Description: <b>5-day diet to mimic fasting without fasting.</b><br>
FMDs are caloric-restricted plant–based diets containing low proteins, low sugar and high fats which represent a more feasible and safer option to water-only fasting.<br>
<pre>
Fasting modality Approx CRIS
-------------------------------------- ----------
Time-restricted eating (12–16 h) –3 to –4
Early time-restricted eating (eTRE) –4
Intermittent fasting (24 h 1–2x/week) –4
Periodic fasting / FMD –4 to –5*
Calorie restriction (chronic) –3 (risk tradeoffs)
Compare STF(short term Fasting) to FMD
IGF-1 / insulin suppression (core driver)
| Aspect | STF | FMD |
| ----------------- | ------------------- | -------- |
| Depth | **Very deep** | Moderate |
| Speed | **Rapid (24–48 h)** | Gradual |
| Tumor stress | **High** | Medium |
| Normal protection | High | High |
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Fasting-Mimicking Diet (FMD; ~5-day low-protein, low-calorie cycle) Cancer vs Normal Cell Effects
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Label</th>
<th>Primary Interpretation</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>Insulin / IGF-1 signaling</td>
<td>↓ IGF-1 signaling (chronic stress)</td>
<td>↓ IGF-1 with regenerative priming</td>
<td>Driver</td>
<td>Sustained growth factor suppression</td>
<td>Repeated IGF-1 lowering impairs tumor growth programs</td>
</tr>
<tr>
<td>2</td>
<td>AMPK → mTOR nutrient sensing</td>
<td>↓ mTOR; ↑ AMPK (growth inhibition)</td>
<td>↓ mTOR; ↑ AMPK (maintenance mode)</td>
<td>Driver</td>
<td>Prolonged anabolic suppression</td>
<td>More sustained but less acute than STF</td>
</tr>
<tr>
<td>3</td>
<td>Autophagy / mitophagy</td>
<td>↑ autophagy → loss of tumor robustness</td>
<td>↑ autophagy → rejuvenation</td>
<td>Driver</td>
<td>Cellular renewal vs destabilization</td>
<td>Repeated cycles promote organelle quality control</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial metabolism</td>
<td>↓ metabolic resilience</td>
<td>↑ mitochondrial fitness</td>
<td>Secondary</td>
<td>Energy efficiency divergence</td>
<td>Normal cells adapt better across cycles</td>
</tr>
<tr>
<td>5</td>
<td>Inflammatory signaling (NF-κB / cytokines)</td>
<td>↓ pro-tumor inflammation</td>
<td>↓ systemic inflammation</td>
<td>Secondary</td>
<td>Anti-inflammatory milieu</td>
<td>Inflammation reduction contributes to chemopreventive effects</td>
</tr>
<tr>
<td>6</td>
<td>Reactive oxygen species (ROS)</td>
<td>↑ ROS (secondary, context-dependent)</td>
<td>↓ ROS</td>
<td>Secondary</td>
<td>Metabolism-linked redox shift</td>
<td>ROS effects are indirect and less pronounced than STF</td>
</tr>
<tr>
<td>7</td>
<td>NRF2 antioxidant response</td>
<td>↔ modest activation</td>
<td>↑ NRF2 (protective)</td>
<td>Adaptive</td>
<td>Stress adaptation</td>
<td>NRF2 supports normal-cell recovery between cycles</td>
</tr>
<tr>
<td>8</td>
<td>Cell cycle / regeneration</td>
<td>↓ proliferation</td>
<td>↑ regeneration post-cycle</td>
<td>Phenotypic</td>
<td>Degrowth vs regeneration</td>
<td>FMD uniquely promotes regeneration upon refeeding</td>
</tr>
</table>