Description: <p><b>Carnosine</b> (CAR; β-alanyl-L-histidine) is an <b>endogenous dipeptide</b> and <b>dietary supplement</b> (high in meat; also synthesized).<br>
<b>Primary mechanisms (conceptual rank):</b><br>
1) <b>Carbonyl/aldehyde scavenging + anti-glycation (AGE) suppression</b> → proteostasis stress ↓ (P/R)<br>
2) <b>Cancer metabolism interference (Warburg/glycolysis pressure)</b> → proliferation ↓ (model-dependent; often high concentration) (R/G)<br>
3) <b>Metal chelation + ROS/RNS buffering</b> (secondary redox modulation) (P/R; context-dependent)<br>
<b>Bioavailability / PK:</b> Orally absorbed, but <b>rapidly hydrolyzed in human blood by carnosinase (CN1)</b> → very short circulating half-life; sustained systemic CAR exposure is limited vs β-alanine/histidine metabolites.<br>
<b>In-vitro vs realistic exposure:</b> Many anti-proliferative / glycolysis effects are reported at <b>high µM–mM</b> CAR in vitro, commonly exceeding realistic systemic CAR exposure due to rapid serum hydrolysis.<br>
<b>Clinical evidence status (cancer):</b> Predominantly <b>preclinical</b> for direct anti-cancer effects; human oncology evidence is mainly <b>adjunct/supportive</b> (e.g., zinc-L-carnosine for radiation-related symptoms), not established as an anti-tumor monotherapy.</p>
<b>L-Carnosine</b> (usually just called "Carnosine") is a naturally occurring dipeptide composed of L-histidine and β-alanine, found in high concentrations in muscle and brain tissue.<br>
-Source: only found in animals Beef(372mg/100g), ChickenBreast(290mg/100g), Pork(276mg/100g), TurkeyBreast(240mg/100g)<br>
-Anserine is a derivative of carnosine <br>
-Scavenges reactive oxygen species (ROS) <br>
-Inhibits formation of AGEs (advanced glycation end-products), which are linked to aging and neurodegeneration.<br>
-Metal chelator: Binds excess zinc, copper, and iron—important in brain health.<br>
<br>
<br>
<h3>Carnosine (CAR) — Pathway / Axis Effects (Cancer vs Normal)</h3>
<table>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells (↑ / ↓ / ↔)</th>
<th>Normal Cells (↑ / ↓ / ↔)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td><b>Carbonyl stress / anti-glycation (AGE)</b></td>
<td>↓ proteotoxic/carbonyl stress (context-dependent)</td>
<td>↓ glycation damage (protective)</td>
<td>P/R</td>
<td>Cell stress buffering</td>
<td>Core “chemoprotective” chemistry: nucleophilic scavenging of reactive carbonyls; cancer-direction depends on whether tumor relies on carbonyl-stress adaptation.</td>
</tr>
<tr>
<td>2</td>
<td><b>Warburg / glycolysis pressure</b></td>
<td>↓ glycolysis flux (model-dependent; high concentration only)</td>
<td>↔</td>
<td>R/G</td>
<td>Anti-proliferative (subset)</td>
<td>Frequently reported in vitro with supraphysiologic CAR; translation constrained by rapid serum hydrolysis in humans.</td>
</tr>
<tr>
<td>3</td>
<td><b>Mitochondrial function / energetic stress</b></td>
<td>↔ / ↑ energetic stress (model-dependent)</td>
<td>↔ / protective (context-dependent)</td>
<td>R</td>
<td>Growth suppression vs resilience</td>
<td>Direction varies by baseline metabolic state and substrate availability; often secondary to carbonyl/redox effects.</td>
</tr>
<tr>
<td>4</td>
<td><b>ROS</b></td>
<td>↓ ROS (secondary; context-dependent)</td>
<td>↓ oxidative damage (protective)</td>
<td>P/R</td>
<td>Redox buffering</td>
<td>Typically described as antioxidant buffering; paradoxical “ROS ↑” cytotoxicity is not a dominant CAR narrative.</td>
</tr>
<tr>
<td>5</td>
<td><b>NRF2 (stress-response axis)</b></td>
<td>↔ / ↑ cytoprotection (context-dependent; resistance risk)</td>
<td>↔ / ↑ protective</td>
<td>G</td>
<td>Adaptive stress signaling</td>
<td>If NRF2 is already oncogenic (e.g., KEAP1/NFE2L2-altered tumors), further cytoprotection could be undesirable.</td>
</tr>
<tr>
<td>6</td>
<td><b>Ca²⁺</b> (ER/mitochondria stress coupling)</td>
<td>↔ (not primary; model-dependent)</td>
<td>↔</td>
<td>R</td>
<td>Stress modulation (secondary)</td>
<td>Include only as a secondary axis: CAR’s dominant reported levers are carbonyl/redox/metabolic rather than direct Ca²⁺ channel control.</td>
</tr>
<tr>
<td>7</td>
<td><b>Ferroptosis</b></td>
<td>↔ (context-dependent)</td>
<td>↔</td>
<td>R/G</td>
<td>Unclear / secondary</td>
<td>CAR’s anti-lipid-peroxidation tendency could oppose ferroptosis in some contexts; evidence is not central vs carbonyl/AGE chemistry.</td>
</tr>
<tr>
<td>8</td>
<td><i>Clinical Translation Constraint</i></td>
<td colspan="2">Human systemic CAR exposure is constrained by rapid serum hydrolysis (CN1); much in-vitro anti-cancer work uses high µM–mM. Strongest human oncology signal is adjunct/supportive use (e.g., zinc-L-carnosine symptom prevention), not proven tumor regression.</td>
<td>—</td>
<td>PK-limited; adjunct-only</td>
<td>Consider delivery strategies/analogs (e.g., carnosinase-resistant histidine dipeptides) if pursuing systemic pharmacology.</td>
</tr>
</table>
<p><b>TSF legend:</b> P: 0–30 min (primary/rapid effects; direct enzyme/redox interactions) · R: 30 min–3 hr (acute signaling + stress responses) · G: >3 hr (gene-regulatory adaptation; phenotype outcomes)</p>