You’re right. It was overkill. The patient had failed treatment twice so this was our last chance and we had to make it count.
We thought SAMe dosing would be critical because if you give huge doses of something that oxidises, during a situation of high oxidative stress, it could become pro-oxidant and under normal circumstances it would be recycled.. So I contacted Dr Paul Steir who I’d worked with in the past. He did some of the first SAMe studies at UCLA. He said….
“I had the idea of doing a pilot study with HCV and SAMe to see if shifting the transmethylation pathway towards producing glutethion would have a positive impact on liver repair and the ability to limit tissue damage from the virus, but I never really got it off the ground.”
We chose 1600mg because that’s the dose used in one small study we found. Next we asked George who I had just discovered at a forum that had given him his own section to keep him out of the way because nobody understood him and he said…..
“SAMe is just the active form of methionine. But methionine cannot convert to cysteine (hence glutathione) without going through SAMe. Roughly 50% of methionine goes into SAMe (the rest into protein). folic acid and B12 or betaine recycle methionine/SAMe, while B6 converts to cysteine. NAC is the best way to elevate cysteine directly. Now, glycine is a byproduct of the methylation of folic acid/folate (same thing); so a healthy methylation cycle using folate-B12 (rather than betaine) should supply all the glycine you need. But glycine is a common amino acid in any case, as is glutamate/glutamic acid (same thing); cysteine is the rate-limiting one because it is rare.
The other way to elevate glutathione is to recycle it directly, either enzymatically (B2, selenium, niacinamide) or with some special antioxidants – ALA, OPCs, astaxanthin, melatonin. Another way is to spare it by quenching free radicals before they oxidise PUFAs – vitamin E and OPCs will do this; vitamin E at doses of at least 800iu, Grape Seed Extract at 200-600mg daily in 2-3 doses. But don’t take GSE with riibavirin as it can theoretically interfere with absorption in gut (leave a 2-3 hour gap). The beauty of OPCs/GSE is that it definitely recycles vitamin C, very noticably reducing the requirement. All antioxidants help methylation, because B12 is easily oxidized and oxidative stress is a major interference with the methylation cycle.
One additional vitamin I would consider using is niacinamide (not niacin). Firstly, recycling glutathione depends on NADH and supplementing niacinamide is one way of elevating glutathione. It is hepatoprotective for this reason (but because B3 is a methyl acceptor, it is not safe for people with very poor methylation- it may then compete with choline synthesis, elevating AST/ALT. But this only happens to 1.8% of people supplementing high-dose B3 without other supplements or dietary changes. In thousands of patients supplementing high-dose B3 as part of a multi-supplement regime including methylation factors there has never ben a case of elevated enzymes.
But the main reason to supplement niacinamide with interferon has to do with the way that interferon degrades tryptophan to try to make extra NAD(H). This pathway is wasteful of tryptophan (it takes 60mg tryptophan to make 1mg b3) and results in the depression caused by interferon, as well as diarrhea and skin problems. Supplementing 1.5g niacinamide daily elevated tryptophan by 40% in HIV patients, one of many groups suffering the same tryptophan catabolism that interferon causes. If B6 is deficient the tryptophan-B3 pathway becomes a black hole. I have supplemented 2g niacinamide daily for 3 months now without problems, I sleep well, feel “healthy” and my moods are more stable than ever. SAMe makes me anxious and methionine can make me hypomanic, there is a fine balance between methyl donors and methyl acceptors – methyl donors synthesis adrenaline and dopamine, if there are inadequate methyl acceptors (mainly B3 but also B1) the synthesis of stimulant neurotransmitters can be excessive – especially if tryptophan is being catabolised, because serotonin should be in balance with dopamine.
Look up zinc and interferon – zinc definitely increases SVR.
I will get back to you later with more on this. You seem to be on the right track.”
George is a musician. He has no medical background. So we became a team. I mean who needs a medical background when you have wild theories, right?
PP
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