oxidative stress in cfs/me seems to be a common abnormality and the methylation protocols seem to be popular at trying to raise glutathione, our bodies main antioxidant with methyl b12 and methyl folate. What i wont to know is what role to other antioxidants play, specifically q10, al-carnitine, vit e and c and NAC(although seems debatable with folate absorption. But i would think using these other antioxidants would help reduce the need for glutathione raising supps or enhance these methyl supps.
I have been taking these supps for quite sometime and cant say i have noticed any real improvement in cfs symptoms but maybe they are helping me to hold my current level of function as well has having other positive effects on our health. I mainly take these supps as they have quite good science to back them up. In reality the only things i have found to have a noticable effect on cfs symptoms are sleep meds, av's and immmune modulator cycloferron. All these treatments add up financially and im looking at trying to save money and use these that give the best bang for my buck.
I would be interested to know others opinions on this.
cheers!!!
Hi, heapsreal.
I'll offer some comments based on the biochemistry.
Of the antioxidants, some are essential nutrients and must be obtained from the diet, and others can be made in the body from other essential nutrients. Vitamins C and E are essential nutrients. beta-carotene also comes from the diet. The others can normally be made in the body. Coenzyme Q10 and carnitine (which is not an antioxidant but is needed for ushering fatty acids into the mitochondria to be burned) require methylation for their synthesis in the body.
In addition to having the initial antioxidant molecules present, it is also necessary to be able to recycle some of them after they are oxidized as a result of quenching oxidizing free radicals or other reactive oxygen species, so that they can be used over again.
According to the work of Prof. Lester Packer, five of the antioxidants participate in an "antioxidant network." This network operates sort of like a "bucket brigade" for electrons. One antioxidant regenerates another by passing an electron to it, and thus chemically reducing it. This all has to start somewhere, and the source of the electrons is the metabolism of foods (oxidation, which involves removing electrons). So three of the antioxidants are able to get electrons directly from the metabolism, and the others can be regenerated by those that have this access. Glutathione gets its electrons from NADPH, which is generated as part of the pentose phosphate shunt on the glycolysis pathway, so the electrons come originally from burning glucose. Lipoic acid and coenzyme Q10 are also coupled to the metabolism, lipoic acid in the pyruvate dehydrogenase complex that lies between glycolysis and the Krebs cycle, and coenzyme Q10 in the respiratory chain that receives electrons from the Krebs cycle via NADH and FADH2.
So these are three of the antioxidants in the network, and the other two are vitamins C and E. Vitamin C is normally regenerated by glutathione, and vitamin E by vitamin C. There are other regenerating interactions between these various antioxidants also, but those are the main ones.
Beyond these, the other antioxidants are not part of the network, and are not recycled. They are "once-through" antioxidants. The carotenes are an example. Others are things that might be in the diet or supplements, such as citrus bioflavonoids, grape-leaf extract, pycnogenol, ingredients in green tea, and others.
Taking additional antioxidants can help, but it is important to note these interrelationships, because, for example, when glutathione is depleted, it is possible to worsen this situation by taking intermediate-level dosages of vitamin C, which uses glutathione to regenerate itself. The late Dr. Robert Cathcart found that if very large dosages of vitamin C are taken ("bowel tolerance" dosages), it is possible to reverse the "bucket brigade" with respect to the vitamin C--glutathione couple, so that vitamin C will regenerate glutathione. He personally survived on this reaction for many years, apparently because his body was not able to regenerate glutathione normally, perhaps for genetic reasons, though it was not determined.
Taking a lot of one antioxidant by itself can end up having a pro-oxidant effect, instead of an antioxidant effect, because there is not enough support from the others in the "bucket brigade." So keeping them balanced is important.
One way to help with the oxidative stress without incurring problems with this network getting out of balance is to take a lot of a "once-through" antioxidant. Some people have found grape leaf extract to be a good one
NAC is used to supply cysteine, which is usually the rate-limiting amino acid for making glutathione. Some people do not respond well to taking NAC, even in small dosages. Freddd has discussed this on these forums. The other caveat with NAC is that if there is a high body burden of mercury, it is wise not to take more than about 300 mg of NAC per day, according to Dr. David Quig of Doctors Data Lab, because it has been found by Aposhian et al. to be able to move mercury into the brain. Dr. Cheney has reported on two PWCs who took large dosages of NAC and ended up committing suicide, presumably because of depression caused by mercury entering the brain. Even without the mercury, dosages of NAC higher than about a gram per day can potentially cause oxidative stress to increase, according to Dr. Michael Murray.
Best regards,
Rich
