I agree that NAC is a fine glutathione booster but (you made the point before I did lol) it has poor bioavailability and is usually underdosed in commercial supps, which makes the situation worse.
I buy it in powder form by the kilogram for $43.99. I don't take the capsules and it's not mixed in with any other supplements, pure NAC pharm-grade powder.
Even with the poor bioavailability though, it still serves as a reliable method of raising glutathione levels. There's studies showing it doing so both in in vitro and in vivo. A study was performed on people with acute respiratory diseases and it helped being up glutathione levels for them. It is probably the most often used compound to treat acetaminophen OD by medical professionals, it helps treat non-alcoholic fatty liver disease, it can positively influence the activity of inflammatory cells in the bronchoalveolar space of smokers and counteracts the cigarette-smoking-induced decline in the proportion of alveolar lymphocytes and the decreased phagocytic capacity and ability to produce leukotriene B4 of alveolar macrophages in smoker, helps avoid influenza and influenza-like symptoms, new research is underway regarding its recipient shown benefits of improving insulin resistance, and much more. Most of these benefits are shown with 1200-2400mg doses except the acetaminophen OD which requires a lot more. My 1kg bag at these doses easily lasts me over a year and I can reap all these benefits. I've not studied TUDCA much but does it just aid the liver or does it do more?
This is purely hypothetical now but if I was to include orals in a cycle, was aware that they are hepatotoxic and wanted to take precautions. I'd think about the 3 main ways liver damage can be prevented:
1) Metabolic induction of hydrophobic bile acid detoxification
Liver damage is caused by toxic bile acid accumulation so you want to hasten the metabolic conversion of the more toxic bile acids to hydrophilic (less toxic) compounds, or increase the synthesis of hydrophilic bile acids from cholesterol, which would decrease the toxicity of the entire bile pool.
This can be achieved with ursodeoxycholic acid (UDCA), which has been reported to activate bile acid metabolizing enzymes.
I believe NAC has been shown to help reduce BA levels through the following pathway:
"clk-1 mutants are suppressed by mutations of TAT-2, the worm orthologue of an ATPase that is necessary for BA secretion in mammal."
NAC has been shown to prevent TAT-2 mutations.
2) Stimulation of impaired bile secretion
Bile secretion is carried out by transporter proteins: The bile salt export pump (BSEP), the phospholipid export pump (MDR3), the canalicular bilirubin conjugate export pump (MRP2) and a chloride-bicarbonate anion exchanger (AE2).
BSEP is the driving factor behind bile acid secretion, and MRP2/AE2 are the major forces behind bile-acid-independent secretion.
UDCA (and cholic acid) have been shown to activate BSEP by binding to the bile acid receptor, phosphorylate the BSEP protein and increase AE2 levels.
Basically all of this means UDCA and cholic acid enhance secretion of toxic bile acids.
NAC, through one of its metabolites, has been shown also to activate BSEP, MRP2, and AE2 but not sure about MDR3
3) Protection of hepatocytes from the toxic effects of hydrophobic bile acids
Certain toxic bile salts activate the Fas Death Receptor on hepatocytes and ultimately leads to cell death.
UDCA and certain other compounds can diminish induced apoptosis, but I'm not sure on the exact mechanism on this.
NAC also diminishes induced apoptosis due to Fas-induced liver injury. The mechanism of action is by the metabolite glutathione (GSH). GSH synthesis is required for apoptosis protection bc it regulates redox reactions in hepatocytes. NAC treatment significantly reduces Jo2-mediated cell death in Met-deficient cells (Met-KO) by desensitizing Met-KO cells to Jo2-induced apoptosis. "The Number of cells undergoing apoptosis on NAC dropped 4-fold".
"In conclusion, genetic inactivation of c-Met in mouse primary hepatocytes disrupts redox homeostasis that in turn initiates a series of adaptive cellular responses through modulation of NF-***954;B-dependent survival pathway. The findings provide a mechanistic explanation for the high susceptibility of c-Met-deleted cells to Fas-mediated apoptosis and present evidence that intact c-Met signaling is a critical factor in the protection against excessive generation of endogenous ROS."
I'm not positive TUDCA acts through the same pathway (is it a glutathione/GSH precursor or raise levels of GSH?) as NAC does for Fas-induced apoptosis but I would assume it does or does so pretty closely.
Summary:
If I was going to include orals on a cycle I would definetly supplement with UDCA (regardless of price - its your liver bro!).
There are other supplements good for liver health like milk thistle but, as far as I'm aware, they provide weak protection.
I might of missed some points on liver damage so any correction is welcome
I believe TUDCA and NAC do very similar things in regards to liver protection and detoxification. To be quite frank, Im not sure which one works better just that they both work. Im not sure of effective doses for TUDCA but as mentioned, an effective dose of NAC for liver protection can vary from 1200-2400mg for most preventative and acute toxicity but I think it requires much higher dosages for acetaminophen OD and chronic toxicity.
I'm not sold on milk thistle for the liver. I see it more as one of those supplement company marketing gimmicks.
As to the price point, if they both do similar things for the liver why not choose the cheaper one that has a host of other benefits as well? Again I'm assuming (probably incorrectly) that TUDCA just helps the liver bc I just don't know much about it.
