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)
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