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    Fluorouracil

    Drug Information

    Fluorouracil is a chemotherapy drug given intravenously (iv) to treat colon , rectum, breast , stomach, and pancreas cancers. Fluorouracil is also available in creams and solutions for topical treatment of some skin cancers and genital warts .

    Note: Many of the interactions described below, in the text and in the Summary of Interactions, have been reported only for specific chemotherapeutic drugs, and may not apply to other chemotherapeutic drugs. There are many unknowns concerning interactions of nutrients, herbs, and chemotherapy drugs. People receiving chemotherapy who wish to supplement with vitamins, minerals, herbs, or other natural substances should always consult a physician.

    Common brand names:

    Carac, Efudex

    Summary of Interactions with Vitamins, Herbs, & Foods

    Types of interactions: Beneficial Adverse Check

    Replenish Depleted Nutrients

    • Magnesium and Potassium

      The chemotherapy drug cisplatin may cause excessive loss of magnesium and potassium in the urine. Preliminary reports suggest that both potassium and magnesium supplementation may be necessary to increase low potassium levels. Severe magnesium deficiency caused by cisplatin therapy has been reported to result in seizures. Severe magnesium deficiency is a potentially dangerous medical condition that should only be treated by a doctor. People receiving cisplatin chemotherapy should ask their prescribing doctor to closely monitor magnesium and potassium status.

    • Lactobacillus GG

      In a preliminary trial, supplementation with a probiotic (Lactobacillus GG) reduced the frequency of severe diarrhea and the incidence of abdominal discomfort related to the use of 5-FU. The amount of Lactobacillus GG used was 10-20 billion organisms per day during the 24 weeks of chemotherapy.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • N-Acetyl Cysteine

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research.  Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but it clearly shows that antioxidants need not be avoided for fear that the actions of chemotherapy are interfered with. Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Spleen Peptide Extract

      Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a double-blind trial during chemotherapy with cisplatin and 5-FU. The spleen preparation had a significant stabilizing effect on certain white blood cells. People taking it also experienced stabilized body weight and a reduction in the fatigue and inertia that usually accompany this combination of chemotherapy agents.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Taurine

      Taurine has been shown to be depleted in people taking chemotherapy. It remains unclear how important this effect is or if people taking chemotherapy should take taurine supplements.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Reduce Side Effects

    • Acetyl-L-Carnitine

      Acetyl-L-carnitine in the amount of 1,000 mg three times per day for eight weeks has been shown to improve nerve damage (neuropathy) caused by the chemotherapy drug cisplatin.

    • Calcium and Magnesium
      In a double-blind trial, intravenous administration of calcium and magnesium before and after administration of oxaliplatin prevented the development of oxaliplatin-induced nerve damage. However, in another double-blind trial, the same treatment regimen as in the other study did not prevent oxaliplatin-induced nerve damage. It is not known whether oral administration of these minerals would also be beneficial.
    • Fruit-Flavored Drinks

      Often, people who undergo chemotherapy develop aversions to certain foods, sometimes making it permanently difficult to eat those foods. Exposing people to what researchers have called a "scapegoat stimulus" just before the administration of chemotherapy can direct the food aversion to the "scapegoat" food instead of more important parts of the diet. In one trial, fruit drinks administered just before chemotherapy were most effective in protecting against aversions to other foods.

    • Glutamine

      Though cancer cells use glutamine as a fuel source, studies in humans have not found that glutamine stimulates growth of cancers in people taking chemotherapy. In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy, though such effects have not yet been studied in humans.

      Glutamine has successfully reduced chemotherapy-induced mouth sores. In one trial, people were given 4 grams of glutamine in an oral rinse, which was swished around the mouth and then swallowed twice per day. Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some, but not all double-blind research. In another study, patients receiving high-dose paclitaxel and melphalan had significantly fewer episodes of oral ulcers and bleeding when they took 6 grams of glutamine four times daily along with the chemotherapy.

      One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy. However, other studies using higher amounts or intravenous glutamine have not reported this effect.

      Intravenous use of glutamine in people undergoing bone marrow transplants, a procedure sometimes used to allow very high amounts of chemotherapy to be used, has led to reduced hospital stays, leading to a savings of over $21,000 for each patient given glutamine.

      In a double-blind study, supplementation with 18 grams of glutamine per day for 15 days, starting five days before the beginning of 5-FU therapy, significantly reduced the severity of drug-induced intestinal toxicity.

      Intravenous use of glutamine in people undergoing bone marrow transplants, a procedure sometimes used to allow very high amounts of chemotherapy to be used, has led to reduced hospital stays, leading to a savings of over $21,000 for each patient given glutamine.

    • Glutathione

      Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells. However, most scientific research does not support this supposition.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research. Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.

      A new formulation of selenium (Seleno-Kappacarrageenan) was found to reduce kidney damage and white blood cell-lowering effects of cisplatin in one human study. However, the level used in this study (4,000 mcg per day) is potentially toxic and should only be used under the supervision of a doctor.

      Glutathione , the main antioxidant found within cells, is frequently depleted in individuals on chemotherapy and/or radiation. Preliminary studies have found that intravenously injected glutathione may decrease some of the adverse effects of chemotherapy and radiation, such as diarrhea .

    • Melatonin

      Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.

    • Probiotics

      In a preliminary trial, supplementation with a probiotic (Lactobacillus GG) reduced the frequency of severe diarrhea and the incidence of abdominal discomfort related to the use of 5-FU. The amount of Lactobacillus GG used was 10-20 billion organisms per day during the 24 weeks of chemotherapy.

    • Selenium

      Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells. However, most scientific research does not support this supposition.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research. Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.

      A new formulation of selenium (Seleno-Kappacarrageenan) was found to reduce kidney damage and white blood cell-lowering effects of cisplatin in one human study. However, the level used in this study (4,000 mcg per day) is potentially toxic and should only be used under the supervision of a doctor.

    • Vitamin B6

      Fluorouracil occasionally causes problems on the skin of the palms and soles. Preliminary reports have appeared showing that 100 mg per day of vitamin B6 can sometimes eliminate the pain associated with this drug-induced condition.

    • Wheat Grass
      In a preliminary trial, supplementation with 60 ml (about 2 ounces) per day of whet grass juice for 10 weeks during chemotherapy treatment reduced the severity of side effects in patients receiving a chemotherapy regimen that included 5-fluorouracil.
    • Beta-Carotene

      Chemotherapy frequently causes mouth sores. In one trial, people were given approximately 400,000 IU of beta-carotene per day for three weeks and then 125,000 IU per day for an additional four weeks. Those taking beta-carotene still suffered mouth sores, but the mouth sores developed later and tended to be less severe than mouth sores that formed in people receiving the same chemotherapy without beta-carotene.

      In a study of chemotherapy-induced mouth sores, six of nine patients who applied vitamin E directly to their mouth sores had complete resolution of the sores compared with one of nine patients who applied placebo. Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores. Applying vitamin E only once per day was helpful to only some groups of patients in another trial, and not all studies have found vitamin E to be effective. Until more is known, if vitamin E is used in an attempt to reduce chemotherapy-induced mouth sores, it should be applied topically twice per day and should probably be in the tocopherol (versus tocopheryl) form.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Chamomile

      A liquid preparation of German chamomile (Matricaria recutita) has been shown to reduce the incidence of mouth sores in people receiving radiation and systemic chemotherapy treatment in an uncontrolled study.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Eleuthero

      Russian research has looked at using eleuthero (Eleutherococcus senticosus) with chemotherapy. One study of patients with melanoma found that chemotherapy was less toxic when eleuthero was given simultaneously. Similarly, women with inoperable breast cancer given eleuthero were reported to tolerate more chemotherapy. Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ginger

      Ginger (Zingiber officinale) can be helpful in alleviating nausea and vomiting caused by chemotherapy. Ginger powder in tablets or capsules can be taken for nausea, in 500 mg amounts every two or three hours, for a total of 1 gram per day.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • N-Acetyl Cysteine

      NAC, an amino acid-like supplement that possesses antioxidant activity, has been used in four human studies to decrease the kidney and bladder toxicity of the chemotherapy drug ifosfamide. These studies used 1-2 grams NAC four times per day. There was no sign that NAC interfered with the efficacy of ifosfamide in any of these studies. Intakes of NAC over 4 grams per day may cause nausea and vomiting.

      The newer anti-nausea drugs prescribed for people taking chemotherapy lead to greatly reduced nausea and vomiting for most people. Nonetheless, these drugs often do not totally eliminate all nausea. Natural substances used to reduce nausea should not be used instead of prescription anti-nausea drugs. Rather, under the guidance of a doctor, they should be added to those drugs if needed. At least one trial suggests that NAC, at 1,800 mg per day, may reduce nausea and vomiting caused by chemotherapy.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Spleen Peptide Extract

      Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga®) in a double-blind trial during chemotherapy with cisplatin and 5-FU. The spleen preparation had a significant stabilizing effect on certain white blood cells. People taking it also experienced stabilized body weight and a reduction in the fatigue and inertia that usually accompany this combination of chemotherapy agents.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Thymus Extracts

      Peptides or short proteins derived from the thymus gland, an important immune organ, have been used in conjunction with chemotherapy drugs for people with cancer. One study using thymosin fraction V in combination with chemotherapy, compared with chemotherapy alone, found significantly longer survival times in the thymosin fraction V group. A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone. A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone. Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Support Medicine

    • Melatonin

      Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.

    • Thymus Extracts

      Peptides or short proteins derived from the thymus gland, an important immune organ, have been used in conjunction with chemotherapy drugs for people with cancer. One study using thymosin fraction V in combination with chemotherapy, compared with chemotherapy alone, found significantly longer survival times in the thymosin fraction V group. A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone. A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone. Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.

    • Wheat Grass

      In a preliminary trial, taking wheat grass in the amount of 60 ml (about 2 ounces) per day during chemotherapy reduced the incidence of certain chemotherapy-related side effects (including anemia and a decline in white blood cell counts) in women with breast cancer. Taking wheat grass did not appear to interfere with the anticancer effect of the chemotherapy. The chemotherapy used in this study was a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide.

    • Milk Thistle

      Milk thistle's (Silybum marianum) major flavonoids, known collectively as silymarin, have shown synergistic actions with the chemotherapy drugs cisplatin and doxorubicin (Adriamycin®) in test tubes. Silymarin also offsets the kidney toxicity of cisplatin in animals. Silymarin has not yet been studied in humans treated with cisplatin. There is some evidence that silymarin may not interfere with some chemotherapy in humans with cancer.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • PSK

      The mushroom Coriolus versicolor contains an immune-stimulating substance called polysaccharide krestin, or PSK. PSK has been shown in several studies to help cancer patients undergoing chemotherapy. One study involved women with estrogen receptor-negative breast cancer. PSK combined with chemotherapy significantly prolonged survival time compared with chemotherapy alone. Another study followed women with breast cancer who were given chemotherapy with or without PSK. The PSK-plus-chemotherapy group had a 25% better chance of survival after ten years compared with those taking chemotherapy without PSK. Another study investigated people who had surgically removed colon cancer. They were given chemotherapy with or without PSK. Those given PSK had a longer disease-free period and longer survival time. Three grams of PSK were taken orally each day in these studies.

      Although PSK is rarely available in the United States, hot-water extract products made from Coriolus versicolor mushrooms are available. These products may have activity related to that of PSK, but their use with chemotherapy has not been studied.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Reduces Effectiveness

    • none

    Potential Negative Interaction

    • none

    Explanation Required 

    • Antioxidants

      Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells. However, most scientific research does not support this supposition.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research. Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but neither does it show that antioxidants should be avoided for fear that the actions of chemotherapy are interfered with. Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Echinacea

      Echinacea is a popular immune-boosting herb that has been investigated for use with chemotherapy. One study investigated the actions of cyclophosphamide , echinacea, and thymus gland extracts to treat advanced cancer patients. Although small and uncontrolled, this trial suggested that the combination modestly extended the life span of some patients with inoperable cancers. Signs of restoration of immune function were seen in these patients.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Multivitamin

      Many chemotherapy drugs can cause diarrhea , lack of appetite, vomiting, and damage to the gastrointestinal tract. Recent anti-nausea prescription medications are often effective. Nonetheless, nutritional deficiencies still occur. It makes sense for people undergoing chemotherapy to take a high-potency multivitamin-mineral to protect against deficiencies.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • N-Acetyl Cysteine

      NAC, an amino acid-like supplement that possesses antioxidant activity, has been used in four human studies to decrease the kidney and bladder toxicity of the chemotherapy drug ifosfamide. These studies used 1-2 grams NAC four times per day. Th+N110ere was no sign that NAC interfered with the efficacy of ifosfamide in any of these studies. Intakes of NAC over 4 grams per day may cause nausea and vomiting.

      The newer anti-nausea drugs prescribed for people taking chemotherapy lead to greatly reduced nausea and vomiting for most people. Nonetheless, these drugs often do not totally eliminate all nausea. Natural substances used to reduce nausea should not be used instead of prescription anti-nausea drugs. Rather, under the guidance of a doctor, they should be added to those drugs if needed. At least one trial suggests that NAC at 1,800 mg per day may reduce nausea and vomiting caused by chemotherapy.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research.  Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but neither does it show that antioxidants should be avoided for fear that the actions of chemotherapy are interfered with. Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Vitamin A

      A controlled French trial reported that when postmenopausal late-stage breast cancer patients were given very large amounts of vitamin A (350,000-500,000 IU per day) along with chemotherapy, remission rates were significantly better than when the chemotherapy was not accompanied by vitamin A. Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Vitamin A, Vitamin C, and N-Acetyl Cysteine

      Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells. However, most scientific research does not support this supposition.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research. Vitamin C appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but neither does it show that antioxidants should be avoided for fear that the actions of chemotherapy are interfered with. Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Vitamin C

      Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells. However, most scientific research does not support this supposition.

      A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research.  Vitamin C combined with Vitamin K3 appears to increase the effectiveness of chemotherapy in animals and with human breast cancer cells in test tube research. In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but it clearly shows that antioxidants need not be avoided for fear that the actions of chemotherapy are interfered with. Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers' package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

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