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Induced insatiable Hypokalemia and Methylfolate Insufficiency

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
These last few weeks have been the most miserable I've had in the last 9 years. I had onset of Hypokalemia with the worst of all the spasms I've had in a decade. I also have had to take Metoclopromide (causes peristalsis to start up) every day for the last 3 weeks, the first time in more than 10 years for that, no appetite, nausea, bloating etc all for the first time in more than 10 years. Along with that went the worst angular cheilitis and worst IBS, possibly in my life. The cheilitis was actually bleeding and left a scab. Also I had skin infections that looked like staph and wouldn't respond to Neosporin and were expanding rapidly. Fortunately lavender oil (essential oil) knocked them right out. Further, in just 3 weeks, the foot numbness increased significantly. Again, all that goes back more than 10 years. No amount of potassium and no amount of Metafolin that I was willing to try (both items) did more than keep things from getting worse.



Metoclopromide (generic for Reglan) works very well at restoring peristalsis, fortunately. However, extended daily usage can cause tardive dyskinesia which can be permanent.



So now what happened? I have been doing some trials on B-vitamin separates to see if I can improve my balance of vitamins. Several weeks ago I added 100mg B2 and 100mg B3. I took that for 4 days, the number of days’ doses I made up at one time. On day 2 I started with muscle spasms, day three angular cheilitis and day 4 severe IBS and general stomach and intestinal paralysis. When I made up the next 4 days worth the B3 bottle had gone missing so I discontinued that. The only addition then was B2. The next 4 days got worse and worse. I have never had bleeding cheilitis before. I have never needed Metoclopromide for more than a few days a month before. After dropping the B2 after those next four days the cheilitis started backing off slowly. The IBS slowly got better. I was able to reduce the Metoclopromide dose by 50% and now have gone 2 days without.. After a couple of more weeks the nausea has subsided and I was actually hungry the past 2 days. The low potassium symptoms have subsided slowly, as might be expected from a “fast compartment” and “slow compartment” model as potassium has; serum and tissue compartments.



So now, let’s figure this out. Others have mentioned similar results, from paralyzed ileum to insatiable need for Metafolin and potassium. This acts like a startup from hell, overdoing this most extremely. So the question that comes up, is THIS effect then the actual result of “overmethylation” or what should it be called? Yes, I know, it is once again “DETOX”, and once again that is meaningless.. Are B2-B3 somehow the accelerators? Balance appears to be somehow the key to this all.



Order is important in this. It looks like the “last thing in” is the accelerator. However, with B2 at least there is proportionality. With 20mg of B2 daily I have intermittent low potassium and low methylfolate but also extensive healing. B12 and methylfolate appear to turn on very strongly with little proportionality. L-carnitine has very strong proportionality. B2 and/or B3 (not sure of interaction here) has a strong proportionality as there is an amount that allows healing to take place without these severe problems and an adequate balance across the whole range of healing. With too much B2 the side effects get far worse and healing stops and even reverses.



I see a bottle of LOW dose B2 in my future with which I can titrate to best effect and maybe get rid of these intermittent low folate and low potassium effects, or at least find out how they relate. Clearly B2 is very dose proportional in it’s effect and is a most limiting factor at times and appears to be able to drive certain processes beyond useful limits as has been hypothesized about other things like B12 and folate. This appears to be the “throttle” that at least some of us have been looking for.





 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
Hi Freddd. I've noticed your absence, I'm sorry it's been due to such a terrible event. Fascinating that lavender oil was the thing to work on your skin. I'd replicated a commercial spray w/ lavender, aloe, and water some years ago, and it's been at least as, if not more, effective than anything else I ever tried. I've been taking B2 as R5P 36.5 mg and [400mg B1 correction] 500 mg B3 along w/ my 1 mg methylfolate. I consider myself v fortunate to have not run into this cascade of problems. I've spent about 2 months on my current dosages of Deadlock Qtet, and the last 2 days have been able to easily accomplish several extra tasks, which is a big deal. Maybe my metal/bacterial detox is also at an easier stage. Very glad you're back with us. ahmo
 

dbkita

Senior Member
Messages
655
Sorry to hear about your problems Freddd. Hope you feel better soon.

How much b2 were you taking before all of this?
The reason I am curious is the active form r5p is the cofactor for the mthfr enzyme.

Last year switching from 100 mg b2 to 100 mg r5p sodium was one of the main changes that forced me into hypokalemia and not even 11 grams per day could contain it. More recently I wnt to two split two doses of 50 mg of riboflavin and while I had more verve and energy at first, within a few days I had charlie horses and terrible foot cramps.

Be warned that b2 absorption is not linear after 30 mg. It saturates pretty quickly. 100 mg at once might net you 40-50 mg total. That is why I thought to split doses and bam. R5p sodium has no such saturation and high oral bioavailability which is probably why it was so devastating to switch to 100 mg of that almost a year ago.


Edit: Another mechanism may be riboflavin's role in activating virtually all other bvitamins especially b6. But my money is on its effect on mthfr directly.
Good luck and God bless!
 

adreno

PR activist
Messages
4,841
Angular chelitis, IBS, bloating and skin infections sounds like a fungal infection. Lavender is an anti-fungal. Folate can feed the fungus.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Angular chelitis, IBS, bloating and skin infections sounds like a fungal infection. Lavender is an anti-fungal. Folate can feed the fungus.

Hi Adreno,

And a fungus infection looks like what, staph? These were infected follicles with whiteheads and spreading inflammation under the skin. I have had diagnosed staph skin infections in the past and this looked 100% like it. I've also had fungus infections of the skin in those two favorite areas of "athletes", foot and jock. I'm talking my stomach, chest and back here, not confined moist and warm areas as needed for fungus, exposed to fresh air and sunlight (UV) with my summer tan decently progressed already.

Angular cheilitis is my regular early warning low methylfolate signal along with IBS. The bloating and all that was 100% relieved in 30 minutes which I could easily feel happening, by metoclopramide (prescribed by my doc because of these things) which I have had on hand since 2000. Lavender is also an antibacterial, very effective. I don't find anything convincing at all in a suggestion of fungus. I stopped additional B2, went down to 10mg a day and in less than 24 hours the symptoms started relieving, within hours of the first missed dose. Once I worked from the hypothesis that B2 was driving the intensity of this reaction I could deal with it immediately.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Sorry to hear about your problems Freddd. Hope you feel better soon.

How much b2 were you taking before all of this?
The reason I am curious is the active form r5p is the cofactor for the mthfr enzyme.

Last year switching from 100 mg b2 to 100 mg r5p sodium was one of the main changes that forced me into hypokalemia and not even 11 grams per day could contain it. More recently I wnt to two split two doses of 50 mg of riboflavin and while I had more verve and energy at first, within a few days I had charlie horses and terrible foot cramps.

Be warned that b2 absorption is not linear after 30 mg. It saturates pretty quickly. 100 mg at once might net you 40-50 mg total. That is why I thought to split doses and bam. R5p sodium has no such saturation and high oral bioavailability which is probably why it was so devastating to switch to 100 mg of that almost a year ago.


Edit: Another mechanism may be riboflavin's role in activating virtually all other bvitamins especially b6. But my money is on its effect on mthfr directly.
Good luck and God bless!

Hi Dbkita,

I of course immediately thought of you, and several others, when this occurred. Also, a few people that have the stomach paralysis as well. I was taking 10-20mg daily dependent upon if I actually got two b-complexes a day into myself or only 1.

So b2 has a knee; not surprising. Lots of systems saturate. So one thing we are seeing here is that B2 can be a "most limiting factor" once the b12s and folate are in position. I can see why the R5p could be devastating. I'm sure that the reason that isn't better recognized is that once again the basic research for somebody taking active b12 and folate hasn't been done. As I have previously experienced, a b-50 twice a day but without MeCbl, AdoCbl or Metafolin and it had no effect outside of coloring urine, they just seem of little effect, as people expect of vitamins. MeCbl and Metafolin sure turn them into potent items.


Edit: Another mechanism may be riboflavin's role in activating virtually all other bvitamins especially b6. But my money is on its effect on mthfr directly.

Actual, for real "overmethylation" perhaps?


So I can see somebody taking some b-complex with 50 or 100mgs of these b-vits in them to no effect and then starting MeCbl/Metafolin and getting wiped out with uncontrollable hypokalemia and donut hole folate deficiency. If I hadn't had experience with this kind of paralysis of stomach and intestine and if I hadn't had metoclopramide on hand I might have ended up in the ER.

Order is important. Balance is important and may have to be adjust after something new comes in. Looks like time for me to make up some 5mg capsules of these vitamins and get rid of the b-complex for now. Maybe I can come down enough an the b2 and b3 and adjust the balance to get rid of intermittent paradoxical folate deficiency and hypokalemia.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
These last few weeks have been the most miserable I've had in the last 9 years. I had onset of Hypokalemia with the worst of all the spasms I've had in a decade.


So now what happened? I have been doing some trials on B-vitamin separates to see if I can improve my balance of vitamins. Several weeks ago I added 100mg B2 and 100mg B3. I took that for 4 days, the number of days’ doses I made up at one time. On day 2 I started with muscle spasms, day three angular cheilitis and day 4 severe IBS and general stomach and intestinal paralysis. When I made up the next 4 days worth the B3 bottle had gone missing so I discontinued that. The only addition then was B2. The next 4 days got worse and worse. I

So now, let’s figure this out. Others have mentioned similar results, from paralyzed ileum to insatiable need for Metafolin and potassium. This acts like a startup from hell, overdoing this most extremely. So the question that comes up, is THIS effect then the actual result of “overmethylation” or what should it be called? Yes, I know, it is once again “DETOX”, and once again that is meaningless.. Are B2-B3 somehow the accelerators? Balance appears to be somehow the key to this all.
B2 and B3 recycle glutathione. It's probably more likely what dbkita said about B2 increasing methylation, but based on your experience with glutathione I thought I'd mention it.
 

dbkita

Senior Member
Messages
655
B2 and B3 recycle glutathione. It's probably more likely what dbkita said about B2 increasing methylation, but based on your experience with glutathione I thought I'd mention it.
Several things recycle glutathione but vitamin c at high doses for example will do way more recycling I think than 100 mg b2.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Several things recycle glutathione but vitamin c at high doses for example will do way more recycling I think than 100 mg b2.
I sort of figured my theory was unlikely. So what do you consider a high dose of vitamin c? And how often do you have to take it for it to be effective? I've seen timed release vitamin c supplements, but I'm skeptical of timed release supplements in general. I have absolutely no evidence whatsoever to base my skeptism on, but that's just how I feel.
 

Victronix

Senior Member
Messages
418
Location
California
What an ordeal! I'm glad you found your way out of the worst of it. Sorry that you had to go through it, even if there was some important learning, it's a terrible thing to have to go through.

Looks like time for me to make up some 5mg capsules of these vitamins and get rid of the b-complex for now.

Are you getting rid of the B complex because it has too much B2? Or you aren't able to control the situation enough with a mixture in there?
 

dbkita

Senior Member
Messages
655
P5p is the cofactor most people focus on since it controls methionine synthase, shmt, and cystathione beta, and dopamine and serotonin production.

But r5p is the cofactor for mthfr. And r5p will also increase b6 to p5p conversion. This is relevant since anyone taking oral p5p has it all turn to b6 in their stomach due to the low ph (unless enteric coated which is rare). So their b2 levels will regulate their b6 to p5p levels.

My guess is that increasing b2 is ramping your conversion of 5, 10 methylene thf to methylfolate while you are ingesting methylfolate throughout the day. You have lots of thf from driving the methylation cycle, you have no rate limitation on making 5, 10 methylene thf due to adequate p5p and adequate shmt activity, add the b2 at sufficient concentration and even with a defective mthfr you still get a big shift in your equilibrium. Hypokakemia accelerates, and the reaction rates of the folate cycle and the methylation cycle "uncouple" in the new state. You probably are not in methyl trap since you have adequate b12s but for some people that may also come into play if they shift b2 in to high gear.

In my own case I seem ok on 100 mg b2 single dose provided I am not going above 800 mcg of methylfolate. Last year the additional 400-800 mcg of methylfolate, on and off 800 mcg folinic acid, SAM-e, tmg, etc along with 100 mg b2 was a mess with hypokalemia. When I switched to 50 mg b2 and 50 mg r5p it was hypokalemia wasteland.
 

dbkita

Senior Member
Messages
655
I sort of figured my theory was unlikely. So what do you consider a high dose of vitamin c? And how often do you have to take it for it to be effective? I've seen timed release vitamin c supplements, but I'm skeptical of timed release supplements in general. I have absolutely no evidence whatsoever to base my skeptism on, but that's just how I feel.
Depends on if ascorbic acid or mineral ascorbates. Anything above 2 grams ascorbic acid is high dose. Maybe a less for mineral ascorbates due to their higher oral bioavailability and longer serum half-life (especially sodium ascorbate). I take 4 grams of na ascorbate a day over two doses, one in morning, one in afternoon.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
It seems that people sometimes experience "start-up" symptoms from supplementing with nutrients that they are deficient in, but does supplementing with these nutrients actually increase methylation and/or cause a greater need for potassium?
 

dbkita

Senior Member
Messages
655
It seems that people sometimes experience "start-up" symptoms from supplementing with nutrients that they are deficient in, but does supplementing with these nutrients actually increase methylation and/or cause a greater need for potassium?
r5p and p5p if rate limiting certainly will increase methylation.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
r5p and p5p if rate limiting certainly will increase methylation.
R5P and P5P are both involved in methylation and that might explain my reaction to methylfolate (since I was probably also deficient in it), but what about vitamins and minerals in general? This is what Freddd has said: "However, every vitamin is essential and any of them can become most limiting factors as can various minerals." Are you guys talking about the same thing? In one thread for example, someone said taking boron caused an increased need for potassium.
 

dbkita

Senior Member
Messages
655
R5P and P5P are both involved in methylation and that might explain my reaction to methylfolate (since I was probably also deficient in it), but what about vitamins and minerals in general? This is what Freddd has said: "However, every vitamin is essential and any of them can become most limiting factors as can various minerals." Are you guys talking about the same thing? In one thread for example, someone said taking boron caused an increased need for potassium.
No idea where the boron and potassium connection comes from. Sorry I don't buy that.

Not all minerals or vitamins will have same impact on methylation. I am guessing Freddd was talking more about good balance for health and being able to handle the protocol. Things like r5p and p5p have direct biochemical effects on methylation.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
No idea where the boron and potassium connection comes from. Sorry I don't buy that.

Not all minerals or vitamins will have same impact on methylation. I am guessing Freddd was talking more about good balance for health and being able to handle the protocol. Things like r5p and p5p have direct biochemical effects on methylation.
I'm skeptical too. I mainly asked because of what Freddd said, but maybe he'll clarify his theory. I don't want to misstate it. Just because you both used the term "limiting factor" doesn't mean you're talking about the same thing.
 

dbkita

Senior Member
Messages
655
AOR's B complex has a small amount of R5P, 2.5mg per capsule.
2.5 mg is at or below the US RDA so I doubt that will have a big effect. Should be ok I am thinking for most people. I say most since some people on here are simply sensitive to a many things and we don't understand why.
 

aquariusgirl

Senior Member
Messages
1,732
Bit dimwitted tonight.. but seems like both freddd & dbitka ran into problems with hyperkalemia when they added B2 or R5P....Good to know!! What caused the lack of peristalsis? I've experienced this occasionally.