Tryptophan
Essential amino acid with multiple metabolic fates. The precursor to serotonin and melatonin, but most is actually used to make NAD+ through the kynurenine pathway.
🔀 Two Major Pathways for Tryptophan
A common misconception is that tryptophan primarily makes serotonin. In reality, over 95% goes to the kynurenine pathway, which produces NAD+ and other important metabolites:
Serotonin Pathway (1-3%)
Kynurenine Pathway (95%+)
🔥 Inflammation Steals Tryptophan from Serotonin
This is a critical insight for understanding depression and inflammation. When inflammation is present, the immune system activates IDO (indoleamine 2,3-dioxygenase), which shunts more tryptophan into the kynurenine pathway and away from serotonin:
Activates IDO enzyme
More tryptophan diverted here
Less available for mood
This helps explain why chronic inflammation is associated with depression—it's not just "feeling sick," but an actual biochemical theft of serotonin precursors.
🧠Getting Tryptophan to the Brain
Tryptophan must cross the blood-brain barrier to make serotonin in the brain. But it competes with other large neutral amino acids (BCAAs, tyrosine, phenylalanine) for the same transporter.
Protein Paradox
Protein provides tryptophan, but also competing amino acids. High-protein meals may actually reduce brain tryptophan uptake.
Carbohydrate Effect
Carbs trigger insulin, which drives BCAAs into muscle, leaving tryptophan with less competition. May explain carb cravings with low serotonin.
For supplementation: Take tryptophan or 5-HTP away from protein meals for best brain uptake.
🥗 Food Sources
Tryptophan is found in protein-rich foods:
- • Turkey and chicken (turkey isn't uniquely high though)
- • Eggs (especially yolks)
- • Cheese (particularly aged varieties)
- • Fish (salmon, tuna)
- • Nuts and seeds (pumpkin seeds, almonds)
- • Soy products (tofu, tempeh)
- • Oats and bananas
The "turkey makes you sleepy" myth: it's actually the large meal and carbs, not uniquely high tryptophan.
đź’Š Supplementation
L-Tryptophan
500-2000mg. Further upstream, more goes to kynurenine. Take at night, away from protein.
5-HTP
50-200mg. One step closer to serotonin, bypasses kynurenine diversion. More direct but shorter-acting.
Warning: Do not combine with SSRIs or MAOIs—risk of serotonin syndrome. Start low and monitor.
⚗️ The Kynurenine Pathway: More Than NAD+
The kynurenine pathway doesn't just make NAD+—it produces metabolites with significant effects on brain function:
Quinolinic Acid (QUIN)
- • NMDA receptor agonist (excitotoxic)
- • Generates reactive oxygen species
- • Elevated in depression, neurodegeneration
- • Eventually converted to NAD+
Kynurenic Acid (KYNA)
- • NMDA receptor antagonist (neuroprotective)
- • Blocks glutamate excitotoxicity
- • Anti-inflammatory properties
- • May be too high in schizophrenia
The balance between neurotoxic (QUIN) and neuroprotective (KYNA) metabolites matters. Inflammation tends to push toward QUIN. B vitamins (especially B6) influence which branch predominates.
Metabolic Connections
Serotonin
Tryptophan → 5-HTP → serotonin (only 1-3% of tryptophan)
Melatonin
Serotonin → melatonin in the pineal gland at night
Vitamin B6
Required cofactor for converting 5-HTP to serotonin
NAD+
Kynurenine pathway produces NAD+ (uses 95%+ of tryptophan)
BH4
Tetrahydrobiopterin required for tryptophan hydroxylase
Inflammation
Activates IDO enzyme, shunting tryptophan away from serotonin