Hi Rich
I must try your methylation cycle protocol again, doing it more carefully. It is a very intriguing theory. I did try this methylation protocol a few times a while ago, but I was so chaotic at that time - trying loads of protocols simultaneously - that I never really knew what benefits were caused by what. I see that you have a
great list describing different approaches to supplementing with glutathione.
Can I ask some questions on your methylation protocol, about the use of glutathione? I read that the half-life of glutathione is pretty short (can't find any exact figures, but I am guessing that short must mean around a few hours); does this mean that you would really need to take glutathione supplements every couple of hours or so, for best effect, to maintain good glutathione levels in the blood?
Also, if I understand right, it is intracellular glutathione levels that must ultimately be raised. Whey and N-acetyl-cysteine supps I read can help boost intracellular glutathione; but what is the relationship between glutathione in the blood (derived from direct glutathione supplementation), and the levels inside the cells?
Thanks very much.
Hi, Hip.
From 1999 until about late 2004, I encouraged PWCs to attempt to boost their glutathione levels directly by a variety of methods. This provided temporary help to quite a few people, but the results were not permanent for most. Then, in late 2004, I learned of the work by Jill James et al. in autism, in which they found that the glutathione depletion in autism is linked to a partial block in the methylation cycle, which lies upstream. They found that if they treated to lift this block, the glutathione level automatically rose, without directly supporting it. Having studied the biochemical abnormalities in CFS for several years at that point, I immediately saw the similarities between the biochemistry of autism and that of CFS. It was one of those rare "AHA!" moments for me. At that point I began to suspect that the treatments being used in autism would also work for CFS, and I started looking into the DAN! treatments and later, those of Dr. Amy Yasko. I encouraged PWCs to try them, and they seemed to help.
The version of the glutathione augmentation list that you cited was actually written shortly after I had this realization. At that time, I was not yet sure how many PWCs had a partial methylation cycle block and would need to lift it, vs. how many could simply augment glutathione.
As we got more experience, it became clear that the partial methylation cycle block is found in nearly all PWCs, and seems to be the key aspect of the biochemistry, from which everything else in CFS results. So I began to focus my efforts on encouraging PWCs to treat the partial methylation cycle block, rather than attempting to boost glutathione directly.
If you read the other papers, articles and talks at
www.cfsresearch.org, you will see how my thinking developed over time, in response to what I learned from the experiences of many PWCs, as well as more study of the biochemistry. In early 2007 I proposed the GD-MCB hypothesis, and shortly after that, the socalled "Simplified Treatment Approach," which is based on it. This treatment produced good results in many who tried it, and eventually Dr. Neil Nathan was willing to do a clinical study of it in his practice, which we reported in 2009 (see the website cited above). While there was no control group in this study, the results were nevertheless very encouraging, and over time the use of this protocol has been growing. There are also several other protocols now that address the methylation cycle block. They all have in common the combination of high-dose forms of B12 and RDA-level dosages of folates, usually the chemically reduced forms, folinic acid or 5-methyl tetrahydrofolate, or both.
At this point, I don't believe that the glutathione level will stay up in many of the body's affected organs, tissues and cells in CFS unless the partial methylation cycle block is lifted. Nondenatured whey protein and NAC will indeed help the liver to make glutathione, but it will not correct the partial methylation cycle block in these parts of the body.
When glutathione is put directly into the blood, such as by IV administration, about 80% of it is taken out by the kidneys in a few minutes to an hour or so, depending on the dosage given. The kidneys break it down, reform some glutathione, and export some cysteine to the blood. About 10% is used by the lungs. The other 10% goes to a variety of other cells.
There is some temporary benefit from this, but in CFS, if the partial methylation cycle block is not lifted, the glutathione levels will soon drop back down again.
For the past four years, I have focused on lifting the methylation cycle block, and have not been recommending glutathione boosting. This has been significantly helpful for about two-thirds of those who have tried it. However, the treatment can be unpleasant. I think that part of this is due to restart of the detoxication system, which mobilizes toxins and produces detox symptoms. But there also seems to be an increase in excitotoxicity symptoms in many who do this treatment (anxiety, insomnia, a "wired" feeling, hypersensitivity of the senses). I have begun to suspect that this may be due to a temporary additional lowering of the glutathione levels in the astrocytes in the brain when this treatment is begun, the reasoning being that the treatment will divert more homocysteine toward reforming methioninine, rather than going toward feeding synthesis of glutathione. So recently I have suggested that if people have excitotoxicity symptoms on this treatment, they might consider adding some measures to support glutathione. The liposomal glutathione supplements would be one possibility. For those who can tolerate nondenatured whey protein (Whey to Health, True Whey, ImmunoPro, or RenewPro), that might help, also. I recommend caution with using NAC if there could be a significant body burden of mercury, because NAC can move it into the brain.
I hope this is helpful.
Best regards,
Rich