Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Melatonin | Milk Thistle (Silymarin) | |
|---|---|---|
| Category | Supplements | Supplements |
| Standard Dose | 0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision) | 200-400mg silymarin daily (standardized to 70-80% silymarin) |
| Timing | 30-60 minutes before desired sleep onset. For circadian phase advance: 4-6 hours before desired bedtime. Sublingual for faster onset. Dim lights 1-2 hours before taking. | With meals. Split doses for higher amounts. Phytosome form can be taken without food. |
| Cycle Duration | Short-term for jet lag (3-5 days); ongoing at low dose for circadian support if needed; extended for oncological use under supervision | Cycle 8-12 weeks for liver support; ongoing at low dose for maintenance |
| Evidence Level | strong_human | strong_human |
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized from serotonin in the pineal gland, regulated by the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract. It binds MT1 and MT2 G-protein coupled receptors: MT1 activation suppresses neuronal firing in the SCN (sleep onset), while MT2 modulates circadian phase shifting. Beyond sleep, melatonin is a potent antioxidant that scavenges hydroxyl radicals, peroxynitrite, and singlet oxygen, and upregulates antioxidant enzymes (GPx, SOD, catalase) via Nrf2. It has anti-inflammatory properties (NF-kB suppression), immunomodulatory effects, oncostatic activity (anti-proliferative in several cancer types), and mitochondrial protective functions.
0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision)
30-60 minutes before desired sleep onset. For circadian phase advance: 4-6 hours before desired bedtime. Sublingual for faster onset. Dim lights 1-2 hours before taking.
Short-term for jet lag (3-5 days); ongoing at low dose for circadian support if needed; extended for oncological use under supervision
Silymarin is a complex of flavonolignans (silybin A, silybin B, silychristin, silydianin, isosilybin) with silybin being the most active. Hepatoprotective mechanisms: stabilizes hepatocyte cell membranes by altering outer lipid layer composition (preventing toxin penetration), stimulates ribosomal RNA polymerase I (accelerating hepatocyte protein synthesis and regeneration), inhibits NF-kB and TNF-alpha (anti-inflammatory), scavenges free radicals (both ROS and RNS), promotes glutathione synthesis (increases intracellular GSH by 35%), and inhibits hepatic stellate cell activation (anti-fibrotic). Silybin also activates AMPK and enhances bile flow.
200-400mg silymarin daily (standardized to 70-80% silymarin)
With meals. Split doses for higher amounts. Phytosome form can be taken without food.
Cycle 8-12 weeks for liver support; ongoing at low dose for maintenance
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