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How B2 really affects Folate?

Messages
41
One thing I keep reading about on here is the interaction between Riboflavin and Folate. This might be a silly question now that I think about it but...

On one thread I read that B2 by itself is a "methyl accepter" so to speak, which increases the "effectiveness" I guess of methyl groups, from all sources, not just Folate.

On another thread I read that B2 helps to "metabolize" Folate and B12, increasing their overall effectiveness.

But I'm curious if those two things are actually one in the same?

For instance... is Folate (and b12) always as effective regardless of how much B2 you take (or if anything, less effective due to overmethylation), and the only reason B2 seems to help "metabolize" it better, is because it increases the effectiveness of JUST methyl groups attached to it? But doesn't really affect the Folate itself?

OR

Does B2 help BOTH, by splitting them and thus metabolizing them both, so to speak (or by some other similar process)? Making both the Folate itself, and the Methyl attached to it, do their jobs better?

I feel like if I understood the mechanics of this process with B2 and methyl attached nutrients, I might understand why I'm struggling so hard lately... I guess what it comes down to, is, I'm wondering if I'm actually Folate deficient (or more specifically B2 deficient) despite taking relatively large amounts of Folate...
 
Messages
41
And by that logic, are there other B vitamins (or other nutrients) that B2 helps to "metabolize" or increase the effectiveness of?? One that aren't even bound to methyl? Like niacin, niacinamide, b6, b1, choline, etc etc...

Likewise, could B2 potentially increase the effectiveness of B12 in the form of say adenosylcobalamin, or hydroxycobalamin, as well?

I almost wonder if I should just take extra B2 directly with my B-complex (and maybe need r5p as well, even though I don't do as well with it as with Riboflavin)... But I think I'll make another thread on that, since there's other stuff I want to ask.
 
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alicec

Senior Member
Messages
1,572
Location
Australia
B2, in its active forms of flavin mononucleotide (FMN, aka riboflavin 5 phosphate) and flavin adenine dinucleotide (FAD), acts as a cofactor for many enzymes, some of which are involved in the action of other B vitamins.

Some enzymes use only one form of the active cofactor, some use both.

The reactions catalysed are redox reactions - oxidation-reduction reactions which involve transfer of electrons and/ or hydrogen ions.

The cofactor does not accept methyl groups, nor does it directly split or otherwise interact with folate or B12.

It interacts with the folate cycle by acting as a cofactor for the enzyme MTHFR. This enzyme creates methyl tetrahydrofolate (MeTHF) from 5,10 methylene THF.

MeTHF in turn acts as a cofactor for the enzyme methionine synthase (MS), which uses B12 as another cofactor. This latter reaction is at the heart of the methylation cycle.

The cofactor does not directly participate in the reaction catalysed by adenosylB12 (conversion of methylmalonyl CoA to succinylCoA by the enzyme methylmalonylmutase) but it is essential at an earlier stage in the processing of odd-chain fatty acids which lead to this reaction.

The cofactor is required for formation of the active form of B6.

The cofactor is required for the formation of niacin (B3) from tryptophan and it works together with the active form of B3 (NAD/NADH or NADP/NADPH) in many reactions.

The cofactor does not directly interact with B1 but it and active B3 are part of several enzyme complexes involved in energy metabolism which also use active B1.

The cofactor is required for conversion of dietary choline into betaine which then goes on to participate in aspects of the methylation cycle.

So yes, there are many instances where B2 is important to the action of the other substances you mention, though not by the mechanisms you propose. It can indeed be a limiting factor in these actions.

Just supplying riboflavin might not be sufficient either. Formation of the active forms from riboflavin requires energy in the form of ATP (ie good mitochondrial function which many of us don't have) and good thyroid function (which again many of us don't have).

You might need to pay attention to many things other than folate/B12.
 
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Messages
41
Thank you very much for the reply. Some of it's a bit over my head but I get what you're saying for the most part...

The thing is though, I am in fact taking a full B complex, which worked VERY well for me by itself, for a long while... and then suddenly just STOPPED... I started taking additional b12 (adenosyl) and folate (again, since I took just those for months before), on top of the B complex this time, and that worked great... for about a week, and then that all stopped. Now I feel terrible again, and all my old symptoms have returned.

Which is what lead me to believe that maybe I was "depeleting" my B2 and that deficiency was causing other B's to not work as well... But the thing is, there's plenty of B2 in my complex, so I don't know if it's really even necessary? I read on one thread that it's sometimes recommended to take extra B2 on top of what's already in a complex, so I don't really know.

And now it also seems like I either have excessive ammonia or homocysteine levels, or both... and I don't know why. Especially if I'm taking way more than enough b12, b6, and folate to deal with any homocysteine...

I do have a CBS upregulation problem, which was a problem for a while... I got over it once I started the B complex, and now it suddenly seems to be a problem again... Very intolerant to meat again, freezing cold all the time, heart palpitations, kidney problems, BAD anxiety and depression, etc. Maybe that's the reason why I'm struggling with methyl-B's suddenly?

I was also thinking it might be that everything was just an issue of balance. Like by taking too much folate and b12 depleting the other B's in the complex or something... But I'm not sure about that...

But I also wonder if since all I'm taking is B vitamins, if perhaps they're all, instead, depleting all my other glutathione cofactors (since thats what I'm aiming to raise), or just plain other nutrients I guess (like the ones that help deal with ammonia... like manganese, molybdenum, even magnesium). Not really sure if that's even how it works.

I'm also wondering if I'm not getting enough B6, but there's 50mg of p5p in my complex... maybe I need HCL tho? Or maybe the ammonia is the only thing I should focus on for now? I don't know.. sigh. So much involved and I'm losing my freaking mind.

Like I said above though, I'll probably make a seperate thread about these issues in more detail. But I'd still greatly appreciate any more replies here on it.
 
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Messages
41
Sorry, not interested in debating that with you.

I most certainly have issues with ammonia, sulfur and protein - as well as a great deal of symptoms from upregulation my entire life. And have only found benefit to my life-long illness in treating those things, and methylation, ever.

I'm actually starting to realize that an upregulation may very well be my current main issue, as a matter of fact.

So again, thanks for the input, but from the looks of the rest of your posts, no thanks.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
I was also thinking it might be that everything was just an issue of balance.
Balance - that is a very important, and tricky, issue. It definitely involves more than the B vitamins.

As to the B2, you can only utilize about 25 mg at a time. For a larger amount to be useful, it needs to be split into multiple doses of 25 mg or less. You may need manganese with B2.
 

Gondwanaland

Senior Member
Messages
5,092
The thing is though, I am in fact taking a full B complex, which worked VERY well for me by itself, for a long while... and then suddenly just STOPPED...
In my personal experience I have to cycle the use of the B complex, like one month on, on month off. It definetly can turn from beneficial into detrimental probably due the hormonal effects.
Very intolerant to meat again, freezing cold all the time, heart palpitations, kidney problems, BAD anxiety and depression, etc.
You might want to look into uric acid metabolism. Blood levels of uric acid unfortunately don't always reflect tissue burden, body usually won't allow circulation above kidneys capacity.

What I find helpful is balancing B2, B5 and B6 at a personalized ratio. Intake of calcium, magnesium, manganese and molybdenum is tricky. I feel that manganese helps to use molybdenum in other routes than the xanthine oxidase. To slow xanthine oxidase route I have found helpful to avoid vit A and methyl donors like choline for instance (mainly eggs), and take very small protein amount at each meal, being careful not to ingest to many high protein foods at the same time.

B6 is the most helpful and at the same time most detrimental vitamin, since it turns from friend into foe in the long term (thyroid overstimulation).

For more info on how to juggle vitamins and minerals refer to the link in my sig "Balancing nutrients".
 

stridor

Senior Member
Messages
873
Location
Powassan, Ontario
I have a couple of questions and perhaps someone here can help.

a) I have read that the gut can manage only 25 mg of B2 at a time. Does anyone know how studies arrived at 400 mg of B2 for migraine?

b) Is the active form absorbed or transported intact? Or is phosphate removed?

c) If there is a means for active B2 to be absorbed passively, does the 25 mg still apply?
 

alicec

Senior Member
Messages
1,572
Location
Australia
a) I have read that the gut can manage only 25 mg of B2 at a time. Does anyone know how studies arrived at 400 mg of B2 for migraine?

25 mg is a roughly appropriate estimate of the most efficient dose. The transport mechanism is saturable so above this dose there is only marginally more uptake.

I believe the high doses are meant to be divided and taken with food. The latter precaution means that the vitamin has a slower transit through the gut and so has more opportunity to be absorbed. I don't know why they settled on that particular high dose but some of it is probably overkill - ie a significant proportion will be wasted but maximum uptake will be ensured.

b) Is the active form absorbed or transported intact? Or is phosphate removed?

The phosphate is removed in the gut.

I have seen small studies in rats which indicated that at least some P5P is taken up intact by an uncharacterised mechanism independent of the classical uptake which also clips off the phosphate. I haven't seen similar studies for R5P but I assume something like that could be happening since I and others have noticed a difference in response to sub-lingual R5P compared with riboflavin.

However I must say this only happened for a short time. Eventually I switched back to plain riboflavin and pyridoxine because the active vitamins didn't seem to be doing anything special.

c) If there is a means for active B2 to be absorbed passively, does the 25 mg still apply?

The putative direct uptake mechanism would be independent of the classical mechanism which defined the 25 mg. However whether such a mechanism really exists or whether the apparent response to R5P and P5P is due to something else is a bit of a mystery.

I don't really know what was going on with the initial beneficial response to the sublinguals.
 

Gondwanaland

Senior Member
Messages
5,092
I don't really know what was going on with the initial beneficial response to the sublinguals.
B6 only started working for me after a 2-week course of P5P. Before that all the B6 I took would only make symptoms of B6 deficiency worse. And now I try to keep my B6 intake never higher than one milligram (1 mg) per day.
 

stridor

Senior Member
Messages
873
Location
Powassan, Ontario
Gracias @alicec
I think that the goal is to not have any noticeable effect when taking B2. If someone responds to s.l. and they are taking B2 orally then there has to be a problem - most likely with absorption. Not common but it happens.

I am going to try it. I hope that R5P tastes better than the straight B2 I took in 2011 :) I just got some bulk R5P and I will get started.

I ran out of B2 twice when I fired up methylation. The first time my tongue swelled and split - horrible. The second I had a rash on my face and privates, cracks at the corners of my mouth and angry capillaries in my eyes. The thing is that I was taking B2 orally at the time and this threw me off the scent.

I don't absorb this stuff well. I have to take mfolate in the buccal pouches as well.

Somewhere and somehow, B2 played a pivotal role in my development of Chronic Fatigue. A lot of this stuff involving biochemical processes and pathways is over my head.