By James L. Roerig PharmD, BCPP and James E. Mitchell MD, University of North Dakota, Fargo
Reprinted from Eating Disorders Review
July/August 2003 Volume 13, Number 4
©2002 Gürze Books
Individuals with eating disorders no longer have to obtain a prescription or use over-the-counter drugs to lose weight or suppress their appetite. Instead, the whole arena of “dietary supplements” is now open for them to explore.
They may come upon herbal preparations that appear to help in weight loss or appetite suppression, or that promise to raise mood or decrease anxiety. Unfortunately, they may also encounter agents that cause significant side effects and/or drug interactions. Use of such products can also delay appropriate treatment.
Often these agents are thought to be safe because they are “natural.” Extrapolation to over-the-counter and prescription medications may lead consumers to expect that these products must have demonstrated effectiveness because, after all, they are on the market.
In 1994, Congress passed the Dietary Supplement and Education Act (DSHEA),1 which relegated herbal agents to the category of “dietary supplements.” In effect, this removed these products from the purview of the Food and Drug Administration (FDA). Currently there are no standard requirements that herbal products be either safe or effective. In addition, no government agency inspects the manufacture or degree of purity or accuracy of contents of these products. Thus, there is no way to know how much of the ingredients listed are really present in any sample. As a result, herbal products are a completely unregulated source of potentially dangerous products readily available to anyone who wants to lose weight.
A recent review demonstrated how widespread use of these agents is in the general population.2 Between 1990 and 1997, use of herbal therapies increased by 380%, and in 1997 alone consumers spent $5.5 billion on herbal therapies.
Advertising for these agents is also ubiquitous. Magazines, newspapers, TV, and health food stores, grocery stores, and pharmacy outlets are prominent sources that extol the advantages of these preparations. In addition, direct consumer mailings, many targeting teenage girls, encourage patients with eating disorders to read fantastic claims for these agents and how to acquire them. The Internet has exploded with an abundance of claims for various herbal preparations. The question may not be “if” your patient is taking one of these agents, but “when” and “how many” of the preparations are being consumed. Remember that 60% of patients do not tell their physicians that they are using herbal products.2
Types of Agents
We recently published an overview of alternative medications used by eating disorder patients, including a review of locally available preparations.3 A partial list of active ingredients found in the various types of preparations is shown in Table 1.
Weight loss agents. This category includes a number of different types of products. The only type of treatment that has actually produced short-term weight loss is the combination of ephedrine and caffeine.4-7 This type of product may be marketed as a drug combination or as the herbal sources, which include ma huang (ephedrine) and a caffeine source such as guarana seed or Kola (cola) nut. However, extrapolating results from clinical trials that employ pharmaceutical-grade ephedrine and caffeine or research studies using standardized herbal preparations to the use of botanical sources available to a patient is not without difficulties. The botanical sources chosen by the patient may not have the same amounts of either ingredient in the preparation despite the labeling (there could be more or less). Attempts to identify empirical data concerning the effectiveness of other putative weight loss products or ingredients have proven unsuccessful. Unfortunately, the available studies are few and often methodologically flawed. 8, 9
Laxatives. Laxative preparations are often combinations of multiple ingredients, many of which have little to do with producing the laxative effect. Such products may contain either herbal or pharmacological sources of stimulant cathartics, such as bisacodyl, cascara sagrada, or senna. Other potent cathartics, such as magnesium hydroxide or citrate, may be included. Methylcellulose or other bulk laxatives may also be added. At first, these products are quite effective at producing diarrhea. However, over time stimulant cathartics tend to lose their efficacy and can result in a hypoactive bowel.
Diuretics. Diuretic agents are mostly represented by sources of caffeine (guarana seed, cola nut) or the mild diuretic pamabrom. Mild diuresis can be obtained with these products but they are not as effective as prescription agents such as furosemide (Lasix®) or hydrochlorothiazide (HydroDIURIL®).
The magnitude of the risk of side effects associated with herbal therapies is well illustrated by a recent case. An herb, Aristolochia fangchi, was inadvertently substituted for another, Stephania tetrandra, in a weight-loss preparation compounded in Belgium. Seventy individuals who took the herb developed complete renal failure, and 50 more had kidney damage. Cancerous or precancerous lesions were found in 37 of 39 who had a kidney removed.10 This unfortunate incident is a dramatic illustration that “natural” agents can have very undesirable effects.
Caffeine and ephedrine. Caffeine, found in many beverages, can cause mild agitation, insomnia, tremor, and diuresis. However, ephedrine, which is often combined with caffeine in products, generates a larger concern. Sudden death (myocardial infarction), hemorrhagic and ischemic stroke, acute hepatitis, nephrolithiasis, dizziness, tachycardia, headache, tremor, nervousness, and insomnia have all been reported with this combination. 4, 11-17 The most common adverse events identified in a recent report included: hypertension (17 reports), palpitations, tachycardia or both (13), stroke (10), and seizures (7). Ten events resulted in death and 13 events produced permanent disability. Fifty-nine percent of the users were taking the supplements in order to lose weight.11
Yohimbine. Occasionally appetite suppressants will contain yohimbine, an indirect adrenergic agonist. Anxiety, elevated blood pressure, queasiness, sleeplessness, tachycardia, tremor, and vomiting are potential side effects related to this agent.18
St. John’s Wort. St. John’s Wort has been included in many preparations. Photosensitivity, gastrointestinal irritation, allergic reactions, tiredness, and restlessness have been reported, along with drug interactions. Recently St John’s Wort has been reported to stimulate the CYP450 3A4 enzyme, which is involved in the metabolism of many important medications. Stimulation of this enzyme’s activity may lead to a reduction of the blood levels of certain concomitant medications, including cyclosporine, indinavir or possibly oral contraceptives. 19-21
Chromium picolinate. This product has been reported to be associated with cases of hypoglycemia, nephrotoxicity (at high doses), dissolution of muscle tissue, acute generalized pustules, as well as cognitive and personality disturbances. 22-29
Laxatives. As mentioned earlier, laxative products often contain a form of a stimulant cathartic (bisacodyl, cascara sagrada or senna). Problems associated with these agents3 include:
Bisacodyl—GI irritation, fluid and electrolyte loss, cramping, development of tolerance.30
Cascara sagrada—severe vomiting with fresh bark, electrolyte imbalance with misuse, hypokalemia potentiates the toxicity of cardiac glycosides and thiazide diuretics.31
Senna—hepatitis, abdominal cramping, nausea, electrolyte disturbance (e.g., hypokalemia, hypocalcemia, metabolic alkalosis or acidosis). Increased mucus secretion, reduced spontaneous bowel function, and melanotic pigmentation of the colonic mucosa (melanosis coli) may confirm laxative abuse. 32,33
Another ingredient in laxatives, bladder wrack kelp, is a source of iodine, which maypotentiate hyperthyroidism, worsen preexisting acne, or lead to new acneiform eruptions.34, 35
Other herbs. Skullcap has been associated with hepatic toxicity. 41, 42 The berries of wahoo bark are toxic. Reactions may include GI symptoms (colic, bloody diarrhea), elevation of body temperature, circulatory disorders, elevated cerebrospinal fluid pressure, stupor progressing to unconsciousness, or tonic clonic spasms.43 Wild yam root has produced a picrotoxin-like effect (tonic clonic spasms headache, dizziness, nausea) on overdose.44 The mild diuretic uva ursi has been reported to cause nausea and vomiting. 45 Other agents include gingko biloba, which has been associated with headache, GI upset, allergic skin reactions, and several cases of cerebral hemorrhage, possibly related to its interaction with platelet aggregation and thrombolytic therapy.42-46
Herbal therapies may include ingredients that are very potent and pharmacologically active. Along these lines it should not be surprising that adverse reactions and drug interactions may follow. Uncertainty about these issues stems from the lack of data regarding effects of various herbs, concerns as to what the active ingredients may be, the lack of the practice and enforcement of good manufacturing standards and a lack of a mechanism for adverse reaction reporting.
Recently Congress created the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH), which may help in addressing some of these issues. The mission of this organization is “to explore complementary and alternative healing practices in the context of rigorous science; to educate and training CAM researchers; and to disseminate authoritative information to the public and professionals.”46 The Center has set out to investigate certain herbs for efficacy, currently St. John’s Wort, gingko biloba, saw palmetto, and glucosamine/chondroitin, which has shown some evidence of efficacy. This process is long overdue but may not produce clinically applicable data soon.
Thus, clinicians treating patients with eating disorders should attempt to identify any alternative medicine treatments the patient is currently using or has used. Then, consulting the literature and/or individuals knowledgeable about herbs will help in determining if the individual has adverse reactions or drug interactions associated with these therapies.
Note: For a copy of the references to this article, please send a self-addressed stamped envelope to: Eating Disorders Review, 302 S. Pinto Place, Tucson, AZ 85748-6902.