High Dose Vitamin C- Cancer Treatment- Direct Benefits & As Adjunct to Other Treatments

B Windham (Ed), DAMS Intl, 2021

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More than half of colorectal cancers (CRCs) harbor activating mutations in KRAS or BRAF, yet those cancers are the most refractory to current targeted therapies. Our group and others showed that oncogenic mutations in KRAS or BRAF contribute to the Warburg effect and the addiction to glucose in part by upregulating a glucose transporter, GLUT1, that allows cancer cells to take up glucose efficiently. These data suggest a strategy for targeting KRAS or BRAF mutant cancer by exploiting the selective expression of GLUT1 and the metabolic liability that comes with increased reliance on glycolysis. Indeed, by targeting these unique features in these cancer cells, we recently showed that high dose vitamin C could selectively kill KRAS or BRAF mutant CRC cells. While KRAS and BRAF mutations are certainly two of the most frequently mutated oncogenes in human cancer, they are not the only mutations known to affect glucose metabolism and sensitivity towards ascorbate therapy. Now a growing number of preclinical studies are showing how high-dose vitamin C might benefit cancer patients. In our view, the implementation of this treatment paradigm could provide benefit to many cancer patients.

In a 1976 study conducted by Pauling and Dr. Ewan Cameron, a Scottish surgeon, of 100 patients with terminal cancer, those treated with vitamin C had an improved quality of life and a fourfold increase in their mean survival time. ⁹ ^. These results have been later replicated and expanded.

⁽ Later studies done at Mayo Clinic claiming to refute these results were not similar or comparable as explained by NCI doctors.)

Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer , E Cameron , L Pauling, Proc Natl Acad Sci U.S.A. 1976 Oct;73(10): 3685-9 &

Intravenous ascorbic acid: protocol for its application and use, H D Riordon et al, P R Health Sci J, 2003 Sep;22(3):287-90. &

High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis , Chang-Hwan Yeom , et al, J Transi Med, 2009 Aug 11;7:70 &

Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer , O Aguilera et al, Oncotarget . 2016 Jul 26;7(30):47954-47965. https://pubmed.ncbi.nlm.nih.gov/1068480/ ; &

Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach , Curr Oncol 2018 Apr;25(2):139-148. E Klimant et al,

The use of IV C is a safe supportive intervention to decrease inflammation in the patient and to improve symptoms related to antioxidant deficiency, disease processes, and side effects of standard cancer treatments.

Vitamin C as a Modulator of the Response to Cancer Therapy , Molecules, 2019 Jan 28;24(3):453.

Wiktoria Blaszczak et al,

Experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5'-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate , permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron( III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and can also promote activity of specific drugs.

Ascorbic Acid in Cancer Treatment : Let the Phoenix Fly, Cancer Cell, 2018 Nov 12;34(5):700-706.

N Shinoy et al;

Two mechanisms of anti-cancer activity with ascorbate have gained prominence: hydrogen peroxide-induced oxidative stress and DNA demethylation mediated by ten-eleven translocation enzyme activation.

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The Role of Oxidative Stress Modulators (Melatonin) in Breast Cancer , Curr Med Chem 2018;25(33):4084-4101. S Suzen et al

Our data, in accordance with the literature, suggest an important role for melatonin in breast cancer prevention and adjuvant therapy.

Ascobic Acid and Dehydroascorbic Acid Concentrations in Plasma and Peripheral Blood Mononuclear Cells after Orals Liposomal-Encapsulated or Intravenous Ascorbic Acid Delivery

Nina A. Mikirova , PhD, Riordan Clinic

The data from the study indicate that oral delivery of 4 g of vitamin C encapsulated in liposomes produces circulating concentrations of vitamin C that are greater than non-encapsulated oral, but less than achieved by intravenous administration. The levels of ascorbate that were achieved in plasma after 4 grams vitamin C were 1419 uM for intravenous ascorbate, 124 uM for un-encapsulated and 170 uM for encapsulated (liposomal) ascorbate.

High Dose Vit C is effective at treating several types of cancer and as an effective adjunct treatment in several types of cancer,

Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells , Anti-Cancer Res. 2019 Feb;39(2):751-758.

Combining high-dose vitamin C with conventional anti-cancer drugs can have therapeutic advantages against breast cancer cells.

Intravenous Vitamin C and Cancer: A Systematic Review , H Fritz et al, Integrative Cancer Therapies, 2014, Vol. 13(4) 280�300,

There is high-quality clinical evidence on the safety and effectiveness of IVC. The existing evidence is suggestive of a good safety profile and potentially important antitumor activity; IVC has improved the quality of life and symptom severity of some patients with cancer, and several cases of cancer remission have been reported.

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Why high-dose vitamin C kills cancer cells

Low levels of catalase enzyme make cancer cells vulnerable to high-dose vitamin C

Science Daily, January 9, 2017, https://www.sciencedaily.com/releases/2017/01/170109134014.htm

The new study shows that tumor cells with low levels of catalase enzyme activity are much less capable of removing hydrogen peroxide than normal cells, and are more susceptible to damage and death when they are exposed to high doses of vitamin C

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Melatonin : the watchdog of villous trophoblast homeostasis against hypoxia/reoxygenation-induced oxidative stress and apoptosis , Mol Cell Endocrinol 2013 Dec 5;381(1-2):35-45.

This study shows that melatonin protects the villous trophoblast against H/R-induced oxidative stress and apoptosis and suggests a potential preventive and therapeutic use of this indolamine in pregnancy complications characterized by syncytiotrophoblast survival alteration.

The epigenetic role of vitamin C in health and disease , Cell Mol Life Sci 2016 Apr;73(8):1645-58,

Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Entacapone is an Antioxidant More Potent than Vitamin C and Vitamin E for Scavenging of Hypochlorous Acid and Peroxynitrite , and the Inhibition of Oxidative Stress-Induced Cell Death, Med Sci Monit 2016 Mar 1;22:687-96; A Y Chen et al;

Entacapone (ENT), a clinical drug for the treatment of Parkinson's disease, has been shown to have antioxidant effects. ENT is an antioxidant that can scavenge toxic HOCl and ONOO- species and inhibit oxidative stress-induced cell death more effectively than vitamin C and vitamin E. ENT may have new clinical applications as an antioxidant in the treatment of ROS-induced diseases including cardiovascular disease, cancer, and neurodegenerative diseases.

Vitamin C May Help Fight Cancers

There is strong scientific evidence that high doses of vitamin C are a tool against some cancers. According to DiNicolantonio's video, liposomal vitamin C can produce blood levels that have a 50% kill rate against lymphoma cells in vitro � a dramatic finding. ²⁸

Vitamin C has shown effectiveness against prostate, pancreatic, hepatocellular, colon, mesothelioma and neuroblastoma cell lines. ²⁹ According to the Stephenson Cancer Center: ³⁰

"The potential mechanisms through which treatment with high-dose ascorbic acid may exert its effects on cancer cells have been extensively investigated. Several studies have demonstrated that the in vitro direct cytotoxic effect of ascorbic acid on various types of cancer cells is mediated through a chemical reaction that generates hydrogen peroxide.

Treating colon cancer cells with 2 mM to 3 mM of ascorbic acid resulted in downregulation of specificity protein ( Sp ) transcription factors, iron metabolism disruption, and Sp -regulated genes involved in cancer progression.

One study suggested that ascorbate-mediated prostate cancer cell death may occur through activation of an autophagy pathway � Another in vitro study found that ascorbic acid killed colorectal cancer cells with KRAS or BRAF mutations by inhibiting the enzyme glyceraldehyde 3-phosphate dehydrogenase."

^29, ³⁰ Stephenson Cancer Center 2020 ,

Good Food � including herbs, flavonoids, vegetables, etc. is effective in preventing and supporting treatment of Cancer and other chronic conditions-

Vitamin A & Beta-carotene -Cancer

The flavonoids , vitamins, minerals and carotenoids in carrots all contribute to numerous other health benefits. Data have demonstrated the compounds found in carrots have properties that lower the risk of diabetes, cardiovascular disease, high blood pressure and cancer. ²⁴

Data show smokers who eat carrots more than once weekly have a lower risk of lung cancer , ²⁵ and a beta-carotene rich diet may help protect against prostate cancer ²⁶ and colon cancer, ²⁷ and to reduce the risk of gastric cancer. ²⁸

Carrots also contain falcarinol, a natural toxin they use against fungal disease, which may stimulate cancer-fighting mechanisms in your body and has demonstrated the ability to reduce the risk of tumors in rats. ²⁹

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� Pineapple (enzyme bromelain � which is directly linked to reducing inflammatory pain in rheumatoid arthritis and osteoarthritis 33 . promising anti-cancer benefits, Vit C, Vit Bs, manganese, fight virus, bacterial, sinus infections

Cauliflower (vitamin C, potassium, vitamin B6, protein, minerals, and fiber; glucosinolates fight infection and inflammation, anti-cancer. glucosinolates break down into compounds that not only help relieve inflammation but can also fight cancer by protecting your cells from viruses and bacteria.

� According to the Arthritis Foundation of America, antioxidant-rich berries are among the best fruits for arthritis, because they help rid the body of free radicals that promote inflammation and help prevent heart disease and certain cancers 15 .

� Research studies show that proanthocyanidin (antioxidant) compounds from grape seeds and skins may prevent or delay the growth of cancer cells. Some cancers that they may protect from include colon, lung, throat, mouth, pancreas, and prostate 25 .

Papaya- Many researchers believe that oxidative damage contributes to Alzheimer�s disease. In one study, people with Alzheimer�s were given a fermented papaya extract for six months. They experienced a 40% drop in a biomarker that indicated oxidative damage to their DNA and that has also been linked to aging and cancer 30 .

� Preliminary studies indicate that bromelain may also have promising anti-cancer benefits, such as inhibiting tumor development 34 .

� Many studies indicate that lycopene helps impact the progression of cellular carcinogenesis, which can cause cell depletion and create tumors. It does this through many different regulatory functions in the body 39 .

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Garlic- anti-cancer They were found to have a 35% lower risk of colon cancer than their counterparts who did not consume garlic 58 .

Cat�s claw is said to have immune-boosting properties along with its role in fighting inflammation. It may have positive effects on sleep-wake disturbances, fatigue, anxiety, and depression in patients with cancer 76 .

The essential oil of cloves, known as CEO, is where cloves derive their effects from. It has antimicrobial, antiviral, and antioxidant properties that help fight inflammation and tissue remodeling. It also has cancer-fighting properties because of its most active component, which is called eugenol 81 .

Green tea. Here is what it can do with regular consumption 85 : Protect against cancer

Ganoderma Lucidum (Reishi Mushroom) and cancer , J BUON. Jul-Aug 2016;21(4):792-798. Ahmet Unlu et al; https://pubmed.ncbi.nlm.nih.gov/27685898/

when the findings obtained from laboratory studies are considered, it turns that G. Lucidum is likely to have some benefits for cancer patients.

Medicinal mushroom science: Current perspectives, advances, evidences, and challenges, Solomon P Wasser , Biomed J, Nov-Dec 2014;37(6):345-56. https://pubmed.ncbi.nlm.nih.gov/25179726/

Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases.