Any Science Behind the Hype of ‘Natural’ Dietary Supplements?

By Capriotti, Teri

The use of herbs and/or “natural” supplements is common among Americans. The science behind some of the popular supplements – green tea, garlic, fish oils, zinc, soy, and glucosamine- chondroitin – is reported. Dermatology nurses should be familiar with the intended benefits, possible side effects, drug interaction potential, and perioperative consequences of these supplements.

Objectives

This educational activity is designed for nurses and other health care providers who care for and educate patients regarding “natural” supplements. For those wishing to obtain CE credit, an evaluation follows. After studying the information presented in this article, the nurse will be able to:

1. Describe the reported effects of green tea, garlic, fish oils, zinc, soy, and glucosamine-chondroitin.

2. Discuss the investigational evidence of the effectiveness of these supplements.

3. List possible side effects associated with these supplements.

Does green tea prevent cancer? Can consuming fish oils prevent heart disease? Is zinc a remedy for the common cold? Do soy products diminish the uncomfortable symptoms of menopause? Can glucosamine and chondroitin halt the progression of arthritis? These questions are asked commonly by persons seeking a “natural” way to prevent disease. A recent investigation of 458 veteran outpatients revealed that 43% were taking at least one dietary supplement such as an herbal or “natural” preparation along with their prescription medicines (Peng, Glassman, Trilli, Hayes-Hunter, & Good, 2004). Another recent survey of over 2,000 surgical patients revealed that 57% have used herbal medicine (Adusumilli, Ben-Porat, Pereira, Roesler, & Leitman, 2004). Women, persons with high levels of education and income, and patients with chronic illness are the most common consumers of alternative medicine modalities (Straus, 2002). Yet, a great deal of ambiguity exists regarding the effectiveness of many types of alternative medicine. Consumers seek authoritative information and credible research regarding the efficacy and safety of herbal and “natural” remedies. An increasing number of studies provide information regarding the beneficial health effects, possible side effects, toxicity, and drug interactions of herbs and “natural” dietary products, yet many unanswered questions persist. What doses of “natural” supplements are beneficial to health? Can high doses of certain remedies be toxic? Are there dangerous drug interactions with these preparations? Health care providers need answers in order to make fully informed clinical decisions, and to prescribe and perform safe interventions. Significant scientific studies which support or refute the advertised effects of “natural” products are reviewed (see Table 1).

Table 1.

Summary of Review of Studies and Effects of “Natural” Products

Can Drinking Green Tea Prevent Cancer?

Tea has been regarded as an aid to good health for centuries, particularly in the Chinese and Indian cultures. In China, green tea is a mainstay of the diet. All varieties of tea are derived from the leaves of the evergreen plant Camellia sinensis. Tea leaves are picked, rolled, dried, and heated. An additional process of allowing the leaves to ferment and oxidize produces black tea. Green tea is produced when tea leaves undergo less processing than black tea. Tea contains antioxidants called catechins. Possibly because it is less processed, green tea contains higher levels of antioxidants or catechins than black tea. Steeping either green or black tea for about 5 minutes releases 80% of its antioxidant catechins. Instant ice tea, however, contains negligible amounts of these antioxidants (Dufresne & Farnworth, 2001).

The environment contains multiple sources of oxidizing agents called free radicals. Body cells also naturally produce free radicals. Free radicals or oxidants are unstable molecules which steal electrons from other molecules, damaging cell proteins and genetic material in the process. This type of damage leaves cells at risk for changes which can lead to cancer. Free radicals injure cell membranes and leave DNA vulnerable to damage. Tea antioxidants are very effective at scavenging free radicals before cell injury can occur. Tea antioxidants are also believed to target and repair DNA changes caused by the oxidizing free radicals. Laboratory studies show that tea antioxidants inhibit cancer growth in animals in three ways:

* Scavenge free radicals.

* Reduce the incidence and size of chemically induced tumors.

* Inhibit growth of tumor cells.

Animal research has shown that liver, stomach, and skin cancer growth diminished in mice that were fed green and black tea (Hakim & Harris, 2001). However, human research studies show ambiguity. A substantial number of human intervention studies with green and black tea demonstrate a significant increase in plasma antioxidant capacity 1 hour after consumption of moderate amounts of tea (1-6 cups/day) (Rietveld & Wiseman, 2003). In China, one study involving over 18,000 men found tea drinkers were about half as likely to develop stomach or esophageal cancer as men who drank little tea, even after adjusting for smoking and diet factors (Sun et al, 2002). However, an earlier study in the Netherlands did not have similar findings. A study of 58,000 men and 62,000 women ages 55 to 69 found no link between tea consumption and protection against cancer (Goldbohm, Hertog, Brants, van Poppel, & van den Brandt, 1996). Currently, green tea is under investigation for its beneficial effects in different types of cancer as well as in cardiovascular disease. There is no specific quantity of green tea which is known to confer health benefits. Studies have shown health benefits from drinking amounts of 1 to 6 cups of green tea daily, a very broad range. Investigators have focused on steeped hot tea rather than iced tea. In sum, green tea may have antioxidants which can benefit health, and no significant side effects have been reported.

Consumers should not confuse black or green tea with “dieter’s teas” advertised for weight loss. Those products contain senna, aloe, rhubarb root, buckthorn, cascara, or castor oil additives. Dieter’s teas can exert a potent diuretic and/or laxative effect on the body that can lead to serious adverse effects. Diarrhea, electrolyte disturbances, dehydration, cardiac arrhythmias, and hypotension can result from ingesting these teas. Dieter’s teas are considered potentially harmful by the Food and Drug Administration (FDA) (National Cancer Institute, 2002).

Can Garlic Lower Blood Pressure?

Numerous studies have supported as well as refuted the health claims of garlic consumption. Garlic contains antioxidants which have been reported to have anti-cancer and anti-cardiovascular disease effects. According to a 2000 report from the Agency for Healthcare Research and Quality (AHRQ), insufficient evidence exists to allow consumers to draw conclusions about anti-cancer or anti- cardiovascular disease effects of garlic. In a thorough review of the literature, the AHRQ found widespread variability in the dosages and forms of garlic studied (raw, cooked, garlic oil, or commercial supplements). Garlic preparations may have small, positive, short- term effects on lipids; however, a sustained effect is unclear. No consistent reductions in blood pressure were found. Some positive anti-thrombotic effects were recognized by the agency’s critique of the literature. Therefore, garlic should be used with caution in persons with risk for bleeding and those on anticoagulant medications (AHRQ, 2000). In addition, garlic can significantly reduce the levels of protease inhibitor drugs used in AIDS (James, 2001).

Some investigators have found that garlic can affect blood sugar, and caution persons with diabetes about its use (DeSmet, 2002). According to the American Cancer Society (2004), use of a garlic supplement is not associated with decreased risk of any specific types of cancers. Yet, many investigators continue to assert that garlic has beneficial effects on cancer and cardiovascular disease risk factors.

Numerous recent studies show garlic increases endothelial vasodilation reactivity, reduces hypertension, and diminishes arteriosclerotic plaque formation (Ashraf, Hussain, & Fahim, 2004; Ganado, Sanz, Padilla, & Tejerina, 2004; Siegel et al, 2004; Wilburn, King, Glisson, Rockhold, & Wofford, 2004). Another recent study demonstrated that allicin, garlic’s major biologically active component, induces apoptosis and inhibits growth of cancer cells of mouse and human origin in vitro (Oommen, Anto, Srinivas, & Karunagaran, 2004). Animal models were used in another study, which showed that the organosulfur compounds in garlic induced anti-tumor activity by active free radical scavenging (Thomson & AIi, 2003). In sum, the scientific community is divided about the health benefits of garlic, and investigations will likely continue.

Can Consumption of Fish oils Prevent Heart Disease?

In the 1970s, Danish investigators found that the Inuit Eskimos of Greenland had a very low mortality rate from coronary heart disease despite a diet rich in fat. Their diet consisted largely of fish, whale, seal, and walrus, resulting in a high intake of omega 3 fatty acids (Dyerberg, Bang, & Hjorne, 1975). In contrast, the typical Western diet is rich in omega 6 fatty acids which are derived from vegetable oils and cannot be converte\d to omega 3 fatty acids. Studies have shown an inverse relationship between fish consumption and risk of coronary heart disease (Daviglus et al., 1997; Kromhout, Bosschieter, & De Lezenne Coulander, 1985). A review of the literature by British investigators found several proposed cardioprotective mechanisms of omega 3 fatty acids. Consumption of omega 3 fatty acids can lower triglycerides and have anti- inflammatory, antithrombotic, and anti-arrhythmic effects, as well as dilatory effects on endothelial function (Din, Newby, & Flapan, 2004).

A recent study showed that patients with carotid atherosclerosis who consumed fish oil capsules had atherosclerotic plaque which contained less-inflammatory infiltrate. The carotid plaque was more stable and less vulnerable to rupture (Thies et al., 2003). Another study showed that in large doses (3 to 5 grams/day), omega 3 fatty acids reduced platelet aggregation and thereby reduced the risk of the formation of thromboses. Small doses were not associated with this anti-thrombotic effect (Mori, Beilin, Burke, Morris, & Ritchie, 1997). Additionally, patients with hypertriglyceridemia who ingested high doses of omega 3 fatty acids (4 grams per day) were able to decrease triglycerides by 25% to 30%. Smaller doses did not exert this effect (Burr et al., 1989). Blood pressure reduction was also found in a number of studies due to the beneficial effect of omega 3 fatty acids on endothelial vasomotor function, which results in arterial dilation (Din et al, 2004).

To consume omega 3 fatty acids naturally, many persons have increased the amount of fish in their diet. Consumption of fish is recommended as part of a healthy diet because it provides high- quality protein, low-saturated fat, and essential nutrients (FDA Center for Food Safety & Applied Nutrition, 2004). However, recent studies show that nearly all fish and shellfish contain traces of mercury from the environment (FDA Center for Food Safety & Applied Nutrition, 2004), and clearance of mercury from the body is a prolonged process. For most adults, the risk of mercury toxicity from eating fish is not a substantial health concern. Yet, some fish and shellfish contain higher levels of mercury that may be harmful to a fetus or young child’s developing nervous system (FDA Center for Food Safety & Applied Nutrition, 2004). The FDA and Environmental Protection Agency recommend that women who may become pregnant, pregnant women, nursing mothers, and young children avoid some types of fish which contain high levels of mercury (shark, swordfish, king mackerel, and tilefish) (FDA Center for Food Safety & Applied Nutrition, 2004). They also advise only eating up to 12 ounces (two average meals) a week of fish and shellfish that are known to be lower in mercury (shrimp, canned light tuna, salmon, pollock, and catfish). Albacore tuna has more mercury than light canned tuna and eating a limit of 6 ounces (one average meal) of albacore tuna per week is advised. “Fast food” fish and fish sticks are usually made from fish with low mercury levels.

Recent guidelines from the American Heart Association (AHA) support the use of fish oil supplements for patients with documented coronary artery disease (KrisEtherton, Harris, & Appel, 2002). According to the AHA (2000), patients with coronary artery disease can benefit from 1 gram of omega 3 fatty acids, preferably from a variety of oily fish twice weekly. Fish oil supplements can be considered in consultation with a physician. Patients with hypertriglyceridemia can benefit from 2 to 4 grams of fish oil capsules under the care of a physician.

Is Zinc a Remedy for the Common Cold?

Zinc lozenges and nasal spray have been publicized widely as remedies for the common cold. While zinc has not been shown to be a cure for the common cold, many clinical studies have shown that zinc can shorten the duration and symptoms significantly (Garland & Hagmeyer, 1998; McElroy & Miller, 2002; Mossad, Macknin, Medendorp, & Mason, 1996; Prasad, Fitzgerald, Bao, Beck, & Chandrasekar, 2000). The different forms of zinc preparations include zinc gluconate lozenges (Cold-Eze, Orazinc), zinc acetate lozenges (FastDry, Galzin), zinc carbonate, zinc sulfate, and zinc gluconate nasal spray and nasal gel (Zirncam) (University of California, Davis, 2001). The majority of studies which show any benefit have involved zinc gluconate lozenges. A particularly convincing study was performed by the Cleveland Clinic (Mossad et al., 1996). Fifty employees with symptoms of the common cold received zinc lozenges containing 13.3 mg of zinc gluconate every 2 hours while awake as long as they had cold symptoms. Another 50 employees with the common cold received a placebo. The time to complete resolution of symptoms was significantly shorter in the zinc group than in the placebo group (4.4 days vs. 7.6 days). The zinc group had fewer days of coughing, headache, hoarseness, nasal congestion, nasal drainage, and sore throat. The groups did not differ in days of fever, muscle aches, or sneezing. Some persons who took zinc had side effects of nausea and/or bad taste. Investigators found that zinc was most effective when taken in the first 24 hours of cold symptoms. However, Turner and Cetnarowski (2000) found zinc had no significant effect on the severity of symptoms in persons with the common cold. Their study compared placebo to two forms of zinc lozenges (zinc gluconate and zinc acetate). In this investigation, the median duration of symptoms was 2.5 days in those who received zinc gluconate, approximately 3.5 days in those who received zinc acetate, and 3.5 days in those who received placebo.

The literature contains a great deal of ambiguity regarding the effectiveness of nasal applications of zinc for the common cold. One study involving nasal zinc gluconate gel did show effectiveness in shortening the duration of cold symptoms (University of California, Davis, 2001). However, other studies have found no significant benefit of intranasal zinc gluconate (Turner, 2001) or zinc sulfate nasal spray (Belongia, Berg, & Liu, 2001) on duration of cold symptoms.

Dietary zinc is an important element for immune function that is found in a wide variety of foods. The daily recommended allowance of 12 to 15 mg of oral zinc is readily obtained from the average American diet. Most people do not need dietary zinc supplements and should use caution because excess zinc in the diet can weaken the immune system (NIH, 2004). Most zinc lozenges contain 4 to 25 mg per lozenge. According to Kendall (1998), adults should not exceed 100 mg of zinc per day. Because some labels instruct that lozenges be taken every 1 to 2 hours while awake, consumers should be aware of the limit of 100 mg per day (Kendall, 1998). The reason for zinc’s effect on the common cold has not been defined. It is proposed that increased zinc ions in and around the nasal cavity adhere to binding sites on the surface of the rhinovirus, thus inhibiting the virus from attaching to body cells (Godfrey, Godfrey, & Novick, 1996). Zinc gluconate lozenges and nasal spray appear to have some effect on diminishing duration of cold symptoms. However, consumers should be vigilant regarding the product dosage and recommended limit of 100 mg of zinc per day.

Do Soy Products Diminish the Uncomfortable Symptoms of Menopause?

During menopause, a decreased amount of estrogen is produced by a woman’s body. This decrease often leads to a variety of uncomfortable side effects such as hot flashes, night sweats, mood swings, insomnia, and vaginal dryness. Cardiovascular disease risk also increases for women after menopause due to loss of the protective effect of estrogen (Duke University, 2004). Among various nutritional supplements that are touted as natural ways to manage menopause, soy is probably the best known. Soy products contain phytoestrogens or isoflavones which are plant-derived estrogen-like substances (Duke University, 2004). According to many investigators, the strongest evidence for the efficacy of soy products exists for the symptom of hot flashes (Burke et al., 2003; Kurzer, 2003; North American Menopause Society, 2004). Huntley and Ernst (2004) performed a systematic review of randomized clinical trials that investigated soy products as treatment for menopausal symptoms. Of 10 clinical trials, 4 suggested soy products were beneficial for decreasing menopausal symptoms and 6 indicated no effect. These investigators found no serious safety concerns with short-term use of soy products. However, according to some experts, women with risk for breast cancer and/or ovarian cancer should use caution with ingestion of soy products due to possible stimulation of estrogen- dependent cancer growth (Duke University, 2004; Kurzer, 2003).

Soy protein can reduce plasma cholesterol and improve endothelial function in postmenopausal hypercholesterolemic women. Arterial dilation function improved following ingestion of soy for 4 weeks (Cuevas, Irribarra, Castillo, Yanez, & Germain, 2003). In a recent review of over 50 studies, soy products significantly reduced low density lipoprotein (LDL), cholesterol, total cholesterol, and triglycerides; and increased high-density lipoprotein (HDL) cholesterol (Hermansen, Dinesen, Hoie, Morgenstern, & Gmenwald, 2003).

Soy products vary widely in the amount of processing they undergo. Whole soy foods such as tofu, soy milk, and edamame (fresh soybeans) are preferable to more highly processed varieties. Experts recommend several servings of soy a week rather than multiple servings a day to obtain health benefits. Women who add 20 grams of soy protein to their diets report less menopausal symptoms. To reduce heart disease, 25 grams of soy protein daily is recommended. However, excessive soy ingestion can interfere with digestion and absorption of other essential nutrients (Duke University, 2004). Information about soy is welcome, particul\arly in light of recent findings of the Women’s Health Initiative study, which found some harmful effects of hormone replacement therapy (Roussow et al., 2002). Soy products may offer many of the benefits of estrogen replacement without the risks.

Can Glucosamine/ Chondroitin Halt the Progression of Arthritis?

Glucosamine and chondroitin are substances in the body that are involved in the synthesis of cartilage. These two substances often are found together in over-the-counter dietary supplements advertised for bone and joint health. The glucosamine and chondroitin in these marketed supplements are extracted from shell fish and animal cartilage (Arthritis Foundation, 2004).

Studies show that some people with mild-to-moderate osteoarthritis (OA) report pain relief after taking glucosamine/ chondroitin supplements for 4 weeks of continuous treatment (University of CaIifornia-Davis, 2001). Some research indicates that these supplements also may slow cartilage degeneration in OA. An important review of 15 human clinical trials showed that these supplements demonstrated efficacy in decreasing symptoms of OA. However, the quality of some research studies is questionable. In a study of 212 patients with OA of the knee, greater pain relief and reduced joint narrowing were found in those who took glucosamine versus placebo over a period of 3 years (McAlindon, LaValley, Gulin, & Felson, 2000). However, the reliability of joint measurement was disputed by scientists who reviewed this study (Reginster et al., 2001). Another study treated patients with OA of the knee for 6 months with 2,000 mg of glucosamine and 1,600 mg of chondroitin sulfate daily (Das & Hammad, 2000). According to one assessment index which measures outcomes in OA, patients in this study experienced significant improvement in pain. Conversely, when another pain assessment tool was used, no benefit was evident. A most recent European study (Bruyere et al, 2004) demonstrated definite beneficial effects of glucosamine in a large sample of postmenopausal women with OA of the knee. Compared to placebo- treated subjects, those using glucosamine over a period of 3 years showed significantly less joint space narrowing. To clarify the effect of these supplements, a division of the NIH currently is performing a study which will compare the effects of glucosamine alone, chondroitin alone, glucosamine and chondroitin together, celecoxib (Celebrex) and placebo (National Center for Complementary and Alternative Medicine [NCAAM], 2004). Pain control, joint space narrowing, and safety of the substances will be compared over a 2- year period in over 15,000 subjects with OA of the knee at 13 medical centers across the country. The results are anticipated to be published in 2005.

A study performed on rats demonstrated that glucosamine impaired insulin secretion (Shankar, Zhu, & Baron, 1998). This caused some experts to advise caution with use of these supplements in patients with diabetes because of a perceived risk of hyperglycemia. However, Scroggie, Albright, and Harris (2003) found that oral glucosamine supplements do not result in clinically significant alterations in hemoglobin AIc levels in persons with type 2 diabetes. Subjects in this study were older adults with type 2 diabetes who were given supplements of 1,500 mg of glucosamine hydrochloride in combination with 1,200 mg of chondroitin sulfate (Cosamin DS) for 90 days. Some investigators continue to find that glucosamine/chondroitin supplements have a diabetogenic effect and warn that persons with diabetes who use these supplements must vigilantly monitor their blood sugar (Chan, Osaki, Chow, Chan, & Cockram, 2002; DeSmet, 2002).

Persons allergic to shellfish should avoid using glucosamine- containing supplements because the glucosamine is derived from the shells of crustaceans (DeSmet, 2002). Glucosamine may interact with anticoagulant drugs to increase risk of bleeding. Some consumers of these products have reported minor gastrointestinal side effects (Arthritis Foundation, 2004).

Conclusion

Use of herbs and/or “natural” supplements is common among Americans. Green tea, garlic, fish oils, zinc, soy, and glucosamine- chondroitin are some of the popular “natural” supplements. Health care providers need to learn the intended benefits, possible side effects, drug interaction potential, and perioperative consequences of these supplements. Most consumers are under the assumption that “natural” supplements are inherently safe and may not report use of these to the health care provider (International Food Information Council Foundation, 1998). The health care provider needs to ask the patient about specific use of any herbal or natural supplements. Many reports in the literature describe harmful drug interactions and perioperative complications associated with these supplements (Ang-Lee, Moss, & Yuan, 2001; DeSmet, 2002; Izzo & Ernst, 2001; Peng et al, 2004). Health care providers should advise patients to discontinue these supplements 2 weeks prior to a surgical procedure. Additionally, most experts advise that pregnant and nursing mothers should avoid using these supplements.

Table 2.

Information Sources for “Natural” Products

Many clinical studies show positive effects of “natural” supplements. However, controversy surrounds some of the widely publicized health benefits of “natural” supplements. Sound scientific evidence is deficient for many over-the-counter “natural’ and herbal remedies, which are regarded as dietary supplements and are not regulated by the FDA. Often, the ingredients and dosages of supplements differ from one brand to another. Some reported evidence is based on unreliable, non-randomized, poorly controlled investigations. Some studies may be tainted by publication bias. Additionally, some dietary supplements can be toxic if ingested in excess. The NCCAM is taking an active role in investigating some of the reported health benefits of these supplements. Experts concur that more sound, scientifically designed studies are needed to confirm the health claims made by most of the widely marketed “natural” supplements.

At this time, health care providers and consumers must rely on widely distributed information from reputable sources in the scientific community, such as government sources, reputable foundations for disease research, medical journals, medical centers, and universities. Suggested sources for health care providers who seek further information are presented in Table 2.

Publisher’s Note: Publication of this article was supported by a grant provided by Nurse Competence in Aging, a 5-year initiative funded by The Atlantic Philanthropies (USA) Inc., awarded to the American Nurses Association (ANA) through the American Nurses Foundation (ANF), and representing a strategic alliance between ANA, the American Nurses Credentialing Center (ANCC), and the John A. Hartford Foundation Institute for Geriatric Nursing, New York University, The Steinhardt School of Education, Division of Nursing.

For more information, contact the John A. Hartford Foundation Institute for Geriatric Nursing, New York University, The Steinhardt School of Education, Division of Nursing, 246 Greene Street, 5th Floor, New York, NY10003, or call (212) 998-9018, or email hartford.ign@nyu.edu or access the Web site at www.hartfordign.org

Health care providers need to learn the intended benefits, possible side effects, drug interaction potential, and perioperative consequences of these suplements.

References

Adusumilli, RS., Ben-Porat, L, Pereira, M., Roesler, D., & Leitman, LM. (2004). The prevalence and predictors of herbal medicine use in surgical patients. Journal of the American College of Surgery, 198(4), 583-590.

Agency for Healthcare Research and Quality (AHRQ). (2000). Garlic: Effects on cardiovascular risks and disease, protective effects against cancer and clinical adverse effects. Summary, Evidence Report/Technology Assessment: Number 20. AHRQ Publication No.01-E022, October 2000. Agency for Healthcare Research and Quality, Rockville, Md. Retrieved June 8, 2004, from http:// ww.ahrq. gov/clinic/epcsums/garlicsum.htm

American Cancer Society (ACS). (2004). Garlic. Retrieved June 12, 2004, from http://www.cancer.org/docroot/ETO

American Heart Association (AHA). (2000). Retrieved June 3, 2004, from http://www.americanheart.org

Ang-Lee, M.K., Moss, J., & Yuan, C.S. (2001). Herbal medicines and perioperative care. Journal of American Medical Association, 286(2), 208-216.

Arthritis Foundation. (2004). Alternative therapies. Glucosamine and chondroitin sulfate. Retrieved June 10, 2004, from www.arthritis.org

Ashraf, M.Z., Hussain, M.E., & Fahim, M. (2004). Endothelium mediated vasorelaxant response of garlic on isolated rat aorta: Role of nitric oxide. Journal of Ethnopharrnacology, 90(1), 5-9.

Belongia, E.A., Berg, R., & Eiu, K. (2001). A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. American Journal of Medicine, 777(2), 103 -108.

Bruyere, O., Favelka, K., Rovati, L.C., Deroisy, R., Olejarova, M., Gatterova, J., et al. (2004). Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: Evidence from two 3 year studies. Menopause, 77(2), 138-143.

Burke, G.L., Legault, C., Anthony, M., Bland, D.R., Morgan, T.M., Naughton, MJ., et al. (2003). Soy protein and isoflavone effects on vasomotor symptoms in peri-and postmenopausal women: The soy estrogen alternative study. Menopause, 70(2), 147-153.

Burr, M.L., Fehily, A.M., Gilbert, J.F., Rogers, S., Holliday, R.M., Sweetnam, P.M., et al. (1989). Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and reinfarction trial (DART). Lancet, 2(8666), 757-761.

Chan, N.N., Osaki, R, Chow, C.C., Chan, J.C.N, & Cockram, C.S. (2002). Drugrelated hyperglycemia [Letter to the editor]. Journal of the American Medical Associat\ion, 287(G), 714.

Cuevas, A.M., Irribarra, V.L., Castillo, O.A., Yanez, M.D., & Germain, A.M. (2003). Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. European Journal of Clinical Nutrition, 57(8), 889-894.

Das, A., & Hammad, T.A. (2000). Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage, 8, 343-350.

Daviglus, M.L., Stamler, J., Orencia, A. J., Dyer, A. R, Liu, K., Greenlund, P., et al. (1997). Fish consumption and the 30 year risk of fatal myocardial infarction. New England Journal of Medicine, 336, 1046-1053.

DeSmet, P.A.G.M. (2002). Herbal remedies. New England Journal of Medicine, 347(2S), 2046- 2056.

Din, J.N., Newby, D.E., & Flapan, A.D. (2004). Omega 3 fatty acids and cardiovascular disease-fishing for a natural treatment. British Medical Journal, 328(7430), 30-35.

Dufresne, C. J., & Famworth, E.R. (2001). A review of latest research findings on the health promotion properties of tea. Journal of Nutritional Biochemistry, 72(7), 404-421.

Dyerberg, J., Bang, H.O., & Hjorne, N. (1975). Fatty acid composition of the plasma lipids in Greenland Eskimos. Americanjoumal of Clinical Nutrition, 28, 958-966.

Duke University. (2004). Easing menopausal symptoms with soy. (2004). Retrieved June 8, 2004, from www.dukehealth. org

FDA Center for Food Safety & Applied Nutrition. (2004). Overview of dietary supplements. Retrieved June 3, 2004, from http:// www.cfsan.fda.gov

Ganado, P., Sanz, M., Padilla, E., & Tejerina, T. (2004). An in vitro study of different extracts and fractions of allium sativum (garlic): Vascular reactivity. Journal of Pharmacological Science, 54(4), 434-442.

Garland, M.L., & Hagmeyer, K.O. (1998). The role of zinc lozenges in treatment of the common cold. Annals of Pharmacotherapy, 32(1), 63-69.

Godfrey,J.N., Godfrey, NJ., & Novick, S.G. (1996). Zinc for treating the common cold: Review of all clinical trials since 1984. Alternative Therapy Health Medicine, 2(6), 63-72.

Goldbohm, R.A., Hertog, M.G., Brants, H.A. van Poppel, G., & van den Brandt, RA. (1996). Consumption of black lea and cancer risk: A prospective cohort study. Journal of the National Cancer Institute, 05(2), 93-100.

Hakim, I.A., & Harris, RB. (2001). Joint effects of citrus peel and black tea intake on risk of squamous cell carcinoma of skin. British Medical Dermatology, 7(3).

Hermansen, K., Dinesen, B., Hoie, L.H., Morgenstern, E., & Gmenwald, J. (2003). Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: A literature review. Advanced Therapeutics, 2C(I], 50-78.

Huntley, A.L., & Ernst, E. (2004). Soy for the treatment of perimenopausal symptoms: A systematic review. Maturitas, 47(1), 1- 9.

International Food Information Council Foundation. (1998). Herbals – current scientific perspective. Food Insight Newsktter. Retrieved June 3, 2004, from http://www.iflc.org

Izzo, A.A., & Ernst, E. (2001). Interactions between herbal medicines and prescribed drugs: A systematic review. Drugs, 61(15), 2163-2175.

James,J.S. (2001). Garlic reduces saquinavir blood levels 50%; may affect other drugs. AIDS Treatment News, 375, 2-3.

Kendall, P. (1998). Zinc & echinacea: Natural cold busters? Retrieved June 8, 2004, from www.penpages.psu.edu

Kris-Etherton, P.M., Harris, W.S., & Appel, LJ., for the Nutrition Committee. (2002). AHA scientific statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation, 106, 2747-2757.

Kromhout, D., Bosschieter, E.B., & De Lezenne Coulander, C. (1985). The inverse relation between fish consumption and 20 year mortality from coronary heart disease. New Englandjournal of Medicine, 312, 1205-209.

Kurzer, M.S. (2003). Phytoestrogen supplement use by women. Journal of Nutrition, 133 (6), 1983 S-986 S.

McAlindon, T.E., LaValley, M.P, GulinJ.R, & Felson, D.T. (2000). Glucosamine and chondroitin for treatment of osteoarthritis: A systematic quality assessment and meta-analysis. The Journal of the American Medical Association, 283, 1469-1475.

McElroy, B.H., & Miller, S.P. (2002). Effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) against the common cold in school aged subjects: A retrospective chart review. American Journal of Therapeutics, 5(6), 472-475.

Mori, T.A., Beilin, LJ., Burke, V., Morris,J., & Ritchie, J. (1997). Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arteriosclerosis, Thrombosis & Vascular Biology, 17, 279- 286.

Mossad, S.B., Macknin, M.L., Medendorp, S.V., & Mason, P. (1996). Zinc gluconate lozenges for treating the common cold. A randomized, double blind, placebo controlled study. Annals of Internal Medicine, 725(2), 81-88.

National Institutes of Health Clinical Center (NIH). (2004). Facts about dietary supplements. Zinc. Retrieved June 8, 2004, from www.cc.nih.gov/ ccc/supplements/zinc.html

National Cancer Institute (NCI). (2002). NCI fact sheet: Tea and cancer prevention. Retrieved June 3, 2004, from http:// www.cancer.gov/newscenter

National Center for Complementary and Alternative Medicine (NCCAM) (2004). Glucosamine / chondroitin arthritis intervention trial (GAIT) begins patient recruitment. Retrieved June 10, 2004, from hllp://nccam.nih.gov/news

North American Menopause Society. (2004). Treatment of menopause- associated vasomotor symptoms: Position statement of The North American Menopause Society. Menopause, 7/(l), 11-33.

Oommen, S., Anto, RJ., Srinivas, G., & Karunagaran, D. (2004). Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. European Journal of Pharmacology, 485(1-3), 97-103.

Peng, C.C., Classman, P.A., Trilli, L.E., Hayes-HunterJ., & Good, C.B. (2004). Incidence and severity of potential drug-dietary supplement interactions in primary care patients: An exploratory study of 2 outpatient practices. Archives of Internal Medicine, 164{6), 630-636.

Prasad, A.S., Fitzgerald, J.T., Bao, B., Beck, F.W., & Chandrasekar, P.H. (2000). Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double blind, placebocontrolled trial. Annals of Internal Medicine, 133(4), 245-252.

Rietveld, A., & Wiseman, S. (2003). Antioxidant effects of tea: Evidence from human clinical trials. Journal of Nutrition, 133(10), 3285 S-3292 S.

Reginster, J.Y., Deroisy, R., Rovatti, L.C., Lee, R.L., Lejeune, E., Bruyere, O., et al. (2001). Long-term, effects of glucosamine sulphate on osteoarthritis progression: A randomized, placebo- controlled clinical trial. Lancet, 557(9252), 251-256.

Roussow, J.E., Anderson, G.L., Prentice, R.L., LaCroix, A.Z., Kooperberg, C., Stefanik, M.L, et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women’s health initiative randomized controlled trial. Journal of the American Medical Association, 288(3], 321- 333.

Scroggie, D.A., Albright, A., & Harris, M.D. (2003). The effect of glucosamine-chondroitin supplementation on glycoslylated hemoglobin levels in patients with type 2 diabetes mellitus: A placebo-controlled, double blinded, randomized clinical trial. Archives of Internal Medicine, 763(13), 1587-1590.

Shankar, RR, ZhuJ.S, & Baron, AD. (1998). Glucosamine infusion in rats mimics the beta cell dysfunction of non-insulin dependent diabetes mellitus. Metabolism, 47(5), 573-577.

Siegel, G., Malmsten, M., Pietzsch, J., SchmidtA, Buddecke, E., Michel, F., et al. (2004). The effect of garlic on arteriosclerotic nanoplaque formation and size. Phytomedicine, 77(1), 24-35.

Straus, S.E. (2002). Herbal medicines – what’s in the bottle? New England Journal of Medicine, 347(25), 1997-1998.

Sun, CL, Yuan,J.M., Lee. MJ., Yang, C.S, Gao, Y.T., Ross, R.K., et al. (2002). Urinary tea polyphenols in relation to gastric and esophageal cancers: A prospective study of men in Shanghai, China. Cardnogenesis, 23(9), 1497-1503.

Thies, E, GanyJ.M., Yaqoob, P., Rerkasem, K., Williams, J., Shearman, O.P., et al. (2003). Association of omegaS polyunsaturated fatty acids with stability of atherosclerotic plaques: A randomized controlled trial. Lancet, 367( 9356), 477-485.

Thomson, M., & AIi, M. (2003). Garlic (allium sativum): A review of its potential use as an anti-cancer agent Cunent Cancer Drug Targets, J(I), 67-81.

Turner, R.B. (2001). Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clinical Infectious Disease, 33(11), 1865-1870.

Turner, RB, & Cetnarowski, WE. (2000). Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clinical Infectious Disease, 31, 1202-208.

University of Califomia-Davis. (2001). Glucosamine and chondroitin supplementation and osteoarthritis. Nutrition perspectives. Retrieved June 10, 2004, from http:// nutiition.ucdavis.edu

University of California-Davis Medical Center. (2001). What are specific agents for treating colds? Zinc. Retrieved June 8, 2004, from www.ucdmc.ucdavisO .edu/ucdhs/health/a-z/94cold

Wilburn, AJ, King, D.S., GlissonJ, Rockhold, RW, & Wofford, M.R (2004). The natural treatment of hypertension. Journal of Clinical Hypertension. 6(5), 242-248.

Teri Capriotti, DO, MSN, CRNP, is a Clinical Assistant Professor, Villanova University, College of Nursing, Villanova, PA.

Note: This article originally appeared in MEDSURG Nursing, 13(5), 339-345, 350 and is reported here with permission of the publisher.

Copyright Anthony J. Jannetti, Inc. Oct 2005