Nutritional Supplements Adverse Hypertension Tachycardia Articles & Resources

Interestingly, the cadet was never asked about his use of dietary supplements or weight loss products at the clinic. As healthcare professionals, we can easily miss important connections if we do not maintain current knowledge about the use prevalence and associated adverse effects of various diet products. Nurses often elicit careful histories of symptoms and prescriptions taken; but how often do we assess the concurrent use of herbal remedies, dietary supplements and other weight loss products? We must be especially careful when symptoms related to cardiovascular and neurovascular conditions present in young and otherwise fit clients.

Ephedrine Facts

Ephedrine is an adrenergic alkaloid obtained from several species of the shrub Ephedra sinica, or produced synthetically, and used primarily as a bronchodilator or decongestant, as well as a pressor agent (Fetrow & Avila, 1999). In addition, synthetic ephedrine is a main ingredient in the illegal drug methamphetamine or "speed." Marketed for weight loss among other uses, ephedra supplements supposedly burn body fats and sugar more efficiently, and by mobilizing stored fat and carbohydrate reserves, reduce the appetite (Jongeneel, 2002).

Only the botanical form of ephedrine can be legally sold over the counter as a weight-loss preparation. Most commonly it is combined with vitamins, minerals, amino acids and other botanicals. Xanthine alkaloids, such as caffeine, are often used in combination with ephedrine for their synergistic effects. For example, the diet product used by the young cadet also contained 22% guarana, or caffeine.

Although many retailers are advertising "ephedrine-free" dietary supplements following various news reports, products containing ephedrine and caffeine continue to be readily available over-the-counter in health food shops, convenience stores, and on the internet. The products are used not only for weight loss, but also for professed high-energy effects. Interviews with high school athletes reveal common use and high doses of such products right before sprinting races, in the belief that they will maximize performance. School nurses and nurses of campus student health clinics may be the first to come into contact with those youth who are experiencing related adverse effects. Even those who are not athletes may experience similar symptoms after consuming so-called energy drinks available in grocery stores and quick shops found to contain potent mixes of herbal extracts, ephedra, caffeine and sugar.

The range of the problem is greater than most would suspect since a reported 50 percent of the population has taken some form of dietary supplement, with 76 to 100 percent of athletes admitting to using dietary supplements (Ahrendt, 2001). There is some research evidence for the effectiveness of ephedrine, especially in combination with caffeine, in moderate weight loss, and in improved anaerobic performance. However, most of the studies performed have not addressed the safety of the associated products (US GAO, 1997). Lawrence and Kirby (2002) report that there have been few large, multi-center, randomized trials of nutritional supplements that have examined purported claims and potential side effects.

As depicted in Table 1, all forms of ephedrine have various degrees of system stimulant effects that must be considered significant for healthcare professional evaluation during history and review of systems. Moreover, between 1993-1997, the United States Food and Drug Administration (PDA) received more than 800 reports of illnesses, injuries and deaths associated with the use of dietary supplement products, many of them containing or suspected to contain ephedrine alkaloids. A sampling of selected adverse events is summarized in Table 2.

Federal Findings

The Dietary Supplement Health and Education Act (DSHEA) of 1994, forbids the FDA from controlling dietary supplements unless proven dangerous. Because of growing concerns and inadequate information available to the public on the safety of these products, the FDA in 1995 formed an ad hoc working group of its Food Advisory Committee. Medical and other scientific experts from outside the FDA, as well as industry and consumer representatives, carefully considered the evidence on ephedrine (US GAO, 1997). Following at least 17 deaths related to ephedrine-containing products, the FDA labeled ephedrine supplements as dangerous in 1997 (Neergaard, 1997).

The FDA has warned that anyone with heart disease, high blood pressure or neurologic disorders should not use ephedrine due to associated heart attacks, strokes, seizures or death (Neergaard, 1997). But what about young healthy adults? As depicted in Table 2, many cases of adverse events reported to the FDA involved previously healthy young people who, according to the FDA analysis, had been injured after taking the supplements (US GAO, 1997).

Approximately 56 percentof the designated injuries were reported by those under 40 years of age, while another 25 percent of injuries occurred in the 45-49 year age group. Such reports do not represent the ages where adverse cardiovascular and neurovascular events are typically expected to occur (US GAO, 1997). Some of the studies reviewed by the FDA even documented the effects of ephedrine to be increased in lean subjects as compared to findings in obese subjects, secondary to sympathetic stimulation.

FDA reports indicate that 59 percent of the adverse events transpired within four weeks of beginning use of the product, with 14 percent reporting adverse occurrences on the first day of use (US GAO, 1997). Haller, Jacob and Benowitz (2002), found significant cardiovascular effects after a single dose of a supplement containing 20 mg ephedrine alkaloids with 200 mg caffeine, the approximate dose in one serving of the diet product used by the young cadet.

A review of the Adverse Reaction Monitoring System of the FDA, a comprehensive database including clinical records and autopsy reports, found significant relationships between ma huang and serious medical complications. In 926 examined cases of possible ma huang toxicity from 1995-1997, reported adverse events included 16 strokes, 10 myocardial infarctions, and 11 sudden deaths in individuals with a mean age of 45 years (Samenuk et al., 2002).

A number of factors contribute to the potential for diet products to create harm. Pipe and Ayotte (2002), report the dietary supplement industry in the United States to be completely unregulated. Their analysis of the literature combined with interviews with various clinicians revealed that many dietary supplement products contain substances such as ephedrine, which are associated with significant morbidity and mortality, as well as prohibited for use by certain athletes. Although both the International Olympic Committee and the National Football League have banned ephedrine use, there are currently no broad-based restrictions for high school or college athletes, as well as other professional sports.

At least 20 states have now imposed some kind of restriction on the distribution of ephedrine diet supplements. However, ephedrine diet products continue to be readily available in most states, including Kansas. From 1995-1997, the PDA identified over 125 dietary supplement products containing ephedrine, including capsules, tablets, powders and liquids. The number of supplements containing ephedra is now estimated at more than 200 (Banks, 2002).

Healthcare Considerations

Young athletes or older individuals who seem to be highly focused on body image or athletic performance should be carefully questioned during office visits about the use of supplements. Individuals who participate in regular aerobic exercise tend to develop heart rates below or at the low end of normal ranges. Tachycardia or hypertension in a fit individual should always be suspect. A number of other supplemental products may be used by those interested in body building and peak performance, including anabolic steroids and protein compounds. However, in a review of five of the most popular performance-enhancing supplements, Lawrence and Kirby (2002) recommended that only ephedra be removed from the market, due to its serious associated side effects.

Once ephedrine use has been identified, it is important to make consumers aware that concurrent use of certain pharmaceuticals, such as oral contraceptive pills, diuretics and laxatives, has been shown to increase the half-lives of caffeine and ephedrine in supplements, thus increasing their potential for adverse effects (Haller et al., 2002; US GAO, 1997). Because ephedrine already has a mild diuretic effect, the concurrent use of diuretics and laxatives may also exacerbate fluid and electrolyte imbalances, further contributing to cardiovascular system and nervous system risks (US GAO).

Other effects associated with both the botanical and synthetic forms of ephedrine include urinary retention in men without prostatic hypertrophy, and hepatitis in individuals with no previous history of liver disease. Associated symptoms such as urinary tract infection and jaundice should lead the nurse to look more closely at the history of diet supplement use. Dermatologic reactions, including erythematous rashes and angioedema, may also be related to ephedrine use. Verduin and Labbate (2002) reported an exacerbation of psychosis with super-imposed delirium in one schizophrenic patient using an ephedrine product for weight loss.

Nurses need to become better informed about the various diet products on the market, including familiarity with names that may be used for potentially dangerous supplements. Using a reliable neutriceutical reference to evaluate the herbal substances commonly contained in products labeled for weight loss and body building can help to identify those that are most likely to result in harm (see Table 3). A trip to the local herbal and nutrition store could prove to be very educational. For example, ephedrine is also sold under the names of Chinese ephedra, natural ecstasy, and epitonin. Common trade names of weight loss aids containing ephedra include Herbal Phen-Fen, Metabolife 356, and Fat Ignite, to name just a few. Many other products include it as an ingredient.

It may not be clear from the labeling that ephedrine is present in a product. As reported by Ayotte et al. (2001), there have been cases where ephedrine was identified in the lab as an ingredient when it was not included on the label, yet another drawback to unregulated neutriceutical marketing. However, in June 2002, the FDA issued warning letters to six marketers of ephedra products containing ephedrine compounds that appeared to be synthetically derived. The PDA announced a new program in October 2002, to proactively analyze all herbal ephedra products to ensure that they contain natural ingredients as required by law (US FDA, 2002). Perhaps more importantly, studies have now demonstrated that botanical stimulants have been found to have disposition characteristics similar to their pharmaceutical counterparts (Haller et al., 2002), meaning that even increased regulation will not be a guarantee of safety. A review of the botanical ephedra by the Rand Corporation currently continues (US FDA, 2002).

One of the greatest concerns is that those selling the products are often unaware or do not share with consumers potential risk information (Doheny, 2000.) Nurses should strongly advise consumers to become better informed about a product before trying anything that is not regulated by the PDA.

The military has also recently addressed the ephedrine issue. In December 2002, the Air Force Surgeon General issued a notice to airmen regarding potential risks associated with dietary supplements containing ephedra, following the death of a young Air Force member in early November (Military Report, 2002). The announcement indicated that individuals who exercise vigorously are particularly at risk for adverse events.

In the case of our young Air Force Academy Cadet, weakness and dizziness continued weeks after he stopped taking the diet supplement. As a result, he failed another fitness test and his overall fitness scores placed him dangerously low in the Academy hierarchy. Fearing that he would not be able to garner a competitive flight school slot, he transferred away from the Academy. Although he feels fortunate that the lesson he learned did not result in a fatal event, the outcome resulting from his diet product use might have been avoided with better consumer education or early healthcare intervention.

References

Ahrendt, D. M. (2001). Ergonomic aids: Counseling the athlete. American Family Physician, 63(5), 913-922.

Ayotte, C., Levesque, J. F., Cle roux, M., Lajeunesse, A., Goudreault, D., & Fakirian, A. (2001). Sport nutritional supplements: Quality and doping controls. Canadian Journal of Applied Physiology, 26, 120-129.

Banks, D. (2002, May 15). Coaches expect bumpy transition to ephedrine ban. . Retrieved December 29, 2002 from /inside_game/don_banks/ news/2002/05/15/banks_insider_ephedrine/

Doheny, K. (2000, December 11). Got any snake oil?: Buyer, take care. Retrieved December 29, 2002 from .com/content/article/14/ Fetrow, ., & Avila, . (1999). Professional's handbook of complementary and alternative medicines. Springhouse, PA: Springhouse Publishers.

Haller, C. A., Jacob, P., & Benowitz, N. L. (2002). Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clinical Pharmacology Therapy, 71(6), 421-432.

Jongeneel, L. (2002, August). Weight loss. The Ephedra Site. Retrieved January 5, 2003 from ./diet/

Lawrence, M. E., & Kirby, D. F. (2002). Nutrition and sports supplements: Fact or fiction. Journal of Clinical Gastroenterology, 35(4), 299-306.

Military Report (2002, December). Medical official issues notice on ephedra risks. Retrieved December 29, 2002, from .com/MilitaryReport?file=MR_Medical_120302

Neergaard, L. (1997). Ephedrine crackdown. Retrieved December 29, 2002, from .org/news/

Pipe, A. & Ayotte, C. (2002). Nutritional supplements and doping. Clinical Journal of Sports Medicine, 12(4), 245-249.

Rezkalla, S. H., Mesa, J., Sharma, P., & Kloner, R. A. (2002). Myocardial infarction temporally related to ephedra: A possible role for the coronary microcirculation. Wisconsin Medical Journal, 101(7), 64-66.

Samenuk, D., Link, M. S., Homoud, M. K., Contreras, R., Theohardes, T. C., Wang, P. J. & Estes, N. A. (2002). Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clinic Proceedings, 77(1), 12-16.

. General Accounting Office. (1997, June 4). Dietary supplements containing ephedrine alkaloids (Docket No. 95N-0304). Retrieved December 29, 2002, from General Accounting Office Reports Online via GPO Access: ./~lrd/

United States Food and Drug Administration. (2002, October 8). Secretary Thompson urges strong warning labels for ephedra: FDA to propose good manufacturing practices regulations for dietary supplements. Retrieved December 29, 2002, from .gov/opacom/

Verduin, M. L., & Labbate, L. A. (2002). Psychosis and delirium following metabolife use. Psychopharmacology Bulletin, 36(3), 42-45.

Kimberly Riffel, MSN, RN

About the Author

Kimberly Riffel, MSN, RN is an Assistant Professor of Nursing at Fort Hays State University. Her clinical focus is Maternal-Child Nursing and she is an active member of the Association of Women's Health, Obstetric and Neonatal Nursing (AWHONN), for which she serves as the secretary-Treasurer of the Western Kansas Chapter. Kim also holds National Certification as a Breastfeeding Educator and is a member of the Nu Zeta Chapter of Sigma Theta Tau International.