What you need to know about High-Dose Vitamin C and Cancer from the National Cancer Institute (NCI)

By Cancer.gov, Cancer.gov October 14, 2016

• Vitamin C is a nutrient found in food anddietary supplements. It is an antioxidant and also plays a key role in making collagen (see Question 1).
• High-dosevitamin C may be given by intravenous (IV) infusion (through a vein into the bloodstream) ororally (taken by mouth). When taken by intravenous infusion, vitamin C can reach much higher levels in the blood than when the same amount is taken by mouth (see Question 1).
• High-dosevitamin C has been studied as a treatment for patients with cancer since the 1970s (see Question 2).
• Laboratory studieshave shown that high doses of vitamin C may slow the growth and spread ofprostate,pancreatic,liver,colon, and other types of cancercells (see Question 5).
• Some laboratory and animal studies have shown that combining vitamin C with anti cancer therapies may be helpful, while other studies have shown that certain forms of vitamin C may make chemotherapy less effective (see Question 5).
• Animal studies have shown that high-dose vitamin C treatment blocks tumor growth in certain models of pancreatic, liver, prostate, andovarian cancers, sarcoma, and malignant mesothelioma (see Question 5).
• Some human studies of high-dose IV vitamin C in patients with cancer have shown improvedquality of life, as well as improvements in physical, mental, and emotional functions,symptoms of fatigue, nausea and vomiting, pain, andappetiteloss (see Question 6).
• Intravenous high-dose ascorbic acid has caused very few side effects in clinical trials (see Question 7).
• While generally approved as a dietary supplement, theU.S. Food and Drug Administration(FDA) has not approved the use of IV high-dose vitamin C as a treatment for cancer or any other medicalcondition(see Question 9).

Questions and Answers About High-Dose Vitamin C

1. What is high-dose vitamin C?
   • Vitamin C(also called L-ascorbic acid or ascorbate) is anutrientthat humans must get from food ordietary supplementssince it cannot be made in the body. Vitamin C is anantioxidantand helps preventoxidative stress. It also works withenzymesto play a key role in makingcollagen.
   • When taken byintravenous (IV) infusion, vitamin C can reach much higher levels in thebloodthan when it is taken by mouth. Studies suggest that these higher levels of vitamin C may cause the death ofcancercellsin the laboratory.
   • A severedeficiency(lack) of vitamin C in thedietcauses scurvy, a disease withsymptomsof 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.
2. What is the history and use of high-dose vitamin C as a complementary and alternative treatment for cancer?
   • High-dosevitamin C has been studied as a treatment for patients with cancer since the 1970s. A Scottishsurgeonnamed Ewan Cameron worked with Nobel Prize-winning chemist Linus Pauling to study the possible benefits of vitamin Ctherapyinclinical trialsof cancer patients in the late 1970s and early 1980's.
   • Surveys of health care practitioners at United StatesCAMconferences in recent years have shown that high-dose IV vitamin C is frequently given to patients as a treatment forinfections,fatigue, and cancers, includingbreast cancer.
3. 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 inconnective tissuecaused by a lack of vitamin C. In the 1970's, it was proposed that high-doseascorbic acidcould 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.
4. 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 givenintravenously.
5. Have any preclinical (laboratory or animal) studies been conducted using high-dose vitamin C?
   • Laboratory studiesandanimal studieshave been done to find out if high-dose vitamin C may be useful in preventing or treating cancer.
   • Laboratory studies
   • 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 achemicalreaction that makeshydrogen peroxide, which may kill cancer cells.
   • Laboratory studies have shown the following:
     • Treatment with high-dose vitamin C slowed the growth and spread ofprostate,pancreatic,liver,colon,malignant mesothelioma,neuroblastoma, and other types of cancer cells.
     • Combining high-dose vitamin C with certain types ofchemotherapymay be more effective than chemotherapy alone:
       • Ascorbic acid witharsenic trioxidemay be more effective inovarian cancercells.
       • Ascorbic acid withgemcitabinemay be more effective inpancreatic cancercells.
       • Ascorbic acid with gemcitabine andepigallocatechin-3-gallate(EGCG) may be more effective in malignant mesothelioma cells.
     • Another laboratory study suggested that combining high-dose vitamin C withradiation therapykilled moreglioblastoma multiformecells than radiation therapy alone.
   • 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.
   • Animal studies
   • Studies of high-dose vitamin C have been done inanimal 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:
     • High-dose vitamin C blockedtumorgrowth in animal models of pancreatic, liver, prostate, sarcoma, and ovarian cancers and malignant mesothelioma.
     • High-dose vitamin C combined with chemotherapy in amouse modelof pancreatic cancer showed that the combination treatment shrank tumors more than chemotherapy treatment alone.
     • Another study showed that vitamin C made a type oflight therapymore effective when used to treat mice injected with breast cancer cells.
     • A study in a mouse model of ovarian cancer showed that combining intravenous high-dose vitamin C with the anticancer drugscarboplatinandpaclitaxelmade them more effective in treating ovarian cancer.
   • However, other animal studies have shown that vitamin C interferes with the anticancer action of certaindrugs, including the following:
     • Mouse models of humanlymphomaandmultiple myelomatreated with combinations of vitamin C and chemotherapy or the drugbortezomibhad more tumor growth than mice treated with bortezomib alone.
6. 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 alone
     • Intravenous (IV) vitamin C was studied in patients with breast cancer who were treated withadjuvant chemotherapyand radiation therapy. The study found that patients who received IV vitamin C had betterquality of lifeand fewerside effectsthan those who did not.
     • A study of IV vitamin C and high doses of vitamin C taken by mouth was done in patients with cancer that could not becured. Vitamin C was shown to be a safe and effective therapy to improve quality of life in these patients, including physical, mental, and emotional functions, symptoms of fatigue,nauseaandvomiting, pain, andappetiteloss.
     • Vitamin C has been shown to be safe when given to healthy volunteers and cancer patients at doses up to 1.5 g/kg, while screening out patients with certainrisk factorswho should avoid vitamin C. Studies have also shown that Vitamin C levels in the blood are higher when taken by IV than when taken by mouth, and last for more than 4 hours.
   • Studies of vitamin C combined with other drugs
   • Studies of vitamin C combined with other drugs have shown mixed results:
     • In a small study of 14 patients withadvancedpancreatic cancer, IV vitamin C was given along with chemotherapy and treatment with atargeted therapy. Patients had very few bad side effects from the vitamin C treatment. The nine patients who completed the treatment hadstable diseaseas shown byimagingstudies.
     • In another small study of 9 patients with advanced pancreatic cancer, patients were given chemotherapy intreatment cyclesof once per week for 3 weeks along with IV vitamin C twice per week for 4 weeks. These patients had disease that did notprogressfor a period of months. Thecombinedtreatment was well tolerated and no serious side effects were reported.
     • In a 2014 study of 27 patients with advanced ovarian cancer, treatment with chemotherapy alone was compared to chemotherapy along with IV vitamin C. Patients who received IV vitamin C along with chemotherapy had fewer serious side effects from the chemotherapy.
     • Patients withacute myeloid leukemia,refractorymetastaticcolorectal cancer, or metastaticmelanomatreated with IV vitamin C combined with other drugs had serious side effects and the disease got worse.
     • More studies of combining high-dose IV vitamin C with other drugs are in progress.
7. 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.
   • In patients with ahistoryofkidneydisorders,kidney failurehas been reported after ascorbic acid treatment. Patients with a tendency to develop kidney stones should not be treated with high-dose vitamin C.
   • Case reportshave shown that patients with aninheriteddisorder called G-6-PD deficiency should not be given high doses of vitamin C, due to the risk ofhemolysis(aconditionin whichred blood cellsare destroyed).
   • Since vitamin C may makeironmore easily absorbed and used by the body, high doses of the vitamin are not recommended for patients withhemochromatosis(a condition in which the body takes up and stores more iron than it needs).
8. Have any drug interactions been reported from combining high-dose vitamin C with anticancer drugs?
   • Adrug interactionis a change in the way adrugacts 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.
   • Combining vitamin C with an anticancer drug called bortezomib has been studied incell culturesand in animal models. Bortezomib is a targeted therapy that blocks severalmolecular pathwaysin a cell, causing cancer cells to die. Several studies showed that vitamin C given by mouth made bortezomib less effective, including in multiple myeloma cells. A study in mice transplanted with human prostate cancer cells, however, did not show that giving the mice different doses of vitamin C by mouth made bortezomib therapy less effective.
   • Anoxidizedform of vitamin C called dehydroascorbic acid has been studied in cell cultures and in animals with tumors. Several studies have found that high doses of dehydroascorbic acid can interfere with the anticancer effects of several chemotherapy drugs. Dehydroascorbic acid is found in only small amounts in dietary supplements and in fresh foods.
   • SeeQuestion 5andQuestion 6for more information on combining vitamin C with anticancer drugs.
9. Is high-dose vitamin C approved by the U.S. Food and Drug Administration for use as a cancer treatment in the United States?
   • TheU.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.

PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ High-Dose Vitamin C. Bethesda, MD: National Cancer Institute. Updated 12/11/2015. Available at:http://www.cancer.gov/about-cancer/treatment/cam/patient/vitamin-c-pdq. Accessed 10/14/2016. [PMID: 26389507]

https://www.cancer.gov/about-cancer/treatment/cam/patient/vitamin-c-pdq#section/all

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