Description: <b>(Nicotinamide adenine dinucleotide)</b> is a vital coenzyme found in all living cells.<br>
• It exists in two forms: oxidized (NAD⁺) and reduced (NADH), playing central roles in redox reactions, energy metabolism, and various signaling pathways.<br>
• NAD⁺ is essential for critical cellular processes, including ATP production, DNA repair (via enzymes like PARPs), and regulation of sirtuins (a family of NAD⁺-dependent deacetylases involved in cellular stress responses and longevity).<br>
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NAD⁺ is integral to energy metabolism, redox balance, DNA repair, and cellular regulatory functions—processes that are often dysregulated in cancer.<br>
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<a href="https://medicorcancer.com/wp-content/uploads/Momentum-DCA-Brochure.pdf"> Medicor Cancer Centres offers it: </a><br>
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-involved in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation.<br>
-NMN is a precursor to nicotinamide adenine dinucleotide (NAD+)<br>
-alternative form of vitamin B, amide of nicotinic acid<br>
-NAD+ levels decline as we age<br>
-high dose NMN promotes ferroptosis through NAM-mediated SIRT1-AMPK-ACC signaling<br>
-At low doses (10 and 20 mM) and prolonged exposure (48 h), NMN increased cell proliferation, but it induced the suppression of cell proliferation at the high dose (100 mM)<br>
-VitB3 and niacin are precursors for the synthesis of NAD in the body<br>
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NAD in Cancer Is Dual-Edge
Tumors need NAD+ to sustain:
-Glycolysis (Warburg)
-PARP DNA repair
-Sirtuin survival signaling
-Redox buffering
NAD depletion (via NAMPT inhibition or high PARP consumption) can:
-Collapse ATP
-Increase ROS
-Trigger apoptosis
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<!-- Cancer Pathway Table: NAD (Nicotinamide Adenine Dinucleotide) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NAD+ salvage pathway (NAMPT → NMN → NAD+)</td>
<td>NAD+ pool ↑ supports glycolysis, DNA repair, PARP activity; NAMPT often upregulated</td>
<td>Maintains metabolic homeostasis</td>
<td>R, G</td>
<td>Metabolic support node</td>
<td>Many tumors depend on NAMPT-driven NAD+ salvage; NAMPT inhibitors (e.g., FK866) deplete NAD+ and induce energetic collapse.</td>
</tr>
<tr>
<td>2</td>
<td>Glycolysis support (LDH-dependent NAD+ recycling)</td>
<td>NAD+ regeneration sustains Warburg flux</td>
<td>Normal glycolytic tissues also require NAD+</td>
<td>P, R</td>
<td>Warburg sustainment</td>
<td>LDH converts NADH → NAD+ to maintain glycolytic flux; NAD+ availability is a rate-limiting factor in high glycolysis tumors.</td>
</tr>
<tr>
<td>3</td>
<td>PARP-mediated DNA repair (NAD+ consumption)</td>
<td>DNA damage repair ↑; therapy resistance ↑ (context)</td>
<td>Genome stability maintenance</td>
<td>R, G</td>
<td>DNA repair capacity</td>
<td>PARPs consume NAD+ during DNA repair. PARP inhibitors exploit tumors with HR defects (e.g., BRCA).</td>
</tr>
<tr>
<td>4</td>
<td>Sirtuin signaling (SIRT1–7; NAD+-dependent deacetylases)</td>
<td>Context-dependent tumor survival or suppression</td>
<td>Metabolic regulation, longevity pathways</td>
<td>R, G</td>
<td>Epigenetic/metabolic modulation</td>
<td>Sirtuins require NAD+; effects vary by tumor type (pro-survival in some, suppressive in others).</td>
</tr>
<tr>
<td>5</td>
<td>Redox balance (NAD+/NADH ratio)</td>
<td>High NAD+/NADH ratio supports anabolic growth</td>
<td>Redox homeostasis</td>
<td>P, R</td>
<td>Redox control</td>
<td>Altered NAD+/NADH ratios influence ROS, mitochondrial function, and metabolic flexibility.</td>
</tr>
<tr>
<td>6</td>
<td>CD38/CD157 NAD+ degradation</td>
<td>NAD+ depletion influences immune and tumor metabolism</td>
<td>Immune modulation, aging</td>
<td>R, G</td>
<td>Immune-metabolic interface</td>
<td>CD38 overexpression can lower NAD+ pools; relevant in immune microenvironment contexts.</td>
</tr>
<tr>
<td>7</td>
<td>OXPHOS support (mitochondrial NADH supply)</td>
<td>NADH fuels ETC; supports mitochondrial ATP production</td>
<td>Normal energy metabolism</td>
<td>P, R</td>
<td>Mitochondrial respiration support</td>
<td>NADH oxidation via Complex I regenerates NAD+; OXPHOS-dependent tumors rely on this axis.</td>
</tr>
<tr>
<td>8</td>
<td>Therapy resistance modulation</td>
<td>NAD+ restoration may reduce oxidative therapy efficacy</td>
<td>May protect normal tissue from oxidative injury</td>
<td>G</td>
<td>Context-dependent</td>
<td>NAD+ boosting (e.g., NR, NMN) may theoretically support tumor repair pathways; data mixed and context-specific.</td>
</tr>
<tr>
<td>9</td>
<td>NAMPT inhibition (therapeutic strategy)</td>
<td>NAD+ depletion → ATP ↓ → apoptosis ↑</td>
<td>Toxicity risk in high-turnover tissues</td>
<td>R, G</td>
<td>Metabolic collapse</td>
<td>NAMPT inhibitors are being explored as anti-cancer metabolic therapies.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability / supplementation constraint</td>
<td>Systemic NAD+ boosting may not selectively target tumor NAD pools</td>
<td>Systemic NAD+ supports normal tissue repair</td>
<td>—</td>
<td>Translation constraint</td>
<td>Oral precursors (NR, NMN, niacin) increase systemic NAD+ but tumor-specific impact remains unclear.</td>
</tr>
</table>
<p><small>
TSF: P = 0–30 min (redox flux shifts), R = 30 min–3 hr (metabolic signaling changes), G = >3 hr (gene-level adaptation, repair, phenotype changes).
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