Richvank - Anxiety from Methylation Protocol

Discussion in 'Fibromyalgia Main Forum' started by equanimous, Jan 10, 2011.

  1. equanimous

    equanimous New Member

    So I'm finding that the methylation protocol supplements are making me sort of anxious and wired and my heart's racing all the time, but if I try to stop them, I feel a lot more sick (brain fog comes back and whatnot). Does anyone (Rich in particular) have any suggestions? I'm so miserable.

  2. richvank

    richvank New Member

    Hi, equanimous.

    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.

    Best regards,

  3. equanimous

    equanimous New Member

    Thank you so so so so so much for all this information. I did some research on the Yasko forum, but having all of this comprehensive info in one coherent explanation is really helpful. I'm planning on trying to lower some of the supplement dosages while, at the same time, add in liposomal glutathione, vitamin b6 and GABA (one at a time, of course - gotta keep it scientific). I guess I'm just super dubious about liposomal glutathione because everything I've ever heard about glutathione is that it can't be effectively absorbed when administered orally. Are there studies demonstrating the efficacy of liposomal glutathione in raising glutathione levels? I somehow feel like I'm just swallowing snake oil, but I'd like to be disproven.

    Also, when you say that you have not heard of anyone building glutathione during methylation treatment, do you mean specifically with liposomal glutathione or with any type of administration? If the former, have people had success treating the exotoxicity using other methods of increasing glutathione?

    Thanks again,