Vitamin B3,Niacin / ROS 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
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


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↑,
4031- VitB3,    Nicotinamide Riboside-The Current State of Research and Therapeutic Uses
- Review, NA, NA
*cardioP↑, *neuroP↑, *NAD↑, *SIRT1↑, *NADPH↑, *ROS↓, *IL2↓, *IL5↓, *IL6↓, *TNF-α↓, *Inflam↓, *BioAv↝, *BioAv↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

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↓, 2,   SIRT3↑, 1,  

Core Metabolism/Glycolysis ⓘ

NAD↑, 1,   NADPH↑, 1,   SIRT1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   SIRT6↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL2↓, 1,   IL5↓, 1,   IL6↓, 1,   Inflam↓, 2,   MCP1↓, 1,   RANTES↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   memory↑, 1,   motorD↑, 1,   neuroP↑, 1,  
Total Targets: 24

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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