High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice.
Hypoxia-inducible factor-1 (HIF-1) governs cellular adaption to the hypoxic microenvironment and is associated with a proliferative, metastatic, and treatment-resistant tumor phenotype. HIF-1 levels and transcriptional activity are regulated by proline and asparagine hydroxylases, which require ascorbate as cofactor. Ascorbate supplementation reduced HIF-1 activation in vitro, but only limited data are available in relevant animal models. There is no information of the effect of physiological levels of ascorbate on HIF activity and tumor growth, which was measured in this study. C57BL/6 Gulo(-/-) mice (a model of the human ascorbate dependency condition) were supplemented with 3300 mg/L, 330 mg/L, or 33 mg/L of ascorbate in their drinking water before and during subcutaneous tumor growth of B16-F10 melanoma or Lewis lung carcinoma (LL/2). Ascorbate levels in tumors increased significantly with elevated ascorbate intake and restoration of wild-type ascorbate levels led to a reduction in growth of B16-F10 (log phase P < 0.001) and LL/2 tumors (lag growth P < 0.001, log phase P < 0.05). Levels of HIF-1α protein in tumors decreased as dietary ascorbate supplementation increased for both tumor models (P < 0.001). Similarly, tumor ascorbate was inversely correlated with levels of the HIF-1 target proteins CA-IX, GLUT-1, and VEGF in both B16-F10 and LL/2 tumors (P < 0.05). The extent of necrosis was similar between ascorbate groups but varied between models (30% for B16-F10 and 21% for LL/2), indicating that ascorbate did not affect tumor hypoxia. Our data support the hypothesis that restoration of optimal intracellular ascorbate levels reduces tumor growth via moderation of HIF-1 pathway activity.
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Gulonolactone oxidase; VEGF; hypoxia-inducible factor 1; vitamin C
In this trial, the patients had a less than 33% likelihood of achieving a meaningful response from any treatment. In spite of that, three of the 14 patients had increased energy level, functional improvement, and transient stable disease.
Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.
We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalicacid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.
Despite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.
Chikungunya is a viral illness characterized by severe joint pains, which may persist for months to years. There is no effective treatment for this disease. We treated 56 patients with moderate to severe persistent pains with a single infusion of ascorbic acid ranging from 25-50 grams and hydrogen peroxide (3 cc of a 3% solution) from July to October 2014. Patients were asked about their pain using the Verbal Numerical Rating Scale-11 immediately before and after treatment. The mean Pain Score before and after treatment was 8 and 2 respectively (60%) (p < 0.001); and 5 patients (9%) had a Pain Score of 0. The use of intravenous ascorbic acid and hydrogen peroxide resulted in a statistically significant reduction of pain in patients with moderate to severe pain from the Chikungunya virus immediately after treatment.
New article out of New Zealand
Carr, Vissers, and Cook
Fatigue is a common, often debilitating, side effect of cancer chemotherapy.
Pharmacologic vitamin C has been used as an alternative treatment for the disease
itself but its effects on fatigue have not often been documented. Here we report on the
case of a woman with recurrent breast cancer, undergoing weekly chemotherapy, with
lethargy as a major symptom. Vitamin C (50 g/session) was administered twice
weekly and quality of life and multidimensional fatigue symptomology questionnaires
were undertaken. Dramatic decreases in fatigue and insomnia were observed, as well
as increased cognitive functioning. There were no adverse side effects of i.v. vitamin
Nature, BBC, NBC. Our paper that first showed that cancer-killing vitamin C levels could be achieved in people:
Med Hypotheses. 1995 Mar;44(3):207-13.http://www.ncbi.nlm.nih.gov/pubmed/7609676
Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent.
Riordan NH, Riordan HD, Meng X, Li Y, Jackson JA.
This spreadsheet was created by Dr. Joseph Casciari, a dear friend and genius collaborator. It allows for the prediction of plasma levels of ascorbate. Input dose, duration, volume, patient height and weight.Vitamin C Pharmacokinetic Curves