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Foods, Dietary Supplements, and Cancer Therapy Interactions (PDQ®)–Health Professional Version

Overview

This cancer information summary provides an overview of the use of foods, dietary supplements, and cancer therapy interactions.

This summary contains the following key information:

  • The combination of cancer drugs taken by patients and the complementary and alternative medicine used may interact, causing adverse outcomes.
  • Research on dietary supplement and cancer drug pharmacokinetics (PK) interactions is limited, but there is evidence for several possible interactions and adverse reactions.
  • For many specific antioxidant supplements, there is insufficient information available to determine if they are safe and effective as a complementary therapy to standard cancer treatment.
  • Certain constituents of foods and dietary supplements (e.g., St. John’s wort, grapefruit juice, and epigallocatechin gallate from green tea) can alter the PK of specific types of drugs.
  • Some research has shown a dietary supplement/food and drug PK interaction between grapefruit juice and imatinib.

General 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. 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 components involved in the PK of the drug, such as how the drug is metabolized and transported. It is important that these interactions are reported and studied to allow health care professionals to help patients navigate CAM usage with standard cancer therapies, thus avoiding preventable adverse outcomes.

Cytochrome P450 Inhibitors/Inducers

One of the main group of enzymes involved in the metabolism of many cancer drugs is the cytochrome P450 (CYP450) superfamily of enzymes. These enzymes play an important role in the activation and inactivation of various drugs. Another component involved in the metabolism and excretion of many drugs is the transport protein, P-glycoprotein (P-gp). P-gp works in the intestine as a drug efflux pump regulating the bioavailability of the drug. Various anticancer drugs are substrates of P-gp; thus, if P-gp or any CYP450 enzyme is impacted, the drug it is processing will also be impacted.

The PK of a drug predicts therapeutic outcomes for the patient. Various herbs and dietary supplements are known to influence the PK of certain drugs, such as St. John’s wort. Currently, research on dietary supplement and cancer drug PK interactions is limited, but there is evidence for several possible interactions and adverse reactions.[1-3]

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. 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]
  3. 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]

Antioxidants

General Information

Some common dietary antioxidants include the following:

Numerous anticancer agents generate reactive oxygen species, which cause decreased levels of antioxidants, deoxyribonucleic acid damage, and cancer cell death. Antioxidants are taken by many cancer patients because it is thought that the substances will protect and repair healthy cells damaged by cancer therapy.[1] There is insufficient information for many specific antioxidant supplements to determine if they are safe and effective as a complementary therapy to standard cancer treatment.

Laboratory/Animal/Preclinical Studies

A study published in 2018 examined the pharmacokinetic interactions between imatinib (25 mg/kg orally) and vitamin A (12 mg retinol/kg orally), vitamin E (400 IU/kg orally), vitamin D3 (100 IU/kg orally), and vitamin C (500 mg/kg orally) when coadministered in rat animal models. The results showed that there was an increase in the bioavailability of imatinib with vitamins A, E , and D, and a decrease in the bioavailability of imatinib with vitamin C.[2]

A study that examined the oxidized form of ascorbate, dehydroascorbate, as a complementary supplement with chemotherapeutic drugs (i.e., doxorubicin, cisplatin, vincristine, methotrexate, and imatinib) initially found that dehydroascorbate given before doxorubicin treatment caused a reduction of therapeutic efficacy in mice with lymphoma (RL) cell–derived xenogeneic tumors, This form of ascorbate is not generally available as a dietary supplement and is not used clinically, and it has different properties and pharmacology from unoxidized or reduced ascorbate; thus, the potential clinical implications of these findings are unknown.[3]

An in vivo mouse model study observed a possible interaction between vitamin C (40 mg/kg/d) and bortezomib. There was a significant reduction in bortezomib’s anticancer activities with consumption of vitamin C.[4]

Human/Clinical Studies

A study examined antioxidant dietary supplement use pre- and post-diagnosis in postmenopausal breast cancer survivors. The results showed an increased risk of total mortality and worsened recurrence-free survival with antioxidant dietary supplement use during chemotherapy or radiation therapy. This evidence does not seem strong enough to determine for certain the safety of taking antioxidants during breast cancer treatment. However, the evidence does give reason to use these supplements with caution and indicates that more research on this topic is needed.[5]

Alpha-tocopherol, one of eight vitamin E compounds, was investigated in a clinical trial for its impact on adverse effects from chemotherapy and radiation therapy. Initially, some research suggested that alpha-tocopherol may reduce toxicity caused by radiation therapy for head and neck cancer. Two randomized, controlled clinical trials of patients with head and neck cancer who received vitamin E supplementation at a dose of 400 IU/day has shown an association with a higher risk of tumor relapse and a decrease in cancer-free survival.[6,7]

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. 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]
  7. 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]

St. John’s Wort

General Information

The flower of the St. John’s wort (SJW) (Hypericum perforatum) plant is used traditionally for wound healing, insomnia, and kidney and lung problems, and most commonly today for depression. This flower can be taken through teas, tablets, capsules, and extracts. Currently, the evidence for the clinical efficacy of SJW is varied, but there have been reports of interactions and adverse effects with several drugs.[1]

Laboratory/Animal/Preclinical Studies

A 2012 study observed the effects of SJW on the pharmacokinetics (PK) of methotrexate in a rat animal model. After coadministration of SJW (300 mg/kg and 150 mg/kg) and methotrexate, it was found that animals that received 300 mg/kg of SJW had a significant increase in area under the concentration versus time curve (AUC) by 163% and peak serum concentration (Cmax) by 60% for methotrexate. For animals that received 150 mg/kg of SJW, there was a significant increase in AUC (55%) for methotrexate. Overall, the mortality of the rats treated with SJW combined with methotrexate was higher. The researchers suggested using extreme caution if coadministering these two substances.[2]

Human/Clinical Studies

There are two well-known examples of herb-drug interactions impacting drug PK that have clinical evidence. These two interactions are between SJW and both irinotecan and imatinib. After patients were treated with both irinotecan (350 mg/m2) and SJW (900 mg/d), one study found a 42% decrease in plasma levels of SN-38, the active metabolite of irinotecan. The researchers hypothesized that components of SJW extract, pseudohypericin and hyperforin, interacted with CYP3A4 isoform and P-glycoprotein, causing this reduction in SN-38. This interaction may cause a loss of irinotecan efficacy.[3]

A similar outcome occurred in another study that examined treatment with imatinib (400 mg) and SJW (300 mg 3 times a day). SJW use caused a 43% increase in the clearance of imatinib and a 30% decrease in AUC. This interaction is also thought to be caused by the impact of SJW on CYP3A4, the major enzyme that metabolizes imatinib.[4]

Another CYP3A4 substrate that may be impacted by SJW is docetaxel. A 2014 study with ten cancer patients investigated the PK interactions of docetaxel (135 mg IV for 60 min) in combination with SJW (300 mg orally for 14 days). The results showed a statistically significant decrease of 12% in mean AUC and an increased clearance of docetaxel.[5]

Although there is a lack of published research, the use of SJW in patients undergoing treatment with ixabepilone is not recommended. SJW may cause a decrease in plasma concentrations of ixabepilone. The drug label for ixabepilone states a warning for this possible interaction.[6]

References
  1. Field HL, Monti DA, Greeson JM, et al.: St. John's Wort. Int J Psychiatry Med 30 (3): 203-19, 2000. [PUBMED Abstract]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Ixabepilone. Bethesda, Md: TOXNET, 2009. Available online. Last accessed September 11, 2019.

Green Tea

General Information

Green tea, green tea extract, and products of green tea components are commonly taken as foods, dietary supplements, and herbal therapies. Some of the traditional and modern uses of green tea include the following:

Research has been mixed on whether green tea is safe or effective for these uses as well as for coadministration with anticancer drugs.[1] Current research shows that green tea and the polyphenol epigallocatechin gallate (EGCG), an antioxidant component of green tea, can impact the pharmacokinetics (PK) or pharmacodynamics (PD) of certain drugs, thus impacting the metabolism and effectiveness of these drugs.[2]

Laboratory/Animal/Preclinical Studies

As seen in the literature, green tea and its constituent EGCG may be involved in both PK and PD interactions. An interaction between green tea and bortezomib was examined in an in vitro study with human multiple myeloma and glioblastoma cell lines. EGCG blocked bortezomib’s protease inhibitory function by binding to the boronic acid structure in bortezomib, causing the inability to induce cancer cell death and consequently blocking its anticancer abilities. The second portion of this study investigated this interaction within a plasmacytoma xenograft nude mouse model. Bortezomib’s cancer cell apoptosis-inducing effect was completely prevented with intragastric EGCG administration (50 mg/kg).[3] This interaction was also reported in another animal study that examined human prostate cancer xenografts in immune-deficient mouse models. High intravenous (IV) doses of EGCG along with the coadministration of bortezomib resulted in the abrogation of bortezomib’s anticancer effects.[4] Human studies should be conducted to determine clinical significance.

The impact of green tea and EGCG on fluorouracil PK was studied in rats. The results of these studies showed a 151% increase in peak serum concentration (Cmax) and a 425% increase in the area under the concentration versus time curve (AUC) for fluorouracil. It was concluded that green tea greatly impacted the PK of fluorouracil.[5]

A similar study examined the PK of irinotecan (10 mg/kg IV) given in combination with EGCG (20 mg/kg IV) in rats and found that EGCG caused elevated plasma levels and reduced hepatobiliary excretion of irinotecan and its metabolite SN-38. This is possibly because of EGCG’s inhibitory effects on P-glycoprotein.[6]

A 2019 study evaluated the effects of green tea extract on the PK of palbociclib in a rat animal model. The data showed a decrease in the oral bioavailability of palbociclib when it was coadministered with green tea extract, but there was no impact on the elimination of palbociclib. The altered PK was thought to be the result of interference in the absorption of palbociclib. The authors recommended against the coadministration of these compounds.[7]

Research on rat animal models investigated the impact of green tea extract on the oral bioavailability of erlotinib and lapatinib. A decrease was observed in the oral bioavailability for erlotinib and lapatinib after consumption of green tea extract (200 mg/kg). There was a decrease in AUC by 67.60% for erlotinib and 70.20% for lapatinib with short-term administration, and a decrease in AUC by 16.03% for erlotinib and 13.53% for lapatinib with long-term administration.[8]

An in vivo and in vitro study examined the impacts of intragastric coadministration of sunitinib with EGCG. Coadministration of these two solutions resulted in the formation of a precipitate in the stomachs of these mice, thus decreasing its bioavailability. It was also reported that a decrease in the AUC and Cmax of plasma sunitinib with EGCG administration in rats resulted in reduced sunitinib absorption.[9]

A possible interaction was also found between EGCG and tamoxifen. A 2009 study assessed the bioavailability and PK of tamoxifen (2 mg/kg) and its metabolite, 4-hydroxytamoxifen, with coadministration of EGCG (0.5 mg/kg, 3 mg/kg, and 10 mg/kg) in Sprague-Dawley rats. The coadministration of EGCG at doses of 3 mg/kg and 10 mg/kg caused a significant increase in the bioavailability of tamoxifen. In addition, EGCG significantly impacted the formation of 4-hydroxytamoxifen. It is believed that this reaction was caused by EGCG’s inhibitory effect on P-glycoprotein and CYP3A.[10]

The findings of the preclinical studies provide a justification and motivation for human studies to determine appropriate clinical recommendations.

Case Study

In addition to the in vitro and in vivo EGCG and sunitinib study mentioned above, the same researchers published a case study that might demonstrate a possible adverse effect of green tea consumption with sunitinib treatment. A male patient with metastatic renal cell carcinoma who received sunitinib reported worsened symptoms of hyperemia and eye swelling near the site of a metastatic lesion when drinking green tea; the symptoms improved when he stopped taking green tea. The authors hypothesized that the lack of symptom control may result from EGCG’s effects on sunitinib’s anticancer abilities.[9]

References
  1. 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. New York, NY: Informa Healthcare, 2010, pp 402-10.
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  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, 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]
  9. 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]
  10. 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]

Grapefruit

General Information

Grapefruit and other similar fruits, such as Seville orange, pomelo, and lime, have been known to interact with a variety of drugs, including some anticancer drugs. These pharmacokinetic (PK) interactions are thought to be caused by specific components in these fruits, such as the flavonoid naringenin and furanocoumarins. These components have been observed impacting the metabolism of substrates of CYP3A4.[1,2] Grapefruit and its furanocoumarins components are used as supplements for the antioxidative, anti-inflammatory, and anticancer effects demonstrated in some in vivo and in vitro studies.[3]

Human/Clinical Studies

Some research has shown a dietary supplement/food and drug PK interaction between grapefruit juice and imatinib. Grapefruit juice may cause plasma levels of imatinib to increase by inhibiting CPY3A4, in turn triggering organ toxicity.[4]

An interaction has been observed between grapefruit juice and etoposide. A randomized, crossover, pilot study of six participants examined the bioavailability of the oral chemotherapy drug etoposide after coadministration of grapefruit juice. The data showed a decrease in bioavailability between the control group and the experimental group, who were treated with etoposide and grapefruit juice, reducing from approximately 73.2% to 52.4% the bioavailabilty of 50 mg of oral etoposide after pretreatment with 100 mL of grapefruit juice. This resulted in a decrease in the area under the concentration versus time curve (AUC) by 26.2% for etoposide with grapefruit juice, compared with etoposide alone.[5]

Other studies have found an increase in the bioavailability of sunitinib with grapefruit juice exposure,[6] in addition to an increase in AUC by 29% and an increase in Cmax by 60% for nilotinib (400 mg orally) when combined with grapefruit juice (240 mL).[7]

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. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]

Ginseng

General Information

Ginseng root has commonly been used as a dietary supplement in traditional Asian medicine. There are several types of ginseng. While there is no conclusive evidence for the health benefits of ginseng, people currently use it for the following reasons:[1,2]

Laboratory/Animal/Preclinical Studies

Most in vitro research on ginseng’s pharmacokinetic (PK) interactions found little evidence of any effects, determining a low risk of CYP-dependent herb-drug reactions. Overall, the evidence is mixed and inconclusive.[3-5]

Case Study

Ginseng was suspected of being responsible for an incident of hepatotoxicity that occurred in a 26-year-old male taking imatinib. The hypothesized mechanism for this interaction was inhibition of hepatic CYP3A4, the enzyme primarily responsible for metabolizing imatinib. The ginseng was ingested through a ginseng energy drink, which creates uncertainty about whether the ginseng or the other ingredients in the drink caused the adverse effect. Clinical research is needed to confirm if there are any PK interactions between imatinib and ginseng.[6]

References
  1. Wang CZ, Yuan CS: Ginseng, American. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare, 2010, pp 339-47.
  2. Jia L, Soldati F: Ginseng, Asian. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare, 2010, pp 348-62.
  3. 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]
  4. Goey AK, Mooiman KD, Beijnen JH, et al.: Relevance of in vitro and clinical data for predicting CYP3A4-mediated herb-drug interactions in cancer patients. Cancer Treat Rev 39 (7): 773-83, 2013. [PUBMED Abstract]
  5. Haefeli WE, Carls A: Drug interactions with phytotherapeutics in oncology. Expert Opin Drug Metab Toxicol 10 (3): 359-77, 2014. [PUBMED Abstract]
  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]

Scutellaria Baicalensis/Wogonin

General Information

Scutellaria baicalensis, also known as wogonin, Chinese skullcap, or Huang Qin, is a plant used in traditional Chinese medicine to treat various medical conditions, such as the following:[1]

In traditional Chinese medicine, there are some herbal mixtures that contain Scutellaria baicalensis, one being Huang Qin Tang. PHY906, a patented formula derived from Huang Qin Tang, is being studied as a potential adjuvant for cancer therapy, there is some evidence that this herbal mixture potentiates the anticancer effects of certain cancer drugs such as sorafenib.[2] Some research has shown the inhibitory effect of wogonin on the activity of cytochrome P450, but more research is needed to determine interactions with specific drugs.[3]

Laboratory/Animal/Preclinical Studies

A 2018 study examined the pharmacokinetic profile and herb-drug interactions of oral wogonin and intravenous docetaxel in rats. The results found that in rat models receiving oral administration of wogonin in addition to docetaxel, there was an increase in the area under the concentration versus time curve initial Cmax and half-life for docetaxel which the investigators speculated was due to the inhibitory effect of wogonin on CYP3A and P-glycoprotein. More research is needed with human clinical trials, but these results suggest a possible interaction between wogonin and docetaxel.[4]

References
  1. Wang ZL, Wang S, Kuang Y, et al.: A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol 56 (1): 465-484, 2018. [PUBMED Abstract]
  2. Lam W, Jiang Z, Guan F, et al.: PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep 5: 9384, 2015. [PUBMED Abstract]
  3. Li T, Li N, Guo Q, et al.: Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Eur J Drug Metab Pharmacokinet 36 (4): 249-56, 2011. [PUBMED Abstract]
  4. 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]

Foods, Dietary Supplements, and Cancer Drug Interaction Tables

Table 1. Foods, Dietary Supplements, and Cancer Drug Interactions
Herbal Dietary Supplement/Anticancer TherapyEffectStudy Type
AUC = area under the concentration versus time curve; Cmax = peak serum concentration; EGCG = epigallocatechin gallate; SJW = St. John's wort.
SJWIrinotecanIncreased activity of CYP3A4 and decreased AUC of active metabolite SN38Clinical trial [1]
SJWImatinibIncreased clearance and decreased AUC of imatinibClinical trial [2]
SJWMethotrexateIncreased AUC and Cmax of methotrexateAnimal study [3]
SJWDocetaxelIncreased clearance and decreased AUC of docetaxelClinical trial [4]
SJWIxabepiloneMay decrease plasma concentrations of ixabepiloneLabel warning for ixabepilone [5]
Green teaSunitinibDecreased drug absorption and bioavailability of sunitinibAnimal study and case report [6]
Green teaPalbociclibDecreased oral bioavailability of palbociclibAnimal study [7]
Green tea extractErlotinibDecreased AUC and oral bioavailability of erlotinibAnimal study [8]
Green tea extractLapatinibDecreased AUC and oral bioavailability of lapatinibAnimal study [8]
EGCGTamoxifenIncreased bioavailability of tamoxifenAnimal study [9]
EGCGIrinotecanIncreased plasma concentration of irinotecan and decreased hepatobiliary excretion of drug and its metabolite SN-38Animal study [10]
Green tea and EGCGFluorouracilIncreased AUC and Cmax of fluorouracilAnimal and in vitro study [11]
GrapefruitImatinibMay increase plasma levels of imatinib by inhibiting CPY3A4Review [12]
GrapefruitEtoposideDecreased AUC and bioavailability of etoposideRandomized, crossover, pilot study [13]
GrapefruitSunitinibIncreased bioavailability of sunitinibClinical trial [14]
GrapefruitNilotinibIncreased AUC and Cmax of nilotinibClinical trial [15]
Vitamin AImatinibIncreased bioavailability of imatinibAnimal study [8]
Vitamin EImatinibIncreased bioavailability of imatinibAnimal study [8]
Vitamin D3ImatinibIncreased bioavailability of imatinibAnimal study [8]
Vitamin CImatinibDecreased bioavailability of imatinibAnimal study [8]
Scutellaria baicalensisDocetaxelIncreased AUC of drug and exposure to both drug and herbAnimal study [16]
Table 2. Foods, Dietary Supplements, and Cancer Drug Interactions
Anticancer Therapy Herbal/Dietary Supplement Effect Study Type
AUC = area under the concentration versus time curve; Cmax = peak serum concentration; EGCG = epigallocatechin gallate; SJW = St. John's wort.
DocetaxelScutellaria baicalensis Increased AUC of drug and exposure to both drug and herb Animal study [16]
Docetaxel SJWIncreased clearance and decrease AUC of docetaxel Clinical trial [4]
ErlotinibGreen tea extractDecreased AUC and oral bioavailability of erlotinib Animal study [8]
Etoposide Grapefruit Decreased AUC and bioavailability of etoposide Randomized, crossover, pilot study [13]
FluorouracilGreen tea and EGCGIncreased AUC and Cmax of fluorouracil Animal and in vitro study [11]
ImatinibGrapefruit May increase plasma levels of imatinib by inhibiting CPY3A4 Review [12]
ImatinibVitamin A Increased bioavailability of imatinib Animal study [8]
ImatinibVitamin E Increased bioavailability of imatinib Animal study [8]
Imatinib Vitamin D3 Increased bioavailability of imatinib Animal study [8]
ImatinibVitamin C Decreased bioavailability of imatinib Animal study [8]
ImatinibSJWIncreased clearance and decreased AUC of imatinib Clinical trial [2]
Irinotecan SJW Increased activity of CYP3A4 and decreased AUC of active metabolite SN38 Clinical trial [1]
Irinotecan EGCG Increased plasma concentration of irinotecan and decreased hepatobiliary excretion of drug and its metabolite SN-38 Animal study [10]
Ixabepilone SJW May decrease plasma concentrations of ixabepilone Label warning for ixabepilone [5]
Lapatinib Green tea extract Decreased AUC and oral bioavailability of lapatinib Animal study [8]
Methotrexate SJW Increased AUC and Cmax of methotrexate Animal study [3]
Nilotinib Grapefruit Increased AUC and Cmax of nilotinib Clinical trial [15]
Palbociclib Green tea Decreased oral bioavailability of palbociclib Animal study [7]
Tamoxifen EGCG Increased bioavailability of tamoxifen Animal study [9]
Sunitinib Grapefruit Increased bioavailability of sunitinib Clinical trial [14]
Sunitinib Green tea Decreased drug absorption and bioavailability of sunitinib Animal study and case report [6]
Table 3. Foods, Dietary Supplements, and Cancer Therapies Adverse Reaction
Herbal/Dietary SupplementCancer TherapyAdverse ReactionStudy Type
EGCG = epigallocatechin gallate.
Vitamin CDoxorubicin, cisplatin, vincristine, methotrexate, and imatinibDose-dependent decrease in apoptosis with all chemotherapeutic drugs testedAnimal study [17]
Vitamin CBortezomibDecreased bortezomib’s anticancer activitiesAnimal study [18]
Dl-alpha-tocopherol (vitamin E)Radiation therapyHigher risk of tumor relapse and increased all-cause mortalityClinical trial [19,20]
GinsengImatinibIncident of hepatotoxicityCase report [21]
EGCG or green tea extractBortezomibDecreased anticancer effect by neutralizing effects of bortezomibIn vitro and animal study [22]
EGCGBortezomibDecreased bortezomib’s anticancer effectAnimal study [23]
Green teaSunitinibDecreased anticancer effect, worsened symptomsPreclinical research and case report [6]
References
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  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. Ixabepilone. Bethesda, Md: TOXNET, 2009. Available online. Last accessed September 11, 2019.
  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]
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  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]
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  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]

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of foods, dietary supplements, and cancer therapy interactions in people with cancer.. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Foods, Dietary Supplements, and Cancer Therapy Interactions. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/dietary-interactions-pdq. Accessed <MM/DD/YYYY>. [PMID: 33079503]

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