Essiac: a word of caution
Jacob Schor, ND
December 27, 2006
Subject: A research study suggests Essiac may stimulate growth of breast cancer cells.
Essiac tea is one of the most common herbal treatments that patients employ in their self-treatment of cancer. In 2004, the Mayo clinic estimated that about 10% of cancer patients enrolled in phase I drug trials were using Essiac. [i] Of the cancer patients seen at our clinic, the number is far higher. Some weeks it seems that everyone is drinking it.
Essiac has an interesting history. The full story of how Canadian nurse Rene Caisse came upon an Ojibwa herbal formula for treating cancer and then went on to save untold numbers of lives is detailed at great length on the half million or so websites devoted to selling Essiac. Though interesting information, it isn't relevant to this brief discussion.
Given the widespread use of Essiac and the many health food stores and websites that promote and sell it, the extreme paucity of published research on Essiac is surprising. A search for the term “Essiac” on Pub-Med generates a meager 19 hits. Most of these hits turn out to be about alternative medicines used by cancer patients and simply mention Essiac in passing. Actual research on Essiac is almost nonexistent. In contrast, searching for information on ginger yields 664 papers, 73 of which are about cancer.
Several papers have been published on Essiac in the last few years and are worth noting.. One in particular is important because it suggests that using Essiac may be dangerous for patients with breast cancer.
Two papers are about Essiac and prostate cancer and are positive. In August 2004, the Journal of Alternative and Complementary Medicine published a test tube study that showed that Essiac might inhibit prostate tumor cell growth. [ii] The Canadian Journal of Urology published, in October 2005, an anecdotal report about a 64-year-old man with prostate cancer who did well while taking Essiac. [iii]
In February 2004, the Center for Complementary Medicine Research in Vancouver , BC reported on their “in vitro studies on the antiproliferative and differentiation inducing activities” of both Essiac and Flor-Essence teas. They were able to demonstrate some anti-cancer effect from these products but only at very strong concentrations. Often the cells needed to be bathed in a 1/10 dilution of the tea to see any effect. The authors concluded, “Our data show that both ES and FE herbal teas demonstrated antiproliferative and differentiation inducing properties in vitro only at high concentrations.” [iv] In other words they didn't see anything to get excited about.
In November 2005, the same Center for Complementary Medicine Research published data comparing the antioxidant and anti-inflammatory effect of Essiac and Flor-Essence. [v] Both teas increased nitric oxide levels, a trait we generally think of as useful, but did so by increasing inducible nitric oxide synthase (iNOS). This is not something we are eager to see. High levels of iNOS are associated with a worse prognosis for cervical cancer [vi] and increased risk of getting breast cancer from radiation treatment. In fact, high levels of iNOS increases the risk of getting breast cancer from radiation exposure by seven fold. [vii] [viii]
When looking at herbal extracts it is nice if they work in vitro. That is, you add a little of the herbal extract into a test tube filled with cancer cells and some or all of the cancer cells drop dead. Not all herbs that are useful for cancer patients do this. Some herbs may act as immune stimulants, rather than killing the cancer cells directly, they get the immune system to kill the cancer. Mushroom polysaccharides appear to work like this. Digitalis, once used to treat congestive heart disease, decreases breast cancer recurrence by unknown mechanisms. Testing these herbs in vitro, in a test tube, will not tell us if they work; they only work in vivo, that is, in a living animal. Despite the absence of positive Essiac results in vitro, practitioners assumed in vivo tests would yield better results. With this in mind, it was disappointing to see an in vivo experiment published in July 2006 unable to demonstrate the, “purported physiological modifying effects” associated with Essiac use. [ix]
More than disappointing are the data published in August 2006 issue of Breast Cancer Research and Treatment, that say Essiac stimulates growth of breast cancer cells. Knowing how many cancer patients use Essiac, it is of great concern to read:
Essiac may provide some benefit to patients with prostate cancer but there is better research encouraging one to eat ketchup. For other types of cancer, there is little encouraging research and for breast cancer, these results argue against using Essiac.
In this situation we must fall back on the Hippocratic injunction, “First, do no harm.”
Complementary and alternative medicine use by patients enrolled onto phase I clinical trials.
Dy GK ,
Bekele L ,
Hanson LJ ,
Furth A ,
Mandrekar S ,
Sloan JA ,
Adjei AA .
Division of Medical Oncology, Department of Medicine, Mayo Foundation and Mayo Clinic College of Medicine, Rochester , MN , USA .
PURPOSE: To describe the prevalence, clinical characteristics, and pattern of use of complementary and alternative medicine ( CAM ) in patients enrolled onto phase I trials. PATIENTS AND METHODS: Questionnaires were administered to 108 patients with advanced malignancies enrolled onto phase I chemotherapy trials at the Mayo Clinic Comprehensive Cancer Center ( Rochester , MN ). CAM was classified into two modalities, pharmacologic and nonpharmacologic. Clinical and demographic data, including age, sex, and prior cancer treatment, were subsequently obtained from patient charts and examined for any correlation with CAM use, using chi2 analysis. RESULTS: One hundred two survey forms were returned. Among respondents, 88.2% (90 of 102) had used at least one CAM modality; 93.3% (84 of 90) and 53.3% (48 of 90) had used pharmacologic and nonpharmacologic CAM , respectively; and 46.7% (42 of 90) used both modalities. Vitamin and mineral preparations constituted 89.3% (75 of 84) of all pharmacologic CAM used. Intake was highest for vitamins E (48.8% [41 of 84]) and C (38.1% [32 of 84]), and 71.4% (60 of 84) of respondents took nonvitamin/mineral agents. Green tea (29.8% [25 of 84]), echinacea (13.1% [11 of 84]), and essiac (9.5% [8 of 84]) were the most popular. Prayer and spiritual practices were the most commonly used nonpharmacologic CAM , accounting for 52.1% (25 of 48). Chiropractors, the most frequently visited nontraditional medicine practitioners, were consulted by only 10% (9 of 90) of those who practiced CAM . Both CAM modalities were used more frequently by women (53.5% [23 of 43]) than men (40.4% [19 of 47]). CONCLUSION: CAM use is common among patients in phase I trials and should be ascertained by investigators, because some of the agents used may interact with investigational agents and affect adverse effects and/or efficacy.
PMID: 15570083 [PubMed - indexed for MEDLINE]
Inhibition of prostate cancer-cell proliferation by Essiac.
Ottenweller J ,
Putt K ,
Blumenthal EJ ,
Dhawale S ,
Dhawale SW .
Department of Biology, Indiana University-Purdue University Fort Wayne , Fort Wayne , IN , USA .
OBJECTIVE: To assess the ability of Essiac tea extracts (Essiac Canada International, Ottawa , Canada ) to modulate cancer cell proliferation and immune responsiveness. DESIGN: A noncancerous transformed cell line was compared to a cancerous cell line and spleen cells that had been isolated from mice to examine proliferation responses mediated by the addition of an Essiac preparation. RESULTS: We found in vitro evidence of decreased proliferation of both noncancerous transformed (CHO) and cancerous prostate cell line (LNCaP) when Essiac was present in the culture media. A dose response for inhibition was demonstrated by a linear regression performed on the data for both the CHO and LNCaP cells. The percent inhibition of the LNCaP cells was higher than the percent inhibition of the CHO cells suggesting that Essiac may have a more selective effect on cancer cells than transformed cells. In addition, the effects of Essiac were examined in an immune T-lymphocyte proliferation assay. At low doses of Essiac, augmentation of proliferation of these T cells was demonstrated, but at higher doses Essiac was inhibitory to T-cell proliferation. The same doses of Essiac that stimulated spleen cells were inhibitory for LNCaP cell proliferation. CONCLUSIONS: Essiac preparations may be able to inhibit tumor cell growth while enhancing immune response to antigenic stimulation. This may be especially valuable in immune-suppressed individuals.
PMID: 15353028 [PubMed - indexed for MEDLINE]
Remission of hormone-refractory prostate cancer attributed to Essiac.
Al-Sukhni W ,
Grunbaum A ,
Fleshner N .
Division of Urology, The Princess Margaret Hospital, University of Toronto , Toronto , Ontario , Canada .
Essiac is a popular complementary and alternative medicine ( CAM ) that is utilized by many cancer patients in North America . Much anecdotal reporting exists about its cancer-fighting qualities, but so far no clinical trials have been preformed to validate those claims. We describe here the case of a 64-year-old man whose hormone-refractory prostate cancer responded well to Essiac tea.
PMID: 16274521 [PubMed - indexed for MEDLINE]
In vitro comparison of Essiac and Flor-Essence on human tumor cell lines.
Tai J ,
Cheung S ,
Wong S ,
Lowe C .
Center for Complementary Medicine Research, BC Research Institute for Children's and Women's Health, Room L306, 4480 Oak Street , Vancouver , British Columbia V5Z 4H4 , Canada . firstname.lastname@example.org
Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation therapy. In vitro studies on the antiproliferative and differentiation inducing activities of these teas were performed. ES and FE showed negligible antiproliferative activity on Jurkat leukemia cells. Both herbal teas inhibited 50% (IC50) of MCF7 breast cancer cell growth at 1/10 dilution. The IC50 was about 1/40 and 1/10 dilution of FE and ES respectively for MDA-MB-468 human breast cancer cells. The IC50 for HL60 cells was at 1/10 dilution of FE and less than 1/10 dilution of ES . ES at 1/10 dilution induced expression of non-specific esterase in 16% of HL60 cells, compared to about 5% in FE treated cells and untreated controls. ES treatment of HL60 cells induced 47-67% nitroblue tetrazolium positive staining cells compared to 24.6+/-3.1% in cells treated with 1/10 dilution of FE. Flow cytometry analysis showed that both ES and FE treatment between 1/10 and 1/100 dilutions only slightly affected the cell cycle progression of MCF7, MDA-MB-468, Jurkat and HL60 cells. Our data show that both ES and FE herbal teas demonstrated antiproliferative and differentiation inducing properties in vitro only at high concentrations. Further research is needed to elucidate the in vivo activities.
PMID: 14719086 [PubMed - inde
Antioxidant and anti-inflammatory properties of ESSIAC and Flor-Essence.
Cheung S ,
Lim KT ,
Tai J .
Department of Pediatrics, Center for Complementary Medicine Research, BC Research Institute for Children's and Women's Health, University of British Columbia, 4480 Oak Street, Vancouver, British Columbia, Canada.
Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation-therapy. The antioxidant and anti-inflammatory properties of these two herbal teas were assessed in this study. Cell-free Trolox equivalent antioxidant capacity assay shows that at 1/5 dilution, ES and FE have hydroxyl radical scavenging activity equivalent to 10.65 microM and 5.74 microM of Trolox respectively. Treatment with ES at 1/10 and 1/20 dilutions significantly increased nitric oxide (NO) production by murine RAW 264.7 cells, but inhibited NO production in a concentration-dependent manner by lipopolysaccharide (LPS)-stimulated cells . In contrast, FE at 1/10 and 1/20 dilutions did not significantly induce NO production by RAW 264.7 cells, nor did it, at these dilutions, inhibit the NO production by LPS-stimulated RAW 264.7 cells. RT-PCR assay shows that both 1/20 and 1/100 dilutions of ES and FE induced mRNA expression of IL-1beta, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) pro-inflammatory molecules in RAW 264.7 cells compared to untreated controls. Addition of ES and FE at 1/20 and 1/100 dilutions to LPS-stimulated RAW 264.7 cells did not alter IL-1beta, iNOS and COX-2 mRNA expression in these cells. ES and FE treatment did not affect TNFalpha mRNA expression in non-stimulated or LPS-stimulated RAW 264.7 cells. Our data show that ES but not FE stimulated NO release by non-stimulated and inhibited LPS-stimulated RAW 264.7 cells. There were only minor differences between ES and FE in their induction of mRNA expression of pro-inflammatory molecules. Further research is needed to investigate the differential activities of these two herbal teas in stimulating pro-inflammatory mediators release by RAW 264.7 cells.
PMID: 16211307 [PubMed - indexed for MEDLINE]
Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy.
Chen HH ,
Su WC ,
Chou CY ,
Guo HR ,
Ho SY ,
Que J ,
Lee WY .
Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
PURPOSE: To investigate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cervical cancer and their association with clinical outcome in patients treated with radical radiotherapy. METHODS AND MATERIALS: One hundred sixty-seven consecutive patients with FIGO Stages IB-IVA squamous cell cervical cancer underwent radical radiotherapy, including external-beam radiotherapy or high-dose-rate brachytherapy, or both, between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and evaluate the effects of the factors affecting patient survival. RESULTS: Positive immunostainings of iNOS and COX-2 were observed in 58.7% and 64.1% of the participants, respectively. The expression of both iNOS and COX-2 was positively correlated (Spearman correlation coefficient = 0.49, p < 0.01), and their overexpression provided independent predictors of distant metastasis (odds ratio = 5.22 and 10.07, respectively; p < 0.01 for all). iNOS- and COX-2-expressing patients had significantly shorter disease-free survival (p < 0.01, both) and cause-specific overall survival (p = 0.01, p < 0.01, respectively). Patients with iNOS-positive/COX-2-positive tumors had the poorest survival rates. Coexpression of iNOS/COX-2, together with bulky tumor and advanced stage were independent prognostic factors for disease-free survival. CONCLUSION: Overexpression of iNOS or COX-2 or both was associated with decreased survival and a greater propensity to metastasize in cervical cancer patients treated with radiotherapy. Coexpression of iNOS and COX-2 may represent a useful biologic marker in patients receiving radical radiotherapy for cervical cancer.
PMID: 16099602 [PubMed - indexed for MEDLINE]
Nitric oxide produced by inducible nitric oxide synthase is associated with mammary tumorigenesis in irradiated rats.
Inano H ,
Onoda M .
Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, 9-1 Anagawa-4-chome, Inage-ku, Chiba 263-8555, Japan . email@example.com
This study evaluated whether nitric oxide (NO) derived from nitric oxide synthase (NOS) induced by radiation is associated with tumorigenesis in the mammary glands. When rats were exposed to whole-body irradiation with gamma-rays (1.5 Gy) immediately after weaning and then treated with diethylstilbestrol, as an irradiated control, the tumor incidence (85%) was increased 7.6-fold in comparison with that (11.1%) of the non-irradiated control. The tumor incidence declined to 28.6% in the rats injected intraperitoneally with phenyl-N-tert-butylnitrone (PBN, 160 mg/kg), an inhibitor of inducible NOS (iNOS) expression and also a spin trapping agent, 30 min before irradiation. Also, the tumor incidence (25%) in rats orally administered with N-(3-(aminomethyl)-benzyl)-acetamide (1400W, 2.3+/-0.1 mg/day), a highly selective inhibitor of iNOS, dissolved in drinking water for 3 days after the irradiation was less than one-third of that in the irradiated control. On treatment with PBN or 1400W, no adenocarcinoma developed. Many of the mammary tumors that developed in the irradiated rats were positive for the estrogen receptor (ER). In contrast, ER was not detected in the tumors yielded from irradiated rats administered with PBN or 1400W. These results indicate that iNOS-derived NO may participate in the formation of estrogen-dependent mammary adenocarcinomas following radiation.
PMID: 15631943 [PubMed - indexed for MEDLINE]
Role of nitric oxide in radiation-induced initiation of mammary tumorigenesis in rats.
Inano H ,
Onoda M .
Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, 9-1, Anagawa-4-chome, Inage-ku, Chiba-shi, Chiba-ken, 263-8555, Japan. firstname.lastname@example.org
Nitric oxide (NO) and its reaction products have been shown to cause DNA damage and to be mutagenic. To elucidate whether NO produced by irradiation participates in the initiation of mammary tumorigenesis, we performed experiments using the nitric oxide-specific scavenger Fe(2+)-diethyldithiocarbamate complex (Fe(DETC)(2)) or a selective inhibitor for inducible nitric oxide synthase (iNOS), S,S(')-(4-phenylene-bis(1,2-ethanedinyl))bis-isothiourea (1,4-PB-ITU). Mother rats at day 21 of lactation were injected simultaneously with diethyldithiocarbamate intraperitoneally and Fe(2+)-citrate subcutaneously to form Fe(DETC)(2), in vivo, and then irradiated with 1.5Gy gamma-rays immediately after the injection. An additional injection of chemicals followed twice at 8 and 24h after the irradiation in the same manner. Both control and treated rats were then implanted with diethylstilbestrol pellets as a tumor promoter. The mammary tumor incidence in the experimental group was significantly reduced to one-fourth of that in the irradiated-alone group as the control. On the other hand, when mother rats took drinking water containing 0.005% 1,4-PB-ITU for 6 days from 3 days prior to irradiation at day 21 of lactation, a low tumor incidence in the iNOS inhibitor-treated groups was observed in the 1-year period. This report is the first to show that the NO derived from iNOS is an important radical for radiation-induced initiation of tumorigenesis of mammary glands in rats.
PMID: 12620378 [PubMed - indexed for MEDLINE]
An in vivo analysis of the herbal compound essiac.
Leonard BJ ,
Kennedy DA ,
Cheng FC ,
Chang KK ,
Seely D ,
Mills E .
Faculty of Medicine, University of Toronto , Toronto , ON , Canada .
BACKGROUND: Essiac is a herbal compound that has been in common use with cancer patients in North America for over 80 years. Despite its relatively widespread use, there are no peer-reviewed published reports of in vivo studies regarding the use of this compound. MATERIALS AND METHODS: Essiac was administered orally to test animals prior to all experiments. Standard assays to test protection from ethanol-induced gastric ulceration and carbon tetrachloride-induced hepatic injury were performed on Wistar rats. Assays of postglucose-load ICR and BALB/C mice, respectively. RESULTS: Essiac demonstrated a modest gastric protective effect via reduction of ethanol-induced gastric ulceration. However, Essiac did not demonstrate significant hepatoprotective, hypoglycemic or immunomodulatory properties. CONCLUSION: Essiac, administered in established in vivo experimental models, did not significantly demonstrate its purported physiological modifying effects.
PMID: 16886634 [PubMed - indexed for MEDLINE]
Essiac and Flor-Essence herbal tonics stimulate the in vitro growth of human breast cancer cells.
Kulp KS ,
Montgomery JL ,
Nelson DO ,
Cutter B ,
Latham ER ,
Shattuck DL ,
Klotz DM ,
Bennett LM .
Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore , CA 94550 , USA . Kulp2@llnl.gov
BACKGROUND: People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence and Essiac Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence and Essiac for their effects on the growth of human tumor cells in culture. METHODS: The effect of Flor-Essence and Essiac((R)) herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors. Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay. RESULTS: Flor-Essence and Essiac herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls in both estrogen receptor positive (MCF-7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-436) cell lines. Exposure to the tonics also produced a dose-dependent increase in ER dependent luciferase activity in MCF-7 cells. A 10(-7) M concentration of ICI 182,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence and Essiac, but did not affect cell proliferation. CONCLUSION: Flor-Essence and Essiac Herbal Tonics can stimulate the growth of human breast cancer cells through ER mediated as well as ER independent mechanisms of action.
PMID: 16541326 [PubMed - in process]