Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Melatonin | NR (Nicotinamide Riboside) | |
|---|---|---|
| Category | Supplements | Supplements |
| Standard Dose | 0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision) | 300-600mg daily |
| 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. | Morning with or 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 | ongoing |
| Evidence Level | strong_human | Moderate-Strong |
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
NR is converted to NMN by nicotinamide riboside kinases (NRK1/NRK2), then to NAD+ via the salvage pathway. Like NMN, elevated NAD+ activates sirtuins, PARPs, and CD38. NR has demonstrated ability to cross the blood-brain barrier and elevate brain NAD+ levels. It supports mitochondrial function, DNA repair, and circadian rhythm regulation through SIRT1-mediated deacetylation of BMAL1 and CLOCK proteins.
300-600mg daily
Morning with or without food.
ongoing
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