![]() ![]() Your average human cell is using glucose for fuel, but the cell has as much glutathione as glucose in the cytoplasm. Glutathione’s importance is underscored by its large concentrations in every cell in the body. Low ratios GSH:GSSG ratios can send a cell down a senescence pathway, terminating in apoptosis. A healthy cell has GSH:GSSG in the ratio 100 to 1, but a severely stressed sell can have more GSSG than GSH. If the ratio becomes too low, the cell turns on NFkB, which, in turn, initiates an inflammation cascade. Cells sense the ratio of GSH to GSSG to determine if they are in trouble. Another supplement, Alpha Lipoic Acid (ALA) is also helpful in recycling GSSG back to its useful form, GSH. GSSG is just two molecules of glutathione that are linked together by a disulfide bond, and a more complex protein called glutathione reductase comes along to separate the two molecules, recharging the battery. Its reduced form (GSH) is available to detoxify H 2O 2, after which it exists as an oxidized form (GSSG), which must be “recharged”. Glutathione acts like a rechargeable battery. (Also catalase.) Unlike catalase, glutathione can perform diverse other detoxifying roles as well. The last stage is always H 2O 2, which must be neutralized to water. There are various toxic waste products (ROS), and various pathways for reducing them. The energy metabolism has waste products which must be neutralized so they don’t latch on to delicate organic molecules and damage them. Our metabolisms (like all eukaryotes) use REDOX reactions to store and deploy energy, because they are far more energy-dense than the covalent chemistry of organic molecules. Glutathione is a tripeptide, a mini-protein consisting of the 3 amino acids glutamate, cysteine, and glycine. The best promise of NAC (through glutathione) is in preserving our mitochondria, which weaken and reduce in number as we age. Supplementing with N-Acetyl Cysteine (NAC) is the commonly-recommended strategy for raising glutathione levels, and it seems to work. I continue to believe that glutathione promotes health, despite its close association with H 2O 2. One anti-oxidant that survived the massacre was glutathione. Aging of animals turns out to be more complicated than rusting of iron, and part of the complication is hormesis, and ROS (Reactive Oxygen Species), particularly H 2O 2, are part of the signaling cascade that turns on hormetic protections. Trials of anti-aging supplements failed time and again, and often they led to shorter lifespans of test animals. In the 1980s and 1990s, the oxidative theory of aging reached its pinnacle, and anti-oxidant supplements were all the rage. I’m taking this opportunity to review the literature. It’s been such a gradual process, that I don’t remember the reasons that installed NAC in my subconscious as a reliable life extension aid. I notice that now N-Acetyl Cysteine has become my favorite supplement, the one I reach for 3 or 4 times a day when I pass the kitchen cabinet. Long before NAC saved the life of someone dear to me, it was a staple of my supplement stack. ![]()
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