Description: <b>Vitamin B5 (Pantothenic Acid)</b> plays several roles in the brain, and emerging evidence suggests it may be relevant to Alzheimer’s disease (AD)—particularly through its involvement in acetylcholine synthesis, energy metabolism, and oxidative stress response.<br>
-Precursor to Coenzyme A (CoA) <br>
-CoA is essential for mitochondrial energy production, lipid metabolism, and acetylcholine synthesis.<br>
-CoA + choline → acetylcholine. ACh levels are reduced in AD; B5 deficiency may worsen this.<br>
-Pantothenic acid is indirectly involved in cysteamine production, via CoA turnover.<br>
-cysteamine can cross the BBB and increases BDNF levels.
<br>
-Pantothenic Acid (D-calcium pantothenate) Most common, stable, and well-absorbed form, water soluable<br>
-Heat(cooking) may degrade the B5.<br>
-Adequate Intake is 5mg/day. Target 10-15mg/day (300–900 mg/day under supervision)<br>
<br>
-must be replenished daily; no long-term storage<br>
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Beef liver (3 oz cooked) ~8.3 mg
Sunflower seeds (1 oz) ~2.0 mg
Chicken (3 oz cooked) ~1.0 mg
Salmon (3 oz cooked) ~1.6 mg
Avocado (1 whole) ~1.0–2.0 mg
Egg (1 large) ~0.7 mg
Mushrooms (½ cup cooked) ~1.5 mg
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<p><b>Vitamin B5 (Pantothenic Acid; PA)</b> = water-soluble B-vitamin; dietary sources include meats, whole grains, legumes; precursor to <i>Coenzyme A (CoA)</i> and acyl-carrier protein (ACP).<br>
<b>Primary mechanisms (conceptual rank):</b><br>
1) CoA synthesis → central to acetyl-CoA flux (TCA cycle, fatty acid synthesis/β-oxidation, cholesterol/steroid synthesis).<br>
2) Epigenetic substrate control → acetyl-CoA availability influences histone acetylation (H3/H4 acetyl marks).<br>
3) Redox-metabolic integration → CoA-dependent NADH/FADH2 generation (indirect ROS modulation via mitochondrial flux).<br>
4) Rapidly proliferating cell support → high CoA demand in lipogenic tumors (metabolic permissive role rather than direct cytotoxicity).<br>
<b>PK / bioavailability:</b> efficiently absorbed in small intestine via SMVT transporter; plasma levels tightly regulated; excess rapidly excreted; no meaningful tissue “supra-physiologic” accumulation from oral dosing.<br>
<b>In-vitro vs systemic exposure:</b> most cancer cell studies manipulate CoA enzymes (e.g., PANK) rather than achievable oral PA concentrations; in-vitro millimolar exposures exceed physiological serum levels.<br>
<b>Clinical evidence status:</b> no RCT evidence supporting anti-cancer efficacy; primarily nutritional sufficiency role; deficiency rare.</p>
<br>
<h3>Vitamin B5 (Pantothenic Acid) — Cancer-Relevant Pathways</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>CoA synthesis / Acetyl-CoA pool</td>
<td>↑ (supports proliferation)</td>
<td>↑ (physiologic support)</td>
<td>G</td>
<td>Metabolic substrate enabling</td>
<td>Central biochemical role; tumors with high lipogenesis depend on robust CoA flux; PA is permissive, not selectively cytotoxic.</td>
</tr>
<tr>
<td>2</td>
<td>TCA cycle / mitochondrial flux</td>
<td>↑ (fueling)</td>
<td>↑</td>
<td>R→G</td>
<td>Energy metabolism support</td>
<td>Indirectly affects NADH/FADH2 production; not a direct ETC inhibitor or activator.</td>
</tr>
<tr>
<td>3</td>
<td>Fatty acid synthesis (FASN axis)</td>
<td>↑ (lipogenic tumors)</td>
<td>↑</td>
<td>G</td>
<td>Lipid biosynthesis substrate</td>
<td>Acetyl-CoA → malonyl-CoA pathway; high relevance in breast, prostate, liver cancers with lipogenic phenotype.</td>
</tr>
<tr>
<td>4</td>
<td>Histone acetylation (epigenetic)</td>
<td>↑ (context-dependent)</td>
<td>↑</td>
<td>G</td>
<td>Chromatin acetylation permissive</td>
<td>Acetyl-CoA availability influences H3/H4 acetyl marks; effect magnitude depends on metabolic state rather than supplementation alone.</td>
</tr>
<tr>
<td>5</td>
<td>ROS tone</td>
<td>↔ (indirect)</td>
<td>↔</td>
<td>R</td>
<td>Secondary to mitochondrial flux</td>
<td>No primary antioxidant property; ROS shifts occur via altered metabolic throughput.</td>
</tr>
<tr>
<td>6</td>
<td>NRF2 axis</td>
<td>↔</td>
<td>↔</td>
<td>G</td>
<td>No direct activation</td>
<td>Not a canonical NRF2 modulator; any effect is secondary to metabolic stress context.</td>
</tr>
<tr>
<td>7</td>
<td>Ca²⁺ signaling</td>
<td>↔</td>
<td>↔</td>
<td>R</td>
<td>No primary modulation</td>
<td>No established direct Ca²⁺ regulatory role.</td>
</tr>
<tr>
<td>8</td>
<td>Clinical Translation Constraint</td>
<td>—</td>
<td>—</td>
<td>—</td>
<td>Nutrient sufficiency only</td>
<td>Supplementation does not selectively target tumor metabolism; enzyme-level targeting (e.g., PANK inhibitors) is the investigational strategy.</td>
</tr>
</table>
<p><b>TSF Legend:</b> P: 0–30 min | R: 30 min–3 hr | G: >3 hr</p>
<br>
<p><b>Vitamin B5 (Pantothenic Acid; PA)</b> = water-soluble precursor to Coenzyme A (CoA); common supplemental form: D-calcium pantothenate. Present in meats (esp. liver), seeds, fish, eggs, mushrooms; heat-labile to some extent; no long-term storage → requires regular intake.<br>
<b>Primary mechanisms (AD-relevant rank):</b><br>
1) CoA synthesis → acetyl-CoA pool → acetylcholine (ACh) synthesis support.<br>
2) Mitochondrial energy metabolism (TCA flux, β-oxidation) → neuronal bioenergetic stability.<br>
3) Lipid metabolism (membrane phospholipids, myelin maintenance).<br>
4) Indirect redox integration via mitochondrial throughput (secondary ROS modulation).<br>
5) CoA turnover → cysteamine generation (putative BDNF modulation; limited human data).<br>
<b>PK / exposure:</b> efficiently absorbed; plasma tightly regulated; excess rapidly excreted; oral dosing above AI does not proportionally elevate brain CoA once saturation is reached.<br>
<b>Clinical evidence status (AD):</b> mechanistic plausibility strong; direct RCT evidence lacking; not an established disease-modifying therapy. AD relevance likely greater than cancer (where PA is largely metabolically permissive rather than therapeutic).</p>
<h3>Vitamin B5 (Pantothenic Acid) — Alzheimer’s Disease–Relevant Axes</h3>
<table>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cells (neurons/glia)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Acetyl-CoA → Acetylcholine synthesis</td>
<td>↑ (if deficient)</td>
<td>G</td>
<td>Supports ACh production</td>
<td>ACh reduced in AD; PA deficiency could worsen cholinergic deficit; supplementation restores only if suboptimal intake present.</td>
</tr>
<tr>
<td>2</td>
<td>Mitochondrial energy metabolism (TCA)</td>
<td>↑ (bioenergetic support)</td>
<td>R→G</td>
<td>ATP production stabilization</td>
<td>CoA central to acetyl-CoA flux; may support neurons under metabolic stress; not a direct ETC activator.</td>
</tr>
<tr>
<td>3</td>
<td>Lipid metabolism / membrane integrity</td>
<td>↑</td>
<td>G</td>
<td>Phospholipid turnover support</td>
<td>Neuronal membrane composition critical in AD; effect is permissive rather than corrective.</td>
</tr>
<tr>
<td>4</td>
<td>ROS tone (indirect)</td>
<td>↔ / ↓ (secondary)</td>
<td>R</td>
<td>Metabolic-redox coupling</td>
<td>No intrinsic antioxidant action; ROS shifts occur via improved mitochondrial efficiency (context-dependent).</td>
</tr>
<tr>
<td>5</td>
<td>BDNF (via cysteamine from CoA turnover)</td>
<td>↑ (theoretical / limited human data)</td>
<td>G</td>
<td>Neurotrophic modulation</td>
<td>Cysteamine crosses BBB and may increase BDNF; contribution from dietary PA not well quantified clinically.</td>
</tr>
<tr>
<td>6</td>
<td>NRF2 axis</td>
<td>↔</td>
<td>G</td>
<td>No direct activation</td>
<td>Not a canonical NRF2 modulator.</td>
</tr>
<tr>
<td>7</td>
<td>Ca²⁺ signaling</td>
<td>↔</td>
<td>R</td>
<td>No primary modulation</td>
<td>No direct Ca²⁺ regulatory role established.</td>
</tr>
<tr>
<td>8</td>
<td>Clinical Translation Constraint</td>
<td>—</td>
<td>—</td>
<td>Nutritional sufficiency ceiling</td>
<td>Adequate Intake ~5 mg/day; higher doses (10–15 mg/day typical supplementation; 300–900 mg/day under supervision) lack robust AD outcome trials.</td>
</tr>
</table>
<p><b>TSF Legend:</b> P: 0–30 min | R: 30 min–3 hr | G: >3 hr</p>