Medicinal mushrooms are mushrooms that are used as medicine. They have been used to treat infection for hundreds of years, mostly in Asia. Today, medicinal mushrooms are also used to treat lung diseases and cancer. For more than 30 years, medicinal mushrooms have been approved as an addition to standard cancer treatments in Japan and China. In these countries, mushrooms have been used safely for a long time, either alone or combined with radiation or chemotherapy.

In Asia, there are more than 100 types of mushrooms used to treat cancer. Some of the more common ones are Ganoderma lucidum (reishi), Trametes versicolor or Coriolus versicolor (turkey tail), Lentinus edodes (shiitake), and Grifola frondosa (maitake).

Mushrooms are being studied to find out how they affect the immune system and if they stop or slow the growth of tumors or kill tumor cells. It is thought that certain chemical compounds, such as polysaccharides (beta-glucans) in turkey tail mushrooms, strengthen the immune system to fight cancer.

This summary gives an overview of the use of medicinal mushrooms in treating cancer. The following information is given for Trametes versicolor, also called Coriolus versicolor (turkey tail), and Ganoderma lucidum (reishi):

1. What is turkey tail?

   Turkey tail is a type of mushroom that grows on dead logs worldwide. It’s named turkey tail because its rings of brown and tan look like the tail feathers of a turkey. Its scientific name is Trametes versicolor or Coriolus versicolor. In traditional Chinese medicine, it is known as Yun Zhi. In Japan, it is known as kawaratake (roof tile fungus). There are many other types of Trametes mushrooms. It can be hard to tell the difference between turkey tail and other types of Trametes mushrooms without the use of special testing.

   Turkey tail has been used in traditional Chinese medicine to treat lung diseases for many years. In Japan, turkey tail has been used to strengthen the immune system when given with standard cancer treatment.

2. What is PSK?

   Polysaccharide K (PSK) is the best known active compound in turkey tail mushrooms. In Japan, PSK is an approved mushroom product used to treat cancer.

3. How is PSK given or taken?

   PSK can be taken as a tea or in capsule form.

4. Have any laboratory or animal studies been done using PSK?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of PSK on the immune system, including immune cells called natural killer cells and T-cells. For more information on laboratory and animal studies done using PSK, see the Laboratory/Animal/Preclinical Studies section of the health professional version of Medicinal Mushrooms.

5. Have any studies of PSK been done in people?

   PSK has been studied in patients with gastric cancer, breast cancer, colorectal cancer, and lung cancer. It has been used as adjuvant therapy in thousands of cancer patients since the mid-1970s. PSK has been safely used in people for a long time in Japan and few side effects have been reported.

   Gastric cancer

   Studies show that the use of PSK as adjuvant therapy in patients with gastric (stomach) cancer may help repair immune cell damage caused by chemotherapy and strengthen the immune system.

   Studies of PSK as adjuvant therapy for gastric cancer include the following:

   • A randomized clinical trial in Japan done between 1978 and 1981 included 751 patients who had surgery for gastric cancer. After surgery, patients received chemotherapy with or without PSK. On average, the patients who received chemotherapy and PSK lived longer than those who received chemotherapy alone. The researchers believe it might be possible to predict which patients would benefit the most from PSK depending on the numbers of granulocytes and lymphocytes in the patient’s blood.
   • In 1994, a study in Japan followed 262 patients who had successful surgery for gastric cancer and were given chemotherapy with or without PSK. Patients who received chemotherapy and PSK were less likely to have recurrent cancer and lived longer than those who did not. Treatment with PSK caused few side effects. The researchers thought the study showed that PSK and chemotherapy should be given to gastric cancer patients after surgery to remove the cancer.
   • A review published in 2007 combined results from 8 randomized controlled trials in 8,009 patients who had surgery to remove gastric cancers. After surgery, patients in the trials were given chemotherapy with or without PSK. The results suggest that receiving chemotherapy and PSK helped patients live longer after surgery.

   Breast cancer

   To date, PSK studies in patients with breast cancer have focused on changes in the immune system (T-cell and B-cell levels in the blood) rather than on clinical results (patient survival, symptoms, side effects, and quality of life).

   Colorectal cancer

   Studies of PSK as adjuvant therapy for colorectal cancer include the following:

   • PSK was studied in a randomized clinical trial for its effect on the immune system in patients with stage II or stage III rectal cancer. Patients received chemotherapy and radiation therapy, with or without PSK. This study found that PSK increased the number of cancer-killing immune cells and had anticancer effects in tissue that received radiation therapy.
   • A review that combined results from 3 studies in 1,094 patients with colorectal cancer found that patients who received PSK were less likely to have recurrent cancer and lived longer than those who did not.
   • Two groups from Japan studied patients with colorectal cancer who received adjuvant chemotherapy with or without PSK after surgery. In the first study, patients who were treated with both chemotherapy and PSK had markedly better 10-year survival rates. In the second study of patients who were older than 70 years, 3-year survival rates were markedly higher in the group treated with both chemotherapy and PSK.

   Lung cancer

   Studies of PSK as adjuvant therapy for patients with lung cancer include the following:

   • Five nonrandomized clinical trials reported that patients treated with PSK and radiation therapy with or without chemotherapy lived longer.
   • Six randomized clinical trials in patients with lung cancer studied chemotherapy with or without PSK. The studies showed that patients who received PSK improved in one or more ways, including immune function, body weight, well-being, tumor-related symptoms, or longer survival.
6. Have any side effects or risks been reported from turkey tail or PSK?

   There have been few side effects reported in studies of PSK in Japan.

7. Is turkey tail or PSK approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved the use of turkey tail or its active compound PSK as a treatment for cancer or any other medical condition.

   The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of mushroom supplements may not be the same.

1. What is reishi?

   Reishi is a type of mushroom that grows on live trees. Scientists may call it either Ganoderma lucidum or Ganoderma sinense. In traditional Chinese medicine, this group of mushrooms is known as Ling Zhi. In Japan, they are known as Reishi. In China, G. lucidum is known as Chizhi and G. sinense is known as Zizhi.

   There are many other types of Ganoderma mushrooms and it is hard to tell the medicinal mushrooms from the other types.

   Reishi has been used as medicine for a very long time in East Asia. It was thought to prolong life, prevent aging, and increase energy. In China, it is being used to strengthen the immune system of cancer patients who receive chemotherapy or radiation therapy.

2. How is reishi given or taken?

   Reishi is usually dried and taken as an extract in the form of a liquid, capsule, or powder.

3. Have any laboratory or animal studies been conducted using reishi?

   In laboratory studies, tumor cells are used to test a new substance and find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of the active ingredients in reishi mushrooms, triterpenoids and polysaccharides, on tumors, including lung cancer. For information on laboratory and animal studies done using reishi, see the Laboratory/Animal/Preclinical Studies section of the health professional version of Medicinal Mushrooms.

4. Have any studies of reishi mushrooms been done in people?

   Studies using products made from reishi have been done in China and Japan.

   Lung cancer

   Studies suggest that the use of products made from reishi as adjuvant therapy may help strengthen the immune system in patients with lung cancer.

   Studies in patients with lung cancer include the following:

   • In an open-label trial done in China, 36 patients with advanced lung cancer were given an over-the-counter product made from reishi called Ganopoly. The patients were being treated with chemotherapy or radiation therapy, along with other complementary therapies. Some patients had marked changes in the immune responses being studied, such as lymphocyte count and natural killer cell activity, and some patients had no change in immune response.
   • In China, a study was done with 12 lung cancer patients. Their blood was tested to see if taking a product made from reishi could help improve immune response. The study found that the polysaccharides in reishi mushrooms may help cancer-fighting immune cells, called lymphocytes, stay active.

   Colorectal cancer

   The following study looked at reishi for the prevention of colorectal cancer:

   • In Japan, 225 patients with benign colorectal tumors were studied. For 12 months, 123 of the patients were given an extract of the mushroom G. lucidum mycelia (MAK), while 102 patients did not receive treatment with MAK. At 12 months, a follow-up colonoscopy was done on all the patients. The number and the size of the tumors decreased in the group that received MAK, but not in the group that did not receive MAK. The researchers suggest that MAK may help stop benign colorectal tumors from forming.
5. Is reishi approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved the use of reishi as a treatment for cancer or any other medical condition.

   The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of mushroom supplements may not be the same.

Complementary and alternative medicine (CAM)—also called integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM carefully reviews these materials to see if any seem worth further research.

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

CAM on PubMed

NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

This cancer information summary provides an overview of the use of intravenous (IV) vitamin C (also known as ascorbate or L-ascorbic acid) as a treatment for people with cancer. This summary includes a brief history of early clinical trials of the use of IV vitamin C; reviews of laboratory, animal, and human studies; and current clinical trials.

This summary contains the following key information:

Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.

Vitamin C is an essential nutrient that has redox functions, is a cofactor for several enzymes, and plays an important role in the synthesis of collagen.[1] A severe deficiency in vitamin C results in scurvy, which is associated with malaise, lethargy, easy bruising, and spontaneous bleeding.[2] One of the effects of scurvy is a change in collagen structure to a thinner consistency. Normal consistency is achieved with administration of vitamin C.

In the mid-20th century, a study hypothesized that cancer may be related to changes in connective tissue, which may be a consequence of vitamin C deficiency.[3] A review of evidence published in 1974 suggested that high-dose ascorbic acid may increase host resistance and be a potential cancer therapy.[4]

Vitamin C is synthesized from D-glucose or D-galactose by many plants and animals. However, humans lack the enzyme L-gulonolactone oxidase required for ascorbic acid synthesis and must obtain vitamin C through food or supplements.[1]

Some companies distribute vitamin C as dietary supplements. In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved the use of high-dose vitamin C as a treatment for cancer.

References

1. Naidu KA: Vitamin C in human health and disease is still a mystery? An overview. Nutr J 2: 7, 2003. [PUBMED Abstract]
2. Padayatty S, Espey MG, Levine M: Vitamin C. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. Informa Healthcare, 2010, pp 821-31.
3. McCORMICK WJ: Cancer: a collagen disease, secondary to a nutritional deficiency. Arch Pediatr 76 (4): 166-71, 1959. [PUBMED Abstract]
4. Cameron E, Pauling L: The orthomolecular treatment of cancer. I. The role of ascorbic acid in host resistance. Chem Biol Interact 9 (4): 273-83, 1974. [PUBMED Abstract]

The earliest experience of using both oral and intravenous (IV) vitamin C for cancer treatment was by a Scottish surgeon, Ewan Cameron, and his colleague, Allan Campbell, in the 1970s.[1] This work led to a collaboration between Cameron and the Nobel Prize–winning chemist Linus Pauling, further promoting the potential of vitamin C therapy in cancer management.[2,3] As a result, two clinical trials of oral vitamin C were conducted in the late 1970s and early 1980s.[4,5] These two trials did not use IV vitamin C.

For more information about these early studies, see the Human Studies section.

Pharmacokinetic studies later revealed substantial differences in the maximum achieved blood concentrations of vitamin C based on the route of administration. When vitamin C is taken orally, plasma concentrations of the vitamin are tightly controlled, with a peak achievable concentration less than 300 µM. However, this tight control is bypassed with IV administration of the vitamin, resulting in very high levels of vitamin C plasma concentration (i.e., levels up to 20 mM).[6,7] Further research suggests that pharmacological concentrations of ascorbate, such as those achieved with IV administration, may result in cell death in many cancer cell lines.[8]

Health care practitioners attending complementary and alternative medicine conferences in 2006 and 2008 were surveyed about usage of high-dose IV vitamin C in patients. Of the 199 total respondents, 172 had administered vitamin C to patients. In general, IV vitamin C was commonly used to treat infections, cancer, and fatigue.[9]

References

1. Cameron E, Campbell A: The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact 9 (4): 285-315, 1974. [PUBMED Abstract]
2. Cameron E, Pauling L: Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 73 (10): 3685-9, 1976. [PUBMED Abstract]
3. Cameron E, Pauling L: Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 75 (9): 4538-42, 1978. [PUBMED Abstract]
4. Creagan ET, Moertel CG, O’Fallon JR, et al.: Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 301 (13): 687-90, 1979. [PUBMED Abstract]
5. Moertel CG, Fleming TR, Creagan ET, et al.: High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 312 (3): 137-41, 1985. [PUBMED Abstract]
6. Padayatty SJ, Sun H, Wang Y, et al.: Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140 (7): 533-7, 2004. [PUBMED Abstract]
7. Hoffer LJ, Levine M, Assouline S, et al.: Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19 (11): 1969-74, 2008. [PUBMED Abstract]
8. Verrax J, Calderon PB: Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic Biol Med 47 (1): 32-40, 2009. [PUBMED Abstract]
9. Padayatty SJ, Sun AY, Chen Q, et al.: Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 5 (7): e11414, 2010. [PUBMED Abstract]

References

1. Chen P, Stone J, Sullivan G, et al.: Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models. Free Radic Biol Med 51 (3): 681-7, 2011. [PUBMED Abstract]
2. Chen Q, Espey MG, Krishna MC, et al.: Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A 102 (38): 13604-9, 2005. [PUBMED Abstract]
3. Verrax J, Calderon PB: Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic Biol Med 47 (1): 32-40, 2009. [PUBMED Abstract]
4. Chen Q, Espey MG, Sun AY, et al.: Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 105 (32): 11105-9, 2008. [PUBMED Abstract]
5. Frömberg A, Gutsch D, Schulze D, et al.: Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer Chemother Pharmacol 67 (5): 1157-66, 2011. [PUBMED Abstract]
6. Chen P, Yu J, Chalmers B, et al.: Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anticancer Drugs 23 (4): 437-44, 2012. [PUBMED Abstract]
7. Du J, Martin SM, Levine M, et al.: Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res 16 (2): 509-20, 2010. [PUBMED Abstract]
8. Espey MG, Chen P, Chalmers B, et al.: Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic Biol Med 50 (11): 1610-9, 2011. [PUBMED Abstract]
9. Lin ZY, Chuang WL: Pharmacologic concentrations of ascorbic acid cause diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines. Biomed Pharmacother 64 (5): 348-51, 2010. [PUBMED Abstract]
10. Pathi SS, Lei P, Sreevalsan S, et al.: Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr Cancer 63 (7): 1133-42, 2011. [PUBMED Abstract]
11. Takemura Y, Satoh M, Satoh K, et al.: High dose of ascorbic acid induces cell death in mesothelioma cells. Biochem Biophys Res Commun 394 (2): 249-53, 2010. [PUBMED Abstract]
12. Hardaway CM, Badisa RB, Soliman KF: Effect of ascorbic acid and hydrogen peroxide on mouse neuroblastoma cells. Mol Med Report 5 (6): 1449-52, 2012. [PUBMED Abstract]
13. Du J, Cullen JJ, Buettner GR: Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta 1826 (2): 443-57, 2012. [PUBMED Abstract]
14. Levine M, Padayatty SJ, Espey MG: Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr 2 (2): 78-88, 2011. [PUBMED Abstract]
15. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, et al.: O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell 32 (2): 268, 2017. [PUBMED Abstract]
16. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, et al.: Redox active metals and H2O2 mediate the increased efficacy of pharmacological ascorbate in combination with gemcitabine or radiation in pre-clinical sarcoma models. Redox Biol 14: 417-422, 2018. [PUBMED Abstract]
17. Yun J, Mullarky E, Lu C, et al.: Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350 (6266): 1391-6, 2015. [PUBMED Abstract]
18. Hong SW, Lee SH, Moon JH, et al.: SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment. Oncogene 32 (12): 1508-17, 2013. [PUBMED Abstract]
19. Ong PS, Chan SY, Ho PC: Differential augmentative effects of buthionine sulfoximine and ascorbic acid in As2O3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation. Int J Oncol 38 (6): 1731-9, 2011. [PUBMED Abstract]
20. Martinotti S, Ranzato E, Burlando B: In vitro screening of synergistic ascorbate-drug combinations for the treatment of malignant mesothelioma. Toxicol In Vitro 25 (8): 1568-74, 2011. [PUBMED Abstract]
21. Herst PM, Broadley KW, Harper JL, et al.: Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest. Free Radic Biol Med 52 (8): 1486-93, 2012. [PUBMED Abstract]
22. Heaney ML, Gardner JR, Karasavvas N, et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 68 (19): 8031-8, 2008. [PUBMED Abstract]
23. Perrone G, Hideshima T, Ikeda H, et al.: Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 23 (9): 1679-86, 2009. [PUBMED Abstract]
24. Gao P, Zhang H, Dinavahi R, et al.: HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell 12 (3): 230-8, 2007. [PUBMED Abstract]
25. Pollard HB, Levine MA, Eidelman O, et al.: Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer. In Vivo 24 (3): 249-55, 2010 May-Jun. [PUBMED Abstract]
26. Yeom CH, Lee G, Park JH, et al.: 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. J Transl Med 7: 70, 2009. [PUBMED Abstract]
27. Ma Y, Chapman J, Levine M, et al.: High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med 6 (222): 222ra18, 2014. [PUBMED Abstract]

References

1. Cameron E, Campbell A: The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact 9 (4): 285-315, 1974. [PUBMED Abstract]
2. Cameron E, Campbell A, Jack T: The orthomolecular treatment of cancer. III. Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy. Chem Biol Interact 11 (5): 387-93, 1975. [PUBMED Abstract]
3. Cameron E, Pauling L: Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 73 (10): 3685-9, 1976. [PUBMED Abstract]
4. Cameron E, Pauling L: Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 75 (9): 4538-42, 1978. [PUBMED Abstract]
5. Creagan ET, Moertel CG, O’Fallon JR, et al.: Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 301 (13): 687-90, 1979. [PUBMED Abstract]
6. Moertel CG, Fleming TR, Creagan ET, et al.: High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 312 (3): 137-41, 1985. [PUBMED Abstract]
7. Padayatty SJ, Riordan HD, Hewitt SM, et al.: Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 174 (7): 937-42, 2006. [PUBMED Abstract]
8. Yeom CH, Jung GC, Song KJ: Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci 22 (1): 7-11, 2007. [PUBMED Abstract]
9. Nielsen TK, Højgaard M, Andersen JT, et al.: Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Transl Androl Urol 6 (3): 517-528, 2017. [PUBMED Abstract]
10. Padayatty SJ, Sun H, Wang Y, et al.: Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140 (7): 533-7, 2004. [PUBMED Abstract]
11. Hoffer LJ, Levine M, Assouline S, et al.: Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19 (11): 1969-74, 2008. [PUBMED Abstract]
12. Monti DA, Mitchell E, Bazzan AJ, et al.: Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 7 (1): e29794, 2012. [PUBMED Abstract]
13. Welsh JL, Wagner BA, van’t Erve TJ, et al.: Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol 71 (3): 765-75, 2013. [PUBMED Abstract]
14. Ma Y, Chapman J, Levine M, et al.: High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med 6 (222): 222ra18, 2014. [PUBMED Abstract]
15. Hoffer LJ, Robitaille L, Zakarian R, et al.: High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One 10 (4): e0120228, 2015. [PUBMED Abstract]
16. Polireddy K, Dong R, Reed G, et al.: High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study. Sci Rep 7 (1): 17188, 2017. [PUBMED Abstract]
17. Wang F, He MM, Wang ZX, et al.: Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. BMC Cancer 19 (1): 460, 2019. [PUBMED Abstract]
18. Qazilbash MH, Saliba RM, Nieto Y, et al.: Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biol Blood Marrow Transplant 14 (12): 1401-7, 2008. [PUBMED Abstract]
19. Abou-Jawde RM, Reed J, Kelly M, et al.: Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Med Oncol 23 (2): 263-72, 2006. [PUBMED Abstract]
20. Berenson JR, Matous J, Swift RA, et al.: A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin Cancer Res 13 (6): 1762-8, 2007. [PUBMED Abstract]
21. Berenson JR, Boccia R, Siegel D, et al.: Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study. Br J Haematol 135 (2): 174-83, 2006. [PUBMED Abstract]
22. Subbarayan PR, Lima M, Ardalan B: Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic colorectal carcinoma: a clinical experience. Acta Oncol 46 (4): 557-61, 2007. [PUBMED Abstract]
23. Bael TE, Peterson BL, Gollob JA: Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. Melanoma Res 18 (2): 147-51, 2008. [PUBMED Abstract]
24. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, et al.: O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell 32 (2): 268, 2017. [PUBMED Abstract]
25. Campbell RA, Sanchez E, Steinberg JA, et al.: Antimyeloma effects of arsenic trioxide are enhanced by melphalan, bortezomib and ascorbic acid. Br J Haematol 138 (4): 467-78, 2007. [PUBMED Abstract]

Intravenous (IV) high-dose ascorbic acid has been generally well tolerated in clinical trials.[1–9] Renal failure after ascorbic acid treatment has been reported in patients with preexisting renal disorders.[10] One study reported fluid overload related to ascorbic acid infusion, but this may be caused by the delivery method and not the product.[11]

Case reports have indicated that patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency should not receive high doses of vitamin C because of the risk of developing hemolysis.[12–14]

Administration of IV vitamin C at high doses has been shown to interfere with the measurement of serum biochemical parameters. A study of the administration of high-dose IV vitamin C has been observed to interfere with certain laboratory tests such as strip-based glucose meters, showing false elevations in the glucose measurements.[15,16]

References

1. Padayatty SJ, Sun H, Wang Y, et al.: Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140 (7): 533-7, 2004. [PUBMED Abstract]
2. Hoffer LJ, Levine M, Assouline S, et al.: Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19 (11): 1969-74, 2008. [PUBMED Abstract]
3. Chen Q, Espey MG, Sun AY, et al.: Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 105 (32): 11105-9, 2008. [PUBMED Abstract]
4. Monti DA, Mitchell E, Bazzan AJ, et al.: Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 7 (1): e29794, 2012. [PUBMED Abstract]
5. Abou-Jawde RM, Reed J, Kelly M, et al.: Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Med Oncol 23 (2): 263-72, 2006. [PUBMED Abstract]
6. Berenson JR, Matous J, Swift RA, et al.: A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin Cancer Res 13 (6): 1762-8, 2007. [PUBMED Abstract]
7. Qazilbash MH, Saliba RM, Nieto Y, et al.: Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biol Blood Marrow Transplant 14 (12): 1401-7, 2008. [PUBMED Abstract]
8. Ma Y, Chapman J, Levine M, et al.: High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med 6 (222): 222ra18, 2014. [PUBMED Abstract]
9. Polireddy K, Dong R, Reed G, et al.: High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study. Sci Rep 7 (1): 17188, 2017. [PUBMED Abstract]
10. Padayatty SJ, Sun AY, Chen Q, et al.: Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 5 (7): e11414, 2010. [PUBMED Abstract]
11. Nielsen TK, Højgaard M, Andersen JT, et al.: Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Transl Androl Urol 6 (3): 517-528, 2017. [PUBMED Abstract]
12. Campbell GD, Steinberg MH, Bower JD: Letter: Ascorbic acid-induced hemolysis in G-6-PD deficiency. Ann Intern Med 82 (6): 810, 1975. [PUBMED Abstract]
13. Mehta JB, Singhal SB, Mehta BC: Ascorbic-acid-induced haemolysis in G-6-PD deficiency. Lancet 336 (8720): 944, 1990. [PUBMED Abstract]
14. Rees DC, Kelsey H, Richards JD: Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ 306 (6881): 841-2, 1993. [PUBMED Abstract]
15. Katzman BM, Kelley BR, Deobald GR, et al.: Unintended Consequence of High-Dose Vitamin C Therapy for an Oncology Patient: Evaluation of Ascorbic Acid Interference With Three Hospital-Use Glucose Meters. J Diabetes Sci Technol 15 (4): 897-900, 2021. [PUBMED Abstract]
16. Martinello F, da Silva EL: Ascorbic acid interference in the measurement of serum biochemical parameters: in vivo and in vitro studies. Clin Biochem 39 (4): 396-403, 2006. [PUBMED Abstract]
17. Welsh JL, Wagner BA, van’t Erve TJ, et al.: Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol 71 (3): 765-75, 2013. [PUBMED Abstract]
18. Zou W, Yue P, Lin N, et al.: Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clin Cancer Res 12 (1): 273-80, 2006. [PUBMED Abstract]
19. Llobet D, Eritja N, Encinas M, et al.: Antioxidants block proteasome inhibitor function in endometrial carcinoma cells. Anticancer Drugs 19 (2): 115-24, 2008. [PUBMED Abstract]
20. Perrone G, Hideshima T, Ikeda H, et al.: Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 23 (9): 1679-86, 2009. [PUBMED Abstract]
21. Bannerman B, Xu L, Jones M, et al.: Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother Pharmacol 68 (5): 1145-54, 2011. [PUBMED Abstract]
22. Heaney ML, Gardner JR, Karasavvas N, et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 68 (19): 8031-8, 2008. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What is vitamin C?

   Vitamin C is a nutrient that is found in food, such as oranges, grapefruit, kiwi, peppers, and broccoli, and in dietary supplements. Vitamin C is an antioxidant and helps prevent damage to cells caused by free radicals. It also works with enzymes to play a key role in making collagen. Vitamin C is also called L-ascorbic acid or ascorbate.

2. How is vitamin C given or taken?

   Vitamin C may be given by intravenous (IV) infusion or taken by mouth. When given by IV infusion, vitamin C can reach much higher levels in the blood than when it is taken by mouth.

3. Have any laboratory or animal studies been done using IV vitamin C?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective. Laboratory and animal studies are done in animals before a substance is tested in people.

   Laboratory and animal studies have tested the effects of IV vitamin C. Laboratory studies suggest that high levels of vitamin C may kill cancer cells. For information on laboratory and animal studies done using intravenous vitamin C, see the Laboratory/Animal/Preclinical Studies section of the health professional version of Intravenous Vitamin C.

4. Have any studies of IV vitamin C been done in people with cancer?

   Several studies of IV vitamin C given alone or in combination with other drugs in people with cancer include the following:

   Studies of IV vitamin C alone

   • One study found that people with cancer who received IV vitamin C had better quality of life and fewer cancer-related side effects than those who did not receive it.
   • In a single-arm pilot study of people with castration-resistant prostate cancer, IV vitamin C did not lower prostate-specific antigen levels or stop tumors from growing.
   • In a study of healthy volunteers and people with cancer, vitamin C was shown to be safe at doses up to 1.5 g/kg in people who do not have kidney stones, other kidney diseases, or G6PD deficiency. Studies have also shown that vitamin C levels in the blood are higher when given by IV than when taken by mouth, and last for more than 4 hours.

   Studies of IV vitamin C combined with other drugs

   Studies of IV vitamin C given with other drugs have shown mixed results.

   • In a small study of 14 people with advanced pancreatic cancer, IV vitamin C was given along with chemotherapy and targeted therapy (erlotinib). Five study participants did not complete the vitamin C treatment because the tumor continued to grow during treatment. The nine participants who completed the treatment had stable disease as shown by imaging studies. Very few side effects were reported from the vitamin C treatment.
   • In a study of people newly diagnosed with pancreatic cancer, IV vitamin C did not interfere with gemcitabine.
   • In another small study, 9 people with advanced pancreatic cancer were given chemotherapy once a week for 3 weeks along with IV vitamin C twice a week for 4 weeks during each treatment cycle. The cancer did not progress over an average of 6 months in these patients. No serious side effects were reported with the combined treatment.
   • In a study of 27 people with advanced ovarian cancer, chemotherapy alone was compared with chemotherapy and IV vitamin C. IV vitamin C was given during chemotherapy and for 6 months after chemotherapy ended. Those who received IV vitamin C had fewer side effects from the chemotherapy.
   • People with refractory metastatic colorectal cancer or metastatic melanoma were treated with IV vitamin C given along with arsenic trioxide and other drugs. The treatment had no anticancer effect, the tumor continued to grow during treatment, and patients had serious side effects. These studies did not have a comparison group, so it is unclear how much the IV vitamin C affected the side effects.
   • In two pilot trials, people with non-small cell lung cancer or glioblastoma multiforme were given standard therapy plus IV vitamin C. Those who received standard therapy plus IV vitamin C had better overall survival and fewer side effects than the control groups.

   More studies of combining IV vitamin C with other drugs are being done. These include a number of clinical trials combining IV vitamin C with arsenic trioxide, showing mixed results.

5. Have any side effects or risks been reported from IV vitamin C?

   IV vitamin C has caused very few side effects in clinical trials. However, IV vitamin C may be harmful in people with certain risk factors.

   • In people with a history of kidney disease, kidney failure has been reported after treatment with IV vitamin C. People who are likely to develop kidney stones should not be treated with IV vitamin C.
   • One study reported too much fluid in the body (fluid overload) related to IV vitamin C. This may have been caused by the IV delivery method and not the vitamin C.
   • Case reports have shown that people with an inherited disorder called G6PD deficiency should not be given high doses of vitamin C because it may cause hemolysis.
   • Because vitamin C may make iron more easily absorbed and used by the body, high doses of vitamin C are not recommended for people with hemochromatosis (a condition in which the body takes up and stores more iron than it needs).
6. Have any drug interactions been reported from adding IV vitamin C to treatment with anticancer drugs?

   A drug interaction is a change in the way a drug acts in the body when taken with certain other drugs. When IV vitamin C is combined with certain anticancer drugs, the anticancer drugs may not work as well. So far, these effects have been seen only in some laboratory and animal studies. For information on drug interactions while using IV vitamin C, see the Adverse Effects section of the health professional version of Intravenous Vitamin C.

7. Is IV vitamin C approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved the use of IV vitamin C as a treatment for cancer.

   The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of IV vitamin C may not be the same.

Complementary and alternative medicine (CAM)—also called integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM carefully reviews these materials to see if any seem worth further research.

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

CAM on PubMed

NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

This cancer information summary provides an overview of the use of Essiac and Flor Essence, which are proprietary herbal tea mixtures, as treatments for people with cancer. The summary includes a brief history of the development of Essiac and Flor Essence; a review of laboratory, animal, and human studies; and possible side effects associated with Essiac and Flor Essence use.

This summary contains the following key information:

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.

Essiac and Flor Essence are proprietary herbal tea mixtures produced by different manufacturers. Essiac is reported to contain four herbs: burdock root (Arctium lappa L.), Indian rhubarb root (Rheum palmatum L., sometimes known as Turkish rhubarb), sheep sorrel (Rumex acetosella L.), and the inner bark of slippery elm (Ulmus fulva Michx. [synonym Ulmus rubra]).[1–9] Flor Essence is reported to contain the same four herbs as Essiac, plus four potentiating herbs: watercress (Nasturtium officinale R.Br.), blessed thistle (Cnicus benedictus L.), red clover (Trifolium pratense L.), and kelp (Laminaria digitata [Hudson] Lamx.).[2–4,10]

The manufacturers of Essiac and Flor Essence both claim they market the original herbal mixture promoted by the developer.[1,10] Although only one company manufactures Flor Essence,[10] several companies produce and market Essiac-like products.[2,3,9] This summary contains information about the trademarked mixtures only and differentiates between the two products wherever possible. Essiac and Flor Essence may vary in their mixture content and effects.[11]

Essiac and Flor Essence are said to detoxify the body and strengthen the immune system.[1,4,6,8,10] Proponents of Essiac further claim that it helps relieve pain, reduce side effects, improves overall quality of life, may reduce tumor size, and may prolong the survival of patients with various types of cancer. The individual herbs in the Essiac and Flor Essence formulas have been shown to contain molecules that have anticancer, anti-inflammatory, antioxidant, or immunostimulatory activity.[2–4,8,12–15] For more information, see the Laboratory/Animal/Preclinical Studies section. It is said that the benefits of Essiac and Flor Essence are dependent on the presence of the constituent herbs in the correct proportions. In 2004, a mixture of the Essiac herbs showed a decreased proliferation of a prostate cancer cell line.[16] For more information, see the Laboratory/Animal/Preclinical Studies section.

Although the use of Essiac and Flor Essence is generally associated with cancer treatment, both products have been used to treat other health conditions. Essiac has reportedly been used to control diabetes and to treat acquired immunodeficiency syndrome.[6] Flor Essence has reportedly been studied in Russia as a treatment for chronic gastrointestinal diseases (e.g., esophagitis, gastritis, duodenitis, and colitis) and as a treatment for cirrhosis of the liver.[2] However, no controlled data have been published in the peer-reviewed scientific literature to show the safety or the efficacy of Essiac or Flor Essence in patients with cancer or in patients with other health conditions. For more information, see the Human/Clinical Studies section.

Essiac and Flor Essence are sold worldwide as health tonics or herbal dietary supplements.[1,10,2–4,9] In the United States, health tonics and dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition and limits on contamination that may adulterate dietary supplements. Because health tonics and dietary supplements are not formally inspected for manufacturing consistency every year, there may be considerable variation from lot to lot, and there is no guarantee that ingredients identified on product labels are present at all or are present in the specified amounts. The FDA has not approved the use of either Essiac or Flor Essence for the treatment of patients with cancer or any other medical condition.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. An IND application must also be made for clinical evaluation of dietary supplements as agents for the treatment or prevention of disease. The FDA’s IND process is confidential, and the existence of an IND application can be disclosed only by the applicants. No investigator has announced filing an IND application to study either Essiac or Flor Essence in the treatment of patients with cancer.

Essiac and Flor Essence are administered orally in the form of herbal teas.[1,4,6–8,10,17] Originally, an extract of one of the herbs (not specified) was administered to cancer patients by intramuscular injection at or near tumor sites, and the other herbs were administered orally as a tea.

Only minimal information about dose and schedule of administration is freely available from the manufacturer of Essiac.[1] According to the manufacturer, the dose will vary, depending on the reason for ingestion; the manufacturer’s recommended schedules of administration assume a 12-week program of uninterrupted use.[1] Although Essiac is said to be safe for pets, no information is given about its safety in children.[1]

The manufacturer of Flor Essence states that adults may consume from 30 to 360 mL (i.e., 1–12 fl oz) of Flor Essence tea per day, depending on individual requirements, and that it may be used continuously.[10] The manufacturer also suggests that Flor Essence may be safely consumed by infants and children, but its use by pregnant women and nursing mothers is not recommended.[10] However, the promotion of mammary tumors observed in a rat model of breast cancer raises the theoretical concern that Flor Essence may impact normal mammary ductal development during childhood, thereby raising concern about its use.[18]

The manufacturers of Essiac and Flor Essence both state these products can be used in conjunction with other cancer treatments.[1,10] Nonetheless, some proponents of Essiac have recommended that no additional anticancer therapy (such as chemotherapy or radiation therapy) be undertaken while patients are being treated with the mixture.[7] The purported rationale for this statement is that conventional anticancer treatments may alter immune system function and prevent Essiac from working effectively.[7] As indicated previously, no evidence has been reported in the peer-reviewed scientific literature to show either that Essiac is an effective treatment for patients with cancer or that conventional anticancer treatments interfere with its effects.

References

1. Essiac. Kirkland, Canada: Altramed Health Products, 2002. Available online. Last accessed April 11, 2016.
2. Tamayo C, Richardson MA, Diamond S, et al.: The chemistry and biological activity of herbs used in Flor-Essence herbal tonic and Essiac. Phytother Res 14 (1): 1-14, 2000. [PUBMED Abstract]
3. Tamayo C: Essiac for cancer. Alternative Therapies in Women’s Health 2 (3): 19-23, 2000.
4. Kaegi E: Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (7): 897-902, 1998. [PUBMED Abstract]
5. Ernst E, Cassileth BR: How useful are unconventional cancer treatments? Eur J Cancer 35 (11): 1608-13, 1999. [PUBMED Abstract]
6. Locock RA: Essiac. Can Pharm J 130: 18-9, 1997.
7. Herbal treatments. In: US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5. Also available online. Last accessed April 11, 2016.
8. Essiac. Toronto, Canada: Canadian Breast Cancer Research Alliance, 1996.
9. The History of Essiac & Rene Caisse, Canada’s Cancer Nurse. Kirkland, Canada: Altramed Health Products, 2001. Available online. Last accessed April 11, 2016.
10. Flora Flor•Essence®. Burnaby, Canada: Flora Manufacturing & Distributing Ltd. Available online. Last accessed April 11, 2016.
11. Cheung S, Lim KT, Tai J: Antioxidant and anti-inflammatory properties of ESSIAC and Flor-Essence. Oncol Rep 14 (5): 1345-50, 2005. [PUBMED Abstract]
12. Franke AA, Cooney RV, Custer LJ, et al.: Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. In: Manthey JA, Buslig BS, eds.: Flavonoids in the Living System. Plenum Press, 1998. Advances in Experimental Medicine and Biology, 439, pp 237-48.
13. Waladkhani AR, Clemens MR: Effect of dietary phytochemicals on cancer development (review) Int J Mol Med 1 (4): 747-53, 1998. [PUBMED Abstract]
14. de Witte P: Metabolism and pharmacokinetics of anthranoids. Pharmacology 47 (Suppl 1): 86-97, 1993. [PUBMED Abstract]
15. Campbell MJ, Hamilton B, Shoemaker M, et al.: Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro. Anticancer Res 22 (6C): 3843-52, 2002 Nov-Dec. [PUBMED Abstract]
16. Ottenweller J, Putt K, Blumenthal EJ, et al.: Inhibition of prostate cancer-cell proliferation by Essiac. J Altern Complement Med 10 (4): 687-91, 2004. [PUBMED Abstract]
17. LeMoine L: Essiac: an historical perspective. Can Oncol Nurs J 7 (4): 216-21, 1997. [PUBMED Abstract]
18. Bennett LM, Montgomery JL, Steinberg SM, et al.: Flor-Essence herbal tonic does not inhibit mammary tumor development in Sprague Dawley rats. Breast Cancer Res Treat 88 (1): 87-93, 2004. [PUBMED Abstract]

Essiac was popularized in Canada during the 1920s, when the developer, a nurse from Ontario, began to advocate its use as a cancer treatment. In 1922, the developer obtained an herbal tea formula from a female breast cancer patient who claimed the mixture had cured her disease.[1–5] The patient reportedly received the formula from an Ontario Ojibwa American Indian medicine man. The developer subsequently modified the formula, producing both injectable and oral forms of treatment.[2–8]

From 1934 to 1942, the developer operated a cancer clinic in Bracebridge, Ontario, and dispensed Essiac free of charge.[9] In 1938, members of the Royal Cancer Commission of Canada visited the clinic and heard testimonials from patients who had been treated with the mixture.[7] The Cancer Commission concluded there was only limited evidence for the effectiveness of Essiac. After years of controversy, the developer closed the clinic in 1942 but continued to provide Essiac to patients until the late 1970s.[4] For more information, see the Human/Clinical Studies section.

From 1959 until the late 1970s, the developer collaborated with an American physician to conduct clinical and laboratory studies of Essiac and to promote its use.[7] This collaboration led to the development of the eight-herb formula now marketed as Flor Essence. None of the results of these collaborative studies were reported in peer-reviewed scientific journals.

In 1977, the developer provided a four-herb recipe for Essiac to a Canadian corporation.[5,7] In 1978, the corporation filed a preclinical new drug submission with the Canadian Department of National Health and Welfare (Health Protection Branch) and received permission to conduct clinical studies of Essiac’s safety and effectiveness in cancer patients.[4,5,7,8] In 1982, this permission was withdrawn when it was determined that the corporation had not fulfilled commitments to adequately control the manufacturing consistency of Essiac, to isolate and characterize active substances in the mixture, and to design and execute appropriate clinical trials.[4,5] During this period, restrictions were imposed on the promotion of Essiac as a cancer treatment, but the corporation was allowed to distribute it to cancer patients through their physicians under Canada’s Emergency Drug Release Program (also called Health Canada’s Special Access Programme).[7] While the preclinical new drug submission was in effect in Canada, the corporation filed an unsuccessful New Drug Application (NDA) with the U.S. Food and Drug Administration, seeking permission to market Essiac in the United States. Details of the NDA submission, which can be disclosed only by the corporation, have not been made public.[4] For more information, see the Human/Clinical Studies section.

In the early 1980s, the Canadian Department of National Health and Welfare (Bureau of Human Prescription Drugs) conducted a retrospective review of case summaries submitted by physicians whose patients had obtained Essiac under the Emergency Drug Release Program.[2,4,7] The Department found little evidence to suggest that Essiac was effective as a cancer treatment. For more information, see the Human/Clinical Studies section.

Also in the 1980s, the manufacturers of Essiac-like products began to market their formulations as health tonics and to avoid making claims of effectiveness in treating disease. Consequently, the mixtures were no longer subject to regulation as drugs. Essiac is not currently available under Canada’s Emergency Drug Release Program.

In 1995, the corporation that acquired the four-herb recipe for Essiac from the developer dissolved voluntarily.[1] Later that year, a new company was formed to manufacture and distribute this proprietary herbal mixture.[1,5]

References

1. Essiac. Kirkland, Canada: Altramed Health Products, 2002. Available online. Last accessed April 11, 2016.
2. Tamayo C: Essiac for cancer. Alternative Therapies in Women’s Health 2 (3): 19-23, 2000.
3. Locock RA: Essiac. Can Pharm J 130: 18-9, 1997.
4. Herbal treatments. In: US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5. Also available online. Last accessed April 11, 2016.
5. LeMoine L: Essiac: an historical perspective. Can Oncol Nurs J 7 (4): 216-21, 1997. [PUBMED Abstract]
6. Tamayo C, Richardson MA, Diamond S, et al.: The chemistry and biological activity of herbs used in Flor-Essence herbal tonic and Essiac. Phytother Res 14 (1): 1-14, 2000. [PUBMED Abstract]
7. Kaegi E: Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (7): 897-902, 1998. [PUBMED Abstract]
8. Essiac. Toronto, Canada: Canadian Breast Cancer Research Alliance, 1996.
9. The History of Essiac & Rene Caisse, Canada’s Cancer Nurse. Kirkland, Canada: Altramed Health Products, 2001. Available online. Last accessed April 11, 2016.

References

1. Ottenweller J, Putt K, Blumenthal EJ, et al.: Inhibition of prostate cancer-cell proliferation by Essiac. J Altern Complement Med 10 (4): 687-91, 2004. [PUBMED Abstract]
2. Seely D, Kennedy DA, Myers SP, et al.: In vitro analysis of the herbal compound Essiac. Anticancer Res 27 (6B): 3875-82, 2007 Nov-Dec. [PUBMED Abstract]
3. Herbal treatments. In: US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5. Also available online. Last accessed April 11, 2016.
4. Bennett LM, Montgomery JL, Steinberg SM, et al.: Flor-Essence herbal tonic does not inhibit mammary tumor development in Sprague Dawley rats. Breast Cancer Res Treat 88 (1): 87-93, 2004. [PUBMED Abstract]
5. Kulp KS, Montgomery JL, Nelson DO, et al.: Essiac and Flor-Essence herbal tonics stimulate the in vitro growth of human breast cancer cells. Breast Cancer Res Treat 98 (3): 249-59, 2006. [PUBMED Abstract]
6. Tai J, Cheung S, Wong S, et al.: In vitro comparison of Essiac and Flor-Essence on human tumor cell lines. Oncol Rep 11 (2): 471-6, 2004. [PUBMED Abstract]
7. Tamayo C, Richardson MA, Diamond S, et al.: The chemistry and biological activity of herbs used in Flor-Essence herbal tonic and Essiac. Phytother Res 14 (1): 1-14, 2000. [PUBMED Abstract]
8. Tamayo C: Essiac for cancer. Alternative Therapies in Women’s Health 2 (3): 19-23, 2000.
9. Kaegi E: Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (7): 897-902, 1998. [PUBMED Abstract]
10. Essiac. Toronto, Canada: Canadian Breast Cancer Research Alliance, 1996.
11. Franke AA, Cooney RV, Custer LJ, et al.: Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. In: Manthey JA, Buslig BS, eds.: Flavonoids in the Living System. Plenum Press, 1998. Advances in Experimental Medicine and Biology, 439, pp 237-48.
12. Waladkhani AR, Clemens MR: Effect of dietary phytochemicals on cancer development (review) Int J Mol Med 1 (4): 747-53, 1998. [PUBMED Abstract]
13. de Witte P: Metabolism and pharmacokinetics of anthranoids. Pharmacology 47 (Suppl 1): 86-97, 1993. [PUBMED Abstract]
14. Campbell MJ, Hamilton B, Shoemaker M, et al.: Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro. Anticancer Res 22 (6C): 3843-52, 2002 Nov-Dec. [PUBMED Abstract]
15. Boué SM, Wiese TE, Nehls S, et al.: Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem 51 (8): 2193-9, 2003. [PUBMED Abstract]

References

1. Tamayo C: Essiac for cancer. Alternative Therapies in Women’s Health 2 (3): 19-23, 2000.
2. Kaegi E: Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (7): 897-902, 1998. [PUBMED Abstract]
3. Locock RA: Essiac. Can Pharm J 130: 18-9, 1997.
4. Herbal treatments. In: US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5. Also available online. Last accessed April 11, 2016.
5. Essiac. Toronto, Canada: Canadian Breast Cancer Research Alliance, 1996.
6. LeMoine L: Essiac: an historical perspective. Can Oncol Nurs J 7 (4): 216-21, 1997. [PUBMED Abstract]
7. Campbell MJ, Hamilton B, Shoemaker M, et al.: Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro. Anticancer Res 22 (6C): 3843-52, 2002 Nov-Dec. [PUBMED Abstract]
8. Al-Sukhni W, Grunbaum A, Fleshner N: Remission of hormone-refractory prostate cancer attributed to Essiac. Can J Urol 12 (5): 2841-2, 2005. [PUBMED Abstract]

Nausea and vomiting are the only reported adverse effects associated with the use of Essiac.[1] The manufacturer of Flor Essence states that users may experience increased bowel movements, frequent urination, swollen glands, skin blemishes, flu-like symptoms, or slight headaches.[2]

References

1. Herbal treatments. In: US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5. Also available online. Last accessed April 11, 2016.
2. Flora Flor•Essence®. Burnaby, Canada: Flora Manufacturing & Distributing Ltd. Available online. Last accessed April 11, 2016.

To assist readers in evaluating the results of human/clinical studies of integrative, alternative, and complementary therapies for cancer, a scoring system has been devised that allows studies of individual treatments to be ranked according to the strength of their evidence (i.e., their level of evidence). Not all studies, however, are given a level of evidence score. To be eligible, a study must:

Evidence from studies that do not meet these requirements is considered extremely weak. In addition to scoring individual studies, an overall level of evidence assessment is usually made.

Because no study of the use of Essiac or Flor Essence in humans has been reported in a peer-reviewed scientific journal, no level-of-evidence analysis is possible for these mixtures. The data that are available, however, do not support claims that Essiac and Flor Essence can detoxify the body, strengthen the immune system, or fight cancer. At this time, evidence does not support the use of either Essiac or Flor Essence in the treatment of cancer patients outside the context of well-designed clinical trials.

Separate levels-of-evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For additional information about levels of evidence analysis, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

General Information

Revised text to state that in the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. Also added text to state that the quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What are Essiac and Flor Essence?

   Essiac and Flor Essence are herbal tea mixtures that have been used as anticancer treatments. They have been used to treat other health conditions, including diabetes, AIDS, and gastrointestinal diseases.

   Essiac is reported to contain 4 herbs:

   • Burdock root.
   • Indian rhubarb root.
   • Sheep sorrel.
   • Slippery elm (the inner bark).

   Flor Essence is reported to contain the same 4 herbs found in Essiac plus these 4 other herbs:

   • Watercress.
   • Blessed thistle.
   • Red clover.
   • Kelp.

   Different batches of these mixtures may contain different ingredients or amounts and the effects may not always be the same.

   Essiac and Flor Essence are sold worldwide as health tonics or herbal dietary supplements. One company sells Flor Essence and several companies make and sell mixtures called Essiac. This summary refers to the trademarked (brand name) mixtures only.

2. How is Essiac or Flor Essence given or taken?

   Essiac and Flor Essence are taken orally as herbal teas.

3. What laboratory or animal studies have been done using Essiac or Flor Essence?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of Essiac and Flor Essence. For more information on laboratory and animal studies done using Essiac or Flor Essence, see the Laboratory/Animal/Preclinical Studies of the health professional version of Essiac/Flor Essence.

4. Have any studies of Essiac or Flor Essence been done in people?

   No results of clinical studies with people of Flor Essence have been reported. In addition, no reports of clinical trials of Essiac have been reported in peer-reviewed scientific journals.

   A case study was reported on a patient with prostate cancer who began drinking Essiac tea after having a rising prostate-specific antigen (PSA) level while on hormone therapy. The patient reported a drop in PSA level soon after starting Essiac that lasted for several months. The authors of the study reported that the PSA response could not be linked to Essiac.

5. Have any side effects or risks been reported from Essiac or Flor Essence?

   The only reported side effects caused by Essiac are nausea and vomiting. According to the company making Flor Essence, side effects may include increased bowel movements, frequent urination, swollen glands, skin blemishes, flu-like symptoms, and slight headaches.

6. Is Essiac or Flor Essence approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved Essiac or Flor Essence to treat cancer or any other medical condition.

   Essiac and Flor Essence are available in the United States as dietary supplements. The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of Essiac and Flor Essence supplements may not be the same.

Complementary and alternative medicine (CAM)—also called integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM carefully reviews these materials to see if any seem worth further research.

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

CAM on PubMed

NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

1. What is curcumin?

   Curcumin is a substance that comes from the underground stem of Curcuma longa, an East Indian plant. It is contained in a spice commonly called turmeric. The turmeric plant has been used for many years in traditional Asian medicine to treat many conditions.

   Curcumin comes in different forms. The amount of curcumin in each product labeled as curcumin can vary, making it hard to know how much to use to treat medical conditions.

2. How is curcumin taken or given?

   Curcumin is taken by mouth as a dietary supplement. It is also found in curry powder, as a major part of turmeric. Curcumin can also be made into a paste to treat skin conditions.

3. Have any laboratory or animal studies been done using curcumin?

   In laboratory studies, a substance is tested in tumor cells to find out if it has any anticancer effects. In animal studies, a drug, procedure, or treatment is tested in mice or other animals to see if it is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of curcumin. For information on laboratory and animal studies done using curcumin, see Laboratory/Preclinical Studies in the health professional version of this summary.

4. Have any studies of curcumin been done in people?

   Early phase trials have been done with small numbers of people to see if curcumin products are safe and work in the following ways:

   • To prevent cancer.
   • To treat cancer.
   • To improve quality of life.
   • To manage cancer treatment–related side effects.

   Researchers have looked at curcumin products for the prevention and treatment of a variety of cancers, including colorectal cancer, oral cancer, and liver cancer. There is not enough evidence to know if curcumin products can prevent or treat cancer.

   Cancer prevention and treatment trials

   • One study looked at the impact of oral curcumin on lesions in the lining of the colon and the rectum known as aberrant crypt foci (ACF). These lesions can be early warning signs of polyps and colorectal cancer. Although patients who received curcumin saw a decrease in ACF, the differences were not significant when compared to the group who did not receive curcumin.
   • A randomized trial looked at the use of an oral curcumin product in 223 patients with oral leukoplakia (thick white patches in the mouth). Compared to the placebo group, patients who received the curcumin product showed improved conditions that were maintained at 6 months. No further benefit was seen with treatment that lasted longer than 6 months.
   • Results from a study of 102 patients with nonalcoholic fatty liver disease (NAFLD) showed that a curcumin product was linked with reduced body mass index and waist size. Many patients who took the curcumin product showed improved liver ultrasound findings and biomarkers of liver inflammation in the blood, compared to the control group.
   • A later study that combined results from four randomized controlled trials of 228 patients with NAFLD who took curcumin products showed similar results for biomarkers of liver inflammation.
   • Results of studies that used curcumin products with traditional cancer treatments have been mixed. Studies of people with adrenocortical cancer, breast cancer, prostate cancer, pancreatic cancer, or colorectal cancer have shown improved results when using a curcumin product as an adjuvant therapy. Other studies did not show an improvement in disease. For more information on these study results, see the Cancer Treatment section in the health professional version of this summary.

   Curcumin products have been studied in early phase trials to find out their impact on cancer treatment–related side effects and quality of life.

   Cancer treatment–related side effects trials

   • Although studies have been mixed on oral curcumin given to treat radiation-induced dermatitis, a small study reported a topical cream that contained turmeric reduced dermatitis from radiation therapy.
   • Delayed onset and severity of mucositis (often seen as sores in the mouth) has been reported in trials that used a mouthwash product or oral capsule that had curcumin in it.
5. Have any side effects or risks been reported from curcumin?

   Few side effects have been reported from the use of products with curcumin. The most common complaint is digestive problems. A small study of patients who took a curcumin product with an anticancer drug found that one in three people stopped using the curcumin product because of constant bloating.

6. Is curcumin approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved the use of curcumin as a treatment for cancer or any other medical condition.

   Curcumin is available in the United States as a dietary supplement. The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of curcumin supplements may not be the same.

Complementary and alternative medicine (CAM)—also called integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM carefully reviews these materials to see if any seem worth further research.

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

CAM on PubMed

NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

This cancer information summary provides an overview of the use of curcumin as a treatment for people with cancer.

This summary contains the following key information:

Curcumin is a member of the diarylheptanoid class of natural products (curcuminoids) derived from the rhizome of Curcuma longa L., an East Indian plant, commonly called turmeric. The other major curcuminoids present in turmeric are demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin; together, they are termed the curcuminoid complex. The turmeric plant and preparations derived from it have a long history of therapeutic application in traditional Asian medicine. The crude and often dried plant material is widely consumed as a food additive, as part of curry spices, which typically contain numerous other ingredients. Turmeric and its preparations also have a long history of use as herbal medicines and dietary supplements, primarily to treat various inflammatory disorders.

Significant confusion exists in the scientific biomedical literature, as well as the popular literature, about the meaning of curcumin. Consequently, one group has developed a classification scheme that is described below.[1]

Several companies distribute curcumin as a dietary supplement. In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. The FDA can remove dietary supplements from the market that are deemed unsafe. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot. In addition, there is no guarantee that ingredients claimed on product labels are present at all or are present in the specified amounts. The FDA has not approved the use of curcumin as a treatment for cancer or any other medical condition.

References

1. Nelson KM, Dahlin JL, Bisson J, et al.: The Essential Medicinal Chemistry of Curcumin. J Med Chem 60 (5): 1620-1637, 2017. [PUBMED Abstract]
2. Pauli GF, Chen SN, Friesen JB, et al.: Analysis and purification of bioactive natural products: the AnaPurNa study. J Nat Prod 75 (6): 1243-55, 2012. [PUBMED Abstract]

Extensive research over the past two decades suggests that curcuminoids belonging to the diferuloylmethane class of natural products, the major constituents in turmeric (Curcuma longa), interfere with multiple cell signaling pathways, which provides support for the potential role of curcumin in modulating carcinogenesis. These pathways include the following:[1–12]

While these reports can possibly provide support for the potential role of curcumin-containing products in modulating carcinogenesis, definitive conclusions cannot be made, especially in light of the widespread confusion and/or misconception regarding the chemical nature of curcumin-containing products outlined above.

Because of the abundance of in vitro and preclinical studies in the past two decades, there has been a significant increase in the number of clinical trials investigating the therapeutic potential of curcumin-containing products. These clinical trials have used varying formulations and doses of curcuminoids for the prevention and treatment of cancer and to ameliorate symptoms of cancer treatment. This summary will focus on the bioavailability, safety, and effectiveness of curcumin-containing products reported in clinical trials that targeted individuals at high risk of cancer and cancer patients for the prevention and treatment of cancer and ameliorating the symptoms of cancer treatment.

References

1. Alexandrow MG, Song LJ, Altiok S, et al.: Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev 21 (5): 407-12, 2012. [PUBMED Abstract]
2. Panahi Y, Darvishi B, Ghanei M, et al.: Molecular mechanisms of curcumins suppressing effects on tumorigenesis, angiogenesis and metastasis, focusing on NF-κB pathway. Cytokine Growth Factor Rev 28: 21-9, 2016. [PUBMED Abstract]
3. Cho JW, Lee KS, Kim CW: Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med 19 (3): 469-74, 2007. [PUBMED Abstract]
4. Pal S, Bhattacharyya S, Choudhuri T, et al.: Amelioration of immune cell number depletion and potentiation of depressed detoxification system of tumor-bearing mice by curcumin. Cancer Detect Prev 29 (5): 470-8, 2005. [PUBMED Abstract]
5. Sehgal A, Kumar M, Jain M, et al.: Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs. Toxicol Mech Methods 22 (1): 74-80, 2012. [PUBMED Abstract]
6. Dance-Barnes ST, Kock ND, Moore JE, et al.: Lung tumor promotion by curcumin. Carcinogenesis 30 (6): 1016-23, 2009. [PUBMED Abstract]
7. Moghaddam SJ, Barta P, Mirabolfathinejad SG, et al.: Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice. Carcinogenesis 30 (11): 1949-56, 2009. [PUBMED Abstract]
8. Lee JC, Kinniry PA, Arguiri E, et al.: Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res 173 (5): 590-601, 2010. [PUBMED Abstract]
9. Sharma RA, Euden SA, Platton SL, et al.: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10 (20): 6847-54, 2004. [PUBMED Abstract]
10. Cheng AL, Hsu CH, Lin JK, et al.: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21 (4B): 2895-900, 2001 Jul-Aug. [PUBMED Abstract]
11. Carroll RE, Benya RV, Turgeon DK, et al.: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4 (3): 354-64, 2011. [PUBMED Abstract]
12. Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23 (1A): 363-98, 2003 Jan-Feb. [PUBMED Abstract]

References

1. Garcea G, Berry DP, Jones DJ, et al.: Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14 (1): 120-5, 2005. [PUBMED Abstract]
2. Kanai M, Otsuka Y, Otsuka K, et al.: A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients. Cancer Chemother Pharmacol 71 (6): 1521-30, 2013. [PUBMED Abstract]
3. Irving GR, Howells LM, Sale S, et al.: Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration–a clinical pilot study including assessment of patient acceptability. Cancer Prev Res (Phila) 6 (2): 119-28, 2013. [PUBMED Abstract]
4. Sharma RA, McLelland HR, Hill KA, et al.: Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7 (7): 1894-900, 2001. [PUBMED Abstract]
5. Sharma RA, Euden SA, Platton SL, et al.: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10 (20): 6847-54, 2004. [PUBMED Abstract]
6. Cheng AL, Hsu CH, Lin JK, et al.: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21 (4B): 2895-900, 2001 Jul-Aug. [PUBMED Abstract]
7. Kunihiro AG, Brickey JA, Frye JB, et al.: Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone metastatic breast cancer cells and is enriched in bone compared to other tissues. J Nutr Biochem 63: 150-156, 2019. [PUBMED Abstract]
8. Kunihiro AG, Luis PB, Brickey JA, et al.: Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. J Nat Prod 82 (3): 500-509, 2019. [PUBMED Abstract]
9. Schiborr C, Kocher A, Behnam D, et al.: The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 58 (3): 516-27, 2014. [PUBMED Abstract]
10. Stohs SJ, Ji J, Bucci LR, et al.: A Comparative Pharmacokinetic Assessment of a Novel Highly Bioavailable Curcumin Formulation with 95% Curcumin: A Randomized, Double-Blind, Crossover Study. J Am Coll Nutr 37 (1): 51-59, 2018. [PUBMED Abstract]
11. Cruz-Correa M, Shoskes DA, Sanchez P, et al.: Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 4 (8): 1035-8, 2006. [PUBMED Abstract]
12. Cruz-Correa M, Hylind LM, Marrero JH, et al.: Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology 155 (3): 668-673, 2018. [PUBMED Abstract]
13. Carroll RE, Benya RV, Turgeon DK, et al.: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4 (3): 354-64, 2011. [PUBMED Abstract]
14. Kuriakose MA, Ramdas K, Dey B, et al.: A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia. Cancer Prev Res (Phila) 9 (8): 683-91, 2016. [PUBMED Abstract]
15. Golombick T, Diamond TH, Manoharan A, et al.: Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am J Hematol 87 (5): 455-60, 2012. [PUBMED Abstract]
16. Panahi Y, Kianpour P, Mohtashami R, et al.: Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Res (Stuttg) 67 (4): 244-251, 2017. [PUBMED Abstract]
17. Mansour-Ghanaei F, Pourmasoumi M, Hadi A, et al.: Efficacy of curcumin/turmeric on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Integr Med Res 8 (1): 57-61, 2019. [PUBMED Abstract]
18. La Thangue NB, Kerr DJ: Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nat Rev Clin Oncol 8 (10): 587-96, 2011. [PUBMED Abstract]
19. Ghalaut VS, Sangwan L, Dahiya K, et al.: Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J Oncol Pharm Pract 18 (2): 186-90, 2012. [PUBMED Abstract]
20. Hejazi J, Rastmanesh R, Taleban FA, et al.: Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. Nutr Cancer 68 (1): 77-85, 2016. [PUBMED Abstract]
21. He ZY, Shi CB, Wen H, et al.: Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest 29 (3): 208-13, 2011. [PUBMED Abstract]
22. Panahi Y, Saadat A, Beiraghdar F, et al.: Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 28 (10): 1461-7, 2014. [PUBMED Abstract]
23. Plummer SM, Hill KA, Festing MF, et al.: Clinical development of leukocyte cyclooxygenase 2 activity as a systemic biomarker for cancer chemopreventive agents. Cancer Epidemiol Biomarkers Prev 10 (12): 1295-9, 2001. [PUBMED Abstract]
24. Belcaro G, Hosoi M, Pellegrini L, et al.: A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment. Phytother Res 28 (3): 444-50, 2014. [PUBMED Abstract]
25. Zaidi A, Lai M, Cavenagh J: Long-term stabilisation of myeloma with curcumin. BMJ Case Rep 2017: , 2017. [PUBMED Abstract]
26. Dhillon N, Aggarwal BB, Newman RA, et al.: Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14 (14): 4491-9, 2008. [PUBMED Abstract]
27. Demiray M, Sahinbas H, Atahan S, et al.: Successful treatment of c-kit-positive metastatic Adenoid Cystic Carcinoma (ACC) with a combination of curcumin plus imatinib: A case report. Complement Ther Med 27: 108-13, 2016. [PUBMED Abstract]
28. Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al.: Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 9 (1): 8-14, 2010. [PUBMED Abstract]
29. Passildas-Jahanmohan J, Eymard JC, Pouget M, et al.: Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first-line treatment of metastatic castration-resistant prostate cancer. Cancer Med 10 (7): 2332-2340, 2021. [PUBMED Abstract]
30. Epelbaum R, Schaffer M, Vizel B, et al.: Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62 (8): 1137-41, 2010. [PUBMED Abstract]
31. Pastorelli D, Fabricio ASC, Giovanis P, et al.: Phytosome complex of curcumin as complementary therapy of advanced pancreatic cancer improves safety and efficacy of gemcitabine: Results of a prospective phase II trial. Pharmacol Res 132: 72-79, 2018. [PUBMED Abstract]
32. Kanai M, Yoshimura K, Asada M, et al.: A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 68 (1): 157-64, 2011. [PUBMED Abstract]
33. James MI, Iwuji C, Irving G, et al.: Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett 364 (2): 135-41, 2015. [PUBMED Abstract]
34. Howells LM, Iwuji COO, Irving GRB, et al.: Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial. J Nutr 149 (7): 1133-1139, 2019. [PUBMED Abstract]
35. Hassell LA, Roanh le D: Potential response to curcumin in infantile hemangioendothelioma of the liver. Pediatr Blood Cancer 55 (2): 377-9, 2010. [PUBMED Abstract]
36. Ryan JL, Heckler CE, Ling M, et al.: Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 180 (1): 34-43, 2013. [PUBMED Abstract]
37. Ryan Wolf J, Heckler CE, Guido JJ, et al.: Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients. Support Care Cancer 26 (5): 1543-1552, 2018. [PUBMED Abstract]
38. Rao S, Hegde SK, Baliga-Rao MP, et al.: Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study. Medicines (Basel) 4 (3): , 2017. [PUBMED Abstract]
39. Elad S, Meidan I, Sellam G, et al.: Topical curcumin for the prevention of oral mucositis in pediatric patients: case series. Altern Ther Health Med 19 (3): 21-4, 2013 May-Jun. [PUBMED Abstract]
40. Francis M, Williams S: Effectiveness of Indian Turmeric Powder with Honey as Complementary Therapy on Oral Mucositis : A Nursing Perspective among Cancer Patients in Mysore. Nurs J India 105 (6): 258-60, 2014 Nov-Dec. [PUBMED Abstract]
41. Rao S, Dinkar C, Vaishnav LK, et al.: The Indian Spice Turmeric Delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer: An Investigational Study. Integr Cancer Ther 13 (3): 201-10, 2014. [PUBMED Abstract]
42. Delavarian Z, Pakfetrat A, Ghazi A, et al.: Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers. Spec Care Dentist 39 (2): 166-172, 2019. [PUBMED Abstract]
43. Arun P, Sagayaraj A, Azeem Mohiyuddin SM, et al.: Role of turmeric extract in minimising mucositis in patients receiving radiotherapy for head and neck squamous cell cancer: a randomised, placebo-controlled trial. J Laryngol Otol : 1-6, 2020. [PUBMED Abstract]

Most clinical studies of curcuma-containing products have demonstrated few, if any, associated adverse effects. In one small study (N = 17) of patients who received a curcumin-containing product along with gemcitabine chemotherapy, about 30% of patients (N = 5) who received 8,000 mg/day of the curcumin-containing product discontinued the product because of intractable abdominal fullness. Two other patients had a dose reduction to 4,000 mg, also because of abdominal complaints.[1] In this study, seven patients had grade 3 gastrointestinal toxicity and two patients had grade 2 gastrointestinal toxicity.

References

1. Epelbaum R, Schaffer M, Vizel B, et al.: Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62 (8): 1137-41, 2010. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

This cancer information summary provides an overview of the use of coenzyme Q₁₀ in cancer therapy. The summary includes a history of coenzyme Q₁₀ research, a review of laboratory studies, and data from investigations involving human subjects. Although several naturally occurring forms of coenzyme Q have been identified, Q₁₀ is the predominant form found in humans and most mammals, and it is the form most studied for therapeutic potential. Thus, it will be the only form of coenzyme Q discussed in this summary.

This summary contains the following key information:

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.

Coenzyme Q₁₀ (also known as CoQ₁₀, Q₁₀, vitamin Q₁₀, ubiquinone, and ubidecarenone) is a benzoquinone compound synthesized naturally by the human body. The “Q” and the “10” in the name refer to the quinone chemical group and the 10 isoprenyl subunits that are part of this compound’s structure. The term “coenzyme” denotes it as an organic (contains carbon atoms), nonprotein molecule necessary for the proper functioning of its protein partner (an enzyme or an enzyme complex). Coenzyme Q₁₀ is used by cells of the body in a process known variously as:

Through this process, mitochondria produce energy for cell growth and maintenance.[1–4] Coenzyme Q₁₀ is also used by the body as an endogenous antioxidant.[1,2,4–8] An antioxidant is a substance that protects cells from free radicals, which are highly reactive chemicals, often containing oxygen atoms, capable of damaging important cellular components such as DNA and lipids. In addition, the plasma level of coenzyme Q₁₀ has been used in studies as a measure of oxidative stress.[9,10]

Coenzyme Q₁₀ is present in most tissues, but the highest concentrations are found in the following organs:[11]

The lowest concentration is found in the lungs.[11] Tissue levels of this compound decrease as people age, due to increased requirements, decreased production,[11] or insufficient intake of the chemical precursors needed for synthesis.[12] In humans, normal blood levels of coenzyme Q₁₀ have been defined variably, with reported normal values ranging from 0.30 to 3.84 µg/mL.[2,4,13,14]

Given the importance of coenzyme Q₁₀ in optimizing cellular energy production, use of this compound as a treatment for diseases other than cancer has been explored. Most of these investigations have focused on coenzyme Q₁₀ as a treatment for cardiovascular disease.[2,4,15] In patients with cancer, coenzyme Q₁₀ has been shown to do the following:

Stimulation of the immune system by this compound has also been observed in animal studies and in humans without cancer.[21–27] In part because of its immunostimulatory potential, coenzyme Q₁₀ has been used as an adjuvant therapy in patients with various types of cancer.[17,20,28–33]

While coenzyme Q₁₀ may show indirect anticancer activity through its effect(s) on the immune system, there is evidence to suggest that analogs of this compound can suppress cancer growth directly. Analogs of coenzyme Q₁₀ have been shown to inhibit the proliferation of cancer cells in vitro and the growth of cancer cells transplanted into rats and mice.[12,34] In view of these findings, it has been proposed that analogs of coenzyme Q₁₀ may function as antimetabolites to disrupt normal biochemical reactions that are required for cell growth and/or survival and, thus, that they may be useful as chemotherapeutic agents.[12,34]

Several companies distribute coenzyme Q₁₀ as a dietary supplement. In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved coenzyme Q₁₀ for the treatment of cancer or any other medical condition.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is highly confidential, and IND information can be disclosed only by the applicants. No investigators have announced that they have applied for an IND to study coenzyme Q₁₀ as a treatment for cancer.

In animal studies, coenzyme Q₁₀ has been administered by injection (intravenous, intraperitoneal, intramuscular, or subcutaneous). In humans, it is usually taken orally as a pill (gel bead or capsule), but intravenous infusions have been given.[4] Coenzyme Q₁₀ is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound.[2,4] In human studies, supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 mg/day.

References

1. Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993. [PUBMED Abstract]
2. Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999. [PUBMED Abstract]
3. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985. [PUBMED Abstract]
4. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999. [PUBMED Abstract]
5. Beyer RE, Nordenbrand K, Ernster L: The role of coenzyme Q as a mitochondrial antioxidant: a short review. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 5. Elsevier Science Publishers B V (Biomedical Division), 1986, pp 17-24.
6. Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996. [PUBMED Abstract]
7. Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22 (1 Suppl): 73-6, 1997 Jan-Mar. [PUBMED Abstract]
8. Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995. [PUBMED Abstract]
9. Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 247 (1): 166-70, 1998. [PUBMED Abstract]
10. Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol Aspects Med 18 (Suppl): S79-84, 1997. [PUBMED Abstract]
11. Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993. [PUBMED Abstract]
12. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974. [PUBMED Abstract]
13. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997. [PUBMED Abstract]
14. Jolliet P, Simon N, Barré J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 36 (9): 506-9, 1998. [PUBMED Abstract]
15. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 15 (Suppl): s287-94, 1994. [PUBMED Abstract]
16. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep 62 (6): 887-91, 1978. [PUBMED Abstract]
17. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993. [PUBMED Abstract]
18. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 15 (Suppl): s207-12, 1994. [PUBMED Abstract]
19. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38 (2): 335-8, 1982. [PUBMED Abstract]
20. Complementary treatments highlighted at recent meeting. Oncology (Huntingt) 13 (2): 166, 1999. [PUBMED Abstract]
21. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26 (9): 953-4, 1970. [PUBMED Abstract]
22. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176 (2): 786-91, 1991. [PUBMED Abstract]
23. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme, Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69 (4): 493-7, 1978. [PUBMED Abstract]
24. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973. [PUBMED Abstract]
25. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972. [PUBMED Abstract]
26. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Elsevier/North-Holland Biomedical Press, 1977, pp 73-83.
27. Barbieri B, Lund B, Lundström B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers–a single blind placebo-controlled and randomized clinical study. Biofactors 9 (2-4): 351-7, 1999. [PUBMED Abstract]
28. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 15 (Suppl): s231-40, 1994. [PUBMED Abstract]
29. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 199 (3): 1504-8, 1994. [PUBMED Abstract]
30. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995. [PUBMED Abstract]
31. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]
32. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997. [PUBMED Abstract]
33. Hodges S, Hertz N, Lockwood K, et al.: CoQ10: could it have a role in cancer management? Biofactors 9 (2-4): 365-70, 1999. [PUBMED Abstract]
34. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Res Commun Chem Pathol Pharmacol 19 (3): 485-90, 1978. [PUBMED Abstract]

Coenzyme Q₁₀ was first isolated in 1957, and its chemical structure (benzoquinone compound) was determined in 1958.[1,2] Interest in coenzyme Q₁₀ as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer.[2–4] A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q₁₀ deficiency and breast cancer prognosis.[5] Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck.[2,6,7] Furthermore, decreased levels of coenzyme Q₁₀ have been detected in malignant human tissue,[8–12] but increased levels have been reported as well.[8]

A large amount of laboratory and animal data on coenzyme Q₁₀ have accumulated since 1962.[2] Research into cellular energy-producing mechanisms that involve this compound was awarded the Nobel Prize in Chemistry in 1978. Some of the accumulated data show that coenzyme Q₁₀ stimulates animal immune systems, leading to higher antibody levels,[13] greater numbers and/or activities of macrophages and T cells (T lymphocytes),[13,14] and increased resistance to infection.[15–17] Coenzyme Q₁₀ has also been reported to increase IgG (immunoglobulin G) antibody levels and to increase the CD4 to CD8 T-cell ratio in humans.[18–20] CD4 and CD8 are proteins found on the surface of T cells, with CD4 and CD8 identifying helper T cells and cytotoxic T cells, respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer patients.[21,22] Research subsequently delineated the antioxidant properties of coenzyme Q₁₀.[23–27]

Proposed mechanisms of action for coenzyme Q₁₀ that are relevant to cancer include its essential function in cellular energy production and its stimulation of the immune system (which may both be related), as well as its role as an antioxidant. Coenzyme Q₁₀ is essential to aerobic energy production,[1,25,28] and it has been suggested that increased cellular energy leads to increased antibody synthesis in B cells (B lymphocytes).[6,18] As noted previously (General Information section), coenzyme Q₁₀ can also behave as an antioxidant.[1,25–27,29–32] In this capacity, coenzyme Q₁₀ is thought to stabilize cell membranes (lipid-containing structures essential to maintaining cell integrity) and to prevent free radical damage to other important cellular components.[1,25,27,32] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.[11,23,30,33–36]

References

1. Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999. [PUBMED Abstract]
2. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997. [PUBMED Abstract]
3. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995. [PUBMED Abstract]
4. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997. [PUBMED Abstract]
5. Jolliet P, Simon N, Barré J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 36 (9): 506-9, 1998. [PUBMED Abstract]
6. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974. [PUBMED Abstract]
7. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]
8. Chipperfield B: Ubiquinone concentrations in some tumour-bearing tissues. Ubiquinone concentrations in tumours and some normal tissues in man. Nature 209 (29): 1207-8, 1966. [PUBMED Abstract]
9. Eggens I, Elmberger PG, Löw P: Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas. Br J Exp Pathol 70 (1): 83-92, 1989. [PUBMED Abstract]
10. Mano T, Iwase K, Hayashi R, et al.: Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. Am J Med Sci 315 (4): 230-2, 1998. [PUBMED Abstract]
11. Picardo M, Grammatico P, Roccella F, et al.: Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. J Invest Dermatol 107 (3): 322-6, 1996. [PUBMED Abstract]
12. Portakal O, Ozkaya O, Erden Inal M, et al.: Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 33 (4): 279-84, 2000. [PUBMED Abstract]
13. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26 (9): 953-4, 1970. [PUBMED Abstract]
14. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme, Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69 (4): 493-7, 1978. [PUBMED Abstract]
15. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973. [PUBMED Abstract]
16. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972. [PUBMED Abstract]
17. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Elsevier/North-Holland Biomedical Press, 1977, pp 73-83.
18. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38 (2): 335-8, 1982. [PUBMED Abstract]
19. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176 (2): 786-91, 1991. [PUBMED Abstract]
20. Barbieri B, Lund B, Lundström B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers–a single blind placebo-controlled and randomized clinical study. Biofactors 9 (2-4): 351-7, 1999. [PUBMED Abstract]
21. Shaw M, Ray P, Rubenstein M, et al.: Lymphocyte subsets in urologic cancer patients. Urol Res 15 (3): 181-5, 1987. [PUBMED Abstract]
22. Tsuyuguchi I, Shiratsuchi H, Fukuoka M: T-lymphocyte subsets in primary lung cancer. Jpn J Clin Oncol 17 (1): 13-7, 1987. [PUBMED Abstract]
23. Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 247 (1): 166-70, 1998. [PUBMED Abstract]
24. Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol Aspects Med 18 (Suppl): S79-84, 1997. [PUBMED Abstract]
25. Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993. [PUBMED Abstract]
26. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999. [PUBMED Abstract]
27. Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993. [PUBMED Abstract]
28. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985. [PUBMED Abstract]
29. Beyer RE, Nordenbrand K, Ernster L: The role of coenzyme Q as a mitochondrial antioxidant: a short review. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 5. Elsevier Science Publishers B V (Biomedical Division), 1986, pp 17-24.
30. Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996. [PUBMED Abstract]
31. Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22 (1 Suppl): 73-6, 1997 Jan-Mar. [PUBMED Abstract]
32. Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995. [PUBMED Abstract]
33. Aust AE, Eveleigh JF: Mechanisms of DNA oxidation. Proc Soc Exp Biol Med 222 (3): 246-52, 1999. [PUBMED Abstract]
34. Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443 (1-2): 37-52, 1999. [PUBMED Abstract]
35. Burcham PC: Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutat Res 443 (1-2): 11-36, 1999. [PUBMED Abstract]
36. Dreher D, Junod AF: Role of oxygen free radicals in cancer development. Eur J Cancer 32A (1): 30-8, 1996. [PUBMED Abstract]

Laboratory work on coenzyme Q₁₀ has focused primarily on its structure and its function in cell respiration. Studies in animals have demonstrated that coenzyme Q₁₀ is capable of stimulating the immune system, with treated animals showing increased resistance to protozoal infections [1,2] and to viral and chemically-induced neoplasia.[1–4] Early studies of coenzyme Q₁₀ showed increased hematopoiesis (the formation of new blood cells) in monkeys,[4,5] rabbits,[6] and poultry.[5] Coenzyme Q₁₀ demonstrated a protective effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[7–12] Although another study confirmed this protective effect with intraperitoneal administration of doxorubicin in mice, it failed to demonstrate a protective effect when the anthracycline was given intravenously, which is the route of administration in humans.[13]

Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q₁₀ and radiation therapy decreased the effectiveness of the radiation therapy.[14] In this study, mice inoculated with human small cell lung cancer cells (a xenograft study), and then given coenzyme Q₁₀ and single-dose radiation therapy, showed substantially less inhibition of tumor growth than mice in the control group that were treated with radiation therapy alone. Since radiation leads to the production of free radicals, and since antioxidants protect against free radical damage, the effect in this study might be explained by coenzyme Q₁₀ acting as an antioxidant. As noted previously, there is some evidence from laboratory and animal studies that analogs of coenzyme Q₁₀ may have direct anticancer activity.[15,16] See the General Information section.

References

1. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972. [PUBMED Abstract]
2. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Elsevier/North-Holland Biomedical Press, 1977, pp 73-83.
3. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973. [PUBMED Abstract]
4. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997. [PUBMED Abstract]
5. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993. [PUBMED Abstract]
6. Ludwig FC, Elashoff RM, Smith JL, et al.: Response of the bone marrow of the vitamin E-deficient rabbit to coenzyme Q and vitamin E. Scand J Haematol 4 (4): 292-300, 1967. [PUBMED Abstract]
7. Choe JY, Combs AB, Folkers K: Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats. Res Commun Chem Pathol Pharmacol 23 (1): 199-202, 1979. [PUBMED Abstract]
8. Combs AB, Choe JY, Truong DH, et al.: Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. Res Commun Chem Pathol Pharmacol 18 (3): 565-8, 1977. [PUBMED Abstract]
9. Folkers K, Choe JY, Combs AB: Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat. Proc Natl Acad Sci U S A 75 (10): 5178-80, 1978. [PUBMED Abstract]
10. Lubawy WC, Dallam RA, Hurley LH: Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J Natl Cancer Inst 64 (1): 105-9, 1980. [PUBMED Abstract]
11. Shinozawa S, Gomita Y, Araki Y: Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats. Biol Pharm Bull 16 (11): 1114-7, 1993. [PUBMED Abstract]
12. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 12 (1): 75-82, 1982. [PUBMED Abstract]
13. Shaeffer J, El-Mahdi AM, Nichols RK: Coenzyme Q10 and adriamycin toxicity in mice. Res Commun Chem Pathol Pharmacol 29 (2): 309-15, 1980. [PUBMED Abstract]
14. Lund EL, Quistorff B, Spang-Thomsen M, et al.: Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 43 (5): 505-6, 1998. [PUBMED Abstract]
15. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974. [PUBMED Abstract]
16. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Res Commun Chem Pathol Pharmacol 19 (3): 485-90, 1978. [PUBMED Abstract]

Clinical studies on the use of coenzyme Q₁₀ to prevent side effects of cancer treatment, treat side effects of cancer treatment, and/or as a treatment for cancer are very limited. Importantly, clinical trials that examined the use of coenzyme Q₁₀ during cancer treatment to prevent toxicities have not followed patients for long-term outcomes to determine whether coenzyme Q₁₀ decreased the efficacy of cancer treatments (e.g., chemotherapy and radiation therapy). A recent observational study conducted with 1,134 patients with breast cancer enrolled in an National Cancer Institute multi-institution clinical trial (SWOG S0221) suggested that the use of antioxidant supplements, including coenzyme Q₁₀, prior to and during cancer treatment may be associated with increased recurrence rates and decreased survival.[1]

References

1. Ambrosone CB, Zirpoli GR, Hutson AD, et al.: Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol 38 (8): 804-814, 2020. [PUBMED Abstract]
2. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep 62 (6): 887-91, 1978. [PUBMED Abstract]
3. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 12 (1): 75-82, 1982. [PUBMED Abstract]
4. Iwamoto Y, Hansen IL, Porter TH, et al.: Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase, by adriamycin and other quinones having antitumor activity. Biochem Biophys Res Commun 58 (3): 633-8, 1974. [PUBMED Abstract]
5. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985. [PUBMED Abstract]
6. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993. [PUBMED Abstract]
7. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 15 (Suppl): s207-12, 1994. [PUBMED Abstract]
8. Lesser GJ, Case D, Stark N, et al.: A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol 11 (1): 31-42, 2013. [PUBMED Abstract]
9. Iwase S, Kawaguchi T, Yotsumoto D, et al.: Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01). Support Care Cancer 24 (2): 637-646, 2016. [PUBMED Abstract]
10. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997. [PUBMED Abstract]
11. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995. [PUBMED Abstract]
12. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]
13. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997. [PUBMED Abstract]
14. Shidal C, Yoon HS, Zheng W, et al.: Prospective study of plasma levels of coenzyme Q10 and lung cancer risk in a low-income population in the Southeastern United States. Cancer Med 10 (4): 1439-1447, 2021. [PUBMED Abstract]
15. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 15 (Suppl): s231-40, 1994. [PUBMED Abstract]
16. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 199 (3): 1504-8, 1994. [PUBMED Abstract]

No serious toxicity associated with the use of coenzyme Q₁₀ has been reported.[1–4] Doses of 100 mg/day or higher have caused mild insomnia in some individuals. Liver enzyme elevation has been detected in patients taking doses of 300 mg/day for extended periods of time, but no liver toxicity has been reported.[1] Researchers in one cardiovascular study reported that coenzyme Q₁₀ caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from the study.[5] Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[5] headache, heartburn, and fatigue.[6]

In a prospective study that explored the association between supplement use and breast cancer outcomes (SWOG S0221), the use of any antioxidant supplement before and during treatment–including coenzyme Q₁₀, vitamin A, vitamin C, vitamin E, and carotenoids–was associated with a trend showing an increased hazard of recurrence (adjusted hazard ratio, 1.41; confidence interval, 0.98–2.04, P = .06).[7]

Certain lipid-lowering drugs, such as the statins (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q₁₀ and reduce the effects of coenzyme Q₁₀ supplementation.[1,8–10] Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q₁₀-dependent enzyme reactions. The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q₁₀ administration.[1] Coenzyme Q₁₀ can reduce the body’s response to the anticoagulant drug warfarin.[10] Finally, coenzyme Q₁₀ can decrease insulin requirements in individuals with diabetes.

References

1. Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999. [PUBMED Abstract]
2. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999. [PUBMED Abstract]
3. Hodges S, Hertz N, Lockwood K, et al.: CoQ10: could it have a role in cancer management? Biofactors 9 (2-4): 365-70, 1999. [PUBMED Abstract]
4. Heller JH: Disease, the host defense, and Q-10. Perspect Biol Med 16 (2): 181-7, 1973 Winter. [PUBMED Abstract]
5. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 15 (Suppl): s287-94, 1994. [PUBMED Abstract]
6. Feigin A, Kieburtz K, Como P, et al.: Assessment of coenzyme Q10 tolerability in Huntington’s disease. Mov Disord 11 (3): 321-3, 1996. [PUBMED Abstract]
7. Ambrosone CB, Zirpoli GR, Hutson AD, et al.: Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol 38 (8): 804-814, 2020. [PUBMED Abstract]
8. Kaikkonen J, Nyyssönen K, Tuomainen TP, et al.: Determinants of plasma coenzyme Q10 in humans. FEBS Lett 443 (2): 163-6, 1999. [PUBMED Abstract]
9. Thibault A, Samid D, Tompkins AC, et al.: Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res 2 (3): 483-91, 1996. [PUBMED Abstract]
10. Coenzyme Q10. In: Jellin JM, Hitchens K, eds.: Natural Medicines Comprehensive Database. Therapeutic Research Faculty, 1999, pp 241-42.

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the “levels of evidence”) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

References

1. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 15 (Suppl): s231-40, 1994. [PUBMED Abstract]

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.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What is CoQ10?

   CoQ10 is a compound that is made in the body. The Q and the 10 in coenzyme Q10 refer to the groups of chemicals that make up the product. CoQ10 is also known by the following names:

   • Q₁₀.
   • Vitamin Q₁₀.
   • Ubiquinone.
   • Ubidecarenone.

   A coenzyme helps an enzyme do its job. An enzyme is a protein that speeds up the rate at which chemical reactions take place in cells of the body. The body’s cells use CoQ10 to make energy needed for the cells to grow and stay healthy. The body also uses CoQ10 as an antioxidant. An antioxidant protects cells from chemicals called free radicals.

   CoQ10 is found in most body tissues. The highest amounts are found in the heart, liver, kidneys, and pancreas. The lowest amounts are found in the lungs. CoQ10 decreases in the body as people get older.

2. How is CoQ10 given?

   CoQ10 is taken by mouth as a tablet or capsule. It may also be given by injection into a vein (IV).

3. Have any laboratory or animal studies been done using CoQ10?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of coenzyme Q10. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Coenzyme Q10 for information on laboratory and animal studies done using CoQ10.

4. Have any studies of CoQ10 been done in people?

   There have been few clinical trials that study the use of CoQ10 in patients with cancer.

   A trial of 236 breast cancer patients were randomized to receive either CoQ10 or placebo, each combined with vitamin E, for 24 weeks. The study found that levels of fatigue and quality of life were not improved in patients who received CoQ10 compared to patients who received the placebo.

   A randomized trial of 20 children treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma looked at whether CoQ10 would protect the heart from the damage caused by doxorubicin. The results reported that CoQ10 decreased the harmful effects of doxorubicin on the heart.

   Clinical trials have been limited to small numbers of people, and it is not clear if the benefits reported were from the CoQ10 therapy, other dietary supplements, or standard treatments used before or during the CoQ10 therapy.

5. Have any side effects or risks been reported from CoQ10?

   Reported side effects from the use of CoQ10 include the following:

   • High levels of liver enzymes.
   • Nausea.
   • Heartburn.
   • Headache.
   • Pain in the upper part of the abdomen.
   • Dizziness.
   • Rashes.
   • Unable to fall sleep or stay asleep.
   • Feeling very tired.
   • Feeling irritable.
   • Sensitive to light.

   Importantly, clinical trials that studied the use of CoQ10 to prevent toxic side effects during cancer treatments (for example, chemotherapy and radiation therapy) have not followed patients over the long term to find whether CoQ10 made the treatments less effective.

   A recent observational study in patients with breast cancer suggested that the use of antioxidant supplements, including CoQ10, before and during cancer treatment may be linked with increased recurrence rates and decreased survival.

   It is important to check with health care providers to find out if CoQ10 can be safely used with other drugs. Certain drugs, such as those that are used to lower cholesterol, blood pressure, or blood sugar levels, may decrease the effects of CoQ10. CoQ10 may change the way the body uses warfarin (a drug that prevents the blood from clotting) and insulin.

6. Is CoQ10 approved by the FDA for use as a cancer treatment in the United States?

   The FDA has not approved the use of CoQ10 as a treatment for cancer.

   The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of CoQ10 supplements may not be the same.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Complementary and alternative medicine (CAM)—also called integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM carefully reviews these materials to see if any seem worth further research.

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

CAM on PubMed

NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

This cancer information summary provides an overview on cancer therapy interactions with different foods and dietary supplements.

This summary contains the following key information:

For adult cancer patients in the United States, the frequency of complementary and alternative medicine (CAM) use is approximately 36%.[1] It is possible that the combination of cancer drugs taken by these patients and the CAM they use may interact, causing adverse outcomes.[2–4] When dietary supplements/herbs and cancer drugs are taken together, there is always a risk of the supplement having an impact on the pharmacokinetics (PK) or pharmacodynamics (PD) of the drug. Many drug interactions occur from the effects of the supplement on specific enzymes or on components involved in the PK of the drug, such as how the drug is metabolized and transported. Reporting and studying these interactions is important, so health care professionals can help patients navigate CAM usage with standard cancer therapies, thus avoiding preventable adverse outcomes. Integrative oncology consultations available in a number of cancer care settings can engage patients in evidence-based discussions about recommending or stopping supplements, as well as addressing questions about alternative therapies.[5]

In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved the use of dietary supplements as a treatment for cancer patients.

References

1. Collado-Borrell R, Escudero-Vilaplana V, Romero-Jiménez R, et al.: Oral antineoplastic agent interactions with medicinal plants and food: an issue to take into account. J Cancer Res Clin Oncol 142 (11): 2319-30, 2016. [PUBMED Abstract]
2. Wolf CPJG, Rachow T, Ernst T, et al.: Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements. J Cancer Res Clin Oncol 148 (2): 461-473, 2022. [PUBMED Abstract]
3. Lee RT, Kwon N, Wu J, et al.: Prevalence of potential interactions of medications, including herbs and supplements, before, during, and after chemotherapy in patients with breast and prostate cancer. Cancer 127 (11): 1827-1835, 2021. [PUBMED Abstract]
4. Harrigan M, McGowan C, Hood A, et al.: Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions. Nutrients 13 (11): , 2021. [PUBMED Abstract]
5. D’Andre SD, Bauer BA, Hofmann MB, et al.: Dietary supplement use and recommendations for discontinuation in an integrative oncology clinic. Support Care Cancer 31 (1): 40, 2022. [PUBMED Abstract]
6. He SM, Yang AK, Li XT, et al.: Effects of herbal products on the metabolism and transport of anticancer agents. Expert Opin Drug Metab Toxicol 6 (10): 1195-213, 2010. [PUBMED Abstract]
7. Meijerman I, Beijnen JH, Schellens JH: Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist 11 (7): 742-52, 2006 Jul-Aug. [PUBMED Abstract]

References

1. Ozben T: Antioxidant supplementation on cancer risk and during cancer therapy: an update. Curr Top Med Chem 15 (2): 170-8, 2015. [PUBMED Abstract]
2. Maher HM, Alzoman NZ, Shehata SM: Ultra-performance LC-MS/MS study of the pharmacokinetic interaction of imatinib with selected vitamin preparations in rats. Bioanalysis 10 (14): 1099-1113, 2018. [PUBMED Abstract]
3. Heaney ML, Gardner JR, Karasavvas N, et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 68 (19): 8031-8, 2008. [PUBMED Abstract]
4. Perrone G, Hideshima T, Ikeda H, et al.: Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 23 (9): 1679-86, 2009. [PUBMED Abstract]
5. Jung AY, Cai X, Thoene K, et al.: Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy. Am J Clin Nutr 109 (1): 69-78, 2019. [PUBMED Abstract]
6. Ambrosone CB, Zirpoli GR, Hutson AD, et al.: Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol 38 (8): 804-814, 2020. [PUBMED Abstract]
7. Bairati I, Meyer F, Gélinas M, et al.: A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst 97 (7): 481-8, 2005. [PUBMED Abstract]
8. Bairati I, Meyer F, Jobin E, et al.: Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer 119 (9): 2221-4, 2006. [PUBMED Abstract]

References

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6. Bilgi N, Bell K, Ananthakrishnan AN, et al.: Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 44 (5): 926-8, 2010. [PUBMED Abstract]
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11. Wang T, Long F, Jiang G, et al.: Pharmacokinetic properties of wogonin and its herb-drug interactions with docetaxel in rats with mammary tumors. Biomed Chromatogr : e4264, 2018. [PUBMED Abstract]
12. Field HL, Monti DA, Greeson JM, et al.: St. John’s Wort. Int J Psychiatry Med 30 (3): 203-19, 2000. [PUBMED Abstract]
13. Yang SY, Juang SH, Tsai SY, et al.: St. John’s wort significantly increased the systemic exposure and toxicity of methotrexate in rats. Toxicol Appl Pharmacol 263 (1): 39-43, 2012. [PUBMED Abstract]
14. Mathijssen RH, Verweij J, de Bruijn P, et al.: Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 94 (16): 1247-9, 2002. [PUBMED Abstract]
15. Smith P, Bullock JM, Booker BM, et al.: The influence of St. John’s wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy 24 (11): 1508-14, 2004. [PUBMED Abstract]
16. Frye RF, Fitzgerald SM, Lagattuta TF, et al.: Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 76 (4): 323-9, 2004. [PUBMED Abstract]
17. Goey AK, Meijerman I, Rosing H, et al.: The effect of St John’s wort on the pharmacokinetics of docetaxel. Clin Pharmacokinet 53 (1): 103-10, 2014. [PUBMED Abstract]
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21. Chou WC, Wu CC, Yang PC, et al.: Hypovolemic shock and mortality after ingestion of Tripterygium wilfordii hook F.: a case report. Int J Cardiol 49 (2): 173-7, 1995. [PUBMED Abstract]
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References

1. Mouly S, Lloret-Linares C, Sellier PO, et al.: Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John’s Wort? Pharmacol Res 118: 82-92, 2017. [PUBMED Abstract]
2. Singh BN: Effects of food on clinical pharmacokinetics. Clin Pharmacokinet 37 (3): 213-55, 1999. [PUBMED Abstract]
3. Paine MF, Widmer WW, Hart HL, et al.: A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. Am J Clin Nutr 83 (5): 1097-105, 2006. [PUBMED Abstract]
4. Hung WL, Suh JH, Wang Y: Chemistry and health effects of furanocoumarins in grapefruit. J Food Drug Anal 25 (1): 71-83, 2017. [PUBMED Abstract]
5. He SM, Yang AK, Li XT, et al.: Effects of herbal products on the metabolism and transport of anticancer agents. Expert Opin Drug Metab Toxicol 6 (10): 1195-213, 2010. [PUBMED Abstract]
6. Reif S, Nicolson MC, Bisset D, et al.: Effect of grapefruit juice intake on etoposide bioavailability. Eur J Clin Pharmacol 58 (7): 491-4, 2002. [PUBMED Abstract]
7. van Erp NP, Baker SD, Zandvliet AS, et al.: Marginal increase of sunitinib exposure by grapefruit juice. Cancer Chemother Pharmacol 67 (3): 695-703, 2011. [PUBMED Abstract]
8. Yin OQ, Gallagher N, Li A, et al.: Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol 50 (2): 188-94, 2010. [PUBMED Abstract]
9. Sang S, Lambert JD, Ho C, et al.: Green tea polyphenols. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. Informa Healthcare, 2010, pp 402-10.
10. Du GJ, Zhang Z, Wen XD, et al.: Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 4 (11): 1679-91, 2012. [PUBMED Abstract]
11. Golden EB, Lam PY, Kardosh A, et al.: Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 113 (23): 5927-37, 2009. [PUBMED Abstract]
12. Bannerman B, Xu L, Jones M, et al.: Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother Pharmacol 68 (5): 1145-54, 2011. [PUBMED Abstract]
13. Qiao J, Gu C, Shang W, et al.: Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food Chem Toxicol 49 (6): 1410-5, 2011. [PUBMED Abstract]
14. Lin LC, Wang MN, Tsai TH: Food-drug interaction of (-)-epigallocatechin-3-gallate on the pharmacokinetics of irinotecan and the metabolite SN-38. Chem Biol Interact 174 (3): 177-82, 2008. [PUBMED Abstract]
15. Paul D, Surendran S, Chandrakala P, et al.: An assessment of the impact of green tea extract on palbociclib pharmacokinetics using a validated UHPLC-QTOF-MS method. Biomed Chromatogr 33 (4): e4469, 2019. [PUBMED Abstract]
16. Maher HM, Alzoman NZ, Shehata SM, et al.: UPLC-ESI-MS/MS study of the effect of green tea extract on the oral bioavailability of erlotinib and lapatinib in rats: Potential risk of pharmacokinetic interaction. J Chromatogr B Analyt Technol Biomed Life Sci 1049-1050: 30-40, 2017. [PUBMED Abstract]
17. Ge J, Tan BX, Chen Y, et al.: Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability. J Mol Med (Berl) 89 (6): 595-602, 2011. [PUBMED Abstract]
18. Shin SC, Choi JS: Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats. Anticancer Drugs 20 (7): 584-8, 2009. [PUBMED Abstract]
19. Braal CL, Hussaarts KGAM, Seuren L, et al.: Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 184 (1): 107-113, 2020. [PUBMED Abstract]

References

1. Mathijssen RH, Verweij J, de Bruijn P, et al.: Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 94 (16): 1247-9, 2002. [PUBMED Abstract]
2. Frye RF, Fitzgerald SM, Lagattuta TF, et al.: Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 76 (4): 323-9, 2004. [PUBMED Abstract]
3. Yang SY, Juang SH, Tsai SY, et al.: St. John’s wort significantly increased the systemic exposure and toxicity of methotrexate in rats. Toxicol Appl Pharmacol 263 (1): 39-43, 2012. [PUBMED Abstract]
4. Clairet AL, Boiteux-Jurain M, Curtit E, et al.: Interaction between phytotherapy and oral anticancer agents: prospective study and literature review. Med Oncol 36 (5): 45, 2019. [PUBMED Abstract]
5. IXEMPRA – ixabepilone. Bristol-Myers Squibb Company, 2009. Available online. Last accessed May 26, 2022.
6. Ge J, Tan BX, Chen Y, et al.: Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability. J Mol Med (Berl) 89 (6): 595-602, 2011. [PUBMED Abstract]
7. Paul D, Surendran S, Chandrakala P, et al.: An assessment of the impact of green tea extract on palbociclib pharmacokinetics using a validated UHPLC-QTOF-MS method. Biomed Chromatogr 33 (4): e4469, 2019. [PUBMED Abstract]
8. Maher HM, Alzoman NZ, Shehata SM: Ultra-performance LC-MS/MS study of the pharmacokinetic interaction of imatinib with selected vitamin preparations in rats. Bioanalysis 10 (14): 1099-1113, 2018. [PUBMED Abstract]
9. Shin SC, Choi JS: Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats. Anticancer Drugs 20 (7): 584-8, 2009. [PUBMED Abstract]
10. Lin LC, Wang MN, Tsai TH: Food-drug interaction of (-)-epigallocatechin-3-gallate on the pharmacokinetics of irinotecan and the metabolite SN-38. Chem Biol Interact 174 (3): 177-82, 2008. [PUBMED Abstract]
11. Qiao J, Gu C, Shang W, et al.: Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food Chem Toxicol 49 (6): 1410-5, 2011. [PUBMED Abstract]
12. He SM, Yang AK, Li XT, et al.: Effects of herbal products on the metabolism and transport of anticancer agents. Expert Opin Drug Metab Toxicol 6 (10): 1195-213, 2010. [PUBMED Abstract]
13. Reif S, Nicolson MC, Bisset D, et al.: Effect of grapefruit juice intake on etoposide bioavailability. Eur J Clin Pharmacol 58 (7): 491-4, 2002. [PUBMED Abstract]
14. van Erp NP, Baker SD, Zandvliet AS, et al.: Marginal increase of sunitinib exposure by grapefruit juice. Cancer Chemother Pharmacol 67 (3): 695-703, 2011. [PUBMED Abstract]
15. Yin OQ, Gallagher N, Li A, et al.: Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol 50 (2): 188-94, 2010. [PUBMED Abstract]
16. Wang T, Long F, Jiang G, et al.: Pharmacokinetic properties of wogonin and its herb-drug interactions with docetaxel in rats with mammary tumors. Biomed Chromatogr : e4264, 2018. [PUBMED Abstract]
17. Heaney ML, Gardner JR, Karasavvas N, et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 68 (19): 8031-8, 2008. [PUBMED Abstract]
18. Perrone G, Hideshima T, Ikeda H, et al.: Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 23 (9): 1679-86, 2009. [PUBMED Abstract]
19. Bairati I, Meyer F, Gélinas M, et al.: Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol 23 (24): 5805-13, 2005. [PUBMED Abstract]
20. Bairati I, Meyer F, Jobin E, et al.: Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer 119 (9): 2221-4, 2006. [PUBMED Abstract]
21. Bilgi N, Bell K, Ananthakrishnan AN, et al.: Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 44 (5): 926-8, 2010. [PUBMED Abstract]
22. Golden EB, Lam PY, Kardosh A, et al.: Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 113 (23): 5927-37, 2009. [PUBMED Abstract]
23. Bannerman B, Xu L, Jones M, et al.: Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother Pharmacol 68 (5): 1145-54, 2011. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

General Information

Revised text to state that in the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. Also added text to state that the quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.