tbResList Print — VitB3 Vitamin B3,Niacin

Description: <p><b>Vitamin B3 (Niacin)</b> = <b>nicotinic acid</b> (NA; pharmacologic drug + vitamin) and <b>nicotinamide/niacinamide</b> (NAM; vitamin; NAD⁺ precursor). Sources: human PK/PD and receptor biology; NAM high-dose AD Phase 2a; GPR109A mechanistic papers. Primary mechanisms (ranked):<br>
1) <b>NAD⁺/NADP⁺ precursor biology</b> → redox/energy metabolism, mitochondrial support, PARP (DNA repair), sirtuins (stress-response signaling).<br>
2) <b>GPR109A (HCAR2) agonism</b> (mainly <i>nicotinic acid</i>) → rapid anti-lipolysis; immune/epithelial anti-inflammatory signaling; can modulate colonic inflammation/carcinogenesis contextually.<br>
3) <b>High-concentration NAM enzyme inhibition</b> → NAM can inhibit sirtuins (Class III “HDAC” activity) and other NAD⁺-consuming enzymes primarily at <b>high (mM) exposures</b> used in many in-vitro settings.<br>
Bioavailability/PK relevance: NA absorbed rapidly (Tmax ~30–60 min) with short t½ (~1 h after 1 g); ER NA slows/lowers peak. NAM can reach much higher plasma levels only with <b>gram-level dosing</b>; typical supplement doses yield far lower systemic levels.<br>
In-vitro vs oral exposure: many cancer-cell studies use <b>1–20 mM NAM/NA</b>—commonly <b>> physiologic/supplement systemic exposure</b>; mM plasma is mainly plausible in <b>therapeutic gram-dose NAM</b> contexts (historically explored in radiosensitization), not routine supplementation.<br>
Clinical evidence status: robust clinical use for <b>dyslipidemia</b> (NA; limited today by tolerability/toxicity); <b>no established anticancer RCT benefit</b> as monotherapy; NAM explored as adjunct/biomarker-modifier in select contexts; <b>AD: Phase 2a high-dose NAM showed safety/tolerability but did not meet primary CSF p-tau biomarker endpoint</b>.</p>


<b>Vitamin B3, also known as niacin, nicotinamide, or nicotinic acid</b>, plays a crucial role in energy metabolism and DNA repair.<br>
SEE ALSO <a href="https://nestronics.ca/dbx/tbTargEdit.php?tid=815"> NAD</a> Target
<pre>
Forms of Vitamin B3 and Relevance
Form Notes
Nicotinamide (NAM) Used in most AD and cancer research; does not cause flushing
Nicotinic acid More common in cardiovascular use; causes flushing
Nicotinamide riboside (NR) NAD⁺ precursor with neuroprotective and anti-aging interest
Nicotinamide mononucleotide (NMN) Also boosts NAD⁺; used in aging and cognitive studies

Cancers:
-Many cancers show depleted NAD⁺ levels. Restoring NAD⁺ via niacin or precursors may decrease growth
-Nicotinamide can inhibit sirtuins (SIRT1), which are overexpressed in some cancers
-anti-inflammatory
-In certain cancers, high NAD⁺ levels may support tumor metabolism (Warburg effect).

Alzheimer’s Disease (AD):
-reduces ROS
-Reduces neuroinflammation: Via SIRT1 activation and NF-κB inhibition.
-reduce tau phosphorylation and improve cognitive function.
-Boosting NAD⁺ levels may support memory formation

Food Niacin (mg per 100g) Notes
Tuna (yellowfin, cooked) ~22 mg Among the highest natural sources
Chicken breast (roasted) ~14.8 mg Lean, rich source
Turkey (light meat) ~12 mg Contains tryptophan, also converted to niacin
Beef liver (cooked) ~14 mg Extremely rich in many B vitamins
Salmon (cooked) ~8.5 mg Also provides omega-3s
Pork (lean, cooked) ~6–8 mg Good source of both niacin and thiamine



</pre>


<br>
<h3>Vitamin B3 (Niacin: Nicotinic Acid / Nicotinamide) — Cancer vs Normal Pathway Effects</h3>
<table border="1" cellpadding="4" cellspacing="0">
<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>NAD⁺ pool / Redox capacity (NADH/NADPH)</td>
<td>↑ (often pro-survival; context-dependent)</td>
<td>↑ (cytoprotection; metabolic support)</td>
<td>R→G</td>
<td>Metabolic resilience</td>
<td>Raising NAD⁺ can support tumor metabolism and stress tolerance; also supports normal-cell repair/mitochondria. Directional “benefit” is context- and tumor-genotype dependent.</td>
</tr>

<tr>
<td>2</td>
<td>PARP-mediated DNA repair (NAD⁺-consuming)</td>
<td>↑ capacity if NAD⁺↑; ↓ (high NAM only; model-dependent)</td>
<td>↑ repair capacity if NAD⁺↑; ↓ (high NAM only)</td>
<td>R→G</td>
<td>DNA damage response tuning</td>
<td>Mechanistic bifurcation: NAD⁺ replenishment may enhance repair; high NAM (mM) can functionally inhibit NAD⁺-consuming enzymes in vitro/adjunct contexts.</td>
</tr>

<tr>
<td>3</td>
<td>Sirtuins (Class III “HDAC”) / stress-response programs</td>
<td>↔ (context-dependent); ↓ (high NAM only)</td>
<td>↔; ↓ (high NAM only)</td>
<td>R→G</td>
<td>Epigenetic + mitochondrial signaling modulation</td>
<td>NAM is a known sirtuin reaction product and can inhibit sirtuin activity at sufficiently high concentrations; many “HDAC-like” effects in cell culture are high-dose NAM-driven.</td>
</tr>

<tr>
<td>4</td>
<td>GPR109A (HCAR2) signaling (nicotinic acid >> nicotinamide)</td>
<td>↑ anti-inflammatory / anti-tumor signaling (colon models; context-dependent)</td>
<td>↑ anti-inflammatory signaling; metabolic effects (adipose)</td>
<td>P→R</td>
<td>Immune–epithelial signaling shift</td>
<td>GPR109A activation can suppress colonic inflammation and inflammation-associated carcinogenesis in preclinical models; translational relevance is tissue-context specific.</td>
</tr>

<tr>
<td>5</td>
<td>ROS</td>
<td>↔ (secondary; model-dependent)</td>
<td>↔ (secondary)</td>
<td>R</td>
<td>Redox buffering vs stress</td>
<td>NADPH availability and mitochondrial function can shift ROS handling indirectly; not typically a “direct ROS drug” mechanism unless dosing/model forces oxidative stress.</td>
</tr>

<tr>
<td>6</td>
<td>Ca²⁺ signaling (notably flushing pathway; immune skin cells)</td>
<td>↔ (not core)</td>
<td>↑ (GPR109A-linked Ca²⁺ signaling in specific immune/skin contexts)</td>
<td>P</td>
<td>Trigger-proximal signaling</td>
<td>Ca²⁺ signaling is mechanistically prominent for nicotinic-acid flushing biology; less central as a generalized anticancer axis.</td>
</tr>

<tr>
<td>7</td>
<td>Ferroptosis</td>
<td>↔ (indirect, context-dependent)</td>
<td>↔</td>
<td>R</td>
<td>Lipid-peroxidation sensitivity (indirect)</td>
<td>No canonical “niacin → ferroptosis” axis; any effect would likely be via NADPH/redox network shifts.</td>
</tr>

<tr>
<td>8</td>
<td>HIF-1α / Warburg metabolism</td>
<td>↔ (indirect)</td>
<td>↔</td>
<td>G</td>
<td>Hypoxia/metabolic phenotype (indirect)</td>
<td>NAD⁺ availability can influence glycolytic flux and mitochondrial balance, but direction is strongly model/tumor dependent.</td>
</tr>

<tr>
<td>9</td>
<td><b>Clinical Translation Constraint</b></td>
<td colspan="2">Dose-limited by tolerability/toxicity (NA flushing; hepatotoxicity risk with some regimens; metabolic side effects); many in-vitro concentrations exceed routine systemic exposure.</td>
<td>—</td>
<td>PK / Safety</td>
<td>Anticancer claims are mostly preclinical/contextual; routine supplementation is unlikely to reproduce common in-vitro mM exposures.</td>
</tr>
</table>

<p><b>TSF legend:</b> P: 0–30 min (primary/rapid effects) | R: 30 min–3 hr (acute signaling + stress) | G: &gt;3 hr (gene-regulatory adaptation; phenotype outcomes)</p>






<br>
<h3>Vitamin B3 (Nicotinamide-focused) — Alzheimer’s Disease (AD) / Neurons-Glia (Normal-cell context)</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cells (↑ / ↓ / ↔)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>

<tr>
<td>1</td>
<td>NAD⁺ pool / mitochondrial support</td>
<td>↑</td>
<td>R→G</td>
<td>Bioenergetic resilience</td>
<td>High-dose oral NAM can markedly raise plasma NAM (and related metabolites) in clinical settings; intended to support cellular redox/mitochondrial function.</td>
</tr>

<tr>
<td>2</td>
<td>Tau phosphorylation / proteostasis (hypothesized)</td>
<td>↓ (hypothesized; not confirmed clinically)</td>
<td>G</td>
<td>Biomarker-targeting rationale</td>
<td>Phase 2a early-AD trial of high-dose NAM (48 weeks) was safe/tolerable but did <b>not</b> significantly reduce the primary CSF p-tau biomarker endpoint.</td>
</tr>

<tr>
<td>3</td>
<td>Sirtuins / Class III “HDAC” modulation (NAM as inhibitor at high exposure)</td>
<td>↓ (high concentration only)</td>
<td>R→G</td>
<td>Epigenetic/stress-response reprogramming</td>
<td>Mechanistic rationale includes NAM effects on sirtuin-mediated signaling; clinical translation depends on achieving relevant CNS exposure.</td>
</tr>

<tr>
<td>4</td>
<td>Neuroinflammation</td>
<td>↔ (context-dependent)</td>
<td>R→G</td>
<td>Inflammatory tone shift (indirect)</td>
<td>Potential secondary benefit via metabolic support and immune signaling; not established as a consistent clinical effect in AD.</td>
</tr>

<tr>
<td>5</td>
<td>ROS / Redox stress</td>
<td>↓ (secondary, indirect)</td>
<td>R</td>
<td>Oxidative stress buffering</td>
<td>Likely mediated by improved NAD(P)H-linked buffering/mitochondrial function rather than direct antioxidant chemistry.</td>
</tr>

<tr>
<td>6</td>
<td><b>Clinical Translation Constraint</b></td>
<td>—</td>
<td>—</td>
<td>Trial outcome limits</td>
<td>High-dose NAM can raise plasma levels substantially; CNS penetration/target engagement may be variable; Phase 2a biomarker outcome negative.</td>
</tr>
</table>

<p><b>TSF legend:</b> P: 0–30 min | R: 30 min–3 hr | G: &gt;3 hr</p>