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Herbs are considered dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) of 1994.[1] An herbal supplement can be a concentrate, metabolite, constituent, or an extract derived from botanical sources; it is usually taken by mouth in the form of tablets, capsules, softgels, gelcaps, liquids, or powders.[1]
The United States (US) Food and Drug Administration (FDA) does not regulate dietary supplements under the same set of regulations it uses for prescription drugs; therefore, manufacturers do not need approval from the FDA before marketing these products.[1,2] Unlike drugs, dietary supplements are not intended to treat, diagnose, prevent, or cure diseases.[1,2]
With a few exceptions, most herbs sold as dietary supplements have not been studied scientifically; their safety and effectiveness are poorly understood.[2]
The computed tomography (CT) scans show retroperitoneal adenopathy in a patient with coexistent immunoglobulin G plasma cell dyscrasia and stage IIIa lymphoma before (left) and 10 months after (right) self-treating with "devil's claw" (Harpagophytum procumbens[3]) and Essiac (an herbal tea mixture[4]). Although a partial regression of the adenopathy can be seen on the right image, the patient subsequently developed myeloma, discontinued both herbal supplements, and underwent high-dose chemotherapy and stem cell transplantation. No lymphoma progression occurred thereafter.
Images courtesy of Wilson KS. Curr Oncol. 2009;16(4):67-70. [Open access.] PMID: 19672427, PMCID: PMC2722058.
Compared with the general population, cancer survivors are more likely to use complementary and alternative medicine (CAM), including herbs.[5] One study reported that approximately half of cancer survivors with chronic illnesses use herbal supplements.[6]
Although consumption of these products among this population greatly increases the risk of herb–drug interactions, only about one-quarter of oncologists discusses herbal supplement usage with their patients, and about two-thirds of oncologists feel they lack the knowledge to answer patient questions regarding herbal supplements.[7]
On the basis of these findings, there is a need to improve physician education about herbal supplements to facilitate communication with patients and other clinicians.
Image courtesy of Dreamstime/Alexan24.
Patients use herbal medicine for several reasons, including the following[8]:
Adapted illustrated plate courtesy of Hill J. Plate I. The British Herbal: an History of Plants and Trees, Natives of Britain, Cultivated for Use, or Raised for Beauty. London, UK: For T Osborne and J Shipton, J Hodges, J Newberry, B Collins, S Crowder and H Woodgate; 1759. [Public domain.] Via Wikimedia Commons.
The general public commonly uses echinacea, cranberry, garlic, ginseng, and ginkgo supplements.[9] However, cancer patients tend to use different products, as influenced by geographic location, patient ethnicity, and commercial promotion.
The following slides highlight nine herbs often used by cancer patients. The selection of these herbs was made on the basis on their current popularity and e-mail requests to the Memorial Sloan Kettering Cancer Center "About Herbs" Website.
Image courtesy of Dreamstime/Le-thuy Do.
The rhizome of the turmeric plant (Curcuma longa) has a 5,000-year-long history of medicinal and culinary use in India and China.[10] Its active compounds include curcuminoids and turmerones.[10]
Current research focused on curcumin, the principal curcuminoid of turmeric, shows it has anti-inflammatory, neuroprotective, and chemopreventive effects.[11] Preliminary data indicate that curcumin reduces cachexia in cancer patients, and it is safe when taken with docetaxel and gemcitabine.[12-14] Clinical trials are under way in patients with cancer—and to address the adverse effects induced by cancer treatments.[15]
Turmeric has been shown to inhibit CYP450 and P-glycoprotein, major players in the metabolism of several prescription drugs[16,17]; it also inhibits the actions of cyclophosphamide and doxorubicin in vitro.[18]
It is important to note that limitations of research on turmeric include its inherent poor absorption, rapid metabolism, and complex mechanistic profile.
Images courtesy of H Zell (left) and Badagnani (inset), both via Wikimedia Commons.
Ginseng, or Panax ginseng,[19] is a slow-growing perennial herb native to Northeast Asia that has been used as a revitalizing agent over several centuries[10]—traditional Chinese medicine practitioners believe that the ginseng root has "tonification" properties.
Ginsenosides, saponin glycosides present in the root and other parts of the plant, are the bioactive compounds[20]; they have been reported to have anticancer properties[21] and show efficacy in the treatment of erectile dysfunction.[22]
Epidemiologic data show ginseng improves quality of life (QOL) in cancer patients[23] as well as reduces the incidence of all cancers.[24]
Note that ginseng increases the hypoglycemic effects of insulin and sulfonylureas[25] and antagonizes the effects of anticoagulants.[26]
Images courtesy of FloraFarm GmbH/Katharina Lohrie (left) and Richard Fabi (right), both via Wikimedia Commons.
Green tea as a beverage originated in China more than 4,000 years ago.[27] The tea is derived from the leaves of an evergreen plant (Camellia sinensis) and is consumed worldwide for its health-promoting effects.
Epigallocatechin-3-gallate (EGCG) is a bioactive polyphenolic compound isolated from the leaves[27] and has been reported to have antiproliferative, antimutagenic, antioxidant, antibacterial, antiviral, and chemopreventive effects.[28] EGCG has been shown to block the effects of bortezomib[29] and to increase the toxicity of irinotecan.[30]
Consumption of green tea has been associated with reducing the risk of hypertension[31] and mortality[32] due to cardiovascular disease. Green tea extract may benefit patients with chronic lymphocytic leukemia (CLL),[33] and it may reduce the risk of colorectal and stomach cancers in women.[34]
Several clinical trials are under way to evaluate the effects of green tea on prevention and treatment of prostate, breast, and cervical cancers.[35]
Images courtesy of Qwert1234 (left) and KENPEI (right), both via Wikimedia Commons.
Maitake, or Grifola frondosa, is an edible mushroom native to Japan and China that is used as an important ingredient in Asian cuisine and valued for its health benefits. Its bioactive compounds are polysaccharides known as beta glucans.[36]
This herb appears to enhance hematopoiesis and reduces doxorubicin toxicity in vitro.[36] Patients with myelodysplastic syndrome have shown improved neutrophil and monocyte function with maitake consumption.[37]
Maitake extract has also been reported to cause tumor regression or significant symptom reductions in cancer patients,[38] as well as have immunomodulatory effects in postmenopausal breast cancer patients.[39]
Note that maitake may interact with warfarin, resulting in an elevated international normalized ratio (INR),[40] and it may also increase the effects of hypoglycemic medications.[41]
Image courtesy of Wikimedia Commons/Patrick Harvey.
Graviola, also known as soursop or Annona muricata, is native to tropical areas in Central America, South America, and the Caribbean, and it has a long history of medicinal use.[42,43,44] All parts of the tree, including the bark, leaves, fruits, and roots, are used in herbal medicine. Its major bioactive compounds are annonaceous acetogenins, which can be extracted from different parts of the tree.[43-45]
Although graviola has not yet been studied as an anticancer treatment in humans, preclinical data in experimental animals indicate it may have anti-inflammatory,[46] antiparasitic,[46] antirheumatic,[42] and anticancer[47] effects. However, despite the lack of substantial evidence, graviola is heavily promoted in the United States and Europe as a cancer-fighting herb.
Note that consumption of graviola fruit is associated with neurotoxicity involving movement disorders and myeloneuropathy, with symptoms mimicking Parkinson disease.[43,48] Graviola ingestion also negatively affects the uptake of radiopharmaceutical agents used in nuclear imaging,[49] and it lowers platelet counts.[50]
Image courtesy of the California Department of Food and Agriculture via Wikimedia Commons.
Dong quai is derived from Angelica sinensis, a perennial herb indigenous to China, Japan, and Korea; its root has been used for hundreds of years as a spice, tonic, and medicine.[51] In traditional Chinese medicine, dong quai has been used to treat menstrual disorders, menopausal symptoms, and anemia, as well as to improve blood circulation.[51]
In animal models, polysaccharides from the dong quai root appear to protect against cyclophosphamide-induced toxicity,[52] doxorubicin-induced cardiotoxicity,[53] and radiation-induced pneumonitis.[54] Clinical data on menopausal symptoms have been inconclusive,[55] and it has not proven effective against hot flashes in men.[56]
Note that dong quai is known to potentiate the effects of anticoagulants,[57] and because it has estrogenic effects,[58] this herb may not be appropriate for patients with hormone-sensitive cancers.
Image courtesy of Dreamstime/Viroj Suttisima.
Boswellia serrata is a tree that is prevalent in India, the Middle East, and North Africa; its gummy exudate or the resin obtained from the bark has a long history of use in Ayurveda, a system of natural healing in Indian culture, to treat diarrhea, inflammation, and arthritis.[59] The active compounds, boswellic acids, have shown anti-inflammatory[60] and antitumor[61] effects in experimental models.
In clinical trials, boswellia appears to be effective against bronchial asthma[62] and ulcerative colitis,[63] and it has been reported to reduce cerebral edema in patients with brain tumors following radiotherapy.[64] However, there is mixed evidence regarding beneficial effects for osteoarthritis.[65,66]
Note that boswellic acids inhibit the activity of P-glycoprotein (P-gp); therefore, they may affect the transport of drugs mediated by these proteins.[67]
Image courtesy of Wikimedia Commons/JM Garg.
Resveratrol is a polyphenolic compound found in the skin and seeds of red grapes; it has been promoted as an antioxidant, anti-inflammatory, and anti-aging supplement.[68-71]
Consumption of resveratrol-rich grape supplement has been associated with a reduced risk of cardiovascular disease.[72] Preclinical studies with resveratrol show antiproliferative effects,[70] and murine models appear to show protection against chemotherapy-induced cardiotoxicity.[73] However, there have been no confirmatory studies in humans.
Mixed evidence exists regarding the benefits of resveratrol on metabolic syndrome in obese subjects.[68,69]
Note that this compound not only inhibits platelet aggregation—and therefore concurrent use with antiplatelet drugs can increase the risk of bleeding[74]—but it also inhibits cytochrome P450 enzymes, which can affect the levels of drugs metabolized by these enzymes.[71]
Image of red grapes courtesy of Dreamstime/Serhiy Shullye (left), and image of chemical structure of resveratrol courtesy of Wikimedia Commons/Fvasconcellos (inset).
Artemisia annua, also known as wormwood, is an annual plant used in traditional Chinese medicine for reducing fevers and inflammation, as well as for treating malaria.[75] The active compound is artemisinin, a sesquiterpene lactone with antimalarial and antiviral activity.[75,76]
Systematic reviews have shown artemisinin is as effective as quinine in treating both uncomplicated and severe malaria.[77,78] This compound has been also associated with anticancer effects in human lung cell tumor lines (95-D)[79] and has been studied as an anticancer treatment.
Note that artemisinin can induce seizures as well as reduce the efficacy of antiseizure medications.[75,80] In addition, this compound induces cytochrome P450 2B6 and 3A4 enzymes[81] and may therefore affect the serum concentration of drugs metabolized by these enzymes.
Images courtesy of Wikimedia Commons/Kristian Peters (left) and Dreamstime.com/Cefiroa31 (right).
It is essential that clinicians be aware of the following issues surrounding herbal supplements, which can affect patient safety:
Images courtesy of Dreamstime/Mona Makela (left) and Wikimedia Commons/Aleph (right).
Several online subscription-based and free-access dietary supplement databases exist. The FDA provides information on using dietary supplements for consumers, and the National Cancer Institute provides information regarding cancer and CAM for patients and for health professionals.
The "About Herbs" Website, developed by the Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, is the only free-access, cancer-related herbal supplement database. It currently has over 270 entries on herbs, vitamins, minerals, and unproved anticancer therapies.
Image courtesy of Dreamstime/Natallia Khlapushyna.
Clear and open communication between clinicians and patients in all aspects of their care is crucial, and it is a key component of oncologic management. In discussions with patients, take into account the following:
The image shows an example of the components of integrative oncology for breast cancer patients. CAM = complementary and alternative medicine; MBM = mind-body medicine.
Adapted image courtesy of Dobos GJ, Voiss P, Schwidde I, et al. BMC Cancer. 2012;12:539. [Open access.] PMID: 23170989, PMCID: PMC3582454.
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