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    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.

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B2 I love you!

Violeta

Senior Member
Messages
2,952
@ahmo, I had written that message for this thread and then erased it because I thought I may have read something wrong in Tunguska's message and didn't have the energy to go check and change my message. That's strange that it ended up in your emails. I have no idea how that could have happened. I'm very sorry. If it has some meaning to you, then all is well. :)

I have been eating some spinach here and there, but I think I should actually try to add some methylfolate back in. That's interesting that you do ok with the supplement but not the vegetables. But yes, I see what you mean that B2 might help you process the folate from the vegetables.

Yes, I always realize I need something a little bit after I give it away.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Violeta I'm so grateful for your message having made it's way to me. Must have been meant to be:alien::angel:...BECAUSE, it's worked!!! I had some regular B2, not R5P, 100mg caps. the first day I took 1 cap, juiced/ate 4 small lettuce leaves. No symptoms! The second day I used 1/2 cap, 50mg, same amount of lettuce: No symptoms!! Wow, I'm going to be able to eat green veggies!!!!:love:
 

Violeta

Senior Member
Messages
2,952
@Violeta I'm so grateful for your message having made it's way to me. Must have been meant to be:alien::angel:...BECAUSE, it's worked!!! I had some regular B2, not R5P, 100mg caps. the first day I took 1 cap, juiced/ate 4 small lettuce leaves. No symptoms! The second day I used 1/2 cap, 50mg, same amount of lettuce: No symptoms!! Wow, I'm going to be able to eat green veggies!!!!:love:

Pretty wild! That's an amazing application of the info, too.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
Well, it was nice while it lasted.:(By Day 3 of this experiment, taking 50mg B2, I couldn't understand why I was having such an ammonia problem. Day 4 @Gondwanaland reminded me of my B2 intake.
oh_jeez-1018.gif
Of course, B vits are high sulfur. I've felt like I'm drowning in ammonia these past 2 days, doing everything in my toolkit to get rid of it. Needless to say, no B2 today. I'll review B2, green veggies at some later date. Just now, I can't wait for my system to calm down!:aghhh:
 

aaron_c

Senior Member
Messages
691
Hi Yall,

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...

What I take from all this is that the reason why B2 can take time to go from depleted to replete is that it is "stored" in the enzymes that use it. Obviously the picture is somewhat more complicated. It seems to me like b2 acts a little like something that is stored and a little like something that gets excreted fairly quickly.

Nonetheless, for me seeing this calls into question Christine/DogPerson's assertion that taking B6 or vitamin K "uses up" B2. In the short term, as an increase in vitamin K might necessitate an increase in vitamin k-dependent proteins, I can see this happening. But once the necessary tools have been made, I am not sure how much more than normal one would need B2.

Of course, those of us with ME have some weird biochemistry, so I do not mean to say that we do not need B2 at all...and this does not necessarily contradict the idea that we would want a fairly high amount. But I am saying that sober husbandry of B2 might not be a reason to avoid increasing B6 and vitamin k.

It is too bad Christine went "off-grid," since I would like to hear her response. Ah well.

A quick note: My understanding of chemistry is not fantastic, so I welcome any corrections!

@ahmo: Hmm...I see nitrogen in riboflavin, but no sulfur--but in any case, I thought excess riboflavin was excreted more or less whole in the urine. Perhaps riboflavin is increasing activation of B6, which is needed for amino acid catabolism, which produces ammonia? Or is there another pathway I am not seeing?
 

Gondwanaland

Senior Member
Messages
5,095
Nonetheless, for me seeing this calls into question Christine/DogPerson's assertion that taking B6 or vitamin K "uses up" B2. In the short term, as an increase in vitamin K might necessitate an increase in vitamin k-dependent proteins, I can see this happening. But once the necessary tools have been made, I am not sure how much more than normal one would need B2.
Perhaps this plays a role in ahmo's intolerance to leafy greens.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@aaron_c I'll read that riboflavin page tomorrow. I can't find my references to B vitamins and sulfur, and one of my early references is no longer an active page. What I have found is that thiamin (B1) and biotin are high sulfur...Which is to say, the others aren't...

I have only the most minimalist understanding of the pathways. FWIW, here's a partial list of a Kirkman's product, and how these ingredients are interacting. The other link is to a long thread re sulfur from when I was first researching. The fact is, I no longer know much of anything. I do know my response was clearly ammonia, and the only thing different in my life was the B2. Today there's no problem. I'm not sure how any of this relates to my intolerance to leafy greens which are not high thiol, the folinic which seriously blocks my methyl folate. Looks like it's time for me to start all over again in trying to understand this thing. I've noticed that during the past few weeks when I've had the stamina and the need to be more active in the world, my comprehension seems to simultaneously decreased. Seems there's something like a finite amount of energy, and if it's coping w/ worldly things, my eyes glaze over at technical/scientific explanations.o_O I hope the next weeks will be better to getting back to researching and understanding.

The list below refers to taurine making sulfur more available. I tried a msall amount again recently, had the same drastic response as to the B2. Same w/ ALA, NAC, denatured (?) whey (powder) and others.

http://www.mothering.com/community/t/1053485/sulfur-sensitivity/140

http://www.kirkmanlabs.com/ViewProductDetails@Product_ID@95.aspx

Kirkman’s Phenol Assist™ Companion helps optimize the sulfation chemistry associated with phenolic compounds and salicylates competing for the body’s sulfate stores. It is designed to be taken with Kirkman’s Phenol Assist™ or can be used with other enzyme products designed to help regulate phenolic load.

Phenols and polyphenols have antioxidant qualities and protective functions that make them beneficial. Kirkman’s Phenol Assist™ helps reduce the phenolic load on the body’s sulfation capacity. Other nutrients also support the body’s sulfation chemistry. The ingredients in Phenol Assist™ Companion and their role in sulfation are as follows:

Vitamin B-1 assists in making sulfate from sulfur.

Vitamin B-2 helps oxidize sulfite to sulfate.

Magnesium helps activate enzymes used in sulfation.

Molybdenum is necessary to convert sulfite to sulfate.

Taurine supplementation makes more sulfur available because taurine, when ingested, frees up cysteine and sulfur for sulfation.
 
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aaron_c

Senior Member
Messages
691
Hi @ahmo

I hope your brain and body both improve...

If it helps, out of ALA, NAC, taurine, and denatured whey, only NAC, taurine, and denatured whey would contribute to ammonia, while all four would contribute sulfur. From what you quoted above, b2 should help convert toxic sulfites to helpful sulfates. However, I may have found the answer

As you probably know, sulfites and converted to sulfates by sulfite oxidase, which utilizes molybdenum. Some people (myself included) find that we need to take a relatively high amount of molybdenum, else we run into sulfur issues. But I have been wondering if sulfur was not the only drain on molybdenum, and your case might be indicating this.

Although sulfite oxidase is not a flavoprotein (it does not use B2), xanthine oxidase, which also uses molybdenum, is. Xanthine oxidase interconverts hypoxanthine, xanthine, and uric acid. Uric acid, according to wikipedia (citing a study I cannot immediately get access to) accounts for "over half the antioxidant capacity of blood plasma" in humans. Perhaps what happened is that when you added B2, your body increased the activity of xanthine oxidase in order to make more uric acid from xanthine and hypoxanthine, thus quenching some free radicals. In doing so, it also stole molybdenum from sulfite oxidase, making it unable to convert sulfites to sulfates. If this all is the case, it seems like taking extra molybdenum might fix the problem.

Of course, as with any attempt to find a new equilibrium after changing supplement doses, even if this is right, it might not prove to be the end of the story. But perhaps we can hope.

If you would like to visualize this (I know this helps me) check out http://biochemical-pathways.com/#/map/1 and type "xanthine" into the search box. Hypoxanthine is beneath it, and uric acid (they call it urate) is to the right.

Best of luck, wherever your intuition leads you.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@aaron_c I've just been relating to all these substances as having "sulfur/ammonia" properties. But you're saying that's 2 different things. My body was requesting/requiring extra molybdenum during these days, now back to the normal 1 tab/day. I might try increasing it on a regular basis. When I started supplementing for pyroluria, I did use higher doses of Mbd for a time....

Thanks much for the link, I'll be spending some time on it. What about you...have you "eliminated" your sulfur or ammonia issues? Or are those of us w/ CBS going to have to always deal with this, monitoring foods and supps forever??
 

aaron_c

Senior Member
Messages
691
@ahmo

Yes, exactly. Sulfites and ammonia are two different problems that are often lumped together, and there is some reason for this: For people with autism or ME, both excessive sulfur and ammonia would result from increased CBS activity (methionine, cysteine, and taurine are all amino acids that contain sulfur.) And because most of us are deficient in active B6, taking b6--or potentially b2, which plays a role in recycling b6--would increase CBS activity beyond what it would otherwise have been. So for most of us, taking B6 will increase both ammonia and sulfites. I should also point out that taking B6 will increase ammonia entirely apart from the CBS enzyme, as B6 is necessary for any transamination reaction, which is part of breaking down amino acids to produce energy.

In terms of CBS C699T mutation, my current understanding (Thank you Kimsie for this post) is that CBS C699T is still regulated like the wild-type (normal) enzyme. I am guessing this means that when active B6 is rationed, CBS C699T gets a larger share, whereas when we have enough active B6, CBS C699T will act much the same as the wild-type, ie stopping or slowing down when methionine gets low. I think that, once we truly get better, we will be able to forget about CBS, sulfites, and ammonia entirely.

*Knock on wood* but I have effectively eliminated 95% of sulfur and ammonia issues. For ammonia, I take both raw and cooked and cooled potato starch after every meal--here is my post about that, but I will say that I can eat as much protein as I like, and today I started taking high doses of active B6 (heading towards 100 mg/day)...so here is hoping I won't have to eat my words in a day or two! But in any case, the difference will be from 95% to 100% fixed on that front. Oh, and I did not emphasize it in that post, but there is at least some chance that taking a spoonful of psilium husk powder is an important part of it as well.

Sulfur issues have been resolved for nearly a year: I take 1500 mcg molybdenum per day, and that does it for me. Strangely, I think the thread (on phoenixrising) I read about this on seems to be gone... but one important thing I got from it (other than my dose) was that molybdenum does seem to cause initial fatigue that wears off over maybe two weeks as you continue taking it, so you may want to increase gradually. Although if you are already taking some, I suspect the reaction won't be as long-lasting. Fatigue isn't the only side-effect I have seen, but it is the one that I distinctly remember being a healthy (though uncomfortable) side-effect. For what it is worth, I have been taking this dose for nearly a year, and my last hair mineral analysis put me at about the 55th percentile for molybdenum, so I think my dosing has been fairly healthy for me. The other interesting note is that 1500 mcg seems to be about the right dose for me regardless of whether I eat high sulfur foods or not. I do recall some people reporting differently, though.

Not to scare you off, but if you choose to take high amounts of Mo do be careful, and if you experience an adverse reaction other than increased fatigue, maybe take some time to check it out. Since it worked so well for me, I haven't done a lot of research on this, but I do recall that it was an issue for some people.

Best of Luck Ahmo
 
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ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@aaron_c Thanks so much for all this. Really interesting to see your molybd dose. I'll be comong back here tomorrow and really trying to digest all this info. Seems the next thing I really have to wrap my head around. :hug:
 

perchance dreamer

Senior Member
Messages
1,699
At my last appt. at the NeuroSensory Center, I got samples of a new product my doctor created, Methyl Folate Plus. One of the ingredients is 30 MG of B2. Dr. Stewart stresses taking this in addition to, not in place of, other methyl donors.

I think I'll start with 1/4 of a cap and see how I do. Here's the product:

http://www.neurobiologix.com/product-p/170.htm
 
Messages
62
I began taking some B2 as R5P (Thorne) yesterday by a small dose. I have a lot of the symptoms that is part of riboflavin deficiency (particulary pale skin, red eyes, sore throat and anemia-like symptoms). This got worse after attemps on methylation protocol with high B12 and methylfolate, especially the sore throat that has been lingering for quite a while. Never thought about B2 before but from reading I have supplemented with a lot of stuff that supresses B2 absorption, my gut isn't the best shape either (IBS coming and going) so figured I would give this a try.

Yesterday I took around 10-15 mg on empty stomach and later on felt very tired for the rest of the evening, my mind seemed a bit clouded and I was maybe a bit more relaxed in my muscles. Dosed the same this morning and have pretty much all day felt kind of clouded, not necessarily in a bad way. Also this morning, I felt that my eyes were dry (I'm wearing lenses) and felt a bit more fatigued than normal.

What could this mean? Is it normal to have start-up reactions to R5P? So far today I've taken 2x 5-10 mg doses.
 

Tunguska

Senior Member
Messages
516
I don't know if this is relevant for anyone, I've tried to figure out if it could be for me, but apparently Riboflavin is a potent 5-alpha-reductase inhibitor, i.e. inhibits Testosterone to DHT conversion, as are zinc, accutane, propecia, etc.

First listed here:
https://en.wikipedia.org/wiki/5-alpha-reductase_inhibitor#Herbs_and_other_inhibitors

There's a study on herbs given for supposed 5-AR inhibition, where none of the herbs come close to B2's inhibition:
http://www.jams-kpi.com/article/S2005-2901(10)60021-0/fulltext#Discussion
As shown in our data, although emodin showed considerably less potent inhibitory activity than riboflavin, the inhibitory activity of the compound was more potent than that of alizarin, a naturally occurring 5α-reductase inhibitor with an anthraquinone backbone

Compound IC50 (μM)
Emodin 40
Anthraquinone >1000
Alizarin 330
Riboflavin 1.6

This is the PDF linked in wikipedia:
https://www.jstage.jst.go.jp/article/antibiotics1968/43/12/43_12_1615/_pdf

It's not exactly human in vivo but it seems kind of accepted.

Here's a more recent (2010) pharmalogical comparison including finasteride (propecia), investigating "abietic acid", which still doesn't quite reach B2:
http://jhs.pharm.or.jp/data/56(4)/56_451.pdf

Compound IC 50 (μM)
Abietic acid 56±22
Methyl abietate > 1000
Pimaric acid 750±120
Neoabietic acid 120 ± 50
Riboflavin 15 ± 13
Finasteride 0.06
 
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Violeta

Senior Member
Messages
2,952
I began taking some B2 as R5P (Thorne) yesterday by a small dose. I have a lot of the symptoms that is part of riboflavin deficiency (particulary pale skin, red eyes, sore throat and anemia-like symptoms). This got worse after attemps on methylation protocol with high B12 and methylfolate, especially the sore throat that has been lingering for quite a while. Never thought about B2 before but from reading I have supplemented with a lot of stuff that supresses B2 absorption, my gut isn't the best shape either (IBS coming and going) so figured I would give this a try.

Yesterday I took around 10-15 mg on empty stomach and later on felt very tired for the rest of the evening, my mind seemed a bit clouded and I was maybe a bit more relaxed in my muscles. Dosed the same this morning and have pretty much all day felt kind of clouded, not necessarily in a bad way. Also this morning, I felt that my eyes were dry (I'm wearing lenses) and felt a bit more fatigued than normal.

What could this mean? Is it normal to have start-up reactions to R5P? So far today I've taken 2x 5-10 mg doses.


B2 affected me similarly when I started taking it. Not long after a dose I would get so tired that the only thing I could do was take a nap. I'd been tired but wired for so long that it felt good. My husband and I both got itchy eyes on and off, and as time went on, the dose would improve the itchiness and when it would come back I knew I needed another dose. Vitamin a and zinc work well with it. I can't remember what exactly it does for the eyes, but I think there's something about that in the journal of nutrition paper.
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
Wow...I have definitely had the angular chelitis, pale skin and 'sore throats' before. I have a sore throat now. And a history of being unable to tolerate methylfolate. I'd be willing to bet low B2 plays a part.
 

Tunguska

Senior Member
Messages
516
Random fact #6345, I tried both Thorne R5P and Source Naturals sublingual FMN. The Thorne (taken sublingually and held there, although very bitter) has been better than the SN for me from the start. I don't think I saw a single positive effect from the FMN and I wonder if one of the additives (sorbitol, mannitol, peppermint) disagrees with me, while I can still feel very slight effects from the Thorne in my current state. I thought switching to one designed for sublingual would work better but didn't pan out.
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
:heart::star::pill:B2, I LOVE YOU! :pill::star::heart:

TL,DR: I have never been able to take methylfolate: even small doses caused excitotoxicity and inflammatory hell. :devil: But raising my B2 levels made me more able to tolerate methylfolate!

------------------------------------------------

Lately I heard that many of us MTHFR / MAO A people may need extra B2.

So I started supplementing with 35mg day, split into 3 doses. 1 dose as the 10.7 mg as my NatureMade B-complex w/ C with breakfast.. And then 1 quarter of a Solgar B2 50mg with lunch and dinner.

I learned from @Freddd and @picante that taking B2 drives the need for both potassium and methylfolate.

About 2 days after supplementing B2 I started to suddenly feel lower back inflammation, whole body inflammation, muscle inflammation, foggy thinking, itchy scalp, itchy face (around eyes) - even when I was resting and unstressed. I recognized some of these symptoms as signs of folate deficency that Freddd (in his comprehensive list of symptoms) and Picante posted about.

Yesterday morning I took 200mcg of methylfolate and 250mcg of mB12 - wow! It felt wonderful. My day was good until about 5pm and I started to feel inflammation, brain fog, 'blurryness', face and scalp itching. Yep - signs of methylfolate deficiency. I sucked on a crumb of a methylfolate tablet and felt some relief, was able to sleep.

This morning: 200mcg methylfolate and 1000mcg of Me + AbB12 sublingual. I felt an intense "startup" reaction - a body buzz like some sort of mind altering drug was going to kick in. I worried a little bit but went to look at my garden and it looked beautiful in the morning light - very natural, I felt relief. No it wasn't a 'bad reaction' - it was a good reaction of a nutrient I needed being slurped up by my cells.:lol: Life with folate! After an hour or two the intensity subsided and I felt really good - like I was methylating properly - maybe for the first time in ages. I could swear that I felt a sense of relief extremely similar to how I felt when taking supplemental glutathione. Could my glutathione production have noticably increased in just 2 or 3 hours??!?!:woot:

I have been studying Methylation on here for 10 months, lots of frustrating trials and errors, and today was my first taste of success. I hope and pray it will continue. Thank you for the education and inspiration, Phoenix Rising. And thank you B2.
 
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