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Started Freddd Protocol about a week ago...

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by nkm, Jun 19, 2013.

  1. nkm

    nkm

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    Hey all,

    I have had CFS from the age of 8 (now 30). I have thought all the crap to be normal but as it turns out, nothing is normal and in hindsight, ive had a pretty crappy and boring life.

    My symptoms spectrum includes neurological, fatigue, fibromyalgia (tender points, muscle pain, back pain, extreme heat sensitivity etc), depression/anhedonia (actually have most of the common symptoms associated with ser,dopa,ep/norep deficiency) and the one I HATE THE MOST...extreme social phobia! My life has been descimated by the social phobia more than any other symptom!!!

    I have had a few tests done and it turns out I do have a problem with the methylation cycle and glutathione depeltion and folate dysfunction.

    Here is a very brief summary of my test results:

    Nutritional Profile:
    - Essential amino acids are all within range, which is a good start!
    - glycine, serine low. alanine sarcosine, ethanolamine, proline high
    - Arginine high, aspartic acid low
    - High homocysteine
    Low potassium
    - Pyruvate elevated, lactate normal. Krebs VERY slow! All markers are either low or "DL" (below detection limit).
    - Dysbiosis markers are normal, no yeast etc.
    - Most Omega 6 are borderline high and nonadecanoic is through the roof!

    Heavy metals:
    - Three day DMSA chelation test revealed no heavy metal overload...another good result! (apparently, a one-off DMSA provocation is not accurate as it just "picks up the low lying fruit" as my nutritional MD put it)

    Methylation:
    Genetics: MTHFR C677T +/-, MTR +/-, MTRR +/- (several of the MTRR are hetero), CBS A360A +/-, MAO A +/+.

    Methylation cycle:
    - low GSH:GSSG (3.3:0.53) confirmed glutathione depletion
    - low SAM:SAH (216:52.6) confirmed SAMe imbalance
    - low 5MTHF (7.9), low THF (0.5), Low folic acid (324) confirmed folate dysfunction
    - Elevated adenosine (don't know what this means, I assume it is a marker for the rate of SAH to HCY conversion, where the adenosine is removed, leaving HCY).
    I have attached the table of results for this test, as it is probably the #1 most appropriate test for the methylation/GSH/folate hypothesis behind CFS.

    I have tried lots of different treatment protocols over the last few years and have not had much of anything happen.

    I find I am the opposite to supplement hyper-sensitive, I just have nothing happen! It's so frustrating that no matter what I do, I just have nothing happen!

    A week ago I started the Freddd version of the protocol (Rich's (RIP my friend) version with low dose methylfolate and PerqueB12/hydroxyB12 didn't do anything).

    I am taking:
    - 5mg Quatrefolic methylfolate every morning before breakfast (I just split the 10mg capsule into two caps)
    - 2.5mg adB12 sublingual before breakfast
    - 2.5mg mB12 sublingual in the evening
    - Fulvic minerals morning and night
    - B-complex with breakfast (Country Life. The one with the mix of inactive and coenzyme forms. I don't think I have a hypersensitivity to the folic acid in it)
    - 1200mg slow release Potassium, will increase to 1800mg as of tomorrow
    - Milk thistle with dinner
    - Selenium with dinner

    The plan going forward:
    I will be adding 1/4 tablet of lithium to this mix tomorrow and then a week later, i'll double the mB12 and adB12. I'm hoping that while the methylfolate is working on the BH4 increase and therefore, better neurotransmitter production, the mB12 will improve methylation and the adB12 will drive nonadecanoic and some amino's into the Krebs cycle, which truly needs a boost!!!

    My plan is to basically keep increasing on a weekly basis until I feel a change. I don't care what it is as long as I feel something!!! After next weeks increase, i'll increase mB12 in 5mg increments and the adoB12 in 2.5mg increments. I'm not sure whether I should try the full 10mg methylfolate but then again, I would really love the benefits of a proper functioning monoamine neurotransmitter system.

    Any input, thoughts, technical analyses etc are welcome and encouraged. One thing ive come to learn about our stupid illness is that we have to help each other out!!

    Cheers,
    Neil
     

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  2. nkm

    nkm

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    Slight change of plans...

    The more I think about it, the more I want to try the 10mg methylfolate/day so as of tomorrow, i'm going to have 5mg morning and 5mg evening and see how I feel after a week before I add lithium and increase ad/mB12.

    If I feel nothing on 10mg methylfolate, I will be concerned and very disappointed.
     
  3. caledonia

    caledonia

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    How long were you on Rich's protocol? There can be a honeymoon period of 6 weeks or so, then BAM.
     
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  4. caledonia

    caledonia

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    I would also like to add, that if you decide to try this protocol, you should have the nicotinic acid from of niacin on hand. If you run into trouble getting overmethylated, you can take 50-100mg to soak up methyl groups and stop methylation. Otherwise you can be suffering for a very long time waiting for methylation to slow down.
     
    Beyond likes this.
  5. Red04

    Red04 Senior Member

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    Freddd's protocol includes L-Carnitine Fumarate. Also, I would drop the folic acid just to be sure. Also, consider adding vit A,D,E,C, Magnesium, Calcium, Zinc
     
  6. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    About the DMSA... that only shows you dont have extracellular mercury or lead. A pretty shitty test in my opinion at showing heavy metal load.

    Dont worry, if you have ,methylation blocks, low GSH and etc, you will have a nice store of crap from 30 years moving around a toxic enviroment. Ahh yes they start putting it in you with syringues when you are a kid, just to make sure. In the past it was Thimerosal, (ethylmercury) but now that someone realised that they were injecting mercury to children its Aluminum Hydroxide among other goodies like mutagenic ADN from animals. :mad:

    http://www.remedyspot.com/showthrea...ercellular-will-DMSA-chelate-Hg-from-Adrenals

    Yeah, indeed my brother and sister also are sick but they wont recognize it until it crash in their faces. Its not normal to be anhedonic, "lazy" (i.e. fatigued and depressed actually), sleep like shit and have haggard face, be emotionally vulnerable and obsessive and have social problems (only my sister and me it seems). But when someone visits my house its common for everyone to "hide", especially me and my 25 year old sister. And my other younger brother has trouble with studying and its very addictive with videogames (like me and our other brother) and violent at times.

    Personally im sure that an addictive behaviour can originate from genetic mutations and for sure "underground low grade depression". I know I have always been unhappy in retrospect, and frantic dedication to self-stimulation like videogaming made me feel better. So I see the genetic component! All this stuff its involved with autism, thats why we have social phobia IMO apart from being less able to do and achieve things than others. Plus when you feel and look bad putting up with the "pleasure" of interacting with normal people just doesnt pay off.
     
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  7. nkm

    nkm

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    I was on Rich's protocol for about 3 months with differing doses. I went up to 3.2mg of metafolin and around I had used perqueB12 and also some meB12. The meB12 was not sustained very long though.

    My metabolic profile showed lots of plasma fatty acids were at the high end. Rich said this was likely due to a lack of NADH which "presents" the fatty acids to the mitochondria. I took 50mg NAD per day and my liver enzymes went through the roof! This is good evidence that B3 does reduce methylation function but I feel it is only of consequence when there is a lack of methylation and possibly not when the MTR enzyme is being "topped-out" with meB12 and meFolate.

    On another note, I read peroxynitrite destroys NADH, which helps me understand the above regarding the elevated fatty acids. When the methylation cycle is running better, peroxynitrite will reduce, NADH will increase and help present fatty acids to te mitochondria and carnitine, which will also increase due to better methylation, will catalyse beta-oxidation. I am learning more and more how crucial methylation is for sooooo many different crucial functions.

    I would prefer carnitine to be formed naturally as methylation comes back on line, since methylation produces carnitine from lysine. I am taking fulvic minerals, which is arguably the best form and balance of minerals for human's. I also take 5,000IU vit D and 1mg vit C per day.

    My MD was saying the one-off DMSA gets all the extracellular stuff while the 3 day challenge (with a couple of doses of NAC in between) gives a much better indication. I know there is likely to be quite a lot of stuff there but at the same time, the MD has done hundreds of these profiles (as he does chelation therapy) and has good experience to recognise heavy metal burden.

    Your description of "life" resonates with my feelings of life. Trying to push through it all and spend time with others seems like a great idea in theory but when it comes down to it, I take no action and don't really want to...at the same time, knowing it is not the "normal" way to live. Since I have been in this situation from age 8, I never knew any different and thought "it's just me". But now I know it is anything but normal!!
     
  8. fishersta

    fishersta

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    Have you ever tried Lexapro (antidepressant, SSRI) for the social phobia? I had severe social phobia long before CFS & Lexapro changed my life.
     
  9. nkm

    nkm

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    Oh, I forgot to ask a couple of questions:

    1- I took heed of the suggestion and limited methylfolate (quatrefolic) to 5mg instead of 10mg/day. I further split this into 2.5mg morning and night. Is it better to split the dose to have a more sustained action?

    2- Same question as above for the meB12...better to split the 5mg dose into 2.5mg morning and night or 5mg in one hit?

    I read Freddd's analyses of B12 and he states a larger single dose will get more diffusion into CNS but again, isn't it better to have sustained delivery so the potential of a "rollercoaster" is minimised?
     
  10. Jarod

    Jarod Senior Member

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    planet earth
    Beyond sounds rough man.

    Always kind of thought the addictive behavior was related to low glutathione.

    nkm you are on it. some other co-factors:
    maybe try out the co-q10, manganese(first thing am on empty stomach)
     
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  11. nkm

    nkm

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    From all my research, I feel if I can restore methylation function and increase/maintain production of the monoamine neurotransmitters, I should be much better off than compared to any SSRI, SNRI, TCA, benzo etc etc. When all research points to the direction that SSRI et al. deplete neurotransmitters after the intended short term use doesn't sit well with me.

    Something to note is that using natural/nutritional medicine, I was able to correct many metabolic issues such as liver enzymes back in range, thyroid anti-bodies nearly back in range, insulin resistance/elevated glucose back in range, reduced the threshold of hayfever and chemical allergy triggers.

    So, I have hope that with some time and perseverence with the methylation protocol, I will see positive changes relating to nervous system function. If methylation protocols don't work out for me, I will consider the "new generation" psychiatric approach of SSRI + methylfolate but this will be my last resort.

    Plus, my Mum has CFS but has been treated by "the system" for 20+ years and I have seen first hand what it has done to her so if I can avoid pharma drugs, I will.
     
    Jarod likes this.
  12. nkm

    nkm

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    In the past, I was on 400mg ubiquinol (the reduced form) and surprisingly, it didn't help me at all. My nutritional profile showed CoQ10 levels were actually OK which surprised Rich but as we went through our analysis, it dawned on me that since the Krebs cycle was in such a low state of function in addition to NADH insufficiency, the electron transport chain will not be very functional.
    This also explains why my 8-OHDG was not elevated as most of this type of free radical damage marker comes from mitochondrial free radical production, and in my case the mito function is basically asleep. Rich agreed with all of this and also confirmed to me that it seems pretty much all patterns on my tests can be traced back to his GD-MCB hypothesis.
     
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  13. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    I have been able to achieve the same in both areas, liver and thyroid antibodies. My liver enzymes have never been so low (but in range), they used to be all high. I even (but this was a coincidence) received a result of too low Lactate Dyhydrogenase, and recently discovered that my high consumption of juiced ginger was to blame! Sure natural medicine can be powerful. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785542/

    Jarod I wouldnt be surprised my two brothers are low in GSH as well,
     
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  14. triffid113

    triffid113 Day of the Square Peg

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    I am like you - I feel little of the methylation protocol. However I have been taking less functional supplements my whole life. If I stop altogether I can indeed feel it and after a few days I have to get the program or else! If I were you I would establish a reasonable strategy I felt was not excessive and was STABLE that I could go on with for years and stick with it for a few months then start retesting things.

    I want to caution you that whether you feel it or not, high homocysteine is deleterious leading to strokes and low SAMe leads to cancer and joint problems, etc. So if you never feel the results but can measure them - they are still important results.

    Now to expand your results, consider switching your folate to metafolin (some here have found negative results with the one you are taking), add TMG (1-2g), add P5P - 50mg is good. Take your B complex 2x/day. idk what is in the B complex you take, but anytime a non-active B appears in it, it may block your results. (Seems to do so for some). And here's a stupid way to determine if it's working (the SAMe production, not the glutathione downstream part) - get yourself mosquito bit. If the bites itch for more than 10 minutes, you have not achieved correct methylation. I would test homocysteine via blood test, but inbetween, the 1st thing you notice, and which you can use as a rule of thumb, is that mosquito bites no longer itch for days on end.

    Also note the need for support vitamins. So, for instance, the methyl cycle also needs zinc (and I have read in some places copper). I hear - can't prove, that use of ATP requires magnesium (if you'll look, SAMe production requires ATP). Vitamin D regulates the methyl cycle (have you checked your D levels in blood? Optimal is 70). Free radicals dysregulate the methyl cycle, so consider antioxidants. Also you cannot make BH4 w/o C (not just mfolate).

    Maybe the high folate could help MTHFR 677A>C, or else it will be MORE of a problem for that one. I don;t have that one so no experience. But if you raise that make sure you are on TMG and P5P IMHO so that you don't get a backup of homocysteine if you can't process the mfolate fast enough. P5P helps with anxiety if that's an issue.
     
    nkm likes this.
  15. nkm

    nkm

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    Here is a little update:
    - When I first started methlfolate last week, slightly better concentration and I felt a bit happier/brighter and not as fatigued/lethargic (which IME is a pure nervous system cause and not muscular because if I really push through my "fatigue", I can actually do a bit of weight-training!)

    - I introduced methylB12 and after a couple of days, felt the slight improvements dwindle. About 3 days ago, I switched from 5mg meB12 to 2mg hydroxyB12 (the perque sublinguals) and have continued the methylfolate at 5mg, split into two 2.5mg doses.

    - I notice I am still very fatigued and have pretty much lost any improvement I had gotten. I am feeling very lethargic, no motivation/drive at all...even the smallest tasks are going unattended!! I am in the process of trying to get a job but I can't imagine how i'm supposed do that in my current situation!

    - I also feel my sleep is deeper and not as disturbed (I normally sleep like a cat and the smallest noise would wake me!) but after 9 hours of sleep, I'm waking up even more tired than before!!

    I am taking 1,800mg potassium chloride in a slow release form, split over the day. I will continue the mefolate and OHB12 and see what happens in the next week or so. Maybe it was just too much meB12, which as Rich said can cause the cells to lose regulation of the methionine synthase enzyme and lead to "over-methylation".

    Thanks for your detailed response.
    I am confused about the methylfolate discussion. Whether it's metafolin or quatrefolic, they are both 5MTHF, which would be used by the MTR enzyme etc. I don't understand how the glucosamine salt can make the effects of 5MTHF to different from the calcium salt. Do you have any molecular info on what might give the different effects?

    I'll increase my B-complex to twice a day as suggested. I think this may help as it would provide more of the supporting B vitamins that may be required in this period. I am attempting to lift the methylation block so I don't wish to shortcut it with TMG and from what ive read, BMHT doesn't operate in the CNS so it doesn't seem very useful when trying to life the block in the CNS.

    The histamine release from mosquito bites is something I have been aware of for a while. When I get bit, it itches like hell for several days and if there are enough bites, my sleep gets distrupted due to the itching. So, I wouldn't call your suggestion "stupid", instead, it is actually a very good practical marker to monitor changes in methylation. In my case, I believe I have what is referred to as MCAD (mast cell activation disorder). I believe it because I react to dust, pollen, the smallest exposure to chemicals and even changes in the weather like on very cold days, I have to take an anti-histamine! I hope improving methylation can fix this issue.
     
  16. triffid113

    triffid113 Day of the Square Peg

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    Oh, sooo sorry, but I also have that cold weather dry air allergy and methylation does not help. The problem is dry air and anything you can do to raise the humidity helps. I didn't run a humidifier last winter but even with one my doc says you ned a pan of water in front of your bedroom register to raise the humidity. idk if that will be enough - I did not used to get cold dry air allergy so idk if it is lack of humidity entirely or if it's an over-50 thing. However f you look on google.scholar you will see that they typically use cold dry air to test he effectiveness of allergy meds because they say that "reliably sets off anyone with allergies".

    idk about quatrefolic...just that I recently ran across a few posts here that said something about having a problen with that and not metafolin. So it's just something to bear in mind to keep alert for. You can search for it and see what others have said.

    Many people have said they get energy from 2x daily dose of B complex - just adding that second pill later in the day. This is not the same a recovery from CFS, just everyone gets a bit of extra energy from the extra B (I mean normal people too)...I doubt it by itself is enough to counteract CFS, but every little bit helps IMHO. It helps your body make carnitine which is important for energy metabolism (idk why...it might be interesting for me to look that up). Velha cured herself of CFS (or CFS symptoms - she always said that she could have had something CFS-like that still was not CFS) by taking clse to 5g carnitine fumarate from Doctor's Best (she said most brands were not potent, but that brand and one other). It worked for her sister as well. When she stops, she backslides. She does follow the Freddd protocol but the way she had to modify it to make it work for her was the extra carnitine (so in other words, she takes the B complex etc as well). Interestingly, if one is hyperthyroid, one burns through carnitine at a ferocious rate and the effect is that one runs out and it causes weakness and muscle wasting (which can be prevented with large doses of carnitine).

    I'm not sure about your glucosamine comment. I don't take glucoseamine myself...it is implicated as causing diabetes in dogs so as diabetes runs in my family I would never ake it myself.
     
  17. nkm

    nkm

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    I have noticed it doesn't really matter if the air is dry or not. Yesterday was cold and high humidity and it still set my allergies off. I didn't have allergies a few years ago, it all developed when I was exposed to some construction work that was happening in my work place. With my pre-existing CFS/methylation problems, I imagine I didn't have enough of a buffer to counter that exposure. I was sick with flu-like symptoms for a month, recovered and went back to work and bam! they came right back as the construction was still going on. Since then, my allergies have gotten worse and worse, which makes sense as I have had a very stressful last couple of years.

    The fact that the PWC used high dose carnitine felt better but worsens when she stops it indicates it is just a band-air solution. I would prefer to work on methylation and have that produce the carnitine (which is formed with L-lysine and methylation).

    I wasn't referring to glucosamine as a supplement. I was posing the question of why would a glucosamine salt mfolate (quatrefolic) have a different effect from a calcium salt mfolate (metafolin). I would imagine the people that reacted to quatrefolic would react to metafolin too or they maybe there were other factors/changes that caused the reactions.
     
  18. triffid113

    triffid113 Day of the Square Peg

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    Oh, thanks - I didn't know there was another substance bound to the methylfolate in those supplements. However that does make them different and everyone's biochemistry is different so it's not hard to see that one supplement might work better or worse for another person.

    I agree about making carnitine naturally but not about the bandaide on 2 counts: if you were hyperthyroid and ripped through carnitine at a ferocious rate so that you were OUT and it caused muscle deterioration (as happens) you would be VERY HAPPY of such a 'bandaide' to prevent that muscle wasting and weakness (likewise for anything that causes muscle wasting and weakness). If you had lyme which consumes your B12 and you could completely remove the symptoms by taking B12 you would be VERY GLAD of that. In both cases you would not have got at the root of the problem but you would have been doing WAY better than 99% of people out there who resort to medications that will not spare their muscles or prevent cancer etc. And that gets at (2) - it is not so much a bandaide as a fixing the process downstream of the inital problem but it is still fixing some or all of the process. Ok, in this case, carnitine does not raise SAMe and so you will still be subject to cancer which is pretty serious. So I agree fixing methylation is more important. But it cannot hurt to add carnitine so long as you are fixing methylation to some degree. She does take all the methylation supplements and she went from 'on the couch' to getting a job and moving on with her life. She is hardly ever on this board anymore as she has no need. It's a great success story.

    Where r u from that it was cold yesterday?? I find if it stays above 35 or 40 F degrees I do not get cold dry air allergies. There is a chance your allergies are due to inability to get rid of toxins and could be helped by getting the P5P - magnesium - CBS part of the methylation path working. I only mention this because construction may put pollutants into the air...it may be different from allergic rhinitis.
     
  19. nkm

    nkm

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    I am in Sydney, Australia. It's winter/raining here at the moment.

    Oh, I wasn't trying to say people shouldn't attempt things that may help their situation. I was only speaking on behalf of myself where I have tried many protocols and regimens and haven't improved and for me, I am hoping that optimising methylation fixes all the downstream stuff which then leads to a better quality of life.

    The exposure to the construction was about 6 years ago. I mentioned it because it makes total sense that since I had a methylation block, GSH depletion meant my body couldn't fight the pollutants and this triggered what environmental medicine doc's refer to as TILT (Trigger Induced Loss of Tolerance). So, fast forward 6 years and my allergies are very reactive, although not as bad as about 2 years ago when they were crazy. After I introduced a regimen of fulvic minerals, selenium, milk thistle, chlorella, vit D etc etc things have improved but overall, no where near "good health".
     
  20. Lotus97

    Lotus97 Senior Member

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    Make sure you don't take potassium at the same time as methylfolate. Potassium and vitamin c (especially ascorbic acid) block methylfolate absorption in the gut. If you're taking it sublingually (such as with Solgar's Metafolin) this might not be as much of an issue.
    It's the combination B12 and methylfolate. Overmethylation is more likely caused by too much methylfolate, but each additional methyl donor (methylcobalamin, TMG, SAMe, etc.) will magnify the effect. I don't know what the correct ratio is. That probably depends on the individual. Some people get benefits of B12 or methylfolate independent of methylation so whichever one you take a higher dose you'll need a lower dose of the other. Rich seemed to favor a higher B12 to methylfolate ratio. Part of it might be because methylfolate increases methylation more and he was concerned about overdriving the methylation cycle. Another reason is that b12 is normally protected by glutathione, but since we're depleted of glutathione we need higher than normal amounts of B12
    http://forums.phoenixrising.me/inde...tamin-b12-so-high-for-me-cfs-treatment.15006/
    Quatrefolic and Metafolin are two different brands of 5MTHF. According to this: http://www.methyl-life.com/methylfolate-types.html Metafolin is 1.4 times more potent than Quatrefolic so 1000 mcg Metafolin = 1400 mcg Quatrefolic (assuming the information is accurate).
    Methylation might eventually lower histamine, but several people have reported increased histamine from methylation. There are a couple threads in the methylation/detox forum about this issue.
    nkm
    You might want consider adding/increasing your dosage of R5P and P5P (the coenzymated forms of B2 and B6) before increasing your methylfolate dosage too much. Those b vitamins help you process folate so you'll be using methylfolate much more efficiently and can get the same effect with a lower dose. As with all supplements and medication (and especially methylation supplements) it's good to start at a low dose. This is from dbkita:
    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.

    I take plenty of P5p to saturate the THF to methylene intermediate conversion and plenty of R5p to saturate the methylene intermediate to 5mthf production.
     

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