Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Alpha Lipoic Acid (ALA) | Melatonin | |
|---|---|---|
| Category | Supplements | Supplements |
| Standard Dose | 300-600mg R-ALA daily | 0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision) |
| Timing | On empty stomach, 30-60 min before meals. Split doses for higher amounts. | 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. |
| Cycle Duration | ongoing or cycle 12 weeks on, 4 weeks off | Short-term for jet lag (3-5 days); ongoing at low dose for circadian support if needed; extended for oncological use under supervision |
| Evidence Level | strong_human | strong_human |
ALA is a dithiol compound that functions as a cofactor for mitochondrial alpha-keto acid dehydrogenases (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase). Both ALA and its reduced form DHLA are potent antioxidants capable of regenerating other antioxidants including vitamin C, vitamin E, and glutathione. ALA activates AMPK, improving glucose uptake via GLUT4 translocation, and modulates NF-kB-mediated inflammatory signaling. It chelates redox-active metals (Fe2+, Cu2+).
300-600mg R-ALA daily
On empty stomach, 30-60 min before meals. Split doses for higher amounts.
ongoing or cycle 12 weeks on, 4 weeks off
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
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