posted
I can't tolerate even some of the supplements or even slivers of them, made me feel like I was on speed.
I found this on another site, author rich vank describes what the problem may be and how to help. Thought someone might find the info useful:
Quite a few PWCs have reported experiencing anxiety, a "wired" feeling, insomnia, hypersensitivity of the senses, and in some cases an elevated heart rate, especially when starting the methylation-type treatments. This is thought to be due to excitotoxicity, which means that neurons that incorporate the NMDA glutamate receptor are firing nerve impulses too rapidly because of an elevated ratio of glutamate to GABA. Glutamate is the main excitatory neurotransmitter in the brain, while GABA is the main inhibitory neurotransmitter. Glutamate can be converted into GABA by a reaction that requires vitamin B6.
Normally, the astrocytes, which are "helper" cells in the brain, are in charge of importing glutamate from the synaptic clefts (the little gaps between neurons through which the neurotransmitters convey signals from one neuron to the next) and converting it to glutamine. Then they pass the glutamine back to the neurons, so that they can use it again to make glutamate to send more signals. This is a recycling loop, and it normally keeps glutamate from going too high in the synaptic clefts.
The conversion of glutamate to glutamine by the astrocytes requires energy in the form of ATP, which is produced by the mitochondria. The mitochondria are somewhat dysfunctional in ME/CFS because of glutathione depletion and the partial methylation cycle block.
O.K., now here's why I think the excitotoxicity can worsen when methylation treatment is undertaken:
This treatment raises the activity of the enzyme methionine synthase, which is partially blocked in ME/CFS. When that happens, more of the homocysteine is converted to methionine, closing the methylation cycle. However, that means that less homocysteine enters the transsulfuration pathway, which produces cysteine, the rate-limiting amino acid for the synthesis of glutathione. So the production of glutathione goes down initially, making the glutathione depletion more severe at first. This makes the mitochondria more dysfunctional at first, lowering the ATP production. This raises the glutamate level in the synaptic clefts, and that worsens the excitotoxicity, initially. Eventually, this problem is remedied as the methylation cycle and the rest of the sulfur metabolism is restored to normal, and the mitochondria begin to function better.
So what can be done about this in the meantime? There are several things that can be tried:
1. The dosages of the supplements can be lowered. Particularly important are B12 and the folates, which stimulate methionine synthase.
2. The diet can be adjusted to lower the intake of glutamate. Things like MSG and hydrolyzed protein are especially high in glutamate, but many other foods have a lot of it, too. In her book, Dr. Amy Yasko has presented lists of these foods.
3. Additional supplements can be taken that tend to calm the NMDA neurons. Dr. Yasko has presented lists of them in her materials. They include GABA, magnesium, taurine, Valerian, topical progesterone, theanine, and others.
4. The B6 intake can be increased. B6 is needed by the transsulfuration pathway enzymes, and also for the conversion of glutamate to GABA;, as noted above.
5. Recently I suggested that it might help to build glutathione directly at first, while doing methylation treatment, using one of the liposomal glutathione products. This might counter the initial drop in glutathione that I have described above. I have not heard from anyone who has tried this, so I don't know how well it will work.
I hope this helps. This is one of the most difficult parts to doing this treatment, and Dr.Yasko devotes considerable attention to it in her books. It is an important issue, both because it is very unpleasant and hinders the use of these types of treatments, which are ultimately very helpful to most PWCs, but also because severe neurotoxicity can damage neurons. This is the same issue that has led Dr. Cheney to prescribe Klonopin for PWCs for many years. This lowers excitotoxicity, but some people report that it is very difficult to get off it later.
Posts: 857 | From northern california | Registered: Dec 2009
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Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
Pardon my ignorance, but do KPU disorders involve disruptions in the methylation cycle as well? Are there diffrent disruptions for different disorders?
Posts: 357 | From California | Registered: Jun 2010
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D Bergy
Frequent Contributor (1K+ posts)
Member # 9984
posted
Hydrolyzed protein is MSG and is one of the main ingredients of Bouillon.
I cannot tolerate Bouillon and I do not even have Lyme.
Dan
Posts: 2919 | From Minnesota | Registered: Aug 2006
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lymetwister
Frequent Contributor (1K+ posts)
Member # 19590
posted
The Key is to titrate up on B Vitamins if they are causing problems. I did this and now have no problems like you describe.
To do this, you need to mix your B12 in water and take a few drops throughout the day.
It takes a few weeks to get it down, but soon you will find taking a sublingual B12 is nothing and you will be able to get your levels up.
Hope that helps..
Posts: 1227 | From District of Columbia | Registered: Mar 2009
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quote:Originally posted by mattnapa: Pardon my ignorance, but do KPU disorders involve disruptions in the methylation cycle as well? Are there diffrent disruptions for different disorders?
Yes, it does.
I have KPU and I had a disrupted methylation cycle. Dr. K says you can't lift the methylation block without treating KPU, but I found this false.
I lifted my methylation block, and the difference is night and day. Literally. I no longer feel the need to take B12, Folate, P5P, etc as before my body just craved each and every dose. Oh, and believe me, you have no idea what detoxing means if you don't lift your methylation block! However, there aren't too many with experiences as profound as mine with this protocol.
Posts: 967 | From A deserted island without internet access | Registered: Sep 2009
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Razzle
Frequent Contributor (1K+ posts)
Member # 30398
posted
It may depend on where in the methylation cycle one's block(s) is/are... I have multiple variants and am going nuts trying to figure out what to do to fix them...conflicting info was provided with my test results, and noone where I am has been able to make heads or tails out of it either...too complicated!
-------------------- -Razzle Lyme IgM IGeneX Pos. 18+++, 23-25+, 30++, 31+, 34++, 39 IND, 83-93 IND; IgG IGeneX Neg. 30+, 39 IND; Mayo/CDC Pos. IgM 23+, 39+; IgG Mayo/CDC Neg. band 41+; Bart. (clinical dx; Fry Labs neg. for all coinfections), sx >30 yrs. Posts: 4166 | From WA | Registered: Feb 2011
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Dawn in VA
Frequent Contributor (1K+ posts)
Member # 9693
posted
Agreed with everything ya posted, dogmom. I know several folks (including myself) that have experience difficulty when addressing the methylation cycle, esp at the beginning.
As for glut. supplementation, you may want to consider glut. transdermal lotion as well. I just started using it about 2 month ago and apply it just before bed. You can get it from a compounding pharm. with an Rx, but I've been purchasing ready-made Kirkman's brand from my local one and like it so far.
-------------------- (The ole disclaimer: I'm not a doctor.) Posts: 1349 | From VA | Registered: Jul 2006
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