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No Longer Naive in the Ways of The Beast
After having lived for years with ME/CFS, Jody Smith learned there's more to this beast of an illness than she realized, and that what might help one person may not help others ...
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  1. alwayshopeful

    alwayshopeful

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    I have just started the B12 Methylation Protocol and I can't sleep!! I am starting low and slow, so every 3rd day was taking mb12 injection of .15ml and Metafolin 100 mcg, plus some potassium supplements. One of these gives me total insomnia, as in I don't sleep the whole night even having taken sleep aides!! It only happens on those days and that is the only things I am doing different on those days. So has anyone else had this problem and do you know which supplement is causing it?
  2. richvank

    richvank Senior Member

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    Hi, alwayshopeful.

    I believe that it is the combination of mb12 and Metafolin. These two together will raise the activity of methionine synthase, which is the enzyme that is partially blocked in ME/CFS. The result of this is that more of the homocysteine will be converted back to methionine, and therefore less will be available to enter the transsulfuration pathway to make cysteine, which is usually the rate-limiting amino acid for making glutathione. So glutathione will initially decrease even further.

    When this happens in the astrocytes of the brain, their mitochondria are not able to make ATP at as high a rate as before. That robs the glutamate pumps, which normally remove glutamate from the synapses of the neurons. Glutamate is the main excitatory neurotransmitter in the brain, and when more of it remains in the synapses, it overexcites the NMDA receptors on the following neurons, and that leads to excitotoxicity. One of the symptoms of excitotoxicity is insomnia. Others are anxiety, nervousness, a ''wired" feeling, and hypersensitivity of the senses.

    What can be done about this? One approach is to try to support glutathione, such as by adding liposomal glutathione or acetylglutathione. Some people find that this helps, and others do not. Another approach is to take supplements that counter the NMDA excitotoxicity. Some possibilities are GABA, theanine, magnesium, taurine (if it isn't already high), grape seed extract, pycnogenol, and progesterone cream. Over time, as the methylation cycle recovers, so will glutathione. It may help to add some methionine while doing this treatment, if it is low, as that will help the methylation cycle to recover faster.

    Best regards,

    Rich
    RustyJ, SickOfSickness and mezombie like this.
  3. triffid113

    triffid113 Day of the Square Peg

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    Very enlghtening and very thorough. I would particularly choose the magnesium if the problem is NMDA, and I would not eat high protein because the breakdown product of protein is ammonia, which strips magnesium from the NMDA receptors if you do not have enough magnesium, as magnesium is needed to excrete it. Estrogen has been proven to protect the NMDA receptors fom excitotoxicity, and I make it from DHEA, so I would add DHEA to the list. I have NO excitotoxicity issues (but I used to during PMS before I started DHEA).

    Your explanation indicates the problem occurs much higher up and it is interesting to see all the other possibilities for fixing it. The NMDA problem is at the bottom of the cascade, but it is quite severe (it used to feel life-threatening to me) so I just wanted to add that DHEA/estrogen can really save you on that.

    Trif
  4. alex3619

    alex3619 Senior Member

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    I would like to make an additional suggestion to the idea of taking liposomal glutathione. Not all tissues can absorb glutathione. NAC (N-acetyl cysteine) is highly absorbed by most tissues so far as I am aware. To reach all tissues you either need to fix synthesis (which is one aim of the methylation protocol) or NAC. Liposomal glutathione will help many tissues, particularly the liver, but not all.

    I am insufficiently aware of the tissue distribution of acetylglutathione to comment. It is possible it might be distributed as effectively as NAC.

    Bye, Alex
  5. nanonug

    nanonug Senior Member

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    Just a quick note regarding the conversion of NAC to glutathione.

    I've see a study, and Yasko also talks about this, that elevated levels of cysteine lead to reduced levels of glutathione due to some kind of negative feedback loop. As such, liberally supplementing with NAC might be counterproductive.

    See "Methionine and Methylation: Chicken or the Egg", page 26, inside the light blue box.

    Based on this, I completely ditched NAC in favor of acetyl-glutathione.

    Also, NAC may lead to pulmonary arterial hypertension.
  6. Adster

    Adster Senior Member

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    This study re b12 and lower melatonin levels is interesting http://www.ncbi.nlm.nih.gov/pubmed/1516676

  7. triffid113

    triffid113 Day of the Square Peg

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    Alex, what is liposomal glutathione? Who makes it, where do you buy it? If you have never been tested for GSH levels, do you know if there is any problem taking it if u don't need it? You are a font of unusual knowledge...

    Trif
  8. Valentijn

    Valentijn Activity Level: 3

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    There were a few studies I looked at involving NAC supplementation and glutathione levels. For people with HIV that had low glutathione, supplementing with a high dose of NAC resulted in glutathione levels being raised.

    And I don't seem to have any problems with hypertension even after being on 1800mg/day NAC for 6 months - quite the opposite actually.
  9. justy

    justy Senior Member

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    Hi, so sorry to hear you are having these problems. I only take the mb12 injections, without metafolin and i had excitotoxicity symptoms from that. I was prescribed 0.1ml a day which was 500mcg b12 - i halved it to 0.05ml a day = 250mcg and did this every other day. You do not say how many mcg per ml there is in your injections - do you know the exact dosage? have you tried just the b12 at first before adding the metafolin. You could even consider halving you dose again. I got around the excitotoxicity by lowering my dose until it wasnt a problem and then staying at that level for some weeks before gradually increasing. This approach does seem tpo work and you can move to a higher dose more comfortably.
    All the best, Justy.
  10. alex3619

    alex3619 Senior Member

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    Hi nanonug, the rat study showed that at higher concentrations glutathione synthesis was even higher, but only just - you are looking at percentages, but its a lower percentage of a higher amount. This to me implies there is a limit to the rate of conversion, and that any cysteine over that limit is degraded. So the problem only arises if you saturate the cysteine level. This does not say what happens in NAC. It might be all converted rapidly or not. It might be better to reach that limit or not.

    The issue with pulmonary hypertension is more serious. Its definitely concerning, but we still don't have good data on humans.

    With regard to the negative impact of sulphur, the bad news is that ALL forms of glutathione and glutathione boosting may lead to excess sulphur catabolism. This is an argument for dosing with sulphur based antioxidants in moderation only. In any case I do not advocate high dose NAC or glutathione in any form. Its better to take a lower dose and also support the assisting antioxidants at low doses: vitamins C & E, Lipoic acid and CoEnzyme Q10.

    What I would like to see are some good studies on actylglutathione. Why is it better? Its not a product I have done much research on.

    With regard to lipsomal glutathione, its glutathione encapsulated in a lipid layer for easy absorption without being degraded by stomach enzymes. Its great for boosting serum glutathione levels. I do not use it, but those who have talked about it to me have said they can feel the difference.

    I still think though that many of these problems may relate to the methylation cycle. While I appreciate the long years of research into polymorphisms associated with this, I am beginning to think this is only the tip of the iceberg. There is a thread on here that talks about accumulation of unmetabolized folic acid, and this is immunosuppressive. 78% of post menopausal women have this problem, I do not think the figure is known for other groups:

    http://forums.phoenixrising.me/showthread.php?1148-Folic-Acid-Are-you-taking-it-New-Study

    Here is the relevant bit: "It is perhaps not surprising that Troen et al (16) detected unmetabolized folic acid in fasting plasma samples from 78% of the subjects in their study."

    Competitive inhibition from unmetabolized folic acid might have an impact on any enzyme it has an affinity for, displacing methyl folate. This will create a masked methyl folate deficiency, as standard folate tests will not show a problem. The first thing everyone needs to do to boost glutathione status is avoid folic acid (but not folinic and methyl folate). Its in multivitamins and B complex, but not every brand. Its also fortified in nearly all grain products, from bread to breakfast cereals and white rice. I do wonder if some of us feel better avoiding these products because of the synthetic folate and not other issues like gluten. I also note that the end of the epidemics of ME roughly correspond with the rise of folic acid supplementation. Is there a link? I don't know but its a good question. Its possible that folic acid pushes people over the edge into ME early if they are susceptible, so that epidemics cannot arise - too many get it sporadically. I don't know that this is true, but its something I am thinking about.

    This is the paper that got my attention: http://jn.nutrition.org/content/136/1/189.full
    Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women

    If it can suppress NK cell function its something we do not want, even if it not actually causal in CFS or ME.
    Bye, Alex

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