate right now. Taking it before contributed to a major relapse. Hopefully my body is processing the folate from my food. I'm not taking much folinic acid or B12 either right now. Even if methylation doesn't make me wired to the point where it's uncomfortable, I still end up spending all day at the computer which does make my other symptoms worse.

I'm not sure if I forgot to mention it, but most days I was taking the Thorne with vitamin C and/or potassium so that could explain it. I hope someone will try out Quatrefolic methylfolate because I'm curious if it really is that much more potent or if I'm just sensitive. I do seem to react to too much B12 also so it's probably a combination of both. Swanson's is having a buy one get one free offer on Quatrefolic if anyone's interested (both 400 and 800 mcg)
http://www.swansonvitamins.com/swanson-ultra-folate-5-methyltetrahydrofolic-acid-400-mcg-30-veg-caps
http://www.swansonvitamins.com/swanson-ultra-folate-5-methyltetrahydrofolic-acid-800-mcg-30-veg-caps

I understand your reluctance about methylfolate but if you really are processing the folic acid than the endgame is essentially to convert to methylfolate ignoring the parts that get drained into making DNA / RNA. You may be reacting to methyl donors of any type. This may suggest inflammatory processes or maybe COMT++ intolerance. Before you got sick, what was your mood generally like? Happy a lot? So much so it made other people sick? A lot of drive? Mental energy? Just curious.
 

Asklipia

Senior Member
Messages
999
Hi Lotus,
One short period in my life, when I was on the ski patrol at Sugarloaf, I ate about 1.5 pounds of meat in 5000 calories daily while skiing 25,000-40,000 feet of vertical a day in cold or very cold weather and relatively few veggies, I didn't have angular cheilitis. I healed from 3 months of resistant strep and pneumonia. It was the healthiest time of my life until recently.

Three years ago, when I started supplementing with MK-4 I started eating more meat, because of the necessity to take it with fat. I do not eat beef, so most of the meat was lamb, duck, pork and guinea fowl (for taurine) and a lot of clarified butter and eggs.
Last year I was much better and could reduce my supplementation. From last year I increased dramatically the portions of meat/fish compared to the veggies. I don't know why, maybe because by instinct I wanted more meat? Maybe because here this meat is plentiful and very good? Also I started cooking everything in stews to take a maximum of nutrients with a minimum of work in the kitchen.
I realize now that I really need much bigger portions than what I see in other peoples' plates.
Every day breakfast with two eggs in ghee (I make ghee myself from organic grass-fed butter (Demeter certified which means the cows are even prayed over!:)) with a generous serving of what I call bacon but is fresh breast of pork cut up in cubes and fried in the ghee (before putting in the eggs).
Nothing at night, I am not hugry and go to bed early.
Today Wednesday lunch : baby goat stew (like lamb's stew) in lettuce
Tuesday was a guinea fowl in stew with lots of baby onions and a tomato
Monday was a Madras curry stew with coconut and a kind of huge mackerel in it
Sunday was with guests a roast lamb for Easter but I made soup with the bones for when I feel peckish (frozen in portions).
Saturday was Goan curry shrimps
etc...
All from scratch, no ready ingredients (curries homemade from whole spices).
All least a pound of meat a head, more so if there are a lot of bones.

And the exposure to cold is VERY important. Still doing Bains Derivatifs http://forums.phoenixrising.me/index.php?threads/bains-dérivatifs.15574/#post-251194

I do not count calories, but I don't eat sweets, I just love fish and meat.

I realize now that I must have been eating too many veggies, which I loved. Now that I take most of folates from some animal that has processed it, life is MUCH better.
There is definitely a folate (even from veggies) addiction going on. Hungry for more folates because we cannot absorb them maybe? I do hope that this good time lasts and that I can eat lamb for 40 years or so.
Be well
Asklipia
 

xjhuez

Senior Member
Messages
175
Three years ago, when I started supplementing with MK-4 I started eating more meat, because of the necessity to take it with fat. I do not eat beef, so most of the meat was lamb, duck, pork and guinea fowl (for taurine) and a lot of clarified butter and eggs.
Last year I was much better and could reduce my supplementation. From last year I increased dramatically the portions of meat/fish compared to the veggies. I don't know why, maybe because by instinct I wanted more meat? Maybe because here this meat is plentiful and very good? Also I started cooking everything in stews to take a maximum of nutrients with a minimum of work in the kitchen.

I too feel much better on a meat-heavy Atkins/paleo type diet with eggs, ghee. I still enjoy some fruit, potatoes, fermented cabbage, etc.. but the leafy greens veggies I'm supposed to be eating I mostly avoid. I'd always thought I had an intolerance to something in the plants like salicylates, and never considered that it might be plant folate, but it could be, as I cannot abide supplemental b-complex vitamins or methylfolate. A quarter tablet of the FolaPro makes me ill and gives me the worst metallic taste in my mouth. (If anyone takes this and would like it I'd be happy to send it to you, it's wasted on me). Then again, there are folates in meat.. but perhaps their form, or the prep of the meat or the speed at which they are digested makes an impact. Dunno.

Anyway, at this point I'm wondering if my best bet is to forgo supplemental folate and b vitamins (other than mb12, which does seem to help a bit) and instead do as Asklipia, and stick to what my body can absorb/process via a solid home-prepared diet.
 

Victronix

Senior Member
Messages
418
Location
California
Anyway, at this point I'm wondering if my best bet is to forgo supplemental folate and b vitamins (other than mb12, which does seem to help a bit) and instead do as Asklipia, and stick to what my body can absorb/process via a solid home-prepared diet.

Its best to take B-12 with the other Bs to balance them. Fredd found a B-multi that has no folic, folinic or methylfolate -- http://www.naturemade.com/products/b-complex/b-complex-with-c and its very cheap. I found that if I didn't do a B-multi I was getting irritable and agitated with only B-12.
 

xjhuez

Senior Member
Messages
175
Its best to take B-12 with the other Bs to balance them. Fredd found a B-multi that has no folic, folinic or methylfolate -- http://www.naturemade.com/products/b-complex/b-complex-with-c and its very cheap. I found that if I didn't do a B-multi I was getting irritable and agitated with only B-12.

If you're suggesting that the reason I can't handle the B multi is the folate, that definitely could be. I generally stay away from multivitamins as they almost always make me feel lousy and it's impossible to tell which of the dozen or so substances is the culprit. I suppose since it's cheap it's worth a shot.