Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| L-Theanine | Melatonin | |
|---|---|---|
| Category | Amino Acids | Supplements |
| Standard Dose | 100-200mg daily (or as needed for acute anxiety/focus) | 0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision) |
| Timing | Flexible: morning for calm focus (stack with caffeine), before stressful events, or evening for relaxation/sleep onset. Onset: 30-60 minutes oral, 15-20 min sublingual. | 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 as needed | 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 |
L-Theanine (gamma-glutamylethylamide) crosses the blood-brain barrier via the large neutral amino acid transporter. It increases alpha brain wave activity (8-13 Hz, associated with relaxed alertness), enhances GABA, serotonin, and dopamine levels in the brain, and antagonizes glutamate excitotoxicity by blocking glutamate binding at AMPA, kainate, and NMDA receptors. It also increases BDNF and NGF expression, supporting neuroplasticity. The combination of glutamate antagonism and GABA/serotonin enhancement produces anxiolysis without sedation — a 'calm focus' state.
100-200mg daily (or as needed for acute anxiety/focus)
Flexible: morning for calm focus (stack with caffeine), before stressful events, or evening for relaxation/sleep onset. Onset: 30-60 minutes oral, 15-20 min sublingual.
ongoing or as needed
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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