Rich - questions re potassium & methylation protocol

Discussion in 'Fibromyalgia Main Forum' started by mbofov, Jul 28, 2012.

  1. mbofov

    mbofov Active Member

    I know you've read what Freddd has to say about the potential importance of potassium supplementation when taking folate, and now I see it's true for B12 too. I've experienced low potassium myself due to taking methylfolate and it can be very serious.

    The issue of low potassium when treating megaloblastic anemia is mentioend very briefly in these two articles (and of course there's more info on the web):

    I wish you would address this issue, and what are your thoughts re including the potential importance of potassium supplementation when following the methylation protocol.

    I'm not the only one who's been affected. Several months ago Forebearance decided to try potassium after feeling awful when taking the methylation supplements, and was surprised at how much better she felt.

    It may be a key reason why so many people have trouble with the methylation supplements or have to take such tiny doses.

    I'd appreciate any input - Thanks!

    [This Message was Edited on 07/28/2012]
  2. FaithHopeCure

    FaithHopeCure New Member

    Hi Mary, I found this information on an older post dated 05/21/12. I searched for older posts regarding the Methylation Protocol and there was a post addressed from Rich explaining many reasons why a person may not get the results desired. Below is the paragraph for which he talks about potassium. Thanks for making me aware of this potential problem...

    "Another negative reaction can be caused by development of potassium deficiency. This occurs because as the folates rise in the cells, the cells are able to divide and reproduce more rapidly. Since potassium is the most abundant positive ion inside all cells, this produces a demand for potassium, which is generally low in PWMEs to start with. Symptoms associated with low potassium include heart palpitations and muscle spasms. The blood serum potassium level can be measured with a standard comprehensive blood metabolic panel. Supplementing with potassium supplements or foods high in potassium may help with this."

  3. mbofov

    mbofov Active Member

    I think this is such an important issue, and too often overlooked (I'd never even read about a potential potassium deficiency when I first started the methylation protocol over four years ago - did not read anything about it until Freddd's posts on Phoenix Rising a little over a year ago), that I think some explanation and caveat about possible potassium deficiency should be included in the methylation protocol itself.

    If you don't know that the methylation protocol may cause a sometimes serious potassium deficiency (which can easily be remedied by supplements and food), you're not going to look for information about it. And instead may just experience horrible symptoms (severe fatigue, even heart problems) and not have a clue as to what is going on, and most likely will decide that the methylation protocol just is not for you because you react so badly. When in fact it may be just what someone needs, if only they knew what was going on.

  4. richvank

    richvank New Member

    Hi, Mary.

    Yes, I agree that potassium deficiency is an important issue to watch for and to correct when a person is doing one of the methylation protocols for ME/CFS.

    Freddd is the one who first brought this to our attention, I think because it showed up so strongly with his protocol, which includes relatively high dosages of B12 and folate, compared to what is suggested in the simplified methylation protocol.

    It made sense to me from the standpoint of the biochemistry of ME/CFS when he first mentioned it, though I hadn't thought of it before. Here's why:

    In 2001, Burnet et al in Australia reported measuring the whole-body potassium content of people with CFS compared to healthy normals. This is possible by using a whole-body gamma ray counter, because all potassium, including that in our bodies, contains a small amount of the natural radioactive isotope, potassium-40, which emits an energetic gamma ray. (This potassium isotope has a very long half-life, and is thought to have been present since the formation of the earth, several billion years ago. It has been decaying ever since, but there is still enough to measure because of its long half-life.) Since the current concentration of potassium-40 in potassium is known, it is possible to calculate the total potassium in the body using this measurement.

    Burnet et al. found that the CFS patients who had predominately fatigue but not muscle pain were low in whole-body potassium by more than 10% compared to normal. They also measured the plasma level in the blood serum, and that was found to be normal.

    It is known that at least 95% of the potassium in the human body is inside cells. Potassium is the most abundant positive ion inside all cells. So the measurements of Burnet et al. mean that the CFS patients they studied were significantly low in intracellular potassium.

    The observation of low intracellular potassium in the presence of normal serum potassium means that there is a problem with the membrane ion pumps that normally pump potassium in (and sodium out) of the cells. These pumps require ATP for their energy supply, and that implies that the mitochondria are not able to supply enough ATP.

    We have other evidence now for mitochondrial dysfunction in ME/CFS, so this fits together very well. In the GD-MCB hypothesis, the mito dysfunction is a result of glutathione depletion and a partial methylation cycle block.

    O.K., this part was important to explain, because it means that there is no "cushion" in terms of potassium supply in these PWCs.

    Now, another thing to note is that it is likely that PWCs have a smaller total number of cells than normal. The reason is that measurements have shown a higher rate of die-off of cells (early apoptosis) in CFS, and also an abnormal arrest in the S phase and the G2/M boundary of the cell cycle (Vojdani et al., 1997). What this means is that the cells are dying off early, and are not being replaced as fast as normal.

    According to the GD-MCB hypothesis, the early apoptosis occurs because of damage to the cells by oxidative stress resulting from glutathione depletion.
    The arrest of the cell cycle occurs at the stages where the DNA is supposed to be replicated and the cell is supposed to divide, to form two cells. Something is hindering the DNA replication. What is it?

    According to the GD-MCB hypothesis, this is caused by the inability of the cells to produce new DNA at a normal rate, which in turn is caused by depletion of the folates in the cells. This in turn is caused by the partial block of the methionine synthase reaction, coupled with the methyl trap mechanism and the catabolism of methylfolate by peroxynitrite, which is elevated because of glutathione depletion.

    O.K., so now we have a situation in which the PWC has fewer total cells than normal, and the cells that the PWC does have are lower in potassium than normal.

    Now, enter a methylation protocol, which incorporates at least B12 and methylfolate. The effect of this will be to increase the rate of the methionine synthase reaction. One of the effects of this will be to convert methylfolate into tetrahydrofolate more rapidly, and the latter is then converted to other forms of folate, including those needed to make purines and thymidine, which are necessary for making new DNA.

    All of a sudden, the cells now have enough DNA to overcome the arrest of the cell cycle, and their rate of cell division goes up, making new cells more rapidly.

    These new cells require potassium, and their membrane pumps start pumping it in from the blood plasma. Unfortunately, since the existing cells, which contain 95% of the body's potassium inventory, are already low in potassium, there is no cushion or buffer for the blood plasma potassium level, and if it is not augmented by increased potassium intake from the diet or supplements, the PWC's blood plasma potassium level drops, resulting in hypokalemia. This is hazardous, because it can have detrimental effects on the heartbeat and on other vital processes in the body, such as the use of muscles for breathing.

    So that, in my opinion, is why it is important to watch the potassium level when on methylation treatment.

    I think this is especially important if large dosages (several milligrams per day) of methylfolate and sublingual or injected methyl B12 are used, because this takes control of the rate of the methionine synthase reaction away from the cells and overdrives the methylation cycle. One result of this is that the folate levels rise rapidly, and cell division also rises rapidly. Under these circumstances, the normal supply of potassium from the diet may not be sufficient to supply the extra potassium that is needed. This is one reason why I do not favor taking high dosages of methylfolate and methyl B12 together by a person who has ME/CFS, but if a person chooses to do this, it is important that they monitor their blood potassium level and augment it as needed.

    Note that over-the-counter potassium supplements are limited to 99 mg per pill. The reason for this is that if too much potassium is concentrated in one place in the digestive system, it can damage the wall of the digestive system.
    It is preferable to take the potassium in the form of high-potassium foods or juices, or solutions of potassium salts, as tolerated.

    Best regards,


    [This Message was Edited on 07/28/2012]
  5. IanH

    IanH Active Member

    what I have done for about 7 years is to add potassium to our cooking.
    Table salt (NaCL) is supplemented with 25% KCL and when the following are cooking I add Potassium gluconate (99mg tabs):
    broccoli, cauliflower, green and broad beans, potatoes for mashing and all soups.
    This way I know we get the potassium we need. As Rich mentions potassium in lumps can do damage to the digestive tract, in particular the stomach so I have always avoided taking the potassium tablets (99mg is only 3% RDA)because i would have to take around 6 tablets 6X3 =18%RDA - could be a big problem in my stomach!
    [This Message was Edited on 07/28/2012]
  6. MicheleK

    MicheleK Member

    This is all so interesting and I thank each one of you who either asked a question about the subject or explained in detail the whys and hows of it all. Very good information I can pass on to patients. Thank you! MicheleK
  7. mbofov

    mbofov Active Member

    for your very detailed reply - it all makes sense.

    I understand that Freddd's protocol may have a greater potential for inducing hypokalemia than the simplified methylation protocol because of the higher dosages of B12 and folate in Freddd's protocol. However, I still think it is very important to include information about the potential for hypokalemia with your simplified methylation protocol because I believe it is a very real and potentially dangerous side effect of the protocol.

    When my potassium levels tanked after starting Freddd's protocol, it was a familiar feeling - I had had that exhaustion and lethargy before, only I never knew what it was before or what caused it. It was a familiar feeling, but on Freddd's protocol I was able to figure out what it was because of his warning.

    So my previous experiences with hypokalemia may have been linked to the methylation protocol which I did for so long, but at that time I just thought it was more detoxing or God knows what. I had no idea it was due to low potassium.

    So I think it would be extremely helpful to persons doing your protocol to give them information upfront about the potential for hypokalemia, together with the basic protocol information. And as I said above, I'm not the only one who experienced low potassium. Forebearance did on your protocol, and felt markedly better after adding in potassium. And I'm sure there are others. I might have tolerated the methylation protocol better if I had known about the low potassium issue.

    As to the question of how to best raise low potassium levels, I appreciate all the info you provided.

    Best wishes,

  8. richvank

    richvank New Member

    Hi, Mary.

    I appreciate this advice. I have reposted the information about potassium to the cfs_Yasko group and the Phoenix Rising ME/CFS forums. From now on, I will include a discussion of potassium when I write up the simplified protocol. I'm sorry that I didn't know about this before. As you suggested, it may have been a problem for quite a few others as well.

    Did you experience muscle spasms, problems with the muscles involved in breathing, or heart arrhythmias, in addition to the exhaustion and lethargy? I would like to be able to tell people what symptoms they should be on the lookout for, that may be telling them that they need more potassium.

    Thanks, and Best regards,

  9. mbofov

    mbofov Active Member

    My main symptoms were severe fatigue and lethargy, I think I felt cold, low blood pressure and blurred vision. I didn't have heart arrhythmias or trouble breathing, but I didn't exert myself at all either - I am so used to stopping doing anything the minute I get tired (to avoid crashing) that I might have had more problems if I had tried to do anything. It was a different kind of fatigue than a CFS crash. I would tell people about heart arrhythmias however because all the reading says that that is a very real potential symptom.

    I followed Freddd's advice when I realized what was going on and titrated up slowly on oral potassium - I think 200 mg. two or three times a day on the first day, and worked up to 1,000 mg. and my symptoms were very much relieved by the 3rd day of taking potassium. I think I stayed on that dose for several days, maybe a week, and then went back down gradually and now just take 400 mg. a day (200 twice a day) and do okay.

    I did want to try raising my potassium levels using food but the caloric intake was going to be quite high, and the things that are very high in potassium like bananas and dried apricots and so on are very high in sugar. My stomach tolerates what I'm taking okay. Ian has some good suggestions for raising potassium with food and I may look into that as well.

    Thanks so much Rich!

    Best wishes,

    [This Message was Edited on 08/01/2012]
  10. mbofov

    mbofov Active Member

    Actually I'm not sure if my BP was low with the low potassium, but definitely had all the other symptoms. My BP actually went up when I started taking the folate and I started feeling better, and the potassium helped it go down.

    But when the potassium was very low and I felt like crap, I just don't know what my BP was.

  11. richvank

    richvank New Member

    Hi, Mary.

    O.K. Thanks.

  12. nikku

    nikku New Member

    Hi Mary,
    my first post here and thanks for sounding out on potassium,
    i just happened to be borderline deficient on B12 - 325 pg/ml (refernce 211-911)
    total RBC 4.4 M (reference 4.3-5.9 M)
    MCV 95 (ref 76-100)
    RDW CV 14 (ref 11.5- 14.5)
    haemolgobin 13.9 (reference 13.3- 17.7)
    platelets: 167000 (reference 150,000-400,000)
    I though i had identified cause of my fatigue (i am hypothyroid , corrected with 125 mg of thyronorm) with these reports as attributed to mild anemia due to B12 deficiency.
    one week back i start taking oral mecobalamin tablets morning empty stomach(methylcobalamin 1000mcg,nicotinamide 45 mg, pyroxidine hydrochloride 3mg) , after 3 days during night i get up 2 hours into sleep with very wierd feeling of nervousness, confusion, weekness, spasm in legs,dry lips, thought i was going to pass out, I sit it out for about an hour and then go back to bed feeling somewhat better, decide to stop taking this medication.
    next day i read about possible potassium issues and decide to have coconut water(live in tropical country with easy availibility) and banana's which did help me feel better.While i have stopped taking medicine for 3 days but every singke night i have almost similar episode, its just that now i load myself with coconut water and in about 30-45 minutes feel well enough to go back to sleep.
    i feel perhaps 1000mcg is too high a dose to start with and one should be extremely cautious, i am just hoping when i can be normal again and do not have to dread the night.
    About myself i am 35 year male with no other issue apart from thyroid and fairly active with about 10-15 km jogging every week

  13. mbofov

    mbofov Active Member

    You're right, the potassium issue is very very real. I have found that I have to continue to take potassium supplements daily, and I feel better doing it, am still taking folate in the form of metafolin (l-methylfolate - 800 mcg. a day) and methyl B12 and so on.

    Your MCV of 95 is on the high side and indicates EITHER a B12 OR folate deficiency, or both. Folate deficiency alone can cause a form of anemia (macrocytic anemia), and hence fatigue. B12 deficiency can also do the same thing. I had been taking B12 for years and my MCV was still quite high - 97 or 99. It only went down when I started taking the bioavailable form of folate - metafolin, or l-methylfolate, in addition to B12. I take 800 mcg. of folate a day (2 doses of 400 mcg. each) (Solgar brand - it's a good one)

    Your symptoms probably are, at least in part, from potassium depletion, but you very well may also have a folate deficiency, which will cause fatigue etc. My energy did not pick up until I started taking folate (metafolin) as well as methyl B12. Don't confuse folate with folic acid. Folic acid is a synthetic form of folate, and many people cannot convert it to a form useable by the body. Folic acid can acutally cause a folate deficiency, or macrycytic anemia - folic acid competes for absorption with folate!

    So I think it's very important to take folate in the form of metafolin (Solgar makes a very good one), as well as your methyl B12, and also load up daily on your potassium, however you do it. It's great you have coconut water so easily available! Its' expensive here, so pills are cheaper for me. I think you'll be able to continue with the protocol if you just take lots of potassium daily, and folate, as well as the B12.

    Also, I strongly urge you to read about the B12/metafolin protocol espoused by Freddd of the Phoenix Rising Board. (see He's the one who first alerted me to the very real danger of low potassium in connection with the methylation protoocl and Freddd's protocol and also got me started taking metafolin. I did better on Freddd's protocol than Rich's.

    [This Message was Edited on 11/05/2012]
    [This Message was Edited on 11/05/2012]

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