• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

No love of B2 here - a warning about riboflavin

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
@Gondwanaland Interesting. I have certainly noticed depression on Folate and thought I only needed more--which does seem to have some effect, though I'm not high enough to be able to really judge (1600mcg/day)--and I am MAO A and MAOB ++. I also feel much more pain on MeFolate. I thought this had to do with healing...

As to MAO, I've been working on this a lot in the past few months, as per the directions of Greg Russell-Jones, our fave B-12 Oils guy. In order to get MAO to really work, according to Greg, one must have B2 working, of course, which requires iodine, selenium and molybdenum--which happened to be the sticking point for me. Mine was VERY LOW and I spent two months titrating up from about 6mcg/day to 150, where I am now. I 'm currently feeling reasonable on B2 at about 30-35mg/day including my B-complex.

It's still all a bit of a mystery. Though, of course, we don't want to be going backwards, or doing damage...
 
Last edited:

alicec

Senior Member
Messages
1,572
Location
Australia
@alicec, I have had seemingly-knowledgeable people (such as Greg the b12oils.com PhD biochemist) insist that folic acid and folate, while not identical, are converted from one to the other constantly in the body - so it is pointless to distinguish between them. You appear to understand this stuff. Can you clarify?

Folic acid is a laboratory creation and plays no role in metabolism. It can be converted to a usable form by the enzyme DHFR (dihydrofolate reductase) in a two step process. First it is converted to DHF (dihydrofolate), then the same enzyme converts DHF to THF (tetrahydrofolate), which can enter the folate cycle.

The normal role of DHFR in the body is to make this second conversion. Because of structural similarities it also recognises folic acid and can do the first stage of the conversion.

Studies of this conversion process, such as this example, show that the conversion of folic acid, which occurs in the liver, is very slow and that there is considerable variability in rate among individuals. Folic acid therefore accumulates readily and can inhibit several enzymes in the folate pathway, including DHFR.

So everyone processes folic acid slowly and some people process it very slowly. Folic acid accumulates and this can interfere in the folate pathway.
 

lch1

A New Day, Every Day!
Messages
43
Location
Mid Atlantic area, USA
Hi all, i recently had an Organic Acids Test from Nutreval and it showed high B2 in my body, whether it's inactive or active B2 I don't know.

I tried taking a bit of r5p last night (4mg) to see if I can get p5p to work for me again. This morning I was glued to my bed, woke up very tired and almost slept through my alarm. My vision has problems adjusting to light sensitivity and my eyes are watery for no apparent reason. I've been on mb12, mfolate for more than two weeks, and I just started LCF yesterday but this is a new conundrum for me.

Every time I've taken b2 I've reacted negatively to it, but after starting methylation and improving stomach acid with TMG I thought I'd give it a go, but the problems still persist

Has this happened to anyone with b2? How did you get it to work with p5p?

SuckSmoothie: I took B2 for a few weeks and it was horrible. I did not know what was going wrong, but I figured it out--thanks to South on this forum. I don't recommend supplements of B2--they usually pump way too much into you. It seems like an easy vitamin to get from food, eggs are good, plus other easily found foods. I got to the point where I could hardly get out of bed, and I'm a highly, highly active person. Good luck!
 

alicec

Senior Member
Messages
1,572
Location
Australia
RichV recommended methlyfolate and folinic

Folinic acid is a storage form of folate and can feed into folate pathways other than via the methionine synthase path that converts methylfolate to THF. Rich suggested that it could be a useful addition to folate supplementation, particularly if there is difficulty at methionine synthase.

A number of people reported intolerance of folinic. The reason is not understood but presumably it has something to do with the two enzymes which act on it - MTHFS and SHMT. If it not being processed and so accumulates it can inhibit SHMT (maybe other enzymes also, not sure) and this in turn can affect the folate pathway adversely.

So folinic supplementation may be helpful, PROVIDED THAT it can be processed and there is no way of knowing this in advance. It has to be tested empirically.

It would be good if someone answered garyfritz' question.

I did, in the previous post. Did you miss it, or perhaps you mean you didn't like the answer? What do you mean?
 

CCC

Senior Member
Messages
457
I said Folic Acid because that is what my blood results say.
EDIT- BTW to activate a folic acid supplement or folinic acid it takes B2+Choline, so high blood levels of folic acid or whatever might mean a build up of inactive stuff waiting for B2 or a methyl donor (e.g. choline). Mfolate bypasses that.
This is interesting.

We accidentally started taking folinic with B2 as needed (always together and several times a day). This was just cheap as chips riboflavin, nothing fancy.

Folinic had never done much before, despite supplementing with B2 (as sublingual FMN, but not at the same time as swallowing the folinic).

Take them together (cheap B2 and folinic) and suddenly the body felt like the folinic was doing something neither it nor the methylfolate had ever done.
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
We accidentally started taking folinic with B2 as needed (always together and several times a day). This was just cheap as chips riboflavin, nothing fancy.
You've caught my attention here! My alternative doc just said that given my snps (I forget which ones now) that I might do better on folinic rather than methyl folate. Have you continued to take take the folinic? How does your body feel?
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
Hi all, i recently had an Organic Acids Test from Nutreval and it showed high B2 in my body, whether it's inactive or active B2 I don't know.
Àccording to Greg Russel Jones, who is a font of knowledge on B2, it needs 3 things to be active (I've had very high serum levels, myself). These are iodine, selenium and molybdenum. I was very deficient in molybdenum and B2 never seemed to work for me. His advice to me: "The sequence in synthesis is--
Iodine is used to make T4.
Selenium is used in the conversion of T4 to T3, the active form.
Then later, molybdenum is used in the enzyme that converts FMN to the active variant FAD. FAD is the co-enzyme that you need."

It took me two months to titrate up to 150mcg of molybdenum per day, which he said would likely be enough to refill my tank.

Just now, it seems, I may still need selenium. So, I'm working on that. Good luck!
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
@Gondwanaland I see that selenium has been very helpful for you. What has it assisted or helped? And this is off topic here, but I also noted somewhere that your DH, while not tolerating Folate, also does very well on Folinic, I believe. I've just ordered some myself to run the self-test after my alterna-doc's comments (still with the very tight neck/ shoulders/facial issue). Could you speak to this or guide me to a post where you do?

Thank you!
 

Gondwanaland

Senior Member
Messages
5,095
selenium has been very helpful for you. What has it assisted or helped? A
It reduced my Reverse T3 to the lowest end of range and relives back pain at adrenal height. So clearly low T4=>T3 conversion taxes adrenals. I usually get that back pain after eating, so some foods impair the conversion or require increased conversion, so I always take my Selenium before or after lunch (my biggest meal).
your DH, while not tolerating Folate, also does very well on Folinic
I have given him very small doses of Folic Acid, Folinic Acid and Methylfolate, and yes, no bad reaction to folinic. But I think people have no idea on the amounts of glutamate involved with any form, especially taking high doses which might convert back and forth to forms with more or less glutamate molecules attached.
 

alicec

Senior Member
Messages
1,572
Location
Australia
But I think people have no idea on the amounts of glutamate involved with any form, especially taking high doses which might convert back and forth to forms with more or less glutamate molecules attached.

I don't think it works that way.

Folates in food are polyglutamated but the polyglutamate tail is cleaved in the intestine to allow absorption into blood. Folates in blood (predominantly methylfolate) are monoglutamated.

Folate supplements (regardless of type) are monoglutamated.

Once taken into the cell, folates are again polyglutamated, which helps to keep them inside the cell.

To get them out of the cell, the polyglutamate tail is again removed.
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
So clearly low T4=>T3 conversion taxes adrenals.
I suspect this may be a problem for me, though who knows. My selenium levels look ok, but I still have a very strong reaction to selenium when I take it. It may be that the mercury load I'm carrying (not as bad as it was years ago, but still in the red on the Nutreval Test) has hijacked the selenium, which I understand it does. For the moment I'm trying to add more just to see if it helps--as Greg has suggested that I still have poor B2 conversion (my levels of B2 in June - @ >400.0 NMOL/L Normal Range nmo/L 6.2 - 39.0 nmol/L). Something's wacky, I think!

As to your Folate tails and so on, I'm completely ignorant. I think I must do some reading on this! Does the 'glutamated' part of the folate have anything to do with glutamate or something entirely different? I largely understand glutamate as an excitory neurotransmitter.

My lower back tightness/pain is there all the time. Hmmmm. Though it's possible it's gotten worse as I raised the levels of methyl-folate I was taking. Test have shown I have a problem with folate metabolism, and in fact, I think you, @alicec, mentioned the SLC19A gene related to Folate matabolism, for which I'm +/+ (G;G). Though this particular snp, from what I could find, didn't relate to higher homocysteine--which I don't have.
 

Gondwanaland

Senior Member
Messages
5,095
very strong reaction to selenium when I take it
I had to change from SeMET to SeGLY since methionine gives me brain fog. Also I take only 40mcg, which was enough to put my RT3 in the lower end of range. I know this small amout might be limiting for other Se activities in the body, but as long as I don't have back pain I'm fine with that. I just don't tolerate Brazil nuts, but I might have some other selenium sources from food.
As to your Folate tails and so on, I'm completely ignorant. I think I must do some reading on this! Does the 'glutamated' part of the folate have anything to do with glutamate or something entirely different?
I will have to find the source where I read about that again
 

alicec

Senior Member
Messages
1,572
Location
Australia
Does the 'glutamated' part of the folate have anything to do with glutamate or something entirely different? I largely understand glutamate as an excitory neurotransmitter.

Glutamic acid, in its anionic form known as glutamate, is an amino acid which fulfils several functions. It is part of the structure of proteins, as an isolated amino acid it is an important partner in transamination reactions which are widely used in many metabolic processes, including energy pathways, in conjunction with glutamine it helps control ammonia balance, and as you note, it is an excitatory neurotransmitter.

It is also part of the structure of folates, either as a single molecule on one end - a monoglutamated form - or as a string of usually 4-6 glutamates - a polyglutamated form.
 

CCC

Senior Member
Messages
457
You've caught my attention here! My alternative doc just said that given my snps (I forget which ones now) that I might do better on folinic rather than methyl folate. Have you continued to take take the folinic? How does your body feel?

It's hard to say - partly because it's my son, not me.

What I see is clearer skin, better social interaction, and waking up refreshed for the first time in several years.

My son has mentioned his brain is working a lot better.

He also needs less aB12.
 

CCC

Senior Member
Messages
457
@CCC Thanks for that. Interesting. How much folinic is he taking?

Hard to say how much. It's a 'when he needs it' thing.

The folinic tablets are 800mcg, and I think he is taking at least 4 a day, spread out over the day, with 25 mg of B2 each time.

He was taking much, much more of the LE 5mg methylfolate. But this folinic+B2 seems to work better, and the drop in folate/folinic demand was instant.

I think the B2 is a big part of the picture. It took a few weeks on this regime before he started excreting excess.

And that was after months of taking large doses of the sublingual FMN (again, spread out through the day). Even though he got an instant benefit from the sublingual FMN (thanks to @ahmo for that tip), and he also started excreting the excess B2 after a few months (not a typo), taking the B2 with folinic seems to have made a bigger difference.

I'm happy because he's only 16 and I don't really like the idea of all that potential tooth damage from sublinguals. With folinic+B2 and the B12 oils, we have no more sublinguals. Yay!
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
Folates in food are polyglutamated but the polyglutamate tail is cleaved in the intestine to allow absorption into blood. Folates in blood (predominantly methylfolate) are monoglutamated.

Folate supplements (regardless of type) are monoglutamated.

Once taken into the cell, folates are again polyglutamated, which helps to keep them inside the cell.

Hi Alicec. I'm trying to wrap my head around this. So it seems that we should be more wary of high glutamate foods rather then folate supplements because polyglutamated foods are broken down into monoglutamates and thus release more glutamate into the blood? Whereas folates use glutamate molecules once they enter into cells and reduce the amount of glutamate in the body?
 

alicec

Senior Member
Messages
1,572
Location
Australia
So it seems that we should be more wary of high glutamate foods rather then folate supplements because polyglutamated foods are broken down into monoglutamates and thus release more glutamate into the blood? Whereas folates use glutamate molecules once they enter into cells and reduce the amount of glutamate in the body?

Glutamate in foods and folate glutamation are not really connected, nor does the amount of glutamate used up in polyglutamation of folates within cells have any real impact on overall glutamate balance.

Polyglutamation in foods is peculiar to folates. The presence or absence of a polyglutamate tail is a way of regulating the passage of folates across membranes.

The problematic glutamates in foods are free glutamates, not the glutamate incorporated into protein. However partially hydrolysed protein preparations often contain significant amounts of free glutamate which can be a problem for sensitive individuals.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@CCC I was also concerned about sublinguals and teeth. I switched to using B12 transdermally and then did the same w/ FMN. I've found that I need 1/2 tab FMN/day transdermally, and 1 tab sublingually. I crush the tab onto a piece of fabric, add oil or lotion, and apply to skin. But, seems like you've gotten another solution.:)