Induced insatiable Hypokalemia and Methylfolate Insufficiency

Hi Lotus,

Yes indeed, paradoxical seeming. Makes the answers interesting as the paradox has to be an illusion caused by an incomplete and/or faulty explanation.

The reason I said that it appears to be an accelerator, destructively so, is because it not only causes severe epithelial problems, cheilitis, skin infections (immune problems, terribly severe IBS as well as, and the most severe lack of potassium I have ever had with the most persistent severe low potassium responses. It somehow has to cause ALL those problems and likely more. In 2 weeks I had noticeable worsening of my CNS problems. The gains go away so fast and they are so difficult to gain.

Not sure I see the paradox. Read up on mthfr. R5p is the cofactor for the enzyme. R5p speeds up the enzyme activity Period. Interpretation of clinical effects or causes is just that ... interpretation. The real question is why does tossing more of the mthfr cofactor on top of supplementing methyfolate have these powerful undesirable clinical effects. I am just clarifying since if the "interpretation" is riboflavin is blocking methylfolate and that is why the chelitis, etc. that is not right.

I am wondering if lack of peristalsis might be being caused by something in the mix happenning to the vagus nerve. I don't know what or why.

Hi Violeta,

Since such paralysis is a known result of low potassium AND taking enough potassium keeps that from happening over and over, and that tendency changes slowly as if the slow compartment (tissue, non-serum) has lost and is slowly recovering as would be expected from theory no other explanation needs to by hypothesized. The hypothesized treatment based on the hypothesized cause works. That is usually considered a hit. However all sorts of arabesques can be added as long as it starts with low potassium and ends with high enough potassium.

Yes, I see what you mean. I did then look up vagus nerve plus hypokalemia and it is affected by it, and although it doesn't matter because you would take potassium anyway, some of the articles I found as a result of that search gave me good ideas, such as deep breathing being good for it. I was awake in the middle of the night because of intestinal irritability and the deep breathing helped it calm down. I know that's not the same as paralysis, which I do get and am just getting over a bout of, but still I think that might have been caused by the vagus nerve because one article said impulse is sent back to the brain through the nerve and I can feel that my anxiety last night was coming from my gut.
Top of my list for today is to take more potassium.

I hope you feel better and recoup your gains quickly.

I thought if the enzyme is sped up then that would increase the folate. Therefore B2/R5P would increase folate. Freddd said cheilitis was from folate deficiency (in his case) and yet B2/R5P caused cheilitis. And B2 deficiency is another cause of cheilitis. So either way there's a paradox unless you're saying that speeding up MTHFR decreases folate. Or as I suggested before there's another cause of cheilits.

I thought of the vagus nerve also because of the symptom I've seen (and had) of a raspy hoarse voice when I first start getting symptoms after taking methylfolate. And I know the vagus is key for some gut-brain communications. I've seen research with people who have an implanted vagus nerve stimulator for epilepsy (increases norepinephrine) and in some of those people it caused their voice to go hoarse. So I was wondering if that could be the cause of what happens when I get the voice hoarseness after methylfolate (I don't get that if I have enough potassium, btw).

Interesting that the deep breathing calmed it down.

Good! I can't believe what a difference its made for me, but took awhile to get used to, get the courage up to take enough, etc.

Yes speeding up the enzyme means more conversion of 5, 10 methylene thf into methylfolate. And yes r5p will do this. Remember this will also that large methylfolate doses will convert thf after methyl donation to b12. Assuming no pileup at shmt that thf will ultimately be fed back into mthfr. If mthfr is suddenly effectively upregulated by increasing r5p then there could be an overbalance of methylfolate (I.e. exogenous + converted from thf). This would explain the crushing potassium need. As far as the chelitis goes I honestly don't know. But again r5p is the mthfr cofactor. So adding in a lot more b2 could shift the equilibrium production rates of endogenous methylfolate. Feed that high concentrations of thf and then 5, 10 methylene thf coming from conversion of large doses of exogenous methylfolate and you could have fireworks. As to the clinical symptoms and trying to relate them to other causes that is imo speculation. That is why I think the paradox is an illusion. What would be great is if we could figure out a relationship between mthfr efficiency / r5p and dosages of methylfolate in terms of a functional threshold that defines the onset of the negative overdrive state. Some people who have had trouble raising methylfolate may simply have no genetic defects in mthfr and other related folate cycle enzymes but then ingest standard b-vitamin doses of b2 and regular dosea of methylfolate and bam! I don't think this would explain the extreme cases where a few mcg of methylfolate is a problem (I.e. the amount you get in a hamburger patty) but it might explain things for people like myself who cannot go above 800 mcg or so without significant negative 'reprisals'.

I reduced my R5P dose from 50mg to 12.5mg. I still need the same amount of K.

Yes, it is interesting that deep breathing is supposed to help the vagus nerve, and it did help me last night. I did take some Chinese herbs, too, and that helped a lot. Not only did I have very bad abdominal irritation, I was also urinating from once every hour to 3 times an hour. I don't know why, but the herbs and the breathing helped both problems and I finally fell asleep.

That's interesting that you get a raspy hoarse voice when you first start getting symptoms from taking methylfolate. Do you know of any foods that cause that for you? I have a list of foods that cause that, and if I ignore it I get sick. I never linked it to the vagus nerve, though. I wish I could remember if that happenned before I got sick this past weekend. I had been taking methyl b's for at least a week, maybe a little longer, and then I started drinking tea on top of it. I'll have to watch for that when I start up taking them again, although this time I'm starting with much smaller amounts and will be taking K. Yeah, I don't know how high I will have the courage to go with the K. How much do you take?

Potassium (K), vitamin C, and iron block methylfolate absorption so they need to be taken at separate times.

does the need for potassium drop eventually? Will someone who is on b12 indefinitely need to also take potassium each day? For that matter, does someone with b12 deficiency need to continue taking b12 for the rest of their life?

Also how important is zinc in the equation?

The need for potassium depends on the person, the dosage/type of B12, the dosage of methylfolate, dosage/amount of additional methyl donors. Also, certain medications such as corticosteroids (not sure which types) and supplements such as licorice can also lower potassium. I'm not convinced that taking a dose high enough to cause hypokalemia is necessary, but I'm not sure low potassium necessarily means you're taking too high of a dose either.

I suppose that depends on what's causing the b12 deficiency/chronic illness. Some people might need to take these supplements for the rest of their life, but I'm not sure if that applies to everyone. This is somewhat theoretical since methylation is a relatively new therapy. At least the way people here are doing it.

I've heard it mentioned as a cofactor, but I don't really know the details. Zinc is also needed to convert beta carotene into the active form of vitamin A. I did find this about zinc and methylation:
http://www.ncbi.nlm.nih.gov/pubmed/3968590
Effect of zinc deficiency on methionine metabolism, methylation reactions and protein synthesis in isolated perfused rat liver.

Abstract

A perfusion technique was utilized to assess the rate of absorption and metabolism of L-methionine by livers isolated from rats fed a diet deficient in zinc. The endogenous concentration of S-adenosyl-L-methionine in the livers from the zinc-deficient rats was near normal, while the concentration in pair-fed controls was approximately 50% of that found in normal livers (ad libitum fed). The rate of uptake of methionine by the livers isolated from zinc-deficient rats was significantly less than in the pair-fed or ad libitum-fed controls. The synthesis of L-methionine, S-adenosyl-L-homocysteine and S-adenosylmethionine was not impaired in the livers from the zinc-deficient rats. However, the methyl group of the S-adenosylmethionine turned over much more slowly in the livers from zinc-deficient rats than in either control group. This was reflected in the depressed rates of methylation of various macromolecules, particularly DNA and histones. The synthesis of nuclear proteins (histones and nonhistone chromosomal proteins) was depressed in the livers from zinc-deficient rats. The reduced synthesis of chromosomal proteins and marked reduction in DNA methylation would be consistent with the finding that DNA biosynthesis and cellular proliferation are markedly depressed in zinc-deficient animals.

I found a reason for deep breathing to calm down the abdominal pain when it's caused by vagus nerve response:

"The vagus nerve is the reset button when our alarm system has been set off resulting in flight, fight, or FREEZE response. When the stressor is gone, it tells the body and brain, "It is safe now. All brain and bodily functions can return to normal."

So it can help, but when the nerve is irritated by chemical inbalance, I don't know how much deep breathing can do. I do know that I hold my breath a lot and that my body is stressed just even from subliminal pain, so I could see how deep breathing would help in that sort of case. I had never heard of the FREEZE response to stress, just the fight or flight. I think that's interesting.

One other thing that is good for the vagus nerve is glucose. People with porphyria have found that when the stomach won't empty, glucose will cause it to resume function. Then while googling the vagus nerve, I saw that it's involved in hiccups, and sugar sometimes relieves them. I have found that at times glucose relieves my abdominal pain.

The raspy voice is very transient and doesn't have any immune component, that I can tell, which is what makes me think of the vagus nerve.

I'm taking about 1500 mcg of potassium per day. It took more than a week for me to get up the courage to take that amount, but once I got comfortable with it, it really helped me stabilize. Once I take it (a powder I put in water and juice), it takes at least 40 minutes for the effect to happen. Others have said the effect should happen in about 20 minutes, but I have a lot of digestive issues and thyroid, which slows things, etc.

I started to develop angular chelitis yesterday, after having reduced to 12.5mg R5P since the start of this thread. I raised the dose back to my usual 50mg and now the chelitis is going away.

Someone told me this the other day:

That might be so, but I find it more likely that the dose of B12 and folate I'm taking requires a certain minimum amount of B2.

I would agree. B2 is needed in active form to convert all the other b's into their active form including b6 to p5p. Your chemical equilibrium is probably sitting at a particular spot and when you downshift b2 or something else your equilibrium shifts. Perhaps by lowering b2 you were not converting folate metabolites fast enough into their methylation cycle products?

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This is from the wikipedia:

"Although the sores of angular cheilitis may become infected by the fungus Candida albicans (thrush), or other pathogens, studies have linked the initial onset of angular cheilitis with nutritional deficiencies, namely riboflavin (vitamin B2)and iron deficiency anemia, which in turn may be evidence of poor diets or malnutrition (e.g. celiac disease). Zinc deficiency has also been associated with angular cheilitis.[6] Angular cheilitis can also be a sign of anorexia nervosa and/or bulimia nervosa due both to malnutrition and as a side effect of constant vomiting."

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Makes me wonder if your body has a lot of demands on r5p and dropping to a 1/4 your normal dose to 12.5 mg eventually led to a functional deficiency since so much is being used to turnover the folate cycle at MTHFR or similar places. On the other hand if you went the other way and ramped way up to say 200 mg you may have a lot of acceleration of certain reactions and quite possibly different negative effects.

So if your body has a greater need for certain nutrients it could cause a deficiency? I was just reading that P-5-P and zinc should increase the activity and quantity of SHMT. Too much vitamin A (not beta-carotene) may decrease it. (and in Freddd's case folinic acid might also decrease SHMT too). I don't know if Freddd's still taking a fish source of vitamin A (which is the type that would decrease SHMT), but I wonder if the combination of that and food folates (which could be converted into folinic acid) are inhibiting his SHMT (which would then inhibit MTHF production) then his body would have a greater need for zinc to balance that out (?)