What is high-dose ?Vitamin C (also called L-ascorbic acid or ascorbate) is a nutrient that humans must get from food or dietary supplements since it cannot be made in the body. Vitamin C is an antioxidant and helps prevent oxidative stress. It also works with enzymes to play a key role in making collagen.When taken by intravenous (IV) infusion, vitamin C can reach much higher levels in the blood than when it is taken by mouth. Studies suggest that these higher levels of vitamin C may cause the death of cancer cells in the laboratory.A severe deficiency (lack) of vitamin C in the diet causes scurvy, a disease with symptoms of extreme weakness, lethargy, easy bruising, and bleeding. The lack of vitamin C in patients with scurvy makes collagen thinner in texture; when vitamin C is given, collagen becomes thicker again. What is the history and use of high-dose vitamin C as a complementary and alternative treatment for ?High-dose vitamin C has been studied as a treatment for patients with cancer since the 1970s.
A Scottish surgeon named Ewan Cameron worked with Nobel Prize-winning chemist Linus Pauling to study the possible benefits of vitamin C therapy in clinical trials of cancer patients in the late 1970s and early 1980's. Surveys of healthcare practitioners at United States CAM conferences in recent years have shown that high-dose IV vitamin C is frequently given to patients as a treatment for infections, fatigue, and cancers, including breast cancer. What is the theory behind the claim that high-dose vitamin C is useful in treating cancer?More than fifty years ago, a study suggested that cancer was a disease of changes in connective tissue caused by a lack of vitamin C. In the 1970's, it was proposed that high-dose ascorbic acid could help build resistance to disease or infection and possibly treat cancer.Later studies showed that the levels of vitamin C that collect in the bloodstream depend on how it is taken. How is high-dose vitamin C administered?Vitamin C may be given by intravenous (IV) infusion or taken by mouth, although much higher blood levels are reached when given intravenously.
Have any preclinical (laboratory or animal) studies been conducted using high-dose vitamin C?Laboratory studies and animal studies have been done to find out if high-dose vitamin C may be useful in preventing or treating cancer. Many laboratory studies have been done to find out how high-dose vitamin C may cause the death of cancer cells. The anticancer effect of vitamin C in different types of cancer cells involves a chemical reaction that makes hydrogen peroxide, which may kill cancer cells.Laboratory studies have shown the following:However, not all laboratory studies combining vitamin C with anticancer therapies have shown benefit. Combining dehydroascorbic acid, a particular form of vitamin C, with chemotherapy made it less effective in killing some kinds of cancer cells.Studies of high-dose vitamin C have been done in animal models (animals given a disease either the same as or like a disease in humans). Some of the studies showed the vitamin C helped kill more cancer cells:However, other animal studies have shown that vitamin C interferes with the anticancer action of certain drugs, including the following: Have any clinical trials (research studies with people) of high-dose intravenous (IV) vitamin C been conducted?
Several studies of high-dose vitamin C in patients with cancer have been done in recent years, including the following:Studies of vitamin C aloneStudies of vitamin C combined with other drugsStudies of vitamin C combined with other drugs have shown mixed results:More studies of combining high-dose IV vitamin C with other drugs are in progress. Have any side effects or risks been reported from high-dose vitamin C?Intravenous high-dose ascorbic acid has caused very few side effects in clinical trials. However, high-dose vitamin C may be harmful in patients with certain risk factors. Have any been reported from combining high-dose vitamin C with anticancer drugs?A drug interaction is a change in the way a drug acts in the body when taken with certain other drugs. High-dose vitamin C, when combined with some anticancer drugs, may cause them to be less effective. So far, these effects have been seen only in some laboratory and animal studies. No clinical trials have been done to further research these drug interactions in humans.
See Question 5 and Question 6 for more information on combining vitamin C with anticancer drugs. Is high-dose vitamin C approved by the U.S. Food and Drug Administration for use as a in the United States?The U.S. Food and Drug Administration (FDA) has not approved the use of high-dose vitamin C as a treatment for cancer or any other medical condition.Because dietary supplements are regulated as foods, not as drugs, FDA approval is not required unless specific claims about disease prevention or treatment are made.Recent findings on the mechanism of action and pharmacokinetics of high-dose intravenous vitamin C triggered a renewed interest in its application as an anti-cancer agent. Therefore, several Phase I clinical trials were initiated and the results of one controlled and six uncontrolled trials have been published. Also, eight case studies and five retrospective studies have been reported. Several clinical trials are underway.36While the case series and retrospective studies gave some indications for efficacy, the published clinical trials did not indicate tumour response.
Overall, evidence for the non-toxic character of intravenous high-dose vitamin C, limited evidence for improved quality of life, and some suggestion of synergism with certain conventional therapy was offered.Study details can be found in Table 1.Only one controlled clinical trial has been published. In this Phase I/IIa randomized controlled clinical trial, Ma et al. randomized 27 patients with newly diagnosed stage III/IV ovarian cancer to receive either conventional paclitaxel/carboplatin therapy alone (control group), or combined with intravenous vitamin C (treatment group).37 Addition of intravenous high-dose vitamin C was found to reduce toxicities associated with chemotherapy.Cameron et al. performed three controlled retrospective studies comparing terminal cancer patients receiving vitamin C with historical control patients that had not received vitamin C, and found increased survival times in the vitamin-C-treated groups.11,12,50 The study designs were criticized as they were not randomized nor placebo controlled.
Moreover, some patients were treated with oral vitamin C, the treatment period with intravenous vitamin C was only about 10 days, and the doses were rather low.Vollbracht et al. evaluated intravenous vitamin C administration in the first postoperative year of women with breast cancer, in an epidemiological retrospective cohort study, and found that vitamin C resulted in a significant reduction of complaints induced by the disease and chemo- or radiotherapy. Vitamin C was well-tolerated and had no effect on tumour status after 6 or 12 months.51Intravenous vitamin C was well-tolerated in a pilot clinical study in 24 late-stage terminal cancer patients, and one patient had stabilized disease during the trial.38 Noteworthy, applied doses of vitamin C were low.Several aspects of health-related quality of life were improved after administration of intravenous high-dose vitamin C to 39 terminal cancer patients: i.e., significantly higher scores for physical, role, emotional, and cognitive function, and significantly lower scores for fatigue, nausea/vomiting, pain, and appetite loss.39In a dose-finding Phase I and pharmacokinetics study in 24 patients with advanced cancer or hematologic malignancy refractory to standard therapy
, high-dose intravenous vitamin C was found to be safe and free of important toxicity. Patients receiving 0.6 g or more of vitamin C per kg body weight maintained physical quality of life throughout the trial. No patient experienced an objective anti-cancer response.1The combination of intravenous vitamin C with standard treatment of gemcitabine and erlotinib was tested in an open-label, dose-escalating Phase I trial in 14 patients with metastatic pancreatic cancer.40 Nine subjects completed the study of which seven patients experienced stable disease. No increased toxicity was revealed with the addition of vitamin C to gemcitabine and erlotinib.In a Phase I dose-escalation trial in 17 patients with advanced solid tumours not responding to standard therapy, pharmacokinetics of high-dose intravenous vitamin C were determined.2 Vitamin C was generally well tolerated and no objective antitumour responses were observed. The authors recommend a dose of 70 to 80 g/m2 (i.e., around 2 g per kg body weight) for future studies.
In a Phase I clinical trial in nine patients with biopsy-proven stage IV pancreatic adenocarcinoma, the concurrent administration of high-dose intravenous vitamin C with gemcitabine was well-tolerated and a suggestion of improved efficacy by vitamin C addition was found.41Analysis of a database from 45 patients with different cancers treated with high-dose intravenous vitamin C by Mikirova et al. taught that this treatment affected levels of C-reactive protein and pro-inflammation cytokines, supporting the hypothesis that inflammation in cancer patients may be reduced by high-dose intravenous vitamin C.52Several case reports on the treatment of advanced cancer patients with high-dose intravenous vitamin C have been published.42-49 Vitamin C infusions were either used as sole treatment or combined with conventional therapy. Overall, the results indicated lack of toxicity. Also, in several cases tumour regression or even complete remission was observed.Noteworthy, for all the successful case reports, alternative explanations for cancer remission are possible, e.g. spontaneous remission or remission due to the therapy received before intravenous vitamin C was initiated.