Liposomal Glutathione

Phospholipid-encapsulated GSH does fix the GI bioavailability problem of plain glutathione (B-tier evidence: Sinha 2018 — +25% RBC GSH, +100% PBMC GSH at 2 weeks). But it does not solve the brain delivery problem — intact GSH crosses the BBB poorly without a GSH-conjugated targeting liposome, and the cognitive evidence is thin. For Dylan's brain-priority thesis, NAC 1200 mg (already in V4) + glycine is the cheaper, more evidence-backed substrate path. Skip unless chronic NAC + glycine fails on bloodwork.

Glutathione (GSH) is a tripeptide of glutamate-cysteine-glycine, the body's principal intracellular antioxidant and a substrate for phase II detoxification (GST conjugation), redox balance (GPx, glutaredoxin), and immune function (lymphocyte/NK cell competence).

Plain oral GSH has notoriously poor bioavailability (~3-5%) because:

1. Stomach acid degrades the peptide.
2. Gut γ-glutamyltransferase (GGT) and peptidases hydrolyze it back to constituent amino acids before absorption.
3. What survives is mostly absorbed as free cysteine, glutamate, glycine — i.e., precursors, not intact GSH.

Liposomal encapsulation wraps GSH in a phospholipid bilayer (typically phosphatidylcholine), theoretically:

• Protecting the peptide from gastric acid + GI peptidases.
• Improving lymphatic and enterocyte uptake via fusion/endocytosis.
• Delivering more intact GSH to systemic circulation.

Critical mechanistic distinction: "Liposomal GSH" (the supplement) is a GSH cargo inside a phospholipid vesicle for oral delivery. This is NOT the same as "GSH-PEGylated liposomes" used in BBB drug delivery research, where GSH is conjugated to the OUTER surface of the liposome to exploit the GSH transporter on brain endothelium. The latter improves brain delivery of cargo (often a non-GSH drug); the former mostly raises peripheral GSH. Marketing copy frequently conflates the two.

For Dylan's stack, the more relevant pathway is endogenous GSH synthesis:

• Cysteine is the rate-limiting substrate → NAC delivers cysteine across the BBB (NAC itself crosses, then donates -SH).
• Glycine is the second substrate → V4 already includes 3 g glycine.
• γ-glutamylcysteine ligase (GCLC) ligates Glu-Cys; GSS adds glycine to form GSH.
• This synthesis happens IN the brain, in neurons and astrocytes, exactly where Dylan wants it.