Practical Application of “ABOUT HERBS” website: Herbs and Dietary Supplement Use in Oncology Settings

Abstract

The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains About Herbs (www.aboutherbs.com), which provides summaries of research data including purported uses, adverse effects, and herb-drug interactions for about 284 dietary supplements. Using Google Analytics, we found the website registered over 26,317,000 hits since November 2002. The 10 most searched-for herbs/supplements of 2018 are chaga mushroom, turmeric, ashwagandha, reishi mushroom, graviola, AHCC, boswellia, dandelion, green tea, and Coriolus versicolor. Here we discuss their safety, herb-drug interactions, and appropriate uses in the oncology setting, based on literature searches in PubMed. Over the past 16 years, the evidence for use of these supplements is based mostly on preclinical findings, with few well-designed studies and limited trials conducted in cancer patients. It is important to familiarize healthcare professionals about popular supplements, so patients can be informed to make decisions that maximize benefits and minimize risks.

INTRODUCTION

Surveys show that 50% of American adults take dietary supplements.^1,2 One-third of all cancer survivors reportedly use complementary medicine or herbal products.^3-5 The reasons cited for such use include symptom relief, preventing cancer recurrence, and improving quality of life. Public perception that dietary supplements are natural and safe has remained unchanged over the last few decades. A major concern with dietary supplement use is the potential for herb-drug interactions (HDIs) that may lead to serious adverse drug events, extended hospitalization, and even death.⁶ Such interactions may also alter the efficacy of cancer treatments^7-9 including chemotherapeutic agents and targeted therapies, such as tyrosine-kinase inhibitors. Additional interactions include anticancer hormonal therapies with phytoestrogenic supplements¹⁰ or supplements that increase serum testosterone.

Also concerning is the lack of reliable information about dietary supplements. In a large survey, 40–45% of respondents reported the internet and news media as their primary sources.¹¹ However, when compared to rigorous scientific data, web-based information can often be inaccurate or misleading.^12-14 The knowledge gap about dietary supplements among American physicians does not prepare them for clinical encounters when patients approach them for information,^15,16 whether it be the appropriateness of supplement use or advice about a better alternative for symptom management.

We have attempted to develop an evidence-based practical approach for safe use of herbs and dietary supplements in oncology settings. The Memorial Sloan Kettering Cancer Center’s About Herbs website is a database which provides reliable and objective information about 284 dietary supplements that include herbs, vitamins, and minerals commonly used by cancer patients. We identified the top 10 monographs that were frequently accessed in 2018 (Table 1). Based on available preclinical and clinical data from literature searches on PubMed, we assessed the safety of the above supplements along with the potential for their interactions with common treatments including chemotherapy, radiation, and immunotherapies, as well as targeted and hormonal therapies.

TABLE 1.

Snapshot of Top 10 Monographs Accessed from the About Herbs Database in 2018

Depiction	Common Name	Scientific or Expanded Name	Origin	Key Properties	Key Interaction Concerns*	Avoid in*
	1. Chaga	Inonotus obliquus	Russia; subarctic regions	Antiplatelet Antidiabetic Anti-inflammatory	High in oxalates Anticoagulants Antiplatelets Antihyperglycemic agents	Renal disease Diabetic patient on treatment (acarbose)
	2. Turmeric	Curcuma longa Curcuma domestica	China India	Anti-inflammatory	High in oxalates CYP2C9 enzyme	Renal disease
	3. Ashwagandha	Withania somnifera	India	Tonic Energy level Longevity	Increase testosterone levels in men	Prostate cancer
	4. Reishi mushroom	Ganoderma lucidum	China Japan	Antioxidant Immune-modulating	Anticoagulants Antiplatelets	Radiation therapy
	5. Graviola	Annona muricata	Hispanic cultural food; tropical regions	Analgesic Anti-inflammatory Anti-ulcer	Antihyperglycemic agents	Diabetic patient on treatment
	6. AHCC	Active hexose correlated compound	Japan	Immune-modulating Antioxidant Anti-inflammatory	CYP2D6 enzyme (inducer)	Breast cancer patients on doxorubicin, zofran and aromatase inhibitor (letrozole)
	7. Boswellia	Boswellia serrata	India	Anti-inflammatory Reduce RT-induced cerebral edema	Unknown	Contact dermatitis
	8. Dandelion	Taraxacum mongolicum Taraxacum officinale	China USA	Reduce abscesses Promote lactation Chronic myelomonocytic leukemia (CMML)	CYP1A2 enzyme Diuretic Antihyperglycemic agents Estrogenic activity	Hormone-sensitive breast cancer
	9. Green tea	Camellia sinensis	Asia (China, Japan) USA	Antioxidant Prostate cancer Chronic lymphocytic leukemia (CLL)	High doses or taken on an empty stomach can cause liver toxicity Bortezomib	Elevated liver function tests
	10. Coriolus versicolor	Coriolus versicolor Trametes versicolor	Asia (Japan, China)	Immune-modulating Gastric and colorectal cancers	Unknown	Patient on immunosuppressant (in theory)

^*For a clinical summary and a more comprehensive assessment of potential side effects, interactions, and cautions, visit the About Herbs database at mskcc.org/aboutherbs.

Artwork by Angela Donato for About Herbs.

Preclinical and clinical data needs to be evaluated differently if we want to use the data to guide clinical practice. For example, orally ingested curcumin, one of the most popular searched-for supplements, has poor bioavailability. Oral ingestion of 1 g of curcumin usually leads to serum levels of conjugated curcumin at around C_max of 0.2 μM and around 1 μM in rectal mucosa.¹⁷ Many in vitro studies used curcumin at 10 μM, a concentration too high to be realistically achieved by oral ingestion, and thus irrelevant in clinical settings. Proper advice to patients needs to be guided by data from clinical studies. Unfortunately, clinical data is often not available. In those cases, we may have to make a clinical judgement based on the totality of preclinical data, the mechanisms of action and pharmacokinetics of a specific supplement, and patients’ values and preferences.

We hope the information presented here will be useful to oncologists and cancer patients, and facilitate physician-patient communication on this important topic.

Chaga mushroom (Inonotus obliquus)

Chaga is the Russian name given to a sclerotium or mass of mycelium of the fungus I. obliquus. As a parasite on birch or other trees, it typically grows in subarctic regions around the world. Chaga has traditionally been used in Russia since the 12th century for various maladies.¹⁸ In vitro studies have demonstrated that chaga exhibits antiplatelet¹⁹ and antidiabetic²⁰ properties. In animal studies, chaga has also displayed anti-inflammatory²¹ as well as antidiabetic²² effects. Anti-inflammatory effects in colitis models were related to suppression of tumor necrosis factor-alpha (TNF-α), iNOS, and interleukin (IL)-1beta.²¹

In preclinical cancer studies, chaga extracts have demonstrated inhibitory and proapoptotic effects against colon^23-25 and lung²⁶ cancer cells, and inhibited melanoma cell growth in vivo.²⁷ Inotodiol, a major constituent, exerted antitumor effects against cervical cancer cells.²⁸ To date, no clinical trials have been conducted to assess chaga’s safety and efficacy for disease prevention or for the treatment of cancer, cardiovascular disease, or diabetes.

Chaga mushrooms are high in oxalates and excessive intake may have toxic effects,²⁹ especially in patient with renal disease. Chaga extract inhibited platelet aggregation in a murine model,¹⁹ and thus may have synergistic effects when used with anticoagulant or antiplatelet drugs in mice. Clinical data is lacking. In vitro, chaga extract has shown alpha-glucosidase inhibitory activity similar to acarbose, a drug for diabetes,²⁰ suggesting concurrent use should be monitored in patients who are on oral antihyperglycemic agents.

Practical application:

This product is popular among patients of Russian or Eastern European heritage. Medicinal mushrooms all showed similar immunomodulatory effects in preclinical studies. However, other mushroom extracts have been better studied and have more clinical data than I. obliquus. Physicians should explain to patients the paucity of clinical data on this mushroom extract and caution patients about its potential adverse effects in the setting of chronic kidney disease, diabetic on treatment, and for bleeding or low platelet counts.

Turmeric (Curcuma longa, Curcuma domestica)

Turmeric is part of the ginger family. It has long been used as a spice in culinary cultures across Asia and is the most commonly known major ingredient in curry powder. In traditional medicines, turmeric is valued for its anti-inflammatory and antioxidant properties, and is also used to improve circulation and digestion.

Several studies have been conducted on the effects of turmeric for inflammatory diseases. C. domestica extract, taken as 500 mg of curcuminoids three times daily x 4 weeks, was found equally as effective as ibuprofen to treat osteoarthritis of the knee in a randomized control trial.³⁰ Most products on the market are curcumin, a major curcuminoid constituent in C. longa. A meta-analysis of randomized controlled trials determined that curcumin significantly reduced serum concentrations of TNF-α, a chief inflammatory mediator.³¹

About 30% of patients taking curcumin in the osteoarthritis trial reported adverse events, similar to those taking ibuprofen. Potential side effects with turmeric supplementation can include gastrointestinal issues such as abdominal pain/distension, dyspepsia, and loose stools.³⁰ An in vitro study showed inhibitory effects of curcumin on platelet aggregation, although at a concentration that was not clinically relevant.^17,32,33 A study in rats showed similar effects of turmeric oil. ³⁰ However, the main constituent in turmeric oil is turmerone, not curcumin. A clinical study showed a possible increase in urinary oxalate concentrations, leading to increased risk of kidney stone formation.³⁴

Curcumin has been evaluated in small clinical trials with cancer patients. In advanced breast cancer patients on docetaxel, the maximum tolerated oral dose of curcumin was identified as 8 g per day.³⁵ In a phase II trial of oral curcumin in patients with advanced pancreatic cancer, two of 21 evaluable patients had clinically relevant biological activity with no observed treatment-related toxic effects, 8 g of oral curcumin was well tolerated despite poor absorption,³⁶ and coadministration with gemcitabine was safe and feasible.³⁷ Another safety trial is currently evaluating curcumin in patients with inoperable colorectal cancer undergoing a standard FOLFOX regimen.³⁸ In a pilot study on its potential to alleviate inflammatory side effects of capecitabine treatment, lower rates of hand-foot syndrome were observed with oral curcumin at 4 g daily.³⁹

Curcumin has known HDIs with human liver cytochrome P450 enzymes ^40-43and may interfere with chemotherapy drugs such as doxorubicin and cyclophosphamide.⁴⁴ It may also interact with drug classes like tyrosine kinase inhibitors, which strongly inhibit CYP3A4.⁴⁵ The potential for HDIs specifically with CYP2C9, according to a pre-clinical study showed an inhibitory concentration (IC₅₀) of 4.3 μM,⁴⁶ which can be an achievable curcumin serum level. However, a small-scale clinical study did not show a significant decrease in metabolite levels of the CYP3A4 probe drug midazolam, even with piperine-prepared curcuminoids at a 4 g one-time dose.⁴⁷

Practical application:

An important traditional Ayurvedic and Chinese medicine, turmeric and its main active constituent curcumin are among the most well-studied dietary supplements. Curcumin has been shown to be generally safe and to possess anti-inflammatory activity, and even possible cancer inhibitory activity in small clinical studies. Although it has poor oral bioavailability, most curcumin products are formulated with either piperine (black pepper extract) or liposomes to improve its bioavailability. Based on currently available data, it is prudent for patients with oxalate kidney stones not to take curcumin. Although there are studies showing interactions between curcumin and CYP3A4, the concentration needed is unlikely to be achieved by oral ingestion.

Ashwagandha (Withania somnifera)

Also known as Indian ginseng, ashwagandha is among the most well-known Ayurvedic herbs. In the United States, it is often marketed for stress, strain, and fatigue. Ashwagandha is also used as a general tonic to improve health, energy levels, and longevity.⁴⁸

Preclinical studies suggest immunomodulating, cytotoxic,⁴⁹ chemopreventive,⁵⁰ and radiosensitizing effects,⁵¹ as well as enhanced chromosomal stability.⁵² Withaferin A, a major constituent, enhanced oxaliplatin effects in human pancreatic cancer cells.⁵³ In a murine study, an aqueous extract of W. somnifera reversed paclitaxel-induced neutropenia.⁵⁴

Small-scale human studies suggest that ashwagandha may promote growth in children and improve hemoglobin level and red blood cell count.⁴⁸ In adult patients with knee joint pain, use of a standardized ashwagandha extract resulted in chondroprotective, anti-inflammatory, and analgesic effects.⁵⁵ In an open-label nonrandomized study of breast cancer patients, adjuvant ashwagandha improved chemotherapy-induced fatigue and improved quality of life.⁵⁶ Although results seem positive, larger well-designed clinical trials are needed to confirm these findings.

Ashwagandha is generally safe, and does not interact with CYP3A4 or CYP2D6 enzymes in human liver microsomes.⁵⁷ However, ashwagandha may increase testosterone levels, and should be avoided in patients with prostate cancer.⁵⁸ Pregnant women should also avoid ashwagandha as it may induce abortion at higher doses.⁵⁹ In addition, patients who take anticonvulsants, barbiturates, and benzodiazepines should avoid ashwagandha due to sedating properties and GABAnergic effects in preclinical models.⁵⁹

Practical application:

In Ayurveda, ashwagandha translates to “smell of horse,” emitted from the fresh root. The traditional belief is that if taken, one would take on the strength and vitality of a horse. Due to its safety profile, ashwagandha can be a useful supplement in addressing symptoms such as stress and/or fatigue. However, avoid using ashwagandha in prostate cancer patients, as clinical studies have shown it may increase serum testosterone levels in men.

Reishi mushroom (Ganoderma lucidum)

Deeply rooted in Asian cultures for its longevity properties,⁶⁰ reishi has been used in folk medicine for more than 4000 years. In Japanese, reishi has a literal translation of “spiritual mushroom.” It is also known as lingzhi in Chinese. In vitro and in vivo studies indicate that beta glucans and triterpenes, major constituents in reishi, have immunomodulatory⁶¹ and chemopreventive⁶² effects.

In healthy subjects, reishi increased plasma antioxidant capacity.^63,64 It also enhanced immune responses in cancer patients^65,66 and appeared to suppress development of colorectal adenomas.⁶⁷ In a few cases, remission of hepatocellular carcinoma was observed.⁶⁸ However, there are other case reports of elevated CA72–4 serum levels in gastrointestinal cancer patients who used reishi mushroom spore supplements.⁶⁹ Therefore, despite popular cultural beliefs there is no evidence from clinical trials for the use of reishi in first-line cancer treatment or to prolong long-term cancer survival. Its popularity for cardiovascular health also did not find support in a systematic review of reishi to address cardiovascular risk factors associated with type 2 diabetes.⁷⁰ However, preliminary evidence suggests it may have a role in stimulating host immunity and enhancing tumor response.⁷¹

Reishi may increase bleeding risk when used in combination with anticoagulants or antiplatelets.⁷² Due to its antioxidant capacity, reishi may theoretically interact with chemotherapeutic agents that rely on free radical formation.⁶³ In vitro, reishi polysaccharides inhibited CYP2E1, CYP1A2, and CYP3A.⁷³ It could therefore affect intracellular concentrations of drugs metabolized by these enzymes, although clinical relevance is not known.

Practical application:

In traditional Chinese medicine, lingzhi is believed to be the “herb of longevity,” and is not only used to prevent disease, but also to cultivate one’s virtues. Preliminary evidence suggests immunomodulation effects exhibited by reishi occurs via host immunity stimulation and enhanced tumor response. However, there is currently no evidence of prolonged long-term cancer survival with reishi use. Caution should be taken in patients who are also taking anticoagulants, as reishi extracts may increase bleeding risk.

Graviola (Annona muricata)

Graviola is a heart-shaped tropical fruit that is grown around the tropical regions of the world. It has many names: graviola in Brazil, guanábana in Spanish-speaking countries, fengli shijia in Taiwan, and soursop in the United States. The fruit, seeds, leaves, stems, and roots are used in traditional medicine for symptoms associated with infection and inflammation. In some Caribbean countries, it is part of their cultural belief that using graviola as an herbal remedy is helpful to treat cancer, especially prostate, breast, and colorectal cancers.⁷⁴

Purported health benefits from graviola have been attributed to antioxidant properties.⁷⁵ Annonaceous acetogenins are among the active phytochemicals extracted from the fruit, leaves, bark, and twigs. ⁷⁶ In animal models, graviola extracts have exhibited analgesic,⁷⁷ anti-inflammatory,⁷⁸ and antiulcer⁷⁹ effects. In other preclinical studies, graviola extracts appear to be active against various cancers, including those of the breast,⁸⁰ lung,⁸¹ colon,⁸² and pancreas.⁸³ However, clinical research on graviola products in cancer patients is lacking, with safety and efficacy as yet undetermined.

Potential HDIs with graviola are suggested in murine models, demonstrating additive effects with antidiabetic drugs leading to hypoglycemic effects,⁸⁴ or hypotensive episodes when taken with antihypertensive medications.⁸⁵ The clinical relevance of these interactions has yet to be determined.

Practical application:

Graviola has many names in tropical regions around the world, and its consumption is driven by strong cultural influence. Therefore, it is paramount for physicians to understand patient backgrounds and expectations. Many cultures revere graviola as a cure-all, even for cancer. Although preclinical data has shown graviola extract has anticancer properties, most data were not subjected to clinical trials. Therefore, purported safety and efficacy as a cancer treatment cannot be inferred.

Active hexose correlated compound (AHCC)

AHCC is a nutritional supplement that is derived from shiitake mushroom (Lentinula edodes) mycelia. It shares a number of constituents that may overlap with other mushrooms, such as beta glucans.⁸⁶ However, it is also rich in oligosaccharides, particularly those that contain alpha-1,4-glucans, to which enhanced biologic activities are attributed.⁸⁷

Animal studies suggest AHCC has antioxidant properties and may protect against disorders induced by oxidative stress.⁸⁸ It also has anti-inflammatory effects against colitis,⁸⁹ and may improve resistance to bacterial⁹⁰ and viral infection.⁹¹ Data from preclinical cancer studies suggest AHCC may improve the therapeutic effects of various chemotherapies.^92-94 In mice treated with cisplatin, AHCC also reduced chemotherapy-induced side effects.⁹⁵

In healthy humans, AHCC improved response to influenza vaccine,⁹⁶ and increased T-cell immune response⁹⁷ and dendritic cell number and function.⁹⁸ A few studies of AHCC have also been conducted in the oncology setting. Among patients who received curative resection for hepatocellular carcinoma, those who took AHCC postoperatively experienced improved prognosis.⁹⁹ In smaller studies of patients with advanced cancers, AHCC reduced adverse effects from chemotherapy.^86,100

Despite some studies on the adjuvant use of AHCC with chemotherapy, HDIs may occur with certain medications. AHCC is an inducer of CYP2D6, which may decrease the activity of doxorubicin or ondansetron.¹⁰¹ In murine models, AHCC did not change activity of tamoxifen, a prodrug activated by CYP2D6; but it did interact with letrozole in breast cancer mouse models with COMT variant genotype.¹⁰² In addition, AHCC may render aromatase inhibitors less effective by inducing the aromatase enzyme,¹⁰² although clinical relevance has not been determined.

Practical application:

Active hexose correlated compound (AHCC) is a supplement extracted from shiitake mushroom, with high amounts of α−1,4-glucan oligosaccharides. AHCC is generally safe and exhibits immunomodulating effects by increasing T cell and dendritic cell number and function. AHCC can help alleviate chemotherapy-associated adverse effects in patients with advanced cancers such as those with unresectable pancreatic ductal adenocarcinoma on gemcitabine. However, caution is warranted in breast cancer patients who are placed on doxorubicin, ondansetron, and/or aromatase inhibitors such as letrozole.

Boswellia (Boswellia serrata)

Boswellia is commonly referred to as Indian frankincense, and well known in Ayurvedic medicine for treating inflammatory diseases such as arthritis, ulcerative colitis, and sores. Not to be confused with guggul or myrrh, the resin or olibanum is produced by removing the bark of B. serrata, a tree that is prevalent in North Africa, the Middle East, and India. In the United States, the supplement is often marketed for joint health and mobility.

The major constituent of boswellia is boswellic acid.¹⁰³ It inhibits the enzyme 5-lipoxygenase, which is involved in the production of inflammatory leukotrienes, with dose-dependent anti-inflammatory and anti-arthritic effects.^103,104 In preclinical studies conducted in glioma cell lines, boswellia exhibited cytotoxicity^105-107 and radio-enhancing properties.¹⁰⁸

A few studies have also been conducted in humans. In osteoarthritis of the knee, one trial suggested benefit from supplementation with an enriched boswellic acid extract.¹⁰⁹ In another double-blind pilot, patients who received a B. serrata supplement following radiation therapy had significantly reduced MRI-measured cerebral edema.¹¹⁰ As for prevention of skin damage caused by radiation therapy in breast cancer patients, application of a boswellia-based cream was found to be effective while reducing topical corticosteroid use.¹¹¹

Although generally well tolerated,¹¹² contact dermatitis was reported following the topical application of a cream containing B. serrata extract.¹¹³ An alcohol extract of boswellia may increase risk of bleeding by inhibiting platelet aggregation, but the same effect was not seen in a water extract.¹¹⁴

Practical application:

Ru Xiang (B. carterii) in traditional Chinese medicine is similar to Śallakī (B. serrata) in Ayurveda, with the same active ingredient. In TCM, it is commonly used to alleviate pain and invigorate “Qi” or energy. Boswellia is generally safe and frequently marketed for bone and joint health. Besides a few cases of contact dermatitis, boswellia appears to be well tolerated. Even though there is a clinical study showing significant reduction in cerebral edema in patients who received the supplement following radiation therapy for brain tumors, larger trials are needed to confirm this finding.

Dandelion (Taraxacum mongolicum, Taraxacum officinale)

Known as pu gong ying in traditional Chinese medicine, dandelion has been used to reduce abscesses, especially in the breast and intestines.¹¹⁵ It is also used to promote lactation. The flower, leaf, and root of this plant are used for their diuretic, blood glucose-lowering, and appetite-stimulating properties.^116,117

In preclinical studies, dandelion root extract has exhibited anticancer effects in various cancer types, including melanoma,¹¹⁸ pancreatic,¹¹⁹ and colorectal¹²⁰ cancer cell lines. A dandelion root extract was also found to selectively induce apoptosis in aggressive and resistant chronic myelomonocytic leukemia (CMML) cells.¹²¹ There are also a few case reports of stable or improved hematological parameters in patients with CMML that have been related in part to dandelion root extract.¹²² However, clinical trials have not been conducted.

In vitro and animal models suggest that dandelion has estrogenic activity, as evidenced by increased proliferation of MCF-7 cells, and an increase in uterine weight in immature female rats.¹²³ Other preclinical models suggest that dandelion may inhibit CYP1A2¹²⁴ and CYP3A4¹²⁵ activities, which may alter blood levels of substrate drugs. Due to its diuretic and blood glucose-lowering properties,^116,117 dandelion may induce additive effects when patients are already on diuretics and hypoglycemic agents.

Practical application:

Dandelion is part of traditional medicinal systems in Native America, China, and the Middle East, with broad uses as a general tonic and diuretic to the treatment of specific ailments such as gastrointestinal and skin issues. The whole plant can be used and is an excellent source of vitamin A. Preclinical data suggest that dandelion root extract may be helpful in aggressive and resistant CMML. Although generally considered safe, it should be avoided in hormone-sensitive breast cancer patients.

Green tea (Camellia sinensis)

Green tea is the unfermented preparation of C. sinensis leaves, as opposed to black tea, which is processed or fermented. Green tea is widely consumed as a steeped hot beverage around the world, especially in China and Japan. Active constituents include the polyphenol epigallocatechin-3-gallate (EGCG), caffeine, and theanine. Green tea extract supplements are marketed to maintain cardiovascular health, for weight management, and as an antioxidant. Patients may also be interested in green tea for cancer prevention.

Several preliminary studies of various green tea extracts have been conducted. Whether green tea extract has cancer-preventive effects in humans is inconclusive. In a randomized controlled chemopreventive study of 97 men, powered to detect a drop in prostate cancer risk in 1 year from 30% to 9%, EGCG 400 mg daily was not significantly more effective than placebo, but did significantly lower serum prostate-specific antigen (PSA) and was well tolerated.¹²⁶ In a phase II trial of green tea extract (2 g twice daily x 6 months) in 42 chronic lymphocytic leukemia (CLL) patients, 31% of patients had ≥20% reduction in absolute lymphocyte count and 69% with palpable adenopathy had ≥50% reduction in the sum of the lymph node products.¹²⁷ At this unusually high dose, grade 3 transaminitis, abdominal pain, or fatigue was reported in 2.5% of patients for each adverse reaction.¹²⁷ In a randomized placebo-controlled trial, 199 prostate cancer patients who were under primary active surveillance or watchful waiting following previous interventions were given a whole food supplement containing green tea, turmeric, pomegranate, and broccoli for 6 months. Those taking the supplement had significantly slower rates of PSA increase compared with those taking placebo.¹²⁸ Additional studies are needed to confirm this short-term benefit.

Although the FDA includes tea on their list of Generally Recognized As Safe (GRAS), high-dose green tea extract can cause liver toxicity¹²⁹ and may pose a risk for potential HDIs. In general, 1 cup of green tea contains about 100 mg to 200 mg of EGCG. When taken in a fasting state, it can reach a C_max 5–10 times higher than when taken with food.¹³⁰ Preclinical studies also show a unique antagonizing effect of EGCG at a dose equivalent to 1 g oral ingestion in humans on boronic acid-based proteasome inhibitors, such as bortezomib.¹³¹ Tamoxifen is a prodrug that gets metabolized into its active metabolites by CYP2D6. EGCG inhibits CYP2D6 at an IC₅₀ of 25 ug/mL,¹³² while human oral consumption of 20 mg/kg green tea leaves or 2 mg/kg EGCG extract resulted in C_max of around 80 ng/mL¹³³ and around 1 ug/mL at a much higher green tea dose.¹³⁴ Therefore, oral EGCG even at 3 g, is unlikely to have significant inhibition on CYP2D6 in human enzymes.

Practical application:

Green, black, and oolong teas are all derived from C. sinensis leaves. As one of the most well-studied polyphenols, epigallocatechin-3-gallate (EGCG) alone, or in a combination formulation, has been shown in clinical studies to have potential effects against CLL or prostate cancer. However, high doses equivalent to 5–10 cups of green tea taken in a fasting state, is associated with liver toxicity.¹²⁹ It should also be avoided in patients who are on bortezomib. It is also advisable to always drink green tea or take EGCG supplements with food.

Turkey tail mushroom (Coriolus versicolor, Trametes versicolor)

Frequently referred to as yunzhi, Chinese for “cloud mushroom,” Coriolus or Trametes versicolor is used in traditional Chinese medicine as a tonic. Polysaccharide peptides (PSP) and polysaccharide-K (PSK) isolated from Coriolus are the most studied preparations, with the latter being approved for clinical use in Japan. They are also available as dietary supplements.

Studies in the oncology setting suggest benefit with adjuvant PSK to improve survival rates in patients with gastric^135,136 and colorectal^137-139 cancers. It may also benefit patients with esophageal cancer.¹⁴⁰ A clinical study of PSP used in conjunction with chemotherapy also suggests patients with advanced non-small cell lung cancer may benefit.¹⁴¹ In addition, clinical studies using Coriolus extract alone or in combination with other botanicals suggest positive immunomodulatory effects.^142,143 However, studies in breast cancer,¹⁴⁴ hepatocellular carcinoma,^145,146 and leukemia¹⁴⁷ have produced mixed results.

Coriolus extracts are generally well tolerated and safety data are well established from PSK use in Japan since the mid-1970s, although minor adverse effects, such as gastrointestinal upset, have been reported.^137,148 Because of its immunomodulatory activities, it may interact with immunosuppressants, at least in theory. Many over-the-counter Coriolus products contain only mycelium, not the extracts used in the clinical studies. It is unclear whether they have the same activities as reported in the above studies.

Practical application:

Commonly known as turkey tail mushroom, Coriolus has a long history of medicinal use in China and Native America. Based on available clinical data and chemical structure of the constituents, Coriolus polysaccharide extracts are generally safe and have a low risk for HDIs. Among all the medicinal mushrooms, Coriolus extract appears to be the one supported by the most clinical data for patients with esophageal, gastric, and colon cancer. It is generally well tolerated but is best avoided in patients who are on immunosuppressants.

SUMMARY

Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, dietary supplements are regulated by the FDA. Unlike prescription drugs however, they are not subject to scientific rigor before they become available to the consumer. The FDA does not mandate quality or batch-to-batch consistency of the aforementioned dietary supplements in this review paper. It is up to the consumer to carefully choose the products, or rely on third-party independent testing laboratory, such as Consumer Labs or the United States Pharmacopeial Convention Dietary Supplement Verification Program, to help verify the quality and consistency of these products.

To be truly patient-centered, physicians should be aware of the popular dietary supplements that patients care about and be able to engage in conversations with an open mind. By having a blanket statement discouraging use of herbal supplements, physicians may miss opportunities to be mindful of patients’ concerns. Most patients may heed physician advice about stopping dietary supplement use, but some may choose to continue taking them without the physician’s knowledge leading to problems including HDIs or suspending conventional cancer treatments.

By providing the latest scientific research, summarized at aboutherbs.com, we hope to equip oncologists with tools that foster better physician-patient relationships. Physicians can then help patients make informed decisions about using herbal and dietary supplements in oncology settings.