Vitamin B3,Niacin / SIRT6 Cancer Research Results

VitB3, Vitamin B3,Niacin: Click to Expand ⟱
Features:

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

Vitamin B3, also known as niacin, nicotinamide, or nicotinic acid, plays a crucial role in energy metabolism and DNA repair.
SEE ALSO NAD Target 
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

Vitamin B3 (Niacin: Nicotinic Acid / Nicotinamide) — Cancer vs Normal Pathway Effects

Rank Pathway / Axis Cancer Cells (↑ / ↓ / ↔) Normal Cells (↑ / ↓ / ↔) TSF Primary Effect Notes / Interpretation
1 NAD+ pool / Redox capacity (NADH/NADPH) ↑ (often pro-survival; context-dependent) ↑ (cytoprotection; metabolic support) R→G Metabolic resilience Raising NAD+ can support tumor metabolism and stress tolerance; also supports normal-cell repair/mitochondria. Directional “benefit” is context- and tumor-genotype dependent.
2 PARP-mediated DNA repair (NAD+-consuming) ↑ capacity if NAD+↑; ↓ (high NAM only; model-dependent) ↑ repair capacity if NAD+↑; ↓ (high NAM only) R→G DNA damage response tuning Mechanistic bifurcation: NAD+ replenishment may enhance repair; high NAM (mM) can functionally inhibit NAD+-consuming enzymes in vitro/adjunct contexts.
3 Sirtuins (Class III “HDAC”) / stress-response programs ↔ (context-dependent); ↓ (high NAM only) ↔; ↓ (high NAM only) R→G Epigenetic + mitochondrial signaling modulation 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.
4 GPR109A (HCAR2) signaling (nicotinic acid >> nicotinamide) ↑ anti-inflammatory / anti-tumor signaling (colon models; context-dependent) ↑ anti-inflammatory signaling; metabolic effects (adipose) P→R Immune–epithelial signaling shift GPR109A activation can suppress colonic inflammation and inflammation-associated carcinogenesis in preclinical models; translational relevance is tissue-context specific.
5 ROS ↔ (secondary; model-dependent) ↔ (secondary) R Redox buffering vs stress NADPH availability and mitochondrial function can shift ROS handling indirectly; not typically a “direct ROS drug” mechanism unless dosing/model forces oxidative stress.
6 Ca2+ signaling (notably flushing pathway; immune skin cells) ↔ (not core) ↑ (GPR109A-linked Ca2+ signaling in specific immune/skin contexts) P Trigger-proximal signaling Ca2+ signaling is mechanistically prominent for nicotinic-acid flushing biology; less central as a generalized anticancer axis.
7 Ferroptosis ↔ (indirect, context-dependent) ↔ R Lipid-peroxidation sensitivity (indirect) No canonical “niacin → ferroptosis” axis; any effect would likely be via NADPH/redox network shifts.
8 HIF-1α / Warburg metabolism ↔ (indirect) ↔ G Hypoxia/metabolic phenotype (indirect) NAD+ availability can influence glycolytic flux and mitochondrial balance, but direction is strongly model/tumor dependent.
9 Clinical Translation Constraint Dose-limited by tolerability/toxicity (NA flushing; hepatotoxicity risk with some regimens; metabolic side effects); many in-vitro concentrations exceed routine systemic exposure. — PK / Safety Anticancer claims are mostly preclinical/contextual; routine supplementation is unlikely to reproduce common in-vitro mM exposures.

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


Vitamin B3 (Nicotinamide-focused) — Alzheimer’s Disease (AD) / Neurons-Glia (Normal-cell context)

Rank Pathway / Axis Cells (↑ / ↓ / ↔) TSF Primary Effect Notes / Interpretation
1 NAD+ pool / mitochondrial support ↑ R→G Bioenergetic resilience High-dose oral NAM can markedly raise plasma NAM (and related metabolites) in clinical settings; intended to support cellular redox/mitochondrial function.
2 Tau phosphorylation / proteostasis (hypothesized) ↓ (hypothesized; not confirmed clinically) G Biomarker-targeting rationale Phase 2a early-AD trial of high-dose NAM (48 weeks) was safe/tolerable but did not significantly reduce the primary CSF p-tau biomarker endpoint.
3 Sirtuins / Class III “HDAC” modulation (NAM as inhibitor at high exposure) ↓ (high concentration only) R→G Epigenetic/stress-response reprogramming Mechanistic rationale includes NAM effects on sirtuin-mediated signaling; clinical translation depends on achieving relevant CNS exposure.
4 Neuroinflammation ↔ (context-dependent) R→G Inflammatory tone shift (indirect) Potential secondary benefit via metabolic support and immune signaling; not established as a consistent clinical effect in AD.
5 ROS / Redox stress ↓ (secondary, indirect) R Oxidative stress buffering Likely mediated by improved NAD(P)H-linked buffering/mitochondrial function rather than direct antioxidant chemistry.
6 Clinical Translation Constraint — — Trial outcome limits High-dose NAM can raise plasma levels substantially; CNS penetration/target engagement may be variable; Phase 2a biomarker outcome negative.

TSF legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr
SIRT6, Sirtuin 6: Click to Expand ⟱
Source:
Type:
– SIRT6 is involved in maintaining genomic stability through its roles in DNA repair and chromatin remodeling.
– By promoting efficient DNA repair, SIRT6 may help prevent the accumulation of genetic mutations that drive tumorigenesis.

– In several studies, lower SIRT6 expression has been associated with more aggressive tumor behavior and poorer overall survival, supporting its role as a tumor suppressor in those contexts.
– Conversely, in some cancers, higher SIRT6 expression has been linked to enhanced survival signaling or metabolic reprogramming that might support tumor growth, suggesting a possible oncogenic role.
Scientific Papers found: Click to Expand⟱
4036- NAD,  VitB3,    NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency
- in-vivo, AD, NA
*Inflam↓, *p‑tau↓, *DNAdam↓, *memory↑, *motorD↑, *cognitive↑, *BBB↑, IL1β↓, *TNF-α↓, *MCP1↓, *RANTES↓, *ROS↓, *SIRT3↑, *SIRT6↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,  
Total Targets: 1

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,   SIRT3↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   SIRT6↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   MCP1↓, 1,   RANTES↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   motorD↑, 1,  
Total Targets: 13

Scientific Paper Hit Count for: SIRT6, Sirtuin 6
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:359  Target#:1135  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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