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FMN B2, MAO, Histamines, Oxidative Stress

I'm writing this after 2 weeks using FMN form of Vitamin B2.

For years, long before ME, Relaxation has been my holy grail. My nervous system has been modelled into the warrior polarity of the warrior/worrier seesaw. I had the childhood stressors that intensify things for MAO and COMT aggressive tendency, as well as growing up in a household full of warriors. When I was at my worst, pre-GAPS, the worrier was as enflamed as the warrior. what a mess.

Here’s what I wrote at the end of the first day with FMN: My mood is so different today; kidneys felt stressed yesterday, today nothing. Right now I can’t even remember why I was planning to fast starting in 2 days. My next step, which I must have felt bad enough to want to do sooner than later, was to follow Critterina’s lead, and do a 3 day fast for resetting autoimmune system. I was still fending off the peroxynitrite bear on my back. And I do recall standing, staring into space and unable to put my finger on why this fast had seemed so important. Something dramatic had shifted my physical and emotional states, so much that there was a discontinuity. On the second day I’ve written I really feel calm, much more centered. It feels like I’ve taken off a leaden overcoat.

From mid-January, I spent 10 weeks in an intensive fungal-bacterial-viral removal effort. I was seeking to eliminate all the sources of ammonia in my life. I’d been chasing the source of my excess ammonia/peroxynitrite for a couple months….And this seems to be exactly where FMN has been interacting. I’ve stopped looking for ammonia, though I might still consider Sanum homeopathics to go on w/ Candida, to get on top of the bloating. But for now, peroxynitrite is my focus. Or maybe it’s more accurate to express it as avoiding oxidative stress.

I’d gone up to 6 molybdenum tabs AM/PM to help mop up the ammonia. Now I’m back down to 3. My need for malic acid, another of my primary ammonia solutions, has decreased to needing none some days. Butyrate, also for ammonia, was reduced following my purge regimen, and my need now has reduced further. Same with the ALCAR I’d recently begun to mop up peroxy. (I say mop up because that’s the closest I can come to a description. The cycles are still pretty much beyond my zero-working-memory brain.) Reduced Ubiquinol and manganese. I’d decreased my carnitine (LCF) from 4/day to 3 during my purge period. With the FMN I further reduced it to 2 only. This might coincide with B2’s relationship ATP. Another benefit from my purge was reintroducing nuts and seeds back into my diet, things I’d removed to get on top of autoimmune stressors. But this, and the high carrot intake, seemingly led to weight gain. Since beginning FMN I’ve dropped a couple kilos.

It also has let me introduce a small amount of green veg into my life. I’ve been unable to eat green veg since discovering a year ago that the veg folinic was blocking methylfolate, and pushing my needs for methylfolate into an unending thirst. Inspired by enthusiastic B2 reports, one suggesting it would enable eating green veg., I experimented with 3 days of B2 at the beginning of the year. Results: feeling I’d poisoned myself with ammonia. FMN has made a few sprigs of parsley possible again.

It would appear that I wasn’t totally off the mark during the months that I made comments re MAO suggesting a tendency toward histamine problems. I later couldn’t find specific evidence for this, and that particular research project has not risen to the top of my to-do pile in these many months. However, I started down this FMN path based on the comments @ppodhajski made re FMN being his main response to MAO-A problems. MAO is my single homozygous snp. Yasko’s drops helped during the early days. As my detox practices and implementation of B12/Folate and Deadlock Quartet elements moved on, my body no longer wanted the drops. From daily to a couple times a week, weekly, and now rarely, only when in some version of crisis/crash.

Since adding FMN all of my histamine-reducing and mast cell-stabilising supps have reduced, sometimes none for a whole day. Not only that, I’m now daily consuming a spoonful of fermented kraut or yogurt. And there are onions (high thiol/sulfur) in my sauerkraut, as well as beet, both of which I’d been avoiding for nearly 3 years. Also my need for antioxidants has, thankfully reduced. I think my purge was really taxxing on the body. I can’t otherwise account for what had become an overwhelmingly huge need for antioxidants, met especially with carrots and green tea. Additionally, there are antiox supps, which I also am now needing much less of. I’ve gone from 3l green tea/day to one. I didn’t anticipate the mood downer this would precipitate for a couple days, but I’m now ingesting a lot less caffeine. And less carrots. As I state frequently, I assess my needs and dosages by self-testing. This means there’s a degree of *objectivity*, in that my decisions to, e.g. cut back on green tea, doesn’t come from my mind, an idea, but is the response I get from my body when I ask the question.

I’ve noticed during the 2 years I’ve been working with methylation and detox, that a number of times there have been significant and specific improvements in my state. However, I’ve also become quite aware that there’s fundamentally a very low ceiling to my available energy. My brain doesn’t get any sharper, my body doesn’t get any extra exercise. I don’t know how many more tweaks are available to me. I think I’ll go ahead with the Myarisan experiment, ferment it into yogurt. But I no longer feel the need for a 3 day fast for immune reset. Some very profound changes have happened. Far less histamine and mast cell flares. Less feeling of being on the edge of a crash, although I’m now far more aware and just start eating carrots to ward it off. But the calm, the greater sense of centering, the newly remembered pleasure of enjoying the twilight are very welcome.

Each step of healing, from the moment I dropped gluten and dairy, until this newest addition of FMN, has resulted in a calmer and more resilient nervous system. Whatever has or hasn’t happened in other parts of my body, these shifts have been profound. Meditation has been returned to me. One of these days I may even be able to walk slowly, to stop rushing in all my movements. I feel that this new calm has at least 2 aspects. One is greater energy, so that there’s less energy spent in fighting inertia. And somewhere else there’s less stress. Resulting in calmer adrenals, less provocation for the mast cells which flare when adrenals are stressed.

I also discovered last year that I have significant ataxia, suggesting cerebellar damage. Close my eyes and walk heel-to-toe without falling over...not so easy. I hadn't tried it recently, but I now find it's not nearly so profound. I can't say at what stage this shift came.

I still have only a scant understanding of FMN. Still, I can understand how ppodhajski could say that this is about all he’s using for MAO. It’s been rather remarkable for me.

What I'm using:
Source naturals 18mg FMN
The Benefits of Coenzymated Sublingual Vitamins - In order for vitamins to be utilized by the body, they must first be converted into their active coenzyme forms. Coenzymated B-2 sublingual goes directly into your bloodstream in its active form, ready to go to work immediately. This avoids loss that may occur not only during digestion, but during the liver's conversion process as well. Flavin mononucleotide (FMN), also called riboflavin phosphate, is one of the two metabolically active coenzyme forms of vitamin B-2. FMN is itself the precursor for the other B-2 coenzyme, FAD. FMN is involved in a wide array of enzymes and has many roles in energy production from our food, as well as bio-converting B-6 to its coenzyme form.

Sorbitol, mannitol, natural peppermint flavor, and magnesium stearate.


A few references that influenced me re FMN

I only saw this 2012 thread after I wrote this entry. There's some interesting info re coenzymated vitamins:
http://forums.phoenixrising.me/index.php?threads/are-coenzyme-b-vitamins-bunk.15280/#post-248247

http://forums.phoenixrising.me/inde...lation-protocol-srmp.36344/page-2#post-586710

ppodhajski : This talk of methylation and MAO is confusing to me. The only methyl that helps break down biogenic amines is SAMe and that helps the COMT enzyme, not the MAO enzyme.

But why take B2 when you can take flavin mononucliotide (FMN) as a sublingual? That is all I take for my MAO, plus magnesium for my COMT. I also stopped taking B12 in any form and my levels are normal after being very high for so long. I think all those sups you have listed are a waste.

Also, a low amine diet helps but I find I can eat more amines as long as I take more FMN. And it also took me, and one of my friends only one day to feel the effects from FMN.

My disabling anxiety and neuropathy (among other things) are all gone.

...But I also take FMN (B2) which helps lower catecholamines by fixing my MAOA and MAOB SNPs. And I am also on a low amine diet

I found the sublingual FMN works much faster, like 15 minutes, when I was having epinephrine provoked anxiety.


http://forums.phoenixrising.me/index.php?threads/is-taking-bh4-a-problem-for-comt.36997/#post-588606 Is BH4 a problem with COMT?

ppodhajski : FMN = flavin mononucleotide = riboflavin 5 phosphate = coenzymated B2

Riboflavin is a cofactor for the MAOA and MOAB enzymes. Well, actually FAD is the cofactor, but riboflavin turns into flavin mononucleotide (FMN) and then into flavin adenine dinucleotide (FAD).

By taking FMN we are only one step away from FAD and we save some ATP in the process.
For the full riboflavin pathway see:
http://smpdb.ca/view/SMP00070

For people with CFS and have low ATP so this is important.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/

Why does this help you relax and lessen your stiffness? I don’t know exactly, but I am guessing that it reduces oxidative stress by changing how catecholamines are broken down in the body. If you want to read a long paper on the process see:
http://intl.pharmrev.org/content/56/3/331.full.pdf html

Basically, by speeding up MAO we remove O2 from the cell and create H2O2. Removing O2 from the cell lowers the chances of creating superoxides forming in the cell. (Superoxides are created when and electron is added to O2) Hydrogen peroxide is not as bad as superoxides.

(COMT helps reduce catecholamines but to a lesser extent and in different area in the body. It had more to do with lipid catecholamines)

Since SOD turns superoxides into hydrogen peroxides and SOD SNP will keep even more superoxides around. And then bad GPX SNPs will have a hard time getting rid of the hydrogen peroxide.


http://forums.phoenixrising.me/index.php?threads/bh4-gch1-question.35140/page-2#post-587569
ppodhajski said: ↑
NO/ONOO is a dead end in my opinion. I know why they were so interested in it but the issue is oxidative stress. If you are worried about peroxynitrite you need to get rid of the superoxides, and that is through the SOD2 gene which turns the superoxide into hydrogen peroxide.

My SOD2 SNPs are bad. I take manganese and eat high manganese foods for that.

But this goes back to why the superoxides are being created in the mitochondria in the first place. And that I blame on slow MAO and COMT SNPs.


forums.phoenixrising.me/index.php B2I love you

aaron_c:I feel like I have not been thinking about b2 use as a cofactor in the right sense, so I wanted to share what I found.

The question I had recently is what Christine/DogPerson meant by B2 being “used up” by various other vitamins. Is it used up like ATP gets used up and becomes ADP? Or is it used up because there are more enzymes that require FMN (flavin mononucleotide, aka riboflavin-5-phosphate) as a prosthetic group--meaning it is more like a wrench that all flavoproteins (proteins using FMN or FAD) have to share.

At least in the case of recycling vitamin k via NAD(P)H quinone oxidoreductase, and B6 by pyridoxine 5 phosphate oxidase, the FMN is not “used up,” but is simply necessary for the enzyme to function. I also found an entry for a quinone oxidoreductase that did not mention NAD(P)H as a reactant...but looking around on biogps.org, all I could find was something that probably used NADPH...

Comments

This is a terrific post. I can't say I understand it all. But a lot of it is becoming familiar to me from these forums. And my homozygous MAO had already brought the need for B2 to my attention...not to mention the results of my NutrEval Test that show a high need. Interestingly, I just bought a Solgar B2 from iHerb, but it's not the FMN form. Ironically, the B2 in the Country Life Coenzyme B Complex I've taken and not taken and now am taking again is just this, the riboflavin 5'phosphate form, or FMN. I was taking 50 mg/day for who-knows-how-long; currently only 12.5. But maybe it's why my doc looked at my OAT test results recently and said I didn't seem to be too stressed...

Thanks for pulling the information together with your own clarity.
 
This is very useful in getting me thinking in a new direction, but I don't yet understand it. So I have a very basic question to get me started. I'm ++ MAO A, and I don't find any tests for MAO B. I did some reading and don't find information on why/how this kind of B2 helps, so I can't hazard a guess as to how much FMN is useful/needed. I have ordered the Source Naturals, and my question is how much to take as a starting experimental dose. I know we're all different, but also some supplements don't have any effect at a dose under xyz. Just fishing for information.
 
Interesting @ahmo. Good to hear you're getting good results.

I used to take Source Naturals Coenzymated B1 for about a year or so during most of 2014 and found that it helped considerably with anxiety, irritability and stress. But by the 2nd half of the year I started going downhill dramatically. That could've been due to too much b1 imbalancing the other Bs, but I developed a severe histamine intolerance, and now wonder if this may have also been due to the mannitol in the Source Naturals product.

Mannitol is associated with increased histamine levels -- at least when inhaled. But if you're doing okay with it, maybe it's not an issue?

Here's one of the studies showing a link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884269/
 
Enzymatic Therapies B12 also has mannitol, and I tolerated that for the first year of my methylation protocol. What I can say is that the reduction in my histamine symptoms and needs has been dramatic. I can only suggest taking a piece of a tab for starteers, then add a bit more if there's no negative reaction.
 
I kept hearing about B2 and wondered if it's something I should consider. Thanks for making it so clear how this can be important; I remember FAD from my basic bio classes.... :)
 
Someone commented to me in pm:
I ordered FMN after seeing your message, never knew such thing even existed. Took the first dosage just now. Holy cow!!! It feels like something is rushing to my brain and everything is awaking....

The reaction I get from FMN is much like mb12, but in a much more pleasant form. This did not happen with regular B2....
This might have been the hidden gem, especially given I have several defects in MAO SNP's.

Next day: The FMN effect lasted almost 12 hours yesterday and it did not impact hair loss in any negative ways. I took another pill this morning and my mind is not fogged after 8 hours. There is definitely a massive difference after taking FMN. I am liking it a lot. This is the first supplement that has immediate effect on me that lasts for a long duration.
 
Great post Ahmo! Thanks much for taking the time to write it out for us. I gave it my first go-ariound perusal, and hope to come back tomorrow to digest it all a little better--perhaps after I make a trip to the store to get some FMN. :)
 
Ahmo, How much B2 are you taking at this point, as the Source Naturals FMN or in your daily multi? I've been talking to the B12 oils guy, Greg, and he points out- as you and others may have- that it assists in the metabolism of Folate. I know Fred says to keep the lower Bs low because they can drive the need for folate, but with the homozygous MAO, we may need the extra B2 to help tolerate the methyl groups. I'm getting 20 mg B2 as r-5-p in my multi, but once I reached 7,000 MeB12 and 2,000 mcg Folate, I definitely went off the tracks! I'm going to back up and go with increasing amounts of the FMN---if I can.

Just wondering... Thanks!
 
Im a little late here but you mention a possible link between MAO and histamine and the fact your histamine sx improved. I found that, as you probably know histamine degrades to methylhistamine via the HNMT enzyme and then to another metabolite using MAO (diagram here: http://suzycohen.com/articles/histamine_intolerance_dao_genes_hashimotos/).
Well it turns out that the methyl-histamine is an H1 agonist itself (From the book "The mast cell in health and disease) so if your MAO was sluggish maybe this metabolite was continuing to act like histamine.
 
I'm not sure what this means but it looks like there's some relationship between fmn and nitric oxide cycle, which could be why it helps your ammonia issues
https://examine.com/supplements/arginine/
NOS enzymes work in dimers that are jointed head to head and the catalytic mechanisms is dependent on this dimerization as well as heme, tetrahydrobiopterin, calmodulin, NADPH (as electron donor) and both FMN and FAD.[81][82][83]

I'm working on methylation /ammonia /sulfur issues at present and your comments on the subject have been very helpful!
 
What's the difference between flavin mononucleotide and riboflavin 5 phosphate?
 

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