Quick Comparison
| 5-HTP | Phosphatidylserine | |
|---|---|---|
| Half-Life | 2-5 hours | Not well-characterized orally; brain PS turns over slowly |
| Typical Dosage | Standard: 50-200 mg daily. For mood: 50-100 mg 2-3 times daily. For sleep: 100-300 mg 30-60 minutes before bed. Start low — some people are very sensitive. Take with food to reduce nausea. | Standard: 100-300 mg daily in 1-3 doses. Most studies use 300 mg daily. Soy-derived and sunflower-derived forms are both effective. Take with food for absorption. |
| Administration | Oral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits. | Oral (softgels, capsules). Soy-derived or sunflower-derived. Take with fat for absorption. |
| Research Papers | 10 papers | 10 papers |
| Categories |
Mechanism of Action
5-HTP
5-HTP readily crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1/SLC7A5), unlike serotonin itself which cannot. Once in the brain, aromatic L-amino acid decarboxylase (AADC, also called DOPA decarboxylase) converts 5-HTP to serotonin (5-hydroxytryptamine) using pyridoxal-5-phosphate (active vitamin B6) as a cofactor. This completely bypasses tryptophan hydroxylase (TPH2), the rate-limiting enzyme in the normal serotonin synthesis pathway from dietary L-tryptophan. The result is a reliable, dose-dependent increase in serotonin across multiple brain regions including the dorsal raphe nucleus, hippocampus, and prefrontal cortex. Elevated serotonin activates 5-HT1A autoreceptors (calming), 5-HT2A/2C postsynaptic receptors (mood modulation), and 5-HT3 receptors (gut-brain signaling). In the pineal gland, serotonin is converted by arylalkylamine N-acetyltransferase (AANAT) to N-acetylserotonin, then by hydroxyindole O-methyltransferase (HIOMT) to melatonin — explaining the sleep-promoting effects.
Phosphatidylserine
PS is a structural component of neuronal membranes, maintaining membrane fluidity and supporting receptor function, ion channel activity, and neurotransmitter release. It localizes preferentially to the inner leaflet of the plasma membrane via flippase enzymes (P4-ATPases), where it serves as a cofactor for protein kinase C (PKC) isoforms alpha, beta, and gamma — PKC activation phosphorylates substrates including MARCKS and GAP-43, critical for synaptic plasticity and memory consolidation. PS modulates the HPA axis via glucocorticoid receptor feedback, reducing cortisol by 15-30% in stressed individuals. It facilitates choline transport via high-affinity choline transporter (CHT1) into presynaptic terminals, supporting acetylcholine synthesis by choline acetyltransferase. PS also regulates NMDA receptor function and supports Na+/K+-ATPase activity. Downstream, PS enhances CREB phosphorylation and BDNF expression in hippocampal neurons.
Risks & Safety
5-HTP
Common
Nausea, diarrhea, stomach cramps.
Serious
Serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or tramadol — DO NOT combine without medical supervision.
Rare
Eosinophilia-myalgia syndrome (historical concern from contaminated L-tryptophan, not confirmed with modern 5-HTP).
Phosphatidylserine
Common
Mild gastrointestinal discomfort, insomnia at high doses.
Serious
May interact with blood thinners.
Rare
Allergic reaction in soy-sensitive individuals (use sunflower-derived).
Full Profiles
5-HTP →
5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.
Phosphatidylserine →
A phospholipid that constitutes 15% of the brain's total phospholipid pool and is concentrated in neuronal cell membranes. Phosphatidylserine (PS) supports memory, cognitive function, and cortisol regulation. It is the only nootropic with an FDA-qualified health claim: 'consumption may reduce the risk of cognitive dysfunction in the elderly.' Particularly effective for age-related cognitive decline.