Database Query Results : Selenium, Vitamin C (Ascorbic Acid),

Se, Selenium: Click to Expand ⟱
Features: micronutrient
Naturally occurring element. Selenium is incorporated into selenoproteins, such as glutathione peroxidases (GPxs) and thioredoxin reductases (TrxRs), which play critical roles in protecting cells from oxidative damage.
Involved in GPx, TrxR, ans Selenoprotien P which protect normal cells from oxidative stress.
Important in Thyroid hormone metabolism, immune system regulation, reproductive health, and Brain and heart protection.

-recommended daily allowance (RDA) for selenium is about 55 µg/day for adults. (upper tolerance 400ug/day)
-One Brazil nut may contain 50-300ug/nut

Sodium selenite (Na₂SeO₃) is a selenium compound with well-documented anticancer and chemopreventive properties
-Oxidation state: +4 (selenite form of selenium)
-Type: Inorganic selenium compound (water-soluble)

-Sodium selenite generates reactive oxygen species (ROS) selectively in tumor cells.
-Induces cytochrome c release, caspase-3 activation, and DNA fragmentation.
-Reduces VEGF expression and endothelial cell migration.
-Blocks cell division at G2/M phase
-Suppresses MMP-2 and MMP-9 activity
-Activates p53
-Inhibits NF-κB
-PI3K/Akt/mTOR Suppression
-Inactivation of Thioredoxin/Glutathione systems

Narrow therapeutic window:
-Low micromolar (≤5 µM) → anticancer
-High (>10 µM) → toxic to normal cells

Some Selenium Supplements use Sodium Selenite as the active ingredient.
- NOW Foods Selenium, Nature's Bounty Selenium, etc

Other common form is Selenomethionine, as it is better absorbed (found in brazil nuts), but might be less effective?

Sodium selenite might protect against toxicity of AgNPs. also here

In the chemical synthesis of selenium nanoparticles, a precursor such as sodium selenite (Na₂SeO₃) is dissolved in water to form a homogenous solution. A reducing agent, like ascorbic acid or sodium borohydride (NaBH₄), is then added to the solution. The reducing agent donates electrons to the selenium ions (SeO32−SeO32), reducing them to elemental selenium (Se0Se^0). This reduction process leads to the nucleation of selenium atoms, which subsequently grow into nanoparticles through controlled aggregation.

Se NPs might be hepatoprotective.
(chemoprotective) (radioprotective) (radiosensitizer)

Selenium nanoparticles (SeNPs) are a biocompatible, less-toxic, 
and more controllable form of selenium compared to inorganic salts (like sodium selenite).
Major SeNPs hepatoprotective mechanisms
Mechanism	              Description	                       Key markers affected
1. Antioxidant activity	      SeNPs boost antioxidant enzyme          ↓ ROS, ↓ MDA, ↑ GSH, ↑ GPx
                              systems (GPx, SOD, CAT) and scavenge 
                              ROS directly.	
2. Anti-inflammatory effect   Downregulate NF-κB, TNF-α,              ↓ TNF-α, ↓ IL-1β, ↓ IL-6
                              IL-6, and COX-2 pathways.	
3. Anti-apoptotic action      Balance between Bcl-2/Bax and reduce    ↑ Bcl-2, ↓ Bax, ↓ Caspase-3
                              caspase-3 activation in hepatocytes.	
4. Metal/toxin chelation      SeNPs can bind or transform toxic       ↓ liver metal accumulation
                              metals (Cd²⁺, Hg²⁺, As³⁺) 
                              into less harmful complexes.	
5. Mitochondrial protection   Maintain membrane potential,            Preserved ΔΨm, ↑ ATP
                              prevent mitochondrial ROS burst, 
                              and ATP loss.	
6. Regeneration support	      Stimulate hepatocyte proliferation      ↑ PCNA, improved histology
                              and repair via redox signaling 
                              and selenoproteins.

Comparison: SeNPs vs. Sodium Selenite
Property	             SeNPs	                   Sodium Selenite
Toxicity	             Low	                   Moderate–high
Bioavailability	             Controlled, often slow-       Rapid, less controllable
                             release	
ROS balance	             Adaptive, mild antioxidant	   Can flip to pro-oxidant easily
Safety margin	             Wide	                   Narrow
Hepatoprotection	     Strong, sustained	           Protective at low dose, 
                                                           toxic at high dose


"30 mg of Na2SeO3.5H2O was added to 90 mL of Milli-Q water. Ascorbic acid (10 mL, 56.7 mM) was added dropwise to sodium selenite solution with vigorous stirring. 10 µL of polysorbate were added after each 2 ml of ascorbic acid. Selenium nanoparticles were formed after the addition of ascorbic acid. This can be visualized by a color change of the reactant solution from clear white to clear red. All solutions were made in a sterile environment by using a sterile cabinet and double distilled water."


VitC, Vitamin C (Ascorbic Acid): Click to Expand ⟱
Features:
High-dose vitamin C: Some studies have suggested that high-dose vitamin C may be effective in treating certain types of cancer, such as ovarian cancer and pancreatic cancer.
Symptoms of vitamin C deficiency include fatigue, weakness, poor wound healing, ecchymoses, xerosis, lower extremity edema, and musculoskeletal pain—most of them are often observed in end-stage cancer patients. -Vitamin C is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function.
-Ascorbic Acid, Different levels in different Organs
Homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. -(Note the Oncomagnetic success in the brain also was then under conditions of high Vitamin C)

-Ascorbic acid is an electron donor
Ascorbic Acid, can be a Pro-oxidant
"The pro-oxidative activity of ascorbic acid (Figure 2) is associated with the interaction with transition metal ions (especially iron and copper). Under conditions of high, millimolar ascorbate concentration, vitamin C catalyzes the reduction of free transition metal ions, which causes the formation of oxygen radicals."
Ascorbic Acid, formation of H2O2 (Hydrogen Peroxide)
Many studies indicate the toxicity of ascorbate to cancer cells. Much evidence indicates that the underlying phenomenon is the pro-oxidative activity of ascorbate, which induces the formation of H2O2 and oxidative stress.
"ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2)"
-High dose VitC therapy may not be for those with kidney problems
-Oral supplement up to 10g/day?
-Direct regulator of TET↑
-caution for (G6PD-) deficient patients receiving vitamin C infusions

-Note plasma half-life 30mins to 1hr, 1.5-2hr elimination half-life.
oral BioAv water soluble, but has limitiations as 100mg yeilds 60uM/L in plasma, but 1000mg only yeilds 85uM/L. mM concentration are required for effectiveness on cancer cells. Hence why IV administration is common. Boosting HIF increases the intracellular uptake of oxidized VitC
Pathways:
- high dose induces ROS production in cancer cells. Otherwise well known antioxidant in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Caspases↑, DNA damage↑, cl-PARP↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, NF-κB↓,
- reactivate genes thereby inhibiting cancer cell growth : P53↑, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓,
- Others: PI3K↓, AKT↓, STAT↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective,

- Selectivity: Cancer Cells vs Normal Cells
Selenium supplementation may protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress. Meaning it may decrease effectiveness of high dose VitC.(#4468)


Scientific Papers found: Click to Expand⟱
4459- Se,  VitC,    Nano and mesosized selenium and its synthesis using the ascorbic acid route
*eff↑, The most commonly used reducing agent is ascorbic acid because the reaction may be performed at ambient temperature in water and the ascorbic acid is affordable and non-harmful.
*Dose↝, Sodium selenite (Schuchardt Munchen, Germany), ascorbic acid, and hydrochloric acid (Penta, Czech Repubic) were used. All chemicals were used without further purification. Demineralized water was used for the preparation of all solutions
*Dose↝, 200 ml of the solution of 6 mM sodium selenite was mixed with 40 ml of ascorbic acid solution at different concentrations. The molar quantity ratios in which individual samples were mixed are shown in Table 1.

4460- Se,  VitC,    Ascorbic acid-mediated selenium nanoparticles as potential antihyperuricemic, antioxidant, anticoagulant, and thrombolytic agents
Dose?, see description for method for synthesis

4461- Se,  VitC,    Synthesis, Characterization, and Cytotoxic Evaluation of Selenium Nanoparticles
*Dose?, see description for manufacturing SeNPs

4462- Se,  VitC,    Selenium nanoparticles: influence of reducing agents on particle stability and antibacterial activity at biogenic concentrations
- Study, Nor, NA
*Dose↝, see description for synthesis method
*Bacteria↓,

4463- Se,  VitC,    Selenium nanoparticles: Synthesis, characterization and study of their cytotoxicity, antioxidant and antibacterial activity
- Study, Nor, NA
Dose↝, see description for synthesis

4465- Se,  VitC,    Selenium nanoparticles: Synthesis, in-vitro cytotoxicity, antioxidant activity and interaction studies with ct-DNA and HSA, HHb and Cyt c serum proteins
- Study, NA, NA
*other↝, The aim of this study was the synthesis of selenium nanoparticles (SeNPs) employing vitamin C as a biocompatible and low toxic reducing agent.
*eff↑, ynthesized nano-selenium can bind to the most important blood proteins such as human serum albumin (HSA), human hemoglobin (HHb), and Cytochrome c (Cyt c).
AntiCan↑, reported that Nano-selenium demonstrates anti-tumor and anticancer activity through induction of cancer cell apoptosis with minimal side effects on normal cells
*Dose↝, adequate selenium intake has been reported to be between 55 and 75 μg /day with an upper limit of ∼400 μg
*BioAv↑, Nano-selenium has high biological activity, better bioavailability and low toxicity compared to organic and inorganic Se-compounds such as Se(IV) and Se(VI) [9]
*other↝, synthesis listed in description

4467- Se,  VitC,  Chit,    Nano-chitosan-coated, green-synthesized selenium nanoparticles as a novel antifungal agent against Sclerotinia sclerotiorum in vitro study
- Study, NA, NA
*Dose↝, CS NPs with a tiny particle size of an average diameter of 6.43 ± 0.2 nm
*Dose↝, L.P. -Se NPs with small particle size and good dispersion due to the presence of extract biomolecules that serve as capping agents providing stabilization and reduced particle size with an average diameter of 42.8 ± 18.5 nm

4491- Se,  Chit,  VitC,    Synthesis of a Bioactive Composition of Chitosan–Selenium Nanoparticles
- Study, NA, NA
*ROS↓, chitosan-selenium nanoparticles has a corrective effect on the oxidative processes of the body, reducing the activity of free-radical oxidation in the blood of animals
*selenoP↑, Selenium is included in selenoproteins, which have a wide range of biological effects, including antioxidant and anti-inflammatory effects.
*antiOx↑,
*Inflam↓,
*Risk↓, The lack of selenium in the body is a risk factor for the development of various pathologies.
*toxicity↓, Compared to organic and inorganic forms of selenium, selenium nanoparticles (NPs) exhibit lower toxicity and superior antioxidant, immunomodulatory, bactericidal, and antitumor activity
AntiTum↑,
Dose↝, NPs with sizes of 2–3 nm (33.4 wt %) and ~ 37 nm (66.6 wt %) are formed.

4606- Se,  VitC,    Antibacterial and anti-biofilm efficacy of selenium nanoparticles against Pseudomonas aeruginosa: Characterization and in vitro analysis
- in-vitro, NA, NA
*Dose↝, SeNPs were synthesized using ascorbic acid as a reducing agent and characterized.
*Dose↝, SeNPs demonstrated a round shape with a diameter of 15–18 nm.
*Bacteria↓, SeNPs could be a promising alternative or adjunctive treatment option for combating antibiotic-resistant P. aeruginosa infections.

609- VitC,  ALA,  VitK3,  Se,    Vitamin C and Cancer: Is There A Use For Oral Vitamin C?
OS↑,

4468- VitC,  Se,    Selenium modulates cancer cell response to pharmacologic ascorbate
- in-vivo, GBM, U87MG - in-vitro, CRC, HCT116
eff↓, In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts
TumCD↑, pharmacologic ascorbate raises the serum ascorbate concentration into the millimolar range, a concentration at which ascorbate has been shown to kill cancer cells in vitro
ChemoSen↑, Pharmacologic ascorbate has been shown to synergize with multiple chemotherapeutic agents in animal models and is well-tolerated in human patients [1,4], motivating ongoing clinical trials.
ROS⇅, Indeed, the role of ascorbate as either a pro- or anti-oxidant has been suggested to depend on concentration, with low doses mitigating ROS and high doses generating them
DNAdam↑, H2O2 generation by ascorbate has been associated with DNA damage and subsequent PARP activation, which can deplete NAD and thereby inhibit glycolysis
PARP↑,
NAD↓,
Glycolysis↓,
Fenton↑, Ascorbate cytotoxicity depends on the intracellular labile iron pool (Fig 1a) [3,9]. One explanation for this phenomenon is that ascorbate-generated H2O2 causes toxicity through Fenton chemistry
lipid-P↑, extensive lipid peroxidation
eff↓, More generally, they establish dietary selenium depletion as a potential means of sensitizing tumors to free radical stress.
H2O2↑, High concentrations (mM) of ascorbate have been shown to generate H2O2 in vitro
other↝, Selenium supplementation has been shown to protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,1,   AntiTum↑,1,   ChemoSen↑,1,   DNAdam↑,1,   Dose?,1,   Dose↝,2,   eff↓,2,   Fenton↑,1,   Glycolysis↓,1,   H2O2↑,1,   lipid-P↑,1,   NAD↓,1,   OS↑,1,   other↝,1,   PARP↑,1,   ROS⇅,1,   TumCD↑,1,  
Total Targets: 17

Results for Effect on Normal Cells:
antiOx↑,1,   Bacteria↓,2,   BioAv↑,1,   Dose?,1,   Dose↝,8,   eff↑,2,   Inflam↓,1,   other↝,2,   Risk↓,1,   ROS↓,1,   selenoP↑,1,   toxicity↓,1,  
Total Targets: 12

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