The Liver & Detox Protocol — NAC + Glycine + TUDCA + Milk Thistle
A four-part liver support protocol built on precursors rather than purges. NAC and glycine refill glutathione — the tripeptide that drives phase II conjugation. TUDCA works a separate axis: bile flow and ER stress. Silymarin adds membrane and antifibrotic support. Dosing, timing, why 'detox teas' are the wrong model, and the contraindications that actually matter.
Daily Schedule
Timing and dosage for each step
Morning, 30 minutes before breakfast
600 mg
600 mg. Supplies cysteine, the rate-limiting ingredient for glutathione synthesis. Empty stomach absorbs better; move it to a meal if it causes nausea. This is the workhorse of the protocol.
Evening, before bed
3000 mg
3–5 g. The second glutathione precursor and the half most people ignore — the GlyNAC trials that produced the strongest results in older adults used glycine and NAC together, not NAC alone. Evening timing doubles as sleep support.
With the largest meal of the day
500 mg
250–500 mg. Works on a different axis: bile flow and endoplasmic reticulum stress rather than oxidative load. Start at 250 mg — loose stools, not toxicity, is what limits the dose. ⚠️ Skip entirely with biliary obstruction, gallbladder inflammation, or in pregnancy.
With meals, split morning and evening
420 mg
420 mg silymarin, standardised to 70–80%. Choose a silybin-phosphatidylcholine (phytosome) formulation — plain extract is poorly absorbed and the formulation matters more than the milligram count. Avoid with ragweed/Asteraceae allergy.
Protocol Overview
Your liver is not clogged, and it does not need flushing. It needs substrate — the raw materials for the conjugation reactions it already performs continuously. That is the entire design principle here.
- NAC supplies cysteine, the rate-limiting ingredient in glutathione synthesis.
- Glycine supplies the second precursor amino acid — the half that most stacks leave out.
- TUDCA works a different axis entirely: bile flow and endoplasmic reticulum stress.
- Milk thistle adds membrane stabilisation and antifibrotic signalling.
The reasoning is laid out in full in The Liver Optimization Protocol article.
Dosing Summary
| Role | Supplement | Dose | Timing | Evidence |
|---|---|---|---|---|
| Precursor | NAC | 600–1200 mg | Morning, empty stomach | B |
| Precursor | Glycine | 3–5 g | Evening | B |
| Bile & ER stress | TUDCA | 250–500 mg | Largest meal | C |
| Membrane & fibrosis | Milk thistle (silymarin) | 420 mg | Split with meals | B |
NAC and glycine are the pair that carries the evidence. TUDCA and silymarin are additive layers, not the foundation.
How to Build It
Add in order of evidence, not in order of novelty.
- Weeks 1–4: NAC + glycine. This is the core. Together they are the combination the aging and mitochondrial trials actually tested; separately, NAC alone fixes only one of two bottlenecks.
- Add milk thistle if metabolic or fatty-liver markers are the concern — this is where its trial data sit. Buy a phytosome formulation.
- Add TUDCA last, at 250 mg, and only if the first three are tolerated. It has the most interesting mechanism and the thinnest human outcome data of the four.
- Retest liver enzymes (ALT, AST, GGT) at 12 weeks. If the numbers were normal to begin with, understand that you are supporting function, not correcting a deficit.
Why "Detox" Is the Wrong Word
Commercial detox products promise to remove unnamed toxins on an unstated timescale. A critical review of detox diets found the evidence for that model essentially absent. What the liver actually does is a two-phase process: phase I (cytochrome P450) makes compounds chemically reactive, and phase II conjugates them — largely with glutathione — into water-soluble forms the body can excrete.
That distinction has a practical consequence. Everything in this protocol supports phase II capacity. Nothing here "flushes" anything, and a protocol that pushed phase I without phase II support would be the genuinely bad idea.
Safety & Notes
- TUDCA contraindications are real: complete biliary obstruction, acute cholecystitis, and cholangitis are situations where increasing bile flow is exactly wrong. Avoid in pregnancy on insufficient-data grounds.
- Bile acid sequestrants and aluminium antacids bind TUDCA — separate doses by four hours or more.
- Asteraceae allergy (ragweed, daisies, chrysanthemums) rules out milk thistle.
- NAC tolerability is gastrointestinal: nausea and sulphurous burps track with dose. Split it or take it with food.
- Diagnosed liver disease belongs with a hepatologist. This is a wellness protocol for people with normal or mildly elevated enzymes, not a treatment for hepatitis, cirrhosis, or cholestasis.
Foundations First
Supplements are the smallest lever here, and pretending otherwise would be dishonest. Alcohol reduction, weight management, and treating insulin resistance do more for the liver than any capsule in this protocol — metabolic dysfunction is now the dominant driver of fatty liver disease worldwide. Paracetamol dosing discipline matters more than any antioxidant. Treat this stack as the nutritional layer on top of those, never as permission to skip them.