What is High Dose Intravenous IV Vitamin C Treatment for Cancer?

Many studies have confirmed the safety and indicated the efficacy of High-dose IV Vitamin C in eradicating tumor cells in many different cancers.

1. Oxygen sensing

The internal region of the tumor does not get enough oxygen and adapts to hypoxic conditions. The tumor cells then start growing independent of oxygen availability. To achieve this they activate a transcription factor HIF-1. Vitamin C regulates HIF hydroxylases that are involved in the deactivation of the transcription Factor HIF-1. Many studies have shown a negative correlation between HIF-1 and Vitamin C levels from tumor samples.

2. ROS (Reactive Oxygen Species) Scavenger

Vitamin C is a chain-breaking antioxidant that halts the propagation of peroxidative processes and reacts with membrane-bound oxidized vitamin E, thus reducing it back to its native form.9,10 Vitamin C also plays a role in many enzyme reactions, including those leading to the synthesis of amino acids and peptide hormones. These findings suggest that vitamin C behaves as an ROS scavenger and may be effective in combating oxidative damage under conditions of increasing oxygen concentrations and apoptosis. Several randomized studies of the efficacy of antioxidant vitamins in preventing preeclampsia have shown no beneficial effects of vitamin C and E supplementation during pregnancy with respect to reducing the risk of preeclampsia.11–15 Intriguingly, epidemiological studies have reported a decreasing trend in the incidence of severe preeclampsia among patients with a high dietary intake of vitamin C and increased plasma vitamin C levels.16,17

3. AS A PRO-OXIDANT

Vitamin C in high concentrations (Intravenously) can act as a Pro-oxidant. This will activate the hydrogen peroxide dependent Cytotoxicity in cancer cells but not in normal cells. This is done so by the redox capability of vitamin C on metals such as iron and copper, which are generally abundant in cancer cells.  Hydrogen peroxide reacts with these metal ions to form hydroxyl radicals, which are highly reactive chemical species and can easily damage cellular material Thus killing the cancer cells. Moreover, cancer cells also lack catalase activity which makes them extremely vulnerable to oxidative stress. Increasing oxidative stress in cancer cells can be an important anticancer strategy that works on the same underlying principles such as chemo and radiation therapy.

Effect of glycolysis inhibitors can also be enhanced by high dose vitamin c in ROS dependent manner since both inhibitors increase oxidative stress levels.

4. Cofactor activation

As mentioned earlier vitamin c acts as a reducing agent of iron which makes it crucial for Fe containing protein functions such as mitochondrial respiratory chains, collagen synthesis, and oxidative stress regulation.

5. EMT and Invasion

ECM (extracellular matrix) provides biomechanical and biochemical signals to modulate the behavior of cancer cells whilst maintaining tissue morphology and integrity. The ECM is a dynamic structure that is continually reshaped by a variety of enzymes and signaling molecules. Under pathological conditions, ECM remodeling is often accompanied by cancer growth and cancer metastasis.

Collagen is one of the most important structural proteins which is involved in the adhesion of cells to ECM. regulation of collagen synthesis is a key factor affecting cancer progression.

Collagen forms a tertiary structure called collagen fibrils, these fibrils are responsible to hold a cell and adhere it to ECM. vitamin c is known to stabilize these strong crosslinks and prevent neoplastic invasions. Vitamin C is also shown to target cancer invasion by reversing the process of EMT (epithelial to mesenchymal transition) by deactivating HIF (hypoxia-inducible factor). Later it was also shown that vitamin c also works by increasing the E- cadherin levels and reducing vimentin thus suppressing the EMT and inhibiting cell migration.

6. Effect on chemotherapy

In pre-clinical models, high-dose Vitamin C is reported to enhance the effectivity of a wide variety of chemotherapeutics such as carboplatin [63, 89], cisplatin [51, 89, 100,101,102,103, 179, 180], chlorambucil [181], 5-FU [88, 89, 182], gemcitabine [14, 110, 183, 184] and temozolomide [16, 54] in various cancer cell types, often in a synergistic manner or by enhancing treatment efficacy. This is done so by increasing the number of reactive oxygen species.

7. Immunomodulation

Most immune cells maintain high levels of vitamin c which can affect many processes involved in the immune response. For example, ascorbate is a well-known antioxidant maintained at a high level in immune cells also its cofactor activity for oxygenases has a detrimental role in the innate and adaptive immune response. Vitamin C is also involved in the differentiation and polarization of myeloid and T-cells, development of B-cells, maturation and activation of T-cells, Cytokine production, Chemotaxis, and enhancing NK cell activity to kill cancer cells. Recent studies have also shown that Vitamin C is also involved in regulating the epigenetic profile of immune cells by TET activity restoration in Treg cells which results in Foxp3 re-expression, driving proper immune cell functions.