Hi nanonug, the rat study showed that at higher concentrations glutathione synthesis was even higher, but only just - you are looking at percentages, but its a lower percentage of a higher amount. This to me implies there is a limit to the rate of conversion, and that any cysteine over that limit is degraded. So the problem only arises if you saturate the cysteine level. This does not say what happens in NAC. It might be all converted rapidly or not. It might be better to reach that limit or not.
The issue with pulmonary hypertension is more serious. Its definitely concerning, but we still don't have good data on humans.
With regard to the negative impact of sulphur, the bad news is that ALL forms of glutathione and glutathione boosting may lead to excess sulphur catabolism. This is an argument for dosing with sulphur based antioxidants in moderation only. In any case I do not advocate high dose NAC or glutathione in any form. Its better to take a lower dose and also support the assisting antioxidants at low doses: vitamins C & E, Lipoic acid and CoEnzyme Q10.
What I would like to see are some good studies on actylglutathione. Why is it better? Its not a product I have done much research on.
With regard to lipsomal glutathione, its glutathione encapsulated in a lipid layer for easy absorption without being degraded by stomach enzymes. Its great for boosting serum glutathione levels. I do not use it, but those who have talked about it to me have said they can feel the difference.
I still think though that many of these problems may relate to the methylation cycle. While I appreciate the long years of research into polymorphisms associated with this, I am beginning to think this is only the tip of the iceberg. There is a thread on here that talks about accumulation of unmetabolized folic acid, and this is immunosuppressive. 78% of post menopausal women have this problem, I do not think the figure is known for other groups:
http://forums.phoenixrising.me/showthread.php?1148-Folic-Acid-Are-you-taking-it-New-Study
Here is the relevant bit: "It is perhaps not surprising that Troen et al (16) detected unmetabolized folic acid in fasting plasma samples from 78% of the subjects in their study."
Competitive inhibition from unmetabolized folic acid might have an impact on any enzyme it has an affinity for, displacing methyl folate. This will create a masked methyl folate deficiency, as standard folate tests will not show a problem. The first thing everyone needs to do to boost glutathione status is avoid folic acid (but not folinic and methyl folate). Its in multivitamins and B complex, but not every brand. Its also fortified in nearly all grain products, from bread to breakfast cereals and white rice. I do wonder if some of us feel better avoiding these products because of the synthetic folate and not other issues like gluten. I also note that the end of the epidemics of ME roughly correspond with the rise of folic acid supplementation. Is there a link? I don't know but its a good question. Its possible that folic acid pushes people over the edge into ME early if they are susceptible, so that epidemics cannot arise - too many get it sporadically. I don't know that this is true, but its something I am thinking about.
This is the paper that got my attention:
http://jn.nutrition.org/content/136/1/189.full
Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women
If it can suppress NK cell function its something we do not want, even if it not actually causal in CFS or ME.
Bye, Alex