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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.

Differences in chemosensitivity to ascorbate treatment in breast cancer cell lines may depend on expression of the sodium -dependent vitamin C transporter 2 SVCT Research has suggested that pharmacological doses of ascorbic acid enhance the effects of arsenic trioxide on ovarian cancer cells,[ 19 ] gemcitabine on pancreatic cancer cells,[ 8 ] and combination treatment of gemcitabine and epigallocatechingallate EGCG on mesothelioma cells.

Findings from one study reported in suggested that high-dose ascorbate increases radiosensitivity of glioblastoma multiforme cells, resulting in more cell death than from radiation alone.

However, not all studies combining vitamin C with chemotherapy have shown improved outcomes. Using N-acetylcysteine and vitamin C, researchers showed in that these compounds , both thought to act predominantly as antioxidants , may have antitumorigenic actions in vivo by decreasing levels of hypoxia -inducible factor-1, a transcription factor that targets vascular endothelial growth factor and plays a role in angiogenesis.

Studies have demonstrated tumor growth inhibition after treatment with pharmacological ascorbate in animal models of pancreatic cancer,[ 1 , 7 , 8 ] liver cancer ,[ 3 ] prostate cancer,[ 25 ] sarcoma ,[ 26 ] mesothelioma,[ 11 ] and ovarian cancer.

The effects of high-dose ascorbic acid in combination with standard treatments on tumors have been investigated.

A study explored the efficacy of high-dose ascorbate with gemcitabine or radiation treatment in a mouse sarcoma xenograft model.

Compared with the control group , the combination treatments produced significantly greater inhibition of tumor growth, greater survival rate , and no increase in toxicity, suggesting cancer cell selective toxicity.

There have also been reports of animal studies in which vitamin C has interfered with the anticancer activity of various drugs.

In a study reported in , administration of dehydroascorbic acid to lymphoma-xenograft mice prior to doxorubicin treatment resulted in significantly larger tumors than did treatment with doxorubicin alone.

Treating multiple myeloma xenograft mice with a combination of oral vitamin C and bortezomib resulted in significantly greater tumor volume than did treatment with bortezomib alone.

In the early s, a consecutive case series was conducted in which 50 advanced-cancer patients were treated with large doses of ascorbic acid.

The subjects exhibited a wide variety of responses to treatment, including no or minimal response, tumor regression , and tumor hemorrhage.

However, the authors noted that lack of controls prevented definitive assignment of any beneficial responses to the ascorbic acid treatment.

A case report published in detailed one of the patients who had experienced tumor regression. When the patient's daily dose of ascorbic acid was reduced, some of signs of the disease returned; however, remission was achieved again after the patient reverted to the higher initial dose.

A larger case series of terminal cancer patients treated with ascorbate was reported in The mean survival time for ascorbate-treated patients was days longer than that of the matched controls.

Two studies tried to reproduce earlier results. These studies were randomized , placebo-controlled trials in which cancer patients received either 10 g oral vitamin C or placebo daily until signs of cancer progression.

At the end of each study, no significant differences were noted between the two ascorbate-treated and placebo-treated groups for symptoms , performance status , or survival.

One study reported three case reports of cancer patients who received IV vitamin C as their main therapy. During vitamin C therapy, the patients used additional treatments, including vitamins , minerals , and botanicals.

Histopathologic examination suggested poor prognoses for these patients, but they had long survival times after being treated with IV vitamin C.

Two studies demonstrated that IV vitamin C treatment resulted in improved quality of life and decreases in cancer-related side effects in cancer patients.

Studies have shown that vitamin C can be safely administered to healthy volunteers or cancer patients at doses up to 1.

These studies have also found that plasma concentrations of vitamin C are higher with IV administration than with oral administration and are maintained for more than 4 hours.

A phase I study published in examined the safety and efficacy of combining IV ascorbate with gemcitabine and erlotinib in stage IV pancreatic cancer patients.

Minimal adverse effects were reported for ascorbic acid treatment. Five subjects received fewer than 18 of the planned 24 ascorbate infusions and thus did not have follow-up imaging to assess response.

Three of those patients had clinically determined progressive disease. All of the other nine patients had repeat imaging to assess tumor size, and each met the criteria for having stable disease.

A phase I clinical study NCT evaluated the safety of combining pharmacological ascorbate with gemcitabine in treating stage IV pancreatic cancer patients.

Among nine patients, mean progression-free survival was 26 weeks and overall survival was 12 months. The combination treatment was well tolerated, and no significant adverse events were reported.

Twenty-seven patients were randomly assigned to receive either chemotherapy alone or chemotherapy and IV vitamin C concurrently. Chemotherapy was given for 6 months, and IV vitamin C was given for 12 months.

The addition of IV vitamin C was associated with reduced chemotherapy-related toxicities. High-dose IV vitamin C was analyzed in 14 patients and was generally well tolerated and safe, only causing minor temporary adverse effects such as increased urinary flow, thirst, nausea , vomiting and chills; some of which could be prevented.

Chemotherapy administration did not affect the plasma concentration of vitamin C. Although a few patients experienced temporary stable disease, functional improvement, and increased energy, the sample size is so small that the generalizability of these results is uncertain.

This study consisted of 36 patients with metastatic colorectal cancer or gastric cancer. Patients received chemotherapy treatment on a day cycle with vitamin C infusions occurring for 3 consecutive days for 3 hours at a time.

For the dose-escalation portion of the study, ascorbic acid doses ranged from 0. To determine the optimal administration rate of ascorbic acid, patient cohorts received infusion rates set at 0.

The study showed no dose-limiting toxicity for all doses and dosing rates; thus a maximum-tolerated dose was not reached, leading to a recommended phase II dose of 1.

Overall, no severe adverse reactions occurred, and the treatments were deemed safe and tolerable. Trials of high-dose IV vitamin C with other drugs are ongoing.

Refer to Table 2 for study results. The GBM study was a phase I design with 13 total patients. IV vitamin C was given with both radiation therapy and temozolomide and toxicity, progression-free survival, and overall survival all compared favorably to the outcomes of historical controls.

The disease control and confirmed objective response rates of the study group again compared favorably with those of historical controls.

Limitations of these studies included the use of historical controls and small numbers of enrolled participants.

Various trials of high-dose IV vitamin C with other drugs are ongoing. The four phase II clinical trials are investigating the efficacy of high-dose ascorbate combined with standard anticancer regimens.

The studies are exploring the combination of high-dose ascorbate with standard non-small cell lung cancer therapy, including radiation therapy, carboplatin, and paclitaxel NCT ; standard therapy for metastatic pancreatic adenocarcinoma, including gemcitabine and nab-paclitaxel NCT ; standard therapy for localized pancreatic adenocarcinoma with gemcitabine and radiation therapy NCT ; and standard therapy for glioblastoma multiforme, including temozolomide and radiation therapy NCT A number of studies have included IV ascorbic acid treatment at a fixed dose of 1, mg with arsenic trioxide regimens, with mixed results.

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients.

The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Intravenous IV high- dose ascorbic acid has been generally well tolerated in clinical trials. Case reports have indicated that patients with glucosephosphate dehydrogenase GPD deficiency should not receive high doses of vitamin C because of the risk of developing hemolysis.

Vitamin C may increase bioavailability of iron , and high doses of the vitamin are not recommended for patients with hemochromatosis.

When administered in high doses, vitamin C may result in adverse interactions with some anticancer agents. These interactions have primarily been detected in preclinical studies.

A phase I clinical study evaluated the safety of combining high-dose IV ascorbate with gemcitabine in stage IV pancreatic cancer patients.

The combination therapy was well tolerated by patients, and no significant adverse events were reported. Another study found similar results.

Plasma from healthy volunteers who took 1 g of oral vitamin C per day was shown to decrease bortezomib growth inhibition in multiple myeloma cells and to block its inhibitory effect on 20S proteasome activity.

Several studies have been performed to assess the potential synergistic or inhibitory action of vitamin C on certain chemotherapy drugs , with variable results.

A series of studies in cell culture and in animals bearing tumors has shown that when given at high concentrations or dosages, dehydroascorbic acid an oxidized form of vitamin C can interfere with the cytotoxic effects of several chemotherapy drugs.

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Added text to state that 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 cited Yun et al.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of high-dose vitamin C in the treatment of people with cancer.

It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Board members review recently published articles each month to determine whether an article should:. Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer. Do not contact the individual Board Members with questions or comments about the summaries.

Board members will not respond to individual inquiries. Some of the reference citations in this summary are accompanied by a level-of-evidence designation.

These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. PDQ is a registered trademark.

Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated.

Permission to use images outside the context of PDQ information must be obtained from the owner s and cannot be granted by the National Cancer Institute.

Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online , a collection of over 2, scientific images.

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.

More information about contacting us or receiving help with the Cancer. Questions can also be submitted to Cancer.

Menu Contact Dictionary Search. Understanding Cancer. What Is Cancer? Cancer Statistics. Cancer Disparities.

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For the dose-escalation portion of the study, ascorbic acid doses ranged from 0. To determine the optimal administration rate of ascorbic acid, patient cohorts received infusion rates set at 0.

The study showed no dose-limiting toxicity for all doses and dosing rates; thus a maximum-tolerated dose was not reached, leading to a recommended phase II dose of 1.

Overall, no severe adverse reactions occurred, and the treatments were deemed safe and tolerable. Trials of high-dose IV vitamin C with other drugs are ongoing.

Refer to Table 2 for study results. The GBM study was a phase I design with 13 total patients. IV vitamin C was given with both radiation therapy and temozolomide and toxicity, progression-free survival, and overall survival all compared favorably to the outcomes of historical controls.

The disease control and confirmed objective response rates of the study group again compared favorably with those of historical controls.

Limitations of these studies included the use of historical controls and small numbers of enrolled participants. Various trials of high-dose IV vitamin C with other drugs are ongoing.

The four phase II clinical trials are investigating the efficacy of high-dose ascorbate combined with standard anticancer regimens.

The studies are exploring the combination of high-dose ascorbate with standard non-small cell lung cancer therapy, including radiation therapy, carboplatin, and paclitaxel NCT ; standard therapy for metastatic pancreatic adenocarcinoma, including gemcitabine and nab-paclitaxel NCT ; standard therapy for localized pancreatic adenocarcinoma with gemcitabine and radiation therapy NCT ; and standard therapy for glioblastoma multiforme, including temozolomide and radiation therapy NCT A number of studies have included IV ascorbic acid treatment at a fixed dose of 1, mg with arsenic trioxide regimens, with mixed results.

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria.

General information about clinical trials is also available. Intravenous IV high- dose ascorbic acid has been generally well tolerated in clinical trials.

Case reports have indicated that patients with glucosephosphate dehydrogenase GPD deficiency should not receive high doses of vitamin C because of the risk of developing hemolysis.

Vitamin C may increase bioavailability of iron , and high doses of the vitamin are not recommended for patients with hemochromatosis.

When administered in high doses, vitamin C may result in adverse interactions with some anticancer agents. These interactions have primarily been detected in preclinical studies.

A phase I clinical study evaluated the safety of combining high-dose IV ascorbate with gemcitabine in stage IV pancreatic cancer patients.

The combination therapy was well tolerated by patients, and no significant adverse events were reported. Another study found similar results.

Plasma from healthy volunteers who took 1 g of oral vitamin C per day was shown to decrease bortezomib growth inhibition in multiple myeloma cells and to block its inhibitory effect on 20S proteasome activity.

Several studies have been performed to assess the potential synergistic or inhibitory action of vitamin C on certain chemotherapy drugs , with variable results.

A series of studies in cell culture and in animals bearing tumors has shown that when given at high concentrations or dosages, dehydroascorbic acid an oxidized form of vitamin C can interfere with the cytotoxic effects of several chemotherapy drugs.

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available.

This section describes the latest changes made to this summary as of the date above. Added text to state that 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 cited Yun et al.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of high-dose vitamin C in the treatment of people with cancer.

It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Board members review recently published articles each month to determine whether an article should:. Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer. Do not contact the individual Board Members with questions or comments about the summaries.

Board members will not respond to individual inquiries. Some of the reference citations in this summary are accompanied by a level-of-evidence designation.

These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches.

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated.

Permission to use images outside the context of PDQ information must be obtained from the owner s and cannot be granted by the National Cancer Institute.

Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online , a collection of over 2, scientific images.

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.

More information about contacting us or receiving help with the Cancer. Questions can also be submitted to Cancer. Menu Contact Dictionary Search. Understanding Cancer.

What Is Cancer? Cancer Statistics. Cancer Disparities. Cancer Causes and Prevention. Risk Factors. Cancer Prevention Overview.

Cancer Screening Overview. Screening Tests. Diagnosis and Staging. Questions to Ask about Your Diagnosis. Types of Cancer Treatment.

Side Effects of Cancer Treatment. Clinical Trials Information. A to Z List of Cancer Drugs. Questions to Ask about Your Treatment.

Feelings and Cancer. Adjusting to Cancer. Day-to-Day Life. Support for Caregivers. Questions to Ask About Cancer. Choices for Care. Talking about Your Advanced Cancer.

Planning for Advanced Cancer. Advanced Cancer and Caregivers. Questions to Ask about Advanced Cancer. Managing Cancer Care.

Finding Health Care Services. Advance Directives. Using Trusted Resources. Coronavirus Information for Patients. Clinical Trials during Coronavirus.

Adolescents and Young Adults with Cancer. Reports, Research, and Literature. Cancers by Body Location. Late Effects of Childhood Cancer Treatment.

Pediatric Supportive Care. Rare Cancers of Childhood Treatment. Childhood Cancer Genomics. Study Findings. Metastatic Cancer Research.

Intramural Research. Extramural Research. Cancer Research Workforce. Cancer Biology Research. Cancer Genomics Research.

Research on Causes of Cancer. Cancer Diagnosis Research. Cancer Prevention Research. Cancer Treatment Research.

Cancer Health Disparities. Childhood Cancers Research. Global Cancer Research. Cancer Research Infrastructure. Clinical Trials. Frederick National Laboratory for Cancer Research.

Bioinformatics, Big Data, and Cancer. Annual Report to the Nation. Research Advances by Cancer Type.

Stories of Discovery. Milestones in Cancer Research and Discovery. Terminology Resources. Research Grants. Research Funding Opportunities.

Research Program Contacts. Funding Strategy. Grants Policies and Process. Introduction to Grants Process. NCI Grant Policies. Legal Requirements.

Step 3: Peer Review and Funding Outcomes. Manage Your Award. Grants Management Contacts. Prior Approvals. Annual Reporting and Auditing.

Transfer of a Grant. Grant Closeout. Cancer Training at NCI. Resources for Trainees. Funding for Cancer Training. Building a Diverse Workforce.

Resources for News Media. Media Contacts. Cancer Reporting Fellowships. Advisory Board Meetings. Social Media Events. Cancer Currents Blog. Contributing to Cancer Research.

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External Beam Radiation. Side Effects. Checkpoint Inhibitors. T-cell Transfer Therapy. Monoclonal Antibodies. Cancer Treatment Vaccines. Immune System Modulators.

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Unicode Character Grid Easily navigate through Unicode blocks, copy characters to the clipboard, sample panel or directly insert them from the font manager into background applications.

Notes, Tags, and Ratings Add custom notes to your fonts, give them a rating, and tag your fonts with simple keywords and quickly find the font you need by searching for these keywords.

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