*Centers for Alternative Medicine Research and Health Promotion Research and Development, The University of Texas-Houston School of Public Health **Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center

ABSTRACT:

Objectives: Flor-Essence™ and Essiac™ are widely used herbal tonics. After three decades, little is known about consumers. This pattern of use survey was conducted to 1) profile consumers, 2) characterize cancer patients, and 3) determine reasons for use, benefits, and adverse events.

Methods: A population based study assessed Flor-Essence™ consumers in North America between June 1998 and August 1999. Data are presented in frequencies and proportions.

Results: Of 5,051 consumers (response 6.4%), most were Caucasian, educated, American, long-term users (mean 15.8 months, SD=17.4), and cancer patients. Of 1,577 cancer patients (response 42.4%), 85.3% were treated previously and 36.8% currently with conventional medicine for breast, prostate, or lung cancer. Overall, 64.5% discussed using the tonic with physicians; few (11.4%) exceeded the recommended dose. Most patients reported clinical and quality of life improvement, but 6.6% experienced adverse events. Conclusions: The tonic is widely distributed. Many cancer patients combine conventional treatment with the tonic and attribute benefits to the tonic. The use of herbal formulas is a public health issue; thus, assessment of clinical benefit and potential interaction with cancer treatment is warranted.

BACKGROUND: Flor-Essence™ and Essiac™ are two of the most widely used herbal tonics by cancer patients. An estimated 35% of cancer patients in Canada1 use these tonics, whose long and controversial history spans three decades.2,3 In a recent survey at a large comprehensive cancer center in the United States, 38% of patients reported using herbs and overall, 4.9% used the Flor-Essence™ or Essiac™ tonic4. Both formulas contain four principal herbs: Burdock root (Arctium lappa L.), Turkish rhubarb root (Rheum palmatum L.), Sheep sorrel (Rumex acetosella L.), and Slippery elm bark (Ulmus rubra Muhl.). However, Flor-Essence™ contains four additional herbs that are believed to potentiate the formula: Watercress (Nasturtium officinale R. Br.), Blessed Thistle (Cnicus benedictus L.), Red Clover (Trifolium pratense L.) and Kelp (Laminaria digitata Lmx.). Flor-Essence™ tonic is manufactured in Canada where approximately forty thousand units of tonic and dried herbs are distributed to Canada and the United States each month. A review of the literature on these tonics and the four principal herbs resulted in 107 references. Of those, 68% (n=73) were related to cancer.5 Although 24 pre-clinical evaluations of individual herbs were reported, no pre-clinical or clinical trials of the tonic were identified.5 One clinical study with Essiac™ was discontinued by The Health Protection Branch of Health Canada in 1978 because of limited physician participation. Data from 87 participants was considered inadequate to determine any impact on survival.6 However, no toxicity was reported, but quality of life or pain control were not evaluated.3,7 Subsequently, claims for clinical benefit were discontinued the manufacturers who then began marketing the product as a nutritional supplement with general health claims (i.e., prevent disease, relieve pain, and improve quality of life). Claims as a cancer cure persist, however, with anecdotal reports of reduced tumor growth, improved quality of life, and prolonged survival.8 Although these tonics remain untested for anticancer activity, anti-oxidant activity has been confirmed for the Flor-Essence™ product.9 Moreover, qualitative thin layer chromatography (TLC) has confirmed seven herbs that contain trace elements, minerals, and phytoestrogens.10 Levels of flavonoids, phenylcarboxylic acids, and emodin are monitored regularly in each batch. Pre-clinical and clinical evaluations of Flor-Essence™, in collaboration with the Russian Ministry of Health have assessed acute and chronic toxicity. Acute toxicity studies were unable to determine a lethal dose in albino mice and rats. Furthermore, chronic toxicity tests found no renal or hepatic toxicity doses that were 10 fold the therapeutic dose (15 ml/kg) in albino mice and rats and 5-fold (7.5 ml/kg) in dogs.11 Sponsor initiated in-vivo studies report reduced number and size of chemical mediated gastric ulcerations, protection of capillaries against xylene-mediated leakage, and prevention of chemically induced anti-inflammation.10 Given the historical and widespread use of these tonic, limited preclinical data by manufacturers only, and the anecdotal reports of efficacy from cancer patients, a pattern of use survey of Flor-Essence™ consumers and cancer patients was conducted to 1) profile the general consumers, 2) characterize cancer patients, and 3) determine their reasons for use, perceived benefits, and adverse events. Ultimately, this information will inform the medical community and cancer patients, stimulate manufacturers to prepare the tonics for clinical investigation with an Investigational Drug Application (IND), and guide the development of clinical trials with information on which cancer patients are more likely to use the product.

METHODS:

Individuals who purchased Flor-Essence™ in the United States or Canada between June 1998 and August 1999 were invited to participate, regardless of age, gender, or disease status. The Committee for the Protection of Human Subjects at the University of Texas-Houston approved the study at two levels; participation was voluntary. The manufacturers shipped 20,000 units of product in Canada and 65,245 in the United States over a three month period, beginning in June, 1998. Each product contained an invitation from the owner of Flora Manufacturing and Distributing Ltd to participate so that the company could learn more about who is using the product and why. Each product contained a self-addressed, stamped postcard with the brief pattern of use survey. To ensure confidentiality, each postcard contained a unique identification number. For Phase I, the pattern of use survey of general consumers collected information on demographics (i.e., age, gender, ethnicity, country of residence, marital status, education level, and household income), medical condition (i.e., arthritis, cancer, multiple sclerosis, or other), reasons for use (i.e., prevention, control symptoms, treat a medical condition, or other), duration of use, and perceived benefits using a 5 point rating scale from excellent to poor. Current or former cancer patients were invited to call UT-CAM about the details of a second survey specifically about their experience with the tonic. For Phase II, interested individuals who telephoned UT-CAM and were current or former cancer patients were invited to participate. After obtaining verbal consent, research assistants collected contact information to mail the coded survey. Callers who declined to participate or who were ineligible were encouraged to complete and return the postcard. Flora Manufacturing and Distributing Ltd provided one complimentary product to individuals who completed the cancer specific survey. The cancer specific survey was adapted from an instrument that assessed complementary and alternative medicine (CAM) use in a comprehensive cancer center.12 Cancer patients who were using the tonic provided information on their cancer status (i.e., date of diagnosis, stage and site of disease, current status), conventional treatment (i.e., chemotherapy, radiation, surgery, hormonal), and use of other CAM therapies. We also asked about their reasons and expectations for using Flor-Essence™ as well as information on dose, frequency, adverse events, positive effects, changes in symptoms (i.e., nausea, vomiting, loss of appetite, fatigue, pain). For patients who discussed use with their physicians, we also asked how the physicians responded; otherwise, patients explained their reasons for nondisclosure about the herbal use. RESULTS:

Eligibility and consent rate

Of the 85,245 units distributed, 5,435 (response rate = 6.4%) postcards were received for Phase I. A total of 384 general consumers were excluded because they were treating pets (n=38) or responded after the study closed (n=346) in September, 1999. Of the 5,051 eligible general consumers, 3,749 (74.2%) were eligible for Phase II. Of these, 54.9% (n=2,060) cancer patients consented to participate, but 1,588 (42.4%) actually completed the survey; however, 11 individuals were excluded because they responded after the study closed.

Phase I: Profile of General Consumers

The majority of Flor- Essence™ consumers were educated above the high school level (63.6%), Caucasian (92.0%), married (68.8%), living in the United States (80.0%), 61.6 years of age (SD = 13.9), and approximately equally distributed by gender. Table 1. The average duration of use was 15.79 months (SD = 17.35, range 0-130 months), and primarily (62.4%) to treat a medical condition rather than prevent disease (35.3%) or control symptoms (21.3%). Cancer was the most commonly reported medical condition (75.1%), but health concerns included arthritis (14.5%), multiple sclerosis (1.0%), and other (14.7%) conditions (i.e., allergies/asthma, chronic fatigue, cysts, diabetes, high blood pressure/heart disease, hepatitis/liver disease, osteoporosis, or bladder, prostate, skin, or stomach problems). Most consumers rated the benefits of the tonic as very good/excellent (72.2%), but 24.4% rated the tonic as okay, and 3.4% as not very good/poor.