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Why is potassium supplementation needed in methylation treatment?

Discussion in 'General ME/CFS Discussion' started by Radio, Feb 24, 2014.

  1. Radio



    "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,

  2. xchocoholic

    xchocoholic Senior Member


    Do you have a link with a date for this?
    RichV was great when it came to learning anything he thought might help pwcs and may have changed his opinion after writing this.

    Fwiw, vitamin water has a drink out that contains a large amount of potassium. I've forgotten how much. I think it is called Revive. It made me feel sick right away so I couldn't drink it. I drink the xxx one for an energy source. Fwiw I feel best if I dilute it 50/50 with water.

    I'll google the vit water now and get the figures.

    Eta. Ok. I tried googling the potassium in revive but came up with different amounts. Probably best to check the label on each bottle.
    Last edited: Feb 24, 2014
    SOC likes this.
  3. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    I am not convinced there is a problem with ion transporters involving potassium in most tissues. I suspect the answer is simpler than that. The body maintains serum potassium homeostasis at the expense of tissues. Only about half of us had low intracellular potassium anyway, if my recall is correct which it may not be. Maintaining serum potassium prevents serious and lethal crisis. However then tissue is low, with all that can follow from that.

    This is likely from a kidney or hormonal issue, with the body improperly regulating potassium. Now there might indeed be an issue with kidney potassium transport, I don't know for sure either way.

    There is another issue here too. Maybe we don't really have potassium issues like we think. Potassium acts a bit like a drug, it could be drug effects of potassium and not a real deficiency issue.

    As always I want to know why we have low intracellular potassium so often. I don't like the fact we are forced to guess about it.

    My potassium supplement dissolves in water, and I drink it.
    SOC and Allyson like this.
  4. Allyson


    Australia, Melbourne
    I ag
    I agree with Alex - K is very basic o all our needs
    and we lose too much

    I do due to polyuria

    maybe low blood volume does not help access to K

    I heartily agree with Alex - potassium is very basic and we lose too much

    I think I lose it due to polyuria and nocturia - not sure about others

    Which K+ supp do you take the dissolves please @alex3619 ?


  5. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    I take Chlorvescent, but its because its the only easy one to take at higher dose in Australia. You can also sip it. It is flavoured though, some might find that hard to take. Its just too easy for me. I add it to a bottle of water, or a large mug, or whatever. Tablets are cheaper though, but more likely to cause issues. Chlorvescent has 548mg of potassium, in a balance of bicarbonate and chloride. Its a big enough dose for me most times, and I don't need it all the time but then I am not on methylation at the moment, though I hope to restart soon.

    I drink like a fish (water, not booze) and pee like a horse. I probably have issues with a few electrolytes, not just potassium. I eat loads of salt but have a low sodium value.
  6. vortex

    vortex Senior Member

    I take the revive, it has 880mg of potassium.

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