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Clear need for B2, but not tolerating it. How to get out of the maze?

picante

Senior Member
Messages
829
Location
Helena, MT USA
I just read @ahmo's blog on FMN for her MAO mutations, which was lovely and detailed. I think that will help get my DH on the right track, since he's got MAO + and COMT +/+.

And today my R-5'-P arrived, so I'll be able to report back soon on that.

Is R-5'-P actually different from FMN? They both have phosphorus, don't they? At least this new supp doesn't have any sugar alcohols in it!
 

mgk

Senior Member
Messages
155
@picante: Do you take carnitine by any chance? I was reading up on fatty acid metabolism and noticed that FAD is used as one of the first steps after carnitine transports fatty acids into the mitochondria. In this diagram, look at the yellow oval shaped thing where it says "carnitine shuttle."

Maybe the B2 conversion is working fine, but there's not enough carnitine to keep things going. If this is true, it makes sense that you would have a worse reaction to FMN than to riboflavin since you're driving it harder than it would've gone otherwise.

Personal anecdote: I sometimes got weird reactions from taking carnitine where I would suddenly feel cold to the bone, my hands would become pale, and my fingertips would turn purpleish. I could never figure out why that was. I suspect they were symptoms of a blockage in this pathway.
 
Messages
516
Is R-5'-P actually different from FMN? They both have phosphorus, don't they? At least this new supp doesn't have any sugar alcohols in it!

Afaik they're synonyms http://www.inchem.org/documents/jecfa/jecmono/v16je21.htm
"Riboflavin-5'-phosphate or flavin mononucleotide (FMN) is rapidly
dephosphorylated to free riboflavin by incubation with intestinal
mucosa or intestinal juice from rats (Christensen, 1969)."

Personal anecdote: I sometimes got weird reactions from taking carnitine where I would suddenly feel cold to the bone, my hands would become pale, and my fingertips would turn purpleish. I could never figure out why that was. I suspect they were symptoms of a blockage in this pathway.

That's interesting, has anything else ever caused it? Almost sounds like raynaud's
 

mgk

Senior Member
Messages
155
That's interesting, has anything else ever caused it? Almost sounds like raynaud's
Not supplements. It would sometimes happen after meals, but I didn't notice any pattern with the meals and couldn't pinpoint it to a particular food.

I looked at some pictures of hands with Raynaud's. It's similar but mine didn't get that pale, also the pattern was different. On the palm side, the fingertips would still be reddish, but below the fingertips it would be whitish-yellowish. Also the skin would feel unusually dry. On the back side, underneath the fingernails, it would be purple.
 

Gondwanaland

Senior Member
Messages
5,092
Personal anecdote: I sometimes got weird reactions from taking carnitine where I would suddenly feel cold to the bone, my hands would become pale, and my fingertips would turn purpleish. I could never figure out why that was. I suspect they were symptoms of a blockage in this pathway.
I interpreted these symptoms as being B1 deficiency after too much folate
 

mgk

Senior Member
Messages
155
I interpreted these symptoms as being B1 deficiency after too much folate
I read the link in your signature regarding that. Thanks for pointing it out!

I don't take a lot of folate anymore. Ever since I started on B2, I seem to be able to get by on 800ug-1200ug. I'm much more careful about high-dose anything nowadays since it's usually an indication of something wrong somewhere else. It's so hard to figure out what's going on when the body reacts "well" to things that aren't what's actually missing. There seem to be enough backup mechanisms to make even a non-foggy head spin. o_O
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
Is R-5'-P actually different from FMN? They both have phosphorus, don't they?
Don't know if any of these answers your question...
http://forums.phoenixrising.me/index.php?threads/is-taking-bh4-a-problem-for-comt.36997/#post-588606 Is BH4 a problem w/ COMT?

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/

http://forums.phoenixrising.me/index.php?threads/b2-i-love-you.15209/page-7#post-247316 B2 I Love you #125

How riboflavin actually gets into cells is not fully understood. For example, this paper from 2005 mentions:


Riboflavin transport proteins operating in the plasma membrane thus have an important role in the absorption of the vitamin. However, their sequences remained elusive, and not a single eukaryotic riboflavin transporter is known to date.

(and then it goes on to describe a newly discovered transporter that likely exists in humans)

http://www.jbc.org/content/280/48/39809.long
Also considering that only FAD gets past the blood brain barrier, I think these allow the possibility that sublingual FMN is more effective than oral riboflavin through means that aren’t understood yet.

http://forums.phoenixrising.me/index.php?threads/b2-i-love-you.15209/page-42#post-532708 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 http://en.wikipedia.org/wiki/NADPH:quinone_reductase, and B6 by http://en.wikipedia.org/wiki/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.

My understanding of chemistry is not fantastic, so I welcome any corrections!
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Thanks, @ahmo, I've been going through that thread (slowly) and pulling out stuff, too. Yes, it's all been helping.

When I told my DH about your blog post, he decided to start taking FMN. He seems pretty chipper now, but the improvement started before taking the FMN. I'm sure it kicked part of his methylation cycle into gear, though, because he had loose bowels the first day, and then I gave him methylfolate to take the 2nd day, which took care of it.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Reporting back: The R-5'-P and the liquid MeB12 arrived two days ago. This B12 contains methylcobalamin and water. That's it. It says to take 1/2 dropperful under the tongue. I took 3 drops transdermally (rubbed it on my arm and rubbed a little grapeseed oil over the top).

I took both at bedtime in case the riboflavin made me exhausted. 1/2 capsule sublingually = 5 mg (yay! no sweeteners).

Yesterday I woke up with potassium deficiency. I kept taking potassium all day because the neck spasm just wouldn't go away. The headache did, though. Total: 6 doses, 1900 mg.

Last night: Took R-5'-P again, no MeB12. (I took AdB12 instead.) That was so I could get potassium up to snuff. It worked. I woke up and my neck was fine.

Today: Tried the new MeB12 again -- one puny drop on my skin -- in the afternoon and did fine. R-5'-P again in the evening.

So far, so good!
 

Gondwanaland

Senior Member
Messages
5,092
he had loose bowels the first day, and then I gave him methylfolate to take the 2nd day, which took care of it.
I noticed that my DH always has IBS-D when blood synthesis goes out of whack o_O
Must watch out for B2 - B6 - B9 - B12- Zn - Cu balance :rolleyes:
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Do you take carnitine by any chance?
Yes, I'm taking ALCar daily, and I take LCF on the days I take Adocobalamin.
it makes sense that you would have a worse reaction to FMN than to riboflavin
I've never taken riboflavin. Just FMN.

Since I'm tolerating 5mg of R-5'-P just fine, I'm adding another dose tonight. I couldn't even handle 3 mg of FMN.

So I'm not at all convinced that those two are equivalent.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Well, apparently they are both C17-H21-N4-O9-P, according to Wikipedia.

So I wonder whether one of them is degraded (from light). Both bottles are opaque. One brand is Source Naturals, and the other is Douglas Laboratories.
 

mgk

Senior Member
Messages
155
@Gondwanaland: Thought you might find this interesting. I came across a study which showed that people with G6PD were more likely to be B1-deficient. Maybe I had a genetic predisposition to deficiency and made it worse by taking a lot of folate. I have no idea how you diagnosed it based on such a vague description, but you might be right! It's only been a day of taking extra B1 so I'm not sure about the full effects yet. The most immediate change I've noticed is that it's helping with the burning pain in my hands and feet.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
@mgk, I found out that high-dose potassium depletes thiamine, too. My thiamine deficiency was pretty extreme by the time I figured out what it was (thanks to @Gondwanaland).

The following quotes can all be found here: http://charles_w.tripod.com/kandthiamin.html
It is obvious that if potassium supplements are given, it is very important that the vitamin B-1 intake must be adequate at the same time, and one third of heart disease patients are deficient in thiamin.

The reverse is also the case. Vitamin B-1 supplements should be dangerous for people with low potassium. Since cell potassium is always low in rheumatoid arthritis [30], such people should not take vitamin B-1 without potassium.

Most of the heart disease in western societies is probably either caused by or is greatly enhanced by a potassium deficiency. However it is possible for a dangerous imbalance with respect to thiamine (vitamin B-1) can arise from potassium supplements if animal experiments are an indication. […] During a vitamin B1 deficiency, the heart loses potassium.

Even if the patient is eating foods fairly adequate in vitamin B-1, the patient could still possibly have a problem with vitamin B-1 deficiency if also eating foods that have sulfites in them since sulfites degrade vitamin B-1 in the intestines. Such foods are wine, vinegar, pickles, olives, salad dressing, fresh, frozen, canned, or dried shrimp, gelatin, pectin jelling agents, shredded coconut, canned vegetables (including potatoes), pickled vegetables (including sauerkraut), maple syrup, bottled lemon juice, some baked goods, some dried fruits, and some meat in dog and cat food. [I deleted much of this list.]

Also, the symptoms of a vitamin B-1 deficiency can materialize even if vitamin B-1 is adequate if magnesium is deficient, say from Crohn’s disease. A folate deficiency prevents thiamin absorption in rats. Folate is the most common B vitamin deficiency in the world.”

Ammonium is even synthesized by the kidneys during a potassium deficiency from glutamine, and this is probably a strategy of the body, the purpose of which is to prevent potassium loss. Eating glutamine increases ammonia excretion and decreases potassium excretion.
The following quotes are from this site:

What becomes pertinent is our ability to regulate the level of potassium in serum and in cells… Which leads to the topic of aldosterone – which is essential for regulating serum potassium… The question being, is it possible one might be low in aldosterone at least in part because we are functionally deficient in potassium? And will slowly improving this ratio of K to Na allow our aldosterone levels to rise along with potassium intake?

The info in this book suggests this is generally this case (short of permanent atrophy of the part of the adrenal gland that produces aldosterone – or I suppose secondary adrenal insufficiency will prevent the appropriate signaling for the release of adrenal hormones, no matter how much potassium is available). Regardless, one shouldn’t drastically increase potassium intake without keeping an eye on our serum potassium to ensure that our body is handling it properly – as Andy has told us.”

The only circumstance that I know of that is desperately dangerous is the interaction between potassium and thiamin (vitamin B-1). If potassium is supplemented it is essential that vitamin B-1 be adequate (see http://charles_w.tripod.com/kandthiamin.html ). And of course, if the kidneys have been damaged in such a way as to be unable to excrete potassium there is some danger from supplements. This can easily determined by blood analysis.
 

Gondwanaland

Senior Member
Messages
5,092
I wasn't taking any. I have gluconate at home.

And will have to dig the zinc picolinate out of the "useless" box.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
I've been on T3 (thyroid) for several years. Is T4 needed to convert FMN to FAD?
I started T3 while I was taking B1 and did not notice any difference. Actually, I seldom notice any difference when I change supplements/medications. However I doubt that T4 is needed for that conversion, despite the fact that my notes say that it is. T4 is the inactive form of the hormone. The body converts T4 to active T3 as it is needed. I would guess that it is really T3 that takes part in the conversion.