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Methylation protocol - what should I do next?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by elainepy, Jul 22, 2014.

  1. elainepy

    elainepy

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    I’ve been lurking for a while, appreciating the wisdom and experience on the site, but I haven’t posted before. Apologies if this has been asked before, I did try doing a search.

    I’ve been doing the Simplified Methylation Protocol (Aug 25 2012 version) since the middle of January, and, although I admit I’m not very observant or in tune with my body, I haven’t noticed any effect at all, for good or ill, beyond the bounds of what’s normal for me.

    I’ve increased the Folinic Acid by stages to one full capsule by mid June.
    I’ve increased the Fola Pro by stages to one whole tablet from Sunday.
    (Mostly for practical reasons - because it’s a pain dividing into quarters.)

    I got up to two full ‘All-in-One’ capsules (which seemed to replace the Neuro Health Formula) by mid March and have stayed with that.

    Where do I go from here? Should I increase the ‘All-in-One’ dosage – in what increments, and do I continue to take the whole dose at bedtime or spread through the day?

    What sort of effects should I be hoping/looking for?

    I’d really appreciate any advice or comments.

    I was originally recommended the protocol by Dr AW of the Complete Fatigue Clinic in Bolton UK, but it took me a long time to psych myself up to start and his clinic has closed in the meantime (I downloaded the updated protocol).

    I have thyroid disease (Hashimoto’s) and Lyme borrelia, causing fatigue, cognitive problems, etc.
    I take natural desiccated thyroid, thyroxine, selenium, magnesium, Low Dose Naltrexone, D-ribose.

    Many thanks
  2. Helen

    Helen Senior Member

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    Hi elainepy, welcome to the forum

    It is difficult to give any advice without knowing more about your symptoms. Do you have signs or symptoms of B12 deficiency? Impaired methylation ? Iron deficiency? Were you diagnosed with ME/CFS? Did you have lab tests as your doctor suggested a methylation protocol. Are you on antibiotic for your Lyme? I think you will get advice how to continue if you would give us more facts.

    Best,
    Helen
  3. elainepy

    elainepy

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    Thanks for taking the trouble to reply, I appreciate it. I wasn’t sure how much detail to give.

    My main symptoms are lack of energy, chronic fatigue, depression, and difficulties with memory, concentration, and thinking clearly. I also experience numbness/tingling in my hands and feet, usually only when driving.

    B12: this does fit with signs and symptoms of B12 deficiency; but the only time I had a blood test for this (several years ago) I was in the normal range.

    Methylation and lab tests: I have not had any genetic tests.
    The last test Dr AW had me do (Sept 2009) showed poor glutathione availability, and he then recommended the protocol.

    Iron deficiency: This has been an intermittent problem since I was fifteen (now 54) – Aug 2014 blood test showed ferritin level 54 ug/L (range 11-200).
    I don’t take iron supplements but try to eat lots of apricots. (Gosh that sounds pathetic!)

    ME/CFS diagnosis: Dr AW wrote to my NHS GP (family doctor) that my symptoms satisfy the diagnostic criteria for CFS/ME, and my GP subsequently wrote to my employer that I had depression and CFS; and my employer made me take medical retirement 2005. But I don’t think any doctor has actually eyeballed me and said you have CFS/ME.

    Antibiotics for Lyme: Dr AW did prescribe four courses of antibiotics for Dientamoeba fragilis, Lyme borrelia, Chlamydia pneumoniae, and Cryptostrongylus pneumoni, but the last was March 2009. I can give full details of which abx and when if you want them.

    I originally sought medical help in 1995, was diagnosed with depression, then in 1996 with thyroid disease (Hashi). The depression lifted a lot with anti-depressants (1995-2000), but despite thyroxine I remained unwell with fatigue etc, and felt the NHS was not going to do anything more about it – that was what led me to consult Dr AW (private doctor) at the Complete Fatigue Clinic. He tried differing thyroid treatments, without noticeable improvement, then tested for different things and offered treatment, also without noticeable improvement. His clinic closed in 2010.

    Thanks for taking the time to read all this. All comments gratefully received.

    Elaine
  4. Freddd

    Freddd Senior Member

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    Hi Elaine,

    As you are having no effect with simplified methylation and that pathway, perhaps is time to try active B12 protocol. Rich agreed some years ago that if there is nothing to indicate effectiveness of HyCbl in 3 months its time to try MeCbl. After all, 5-star MeCbl and AdoCbl are about 100 to 10,000 times more effective than HyCbl. A trial is the only way to know if they could be effective. And then, that has no simple version.
    Last edited: Jul 24, 2014
  5. aquariusgirl

    aquariusgirl Senior Member

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    Freddd, what brands of B12 are you recommending theses days?
  6. Freddd

    Freddd Senior Member

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    I did a 3 month or so trial of Country Life 5mg Methyl B12. It had come recommended. I was told that the first batch tis person had tried was slower dissolving and mentioned the newer batch dissolved a lot quicker. I just couldn't get it to absorb adequately for my CNS to not deteriorate. It seemed pretty good in my body.

    Right now I can only suggest the Enzymatic Therapy B12 infusion despite being only 1 mg. I've suggest that a lot of people need to do testing and each try 10 brands. There are a lot of new brands. We need more 5 star b12 brands so there is choice and larger doses. With my only reliably responsive MeCbl symptoms being CNS caused it takes me large doses 3 times a day for several months unless what I am testing is a lot better. A sensitive person with a lot of quick reacting body symptoms can find the most effective MeCbl brand far more quickly. If it doesn't work well on the bodies, it isn't going to work well on the CNS. I'm back on injections. They are a pain, especially traveling. The TSA simply LOVES foil wrapped vials with liquid medication they can't look at without damage in an insulated bag with an icepack in it.
    Last edited: Jul 25, 2014
  7. elainepy

    elainepy

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    Many thanks for replying.

    Would you recommend I completely stop the methylation protocol?
    Or just stop the Perque B12 hydroxycobalamin?
    Or also stop/reduce the Folapro and Folinic Acid (having increased to 800mcg a day each)?

    I've had a look at what I could find on the forum, mainly the threads on Active B12 Protocol Basics and B12 the Hidden Story, but the more I read the more bamboozled I feel. Should I start all the products at once, or one by one, in a big dose or gradually?
    Could you possibly link to a post that will give me an idiot's guide to the latest version of the protocol?

    Thanks again
    Elaine
  8. Freddd

    Freddd Senior Member

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    Hi Elaine,

    I'm very sorry to say there is no "simplified" Active B12 protocol. However, it can be started in certain pieces. Let's look at the simplest way.

    First, the Active B12 Protocol is based on maximizing the probability that a person gets healing started and eliminating, up front, all those things that might interfere. So for instance Folinic acid, just like folic acid, MIGHT be a cause for the whole thing not working. So keep the Folapro (Metafolin) or any other brand of Metafolin (ie Solgar at <$13/100 800mcg). Stop the HyCbl. Also, don't be taking glutathione, NAC, whey, MAXGL or other big glutathione producers So the fundamental pair is Enzymatic Therapy B12 infusion (5 star MeCbl) and Metafolin. For people with suitable symptoms, CFS/FMS/ME symptoms plus many more, these two, along with the basics of A, B-complex, C, D, E, zinc, magnesium, selenium, omega3 oils and lecithin and a trace mineral group (can be part of a calcium/magnesium supplement, will get a startup response within hours to a few days about 80% of the time. The MeCbl/Metafolin protects the nervous system. The B-complex has to not have folic acid or CyCbl. Also it needs to have small doses of B1, B2 and B3 that don't overdrive the system when taking it twice a day. If you keep B1 and B2 under 20mg/day each and B3 under 100mg daily that typically works out ok though some say even less is better. Again, customizing is an important part of this process.

    Lack of MeCbl makes the nervous system very vulnerable and can cause damage. Often on the third day or so a person gets a whole lot of really unpleasant symptoms and can feel pretty sick. About 95% of the time, in this scenario, it is an induced low potassium because potassium is used in large quantity in healing. This can be dangerous if a person doesn't take enough potassium. Some people have ended up in the ER by not getting enough potassium. If that goes on for too long it can be dangerous including fatal. This is equally true if a person gets methylation startup on HyCbl and Folinic acid, it just isn't as likely. No matter what starts it it starts in whole layers at a time. In addition a person may also or instead of low potassium they may have a donut hole paradoxical folate deficiency because it is a PARTIAL methylation block. It is partial by layers in the body. So the layers are things like the epithelial tissues, endothelial tissues, muscles, nerves, heart, CNS (brain and cord). Some can start healing and some can have intense deficiency symptoms at the same time until there is enough MeCbl, AdoCbl, l-methylfolate and LCF for all layers.

    If there is no startup then usually AdoCbl (Anabol Naturals) and LCF will get things going another 15% of the time. If those don't, then there are about a dozen potential other items that generally do get things started in the remaining 5%. In any case AdoCbl and LCF can be started with the MeCbl/Metafolin or after those two have gotten stabilized with the amount of potassium and Metafolin they need.

    That is why it isn't simple. There is no one pathway that works well for everybody and these different pathways need to be followed based on the clues.

    I hope I kept that simple enough. The big thing to understand is that some symptoms that happen in startup are both flags of healing and induced deficiency symptoms. When There is neurological "brightening", that only happens if the person already has neurological "dimming" as a b12 deficiency symptom. That can make everything feel more intense. It also lets a person see the details and clues better.
  9. caledonia

    caledonia

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    Technically you should just able to take the All In One multi plus some active sublingual B12. The All in One has all of the various co-factors you might need. This is the core of what I'm doing.

    I chose to use liquid sublinguals vs. the lozenges. I didn't tolerate hydroxycobalamin, so I'm taking methylcobalamin and adenosylcobalamin. I'm getting some slow but nice progress such as I no longer have autoimmune thyroiditis (aka Hashi's).

    The All in One includes folinic and methylfolate so you don't need to add those separately. It also includes lecithin so you don't need that separately either.

    Folinic - one full capsule 800 mcg (4X what Rich suggests)
    Folapro - one full capsule 800 mcg (4X what Rich suggests)
    All In One multi - two 26.4mcg folate, the B12 doesn't count because it's oral which only absorbs 1-2%
    Perque Hydroxycobalamin - one (I'm assuming) 2000mcg (don't know how well this brand absorbs)
    Lecithin - one (I'm assuming) 1200mg

    So technically, you're taking a bit more B12 than folate, but perhaps the Perque doesn't absorb well enough to make up for all of the extra folate, so that's causing methyl trapping, which will stop methylation (the opposite of what you want).

    Try reading "Roadblocks to Successful Methylation Treatment" linked in my signature. I have the exact B12 brands that I'm taking listed in there. Get some potassium on hand before you switch things up!

    Here's a link to Ahmo's Guide to Freddd's protocol: http://phoenixrising.me/forums/index.php?entries/a-guide-to-freddds-protocol.1618/
  10. elainepy

    elainepy

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    Many thanks for these replies, Fredd and Caledonia, I really appreciate you taking the time and trouble.

    As I understand it, as I haven’t felt any effect from the methylation protocol after 6 months then I’m not likely to, so I should try the B12 protocol.

    I will stop taking the 5 methylation supplements now (pity I’ve just ordered new supplies of them all!), and take a break while I order the new stuff. I don’t think I’ll rush to start the new protocol as I have something on 21 August I don’t want to risk.

    I will order
    Enzymatic Therapy B12 Infusion (this states it is chewable – is this the right stuff?)
    Anabol Naturals Dibencoplex
    Now Potassium gluconate.

    I already have
    Folapro methylfolate

    I also have All-in One – does this meet the requirements of the B-complex etc you mention or does the folate/B12/NAC disqualify it?
    If All-in One is no good, should I order Jarrow B-right instead (it seems to be recommended but also has folate)?

    Does this sound like a reasonable plan?

    Thanks again
    Elaine
  11. Freddd

    Freddd Senior Member

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    Hi Elaine,

    There is no reason to wait for Aug 21st. The thing that many people having not gone through this don't realize is that more and more neurological damage becomes non-repairable as time goes by. When a person goes into methyltrap or severe partial methylation block, demyelination lesions form in about 2 weeks. These are difficult to repair and get larger and more difficult as time goes by.

    No NAC! That can completely prevent effectiveness with active B12 and folate. B1 and b2 below 20mg-30mg daily respectively and b3 < 100mg daily. No Folinic acid, no folic acid, no CyCbl or HyCbl. Jarrow B-right hasn't been suggested for 5 years or more since we found the problem with folic acid. The Enzymatic Therapy is the right thing. "Chewable" is all they can say.
  12. Lynn_M

    Lynn_M Senior Member

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    Freddd,

    Do you know of a biochemical or physiological mechanism that underlies your directive to not take NAC? I have read about your negative experience when you took NAC, but I'm wondering if there is a theoretical basis for why NAC would prevent effectiveness with active B12 and folate. If you've explained this elsewhere, could you please direct me to that discussion.

    My homozygous GSTP1 mutation and my Spectracell micronutrient test both indicate I am low in glutathione, and NAC was the one thing recommended to me for that deficiency. So I'm trying to understand why NAC would interfere with my taking mB12 and mfolate to improve methylation.
  13. xrunner

    xrunner Senior Member

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    Hi @elainepy
    The main measurable effect is an increase in reduced glutathione. To measure that you need a methylation panel.
    If that test shows your methylation isn't working then would reconsider the protocol.

    If instead your methylation is back to normal but there's no improvement in symptoms then I'd follow what Rich suggested i.e. check for Lyme disease, mold sensitivity, mercury and so on. These were the main factors I can recall now (there may be others) from Rich study on CFS patients that would "cancel out" or override any actual improvement in methylation, in other words you can't cure for e.g. Lyme disease with only a methylation protocol.
  14. Freddd

    Freddd Senior Member

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    Hi Lynn,

    I'll try my best to explain it. Remember, the results are pragmatically based, and verified, pragmatically, in many ways. My explanation is based on the whole complicated hypothesis and has changed as understanding has advanced with more data.

    If NAC is the limiting factor in generating glutathione, then a lot of glutathione can be made when a person takes NAC. This then results in a percentage of those doing so forming an excess of glutathione that results in what is popularly called "NAC detox". These "side effects" are documented in Cerefolin with NAC. Further, "NAC detox" matches exactly "Glutathione Detox" as to symptoms and effects. The symptoms, immediate and longer term, match a specific variety of paradoxical folate deficiency symptoms (partial methylation block or methyltrap). If a person is absorbing enough b12 each day that it is at least slightly visible in the urine, within hours of taking NAC;/Glutathione, one can see a flood of B12 in the urine, as if the person was taking 5-10 times as much b12. That is visible in many people when it happens, if they look. It may only happen once. This flood of b12 in the urine happens with cyanide and large doses of nitrous oxide as well. This causes immediate onset of methyltrap. People who were not in methyltrap or a reasonably severe partial methylation block will start noticing symptoms within 1-24 hours of the b12 flush. People already in methyltrap won't see the b12 flush because it is not in their body in sufficient amount to see. People in methyltrap or partial methylation block may not have any noticeable symptoms change or onset. The may feel some changes that feel like benefit. Those who have less partial methylation block and who find the feeling of methylation unpleasant may feel relief as methyltrap takes hold.. Neurological pain diminishes as the nerves cease functioning and go to numb.

    Glutathione attaches to cobalamin that is not in the mitochondria. It appears to combine with AdoCbl and MeCbl at first opportunity. Based on my trials with combinations of cobalamins having less than about 20% of available cobalamin being MeCbl, methyltrap takes place. Glutathionylcobalamin forms very quickly and goes straight out the kidneys very rapidly. This reflects the lack of effective Methylfolate which influences how long the MeCbl/AdoCbl remains in serum. In methyltrap the "fail" symptoms are folate deficiency symptoms one of which is reduced serum half life of cobalamins.

    One researcher I talk with considers glutathione to be "too dangerous to take in any way". I hope that this explanation helps with understanding. It is right now my most up to date hypothesis on how that happened. What happened hasn't changed but the explanation goes a little deeper now.
  15. Freddd

    Freddd Senior Member

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    Hi Lynn,

    When methylation starts you will know it very directly. The first things that happen is usually the brightening of the sensory world, more intensity and literal brightening return to pre-deficiency levels which seems like a big jump because it is, compared to where a person is after years of deficiency. However, it is an on or off thing in each triage layer with MeCbl and Metafolin. Then about 3 days after that startup, there is often a lowering of serum potassium and donut hole paradoxical folate deficiency. They both indicate cell formation has taken a jump.

    It might take as much as 2 weeks for the NAC and resultant glutathione to clear enough that the MeCbl and Metafolin to start working. Once methylation starts up properly plenty of glutathione should be generated. Low glutathione is a result of partial methylation block, not a cause of it.
  16. Valentijn

    Valentijn Activity Level: 3

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    NAC works great for me ... no side effects, and it helps me sleep. It also has a lot of other beneficial effects, according to the published research.

    I wouldn't buy into any scaremongering, especially if there's no direct scientific published evidence supporting those claims.
  17. Freddd

    Freddd Senior Member

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    I wouldn't buy into any scaremongering,

    It's sad to see all the scaremongering that goes on and has here. People so terrified of neurological "brightening" that they avoid healing like the plague. People in methyltrap or partial methylation block buying into the scaremongering so much they don't dare let methylation get going because they fear instantaneous overmethylation. Those who work in the medical industrial research system abdicated knowing anything about nutrition when the ignored the real identity of B12 and continued researching the lab mistake. So 10 of us had increased CNS neurological damage from glutathione and precursors under very specific circumstances. In the specified circumstances the specified result is obtained. It's reproducible from written directions. I don't know what percentage of people will have that reaction from only NAC itself, some do, clearly, from research, as side effects. You can find all sorts of "NAC detox" responses written up by people all over the web. Are you saying they don't have that reaction, that they are all making it up? If these people that are vulnerable to CNS neurological damage should they be aware of the possibility?. Don't you think they ought to be warned that there is a chance of neurological damage especially when a certain set of "detox" symptoms start that just happen to match paradoxical folate deficiency (methyltrap style) symptoms and can be relieved by MeCbl and l-methylfolate. And yet people are very scared of the bogyman (overmethylation) that has a list of symptoms that are most all B12 deficiency symptoms, many of them AdoCbl rather than MeCbl deficiency. That is more of a balance problem.

    If I had been warned very specifically about the neurological damage from glutathione I might not have done that trial and saved myself form damage that hasn't reversed since then. It's a pity that there are no thorough and well done studies that actually document how tests are different when people are taking the active b12s and folate and carnitine in an effective manner. Science literally does not know what a group of people using AdoCbl, MeCbl, l-methylfolate and LCF looks like in tests. So we only work from inside the box of those who decided only the fake vitamins should be studied. Only certain people are allowed to think? Based on 60 years of well established "scientific" papers would have us all be head cases making up our "yuppie flu" because we are all lazy. Science has produced millions of chronically ill people in these man-made deficiency diseases by thinking strictly in their blinding box, the correct answers having been buried in 1959.

    There isn't a person working on any aspect of methylation that stays in the box. Many are vilified, in the UK for instance. The tests ranges for many tests now protect these chronic diseases by defining them as normal during their developmental years.

    As my doc said "I've never seen a more normal person be so sick". Other docs at other times thought I must be a secret alcoholic from some of the blood work, all "in range" but the pattern of being at a lot of extremes within the ranges apparently looked alcoholic to them. Going strictly on all the scientific tests I should have been in perfect health. Over 100 docs failed to trust their eyes and first impression and go with "B12 deficiency". Instead they went with the tests that were worse than useless, they were completely misleading, leading to 100% useless and incorrect treatments. So we all exist in an institutional bind spot and are doomed to illness following the scientific research. I'm not willing to buy into the system that makes me and all my children and grandchildren and many friends a writeoff, a sacrifice to the gods of science. After healing from these deficiency diseases the proper diagnosis is very clear.

    If tested now, my B12 serum level is likely somewhere above 100,000 pg/ml. If it were at the "upper limit" of 1100pg/ml I would be in a wheelchair or dead. These numbers are based statistically on inactive cobalamins. CyCbl in excess of 1100pg/ml is likely as worthless as below 1100pg/ml, so based on untested assumptions, the same thing is assumed about MeCbl and AdoCbl. Great science. We can do better science right here. True, we have to confine ourselves to things with naked eye results since we don't have the budget for expensive toys like NMR and Mass Spectrometers to play with. If I had those I know what questions I would ask. So we are not looking for microscopic ppm or ppb changes to "prove" that CyCbl/HyCbl does x. I, and most people I talk to want naked eye healing. We want to get better and have a healthy life again. If all the microscopic changes don't add up to healing and recovery they are maybe worse than useless for our purposes. So learn to think scientifically and then the studies look different as does the fear mongering. There is a sizable difference between fear mongering and warning of a side effect of unknown frequency but with potentially serious consequences.


    In the business I was in, group health consulting and software, I read hundreds of papers every year. One has to read with a discerning eye because there is so much wrong in so many papers. The quality is very uneven. Many of them would fail as high school lab reports because of poor proofreading and dumb mistakes. Seeing these chronic disease be "normed" out of existence in their early developmental days so that they are not recognized soon enough to possibly prevent the damage and instead are transformed into incurable but maintainable chronic diseases for life enriching big drug companies shows that much of the research is not for our benefit.
    helen1 and Johnmac like this.
  18. Valentijn

    Valentijn Activity Level: 3

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    HydroxoB12 helps me with pain. It doesn't "heal" me. However 6 weeks of IV antibiotics for a 20 year borrelia infection has finally resulted in significant improvement, with another 6 still to go.

    Saying that people "avoid healing" because they are "terrified" is egotistical, insulting, and dead wrong. B12 doesn't heal ME/CFS, regardless of exactly following your personal protocol or any other one. ME/CFS is much much more than a methylation problem, and you don't have the cure for it.

    NAC helps me. It helps a lot of people. Your dogmatic refusal to accept that it might help people far more than it harms them is simplistic, arrogant, and potentially harmful. Ranting when anyone disagrees with you is not going to convince anyone of anything.
    Last edited: Jul 31, 2014
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  19. Freddd

    Freddd Senior Member

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    LOL

    I gather you prefer to knock down your straw men rather than consider what I try very hard to say precisely. You might try actually quoting me, especially sentences or more to keep things in context. There has been tons of fear mongering about what the neurological brightening must be which scares a lot of people. What makes it all so ironic is that the neurological damage and effects on mood and personality of the Deadlock Quartet deficiencies do cause considerable fear and make people excessively vulnerable to fear mongering. To me, it is the demonstration of the neurological effect of these deficiencies, to you it is an egotistical attack and somehow an insult to look at the symptoms and how they affect people.


    ME/CFS is much much more than a methylation problem

    Of course it is. I'm glad to see that you can agree with that after my saying that for 5 or 6 years here. I have no idea why you would even suggest that I would think that it isn't. May I suggest a course on critical thinking? Lot's of people also have comorbidities, such as infections, requiring antibiotics and other treatments.
    Last edited: Aug 1, 2014
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  20. NilaJones

    NilaJones Senior Member

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    I'm very glad to see a new overview thread, as I get overwhelmed and can't keep up with the giant ones :).

    Thank you, everyone who has posted, for your clear and cogent information!

    I would add that, with potassium, you may very well not be able to get enough from supplements. You can google and see that many common foods have far higher amounts of potassium than the available tablets. Coconut water, dates, and carrot juice are my potassium sources. Keep stuff handy, because you may have emergencies. Really.

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