If you are trying a methylation protocol why would taking L-Glutamine be discouraged? It is recommended for Leaky Gut, and lists a number of benefits but is not recommended in this thread. I don't think I actually found an answer to that. A couple people mentioned problems taking it.
Also, can you give me some insight into it and glutamate and excitotoxicity? I found a good link about it but I think I need it dumbed down a bit at the moment. Thanks
Hi, kerrilyn.
I'll take a shot at explaining this, also, for what it's worth.
First, it's a fact that glutamine is the main fuel for the enterocytes, the cells lining the small intestine. (It's also important for fueling the lymphocytes and the fibroblasts in the body.) Some PWCs report that it helps with their gut issues. Glutamine has been used in large dosages for treating gut problems independent of ME/CFS.
Other PWCs find that glutamine supplementation causes them problems. I think there are two hypotheses that have been suggested.
1. Dr. Amy Yasko has suggested that because glutamine is readily converted to glutamate in the body, it can contribute to excitotoxicity, which can be a problem for people with autism and ME/CFS, particularly when they undertake treatment of the methylation cycle partial block.
In excitotoxicity, the neurons in the brain that have so-called NMDA receptors (one of the types of glutamate receptors, named after N-methyl D-aspartate) become overactivated. The symptoms of excitotoxicity are anxiety, insomnia, a "wired" feeling, and hypersensitivity of the senses. (Actually, NMDA itself is not usually present in the body, but it has been found to be a specific stimulant for this type of glutamate receptor, so that's why the receptor is called the NMDA receptor.) Note that glutamate is the main excitatory neurotransmitter in the brain. Excitotoxicity, if uncontrolled, can cause death of neurons, so it's important to try to limit it.
Why does excitotoxicity often become worse when a person starts methylation treatment? I have a hypothesis for that. First, it's known that normally, after a neuron has exported a glutamate molecule into its junction with another neuron (called a synapse), and the glutamate has done its job by stimulating the other neuron via one of its NMDA receptors, then a neighboring astrocyte (a type of cell in the brain that helps the neurons to do their jobs) imports the glutamate, converts it to glutamine, and exports it back to the first neuron, so that it can be converted back to glutamate and used again to excite the second neuron, as needed. Now, here's the hypothesis: If the astrocyte's mitochondria cannot produce ATP fast enough to power the importation of glutamate and its conversion to glutamine, then too much glutamate will stay in the synapse, and this will keep stimulating the second neuron, producing excitotoxicity.
So, why would methylation treatment cause a problem for the mitochondria in the astrocytes? I suggest that when methylation treatment is started, more of the homocysteine is converted back to methionine, completing the methylation cycle. However, that means that initially less homocysteine will feed the transsulfuration pathway, which contributes cysteine to make glutathione. So glutathione production, already too low, will actually go lower at first, and this will worsen the oxidative stress temporarily, which will worsen the mitochondrial dysfunction. In the long run, methioniine will rise, and the sulfur metabolism will become more normally regulated, so that the glutathione level will rise, and the mitochondrial function will improve, but in the short term, the mito function gets a little worse.
Recently I have suggested that it might help to boost glutathione a little in this early stage, such as with one of the liposomal glutathione supplements, or by taking one of the nondenatured whey protein products, if they are tolerated. These include Whey to Health, True Whey, ImmunePro, and RenewPro. I haven't heard from anyone who has tried this, to find out if it actually helps with the excitotoxicity.
2. freddd has reported on this thread that he and several others have found that adding glutathione or amino acids that go into making glutathione, including glutamine or glutamate, to his protocol, which includes high dosages of methylcobalamin, causes a reversal of the benefits of the treatment, and he does not recommend adding them.
Here's what I think is going on in that situation: freddd himself has reported that he has an inborn error of metabolism (a genetic defect) involving the intracellular B12 processing enzymes. His cells are not able to use cyanocobalamin or hydroxocobalamin very well to make the coenzyme forms of B12 that the cells need (methylcobalamin and adenosylcobalamin). So he has found that by swamping his body with high dosages of the coenzyme forms via sublingual supplementation or injection, his cells can apparently get enough of these coenzyme forms directly by diffusion from the blood into the cells, so that the normal B12 metabolism is bypassed. Now, when he adds glutathione or the ingredients that help his body to make more glutathione, apparently what happens is that glutathione reacts with the methylcobalamin to form glutathionylcobalamin, and then his cells are not able to convert it back to methylcobalamin. It is known that glutathione will react readily with methylcobalamin, and it is also known that glutathione is normally involved in the B12 metabolism in the cells, at an intermediate step between the normal import of various forms of B12 and its final conversion to the two coenzyme forms. Normally, glutathione performs a protective role for B12 at this intermediate stage. In the GD-MCB hypothesis for CFS, which I've proposed, depletion of glutathione is actually the thing that allows B12 to be hijacked by reacting with toxins, and that is what brings on the partial block in the methylation cycle and ultimately, CFS itself.
But in freddd's case, and apparently in the cases of several others who have used his protocol. boosting glutathione is actually detrimental. One possible reason is the genetic issue that freddd himself has reported having. Perhaps some others on his protocol have this issue as well. But for people who do not have this genetic problem, I don't think that supplementing glutathione would be detrimental. and may be beneficial, as I've suggested above. The reason I've suggested liposomal forms as something to try is that I think they are more likely to deliver glutathione to the cells with a minimum of raising glutamate than are other approaches. Thus, I think they are more likely to help with the excitotoxicity problem, rather than to make it worse. But so far, I don't have any results as to whether this works.
I hope this is helpful. I do need to add, as always, that people doing the methylation treatment need to be working with a physician, because in a small number of cases, serious adverse effects have been reported by people trying this treatment.
Best regards,
Rich
((. Finally I take 4800mcg of folate along with my b12 shot; is that the right amount to take? Should I take the folate on an empty stomach and wait 30mins before I inject??? Any answers to any of these questions will really be helpful!!!
