Peptide YY
Peptide YY (PYY 3-36)
Peptide YY 3-36 (PYY 3-36) is a truncated form of the gut-derived satiety hormone Peptide YY, naturally released from intestinal L-cells in proportion to caloric intake. It is primarily investigated as an appetite suppressant and anti-obesity agent, with research demonstrating significant reductions in food intake and caloric consumption in both lean and obese subjects following administration.
Mechanism of Action
PYY 3-36 acts as a selective agonist at the neuropeptide Y2 receptor (NPY2R), expressed on orexigenic AgRP/NPY neurons in the hypothalamic arcuate nucleus, inhibiting appetite-promoting neuronal activity. It also slows gastric emptying via vagal pathways and reduces gut motility, producing both central and peripheral satiety signals. The net effect is a sustained reduction in hunger and ad libitum food intake lasting several hours post-administration.
Evidence by Health Goal(18 goals)
Dosing Protocols
30-60 minutes before the largest meal of the day
Cycle: 8 weeks on, 2-4 weeks off
Subcutaneous injection is the most studied route. Start at 200 mcg to assess tolerance for nausea; titrate up over 1-2 weeks. Research protocols have used doses up to 1700 pmol/kg IV but subcutaneous dosing at these ranges is more practical for self-administration.
30 minutes before the main meal
Cycle: 8 weeks on, 2-4 weeks off
Intranasal delivery provides lower bioavailability than injection but may be preferred for ease of use. Bioavailability is highly variable; some users report diminished effect compared to subcutaneous dosing. Add absorption enhancers like cyclodextrin formulations when available.
Safety & Side Effects
PYY 3-36 has a generally acceptable short-term safety profile in controlled research settings, with nausea being the primary dose-limiting side effect; however, long-term safety data in humans remains limited and it is not approved by the FDA or EMA for clinical use, existing only as a research compound. Self-administration outside supervised clinical trials carries meaningful risks including uncontrolled caloric restriction, unknown long-term endocrine effects, and variable peptide purity from research vendors.
Possible Side Effects
- !Nausea, often dose-dependent and most prominent in the first 1-2 weeks of use
- !Reduced appetite beyond desired levels, potentially leading to inadequate caloric intake
- !Vomiting, particularly at higher doses or rapid titration
- !Injection site reactions including redness, bruising, or mild induration
- !Dizziness or lightheadedness, likely secondary to reduced food intake and caloric deficit
- !Fatigue or low energy, associated with significant caloric restriction
- !Headache reported in some clinical study participants
Interactions
- -May potentiate the appetite-suppressing effects of GLP-1 receptor agonists (e.g., semaglutide, liraglutide), increasing risk of severe nausea and excessive caloric restriction
- -Additive effects possible when combined with other satiety peptides such as oxyntomodulin or amylin analogues, requiring dose reduction
- -May slow gastric emptying, potentially delaying absorption and reducing efficacy of orally administered medications requiring rapid uptake
- -Use caution in individuals on insulin or oral hypoglycemics due to indirect effects on postprandial glucose regulation and altered meal timing
- -Theoretical interaction with NPY-system-modulating compounds (e.g., NPY-targeting antidepressant or anxiolytic research agents) due to shared receptor pathway activity
Cost & Where to Buy
Research-grade PYY 3-36 is available from peptide vendors at approximately $40-$120 per vial (1-5 mg); monthly cost depends heavily on dose, vendor purity standards, and whether lyophilized reconstitution supplies are factored in. This is a relatively niche research peptide with limited vendor availability compared to more common compounds.
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