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Issues and Controversies in Botanical Medicine
PATIENT CARE
Issues and Controversies in Botanical Medicine A growing number of scientific studies are being conducted on natural products, allowing more objective examination of their safety and efficacy.
Although the use of herbal remedies is becoming more mainstream in the United States, important questions and controversies remain about the safety and efficacy of many of these products. In this session, June McDermott, MS Pharm, MBA, and Mary Hardy, MD, reviewed the scientific evidence about the use of several popular natural products and explored current issues regarding their safety and efficacy.
Does Echinacea Prevent the Common Cold? Echinacea, which is believed to stimulate the immune system, is one of the most commonly used herbal products. McDermott began the session with a review of studies that investigated the efficacy of echinacea for preventing and treating the common cold. Several double-blind, placebo-controlled studies indicate that echinacea may be beneficial for reducing the symptoms and duration of the common cold. However, evidence supporting the u e of echinacea for preventing colds is weaker. A meta-analysis of 16 trials (8 studying prevention and 8 tudying treatment) surveying a total of 3,396 patients found that, overall, echinacea appears to be more effective than placebo for treating the common cold. 1 However, the authors concluded that additional scientific evidence is required to support this finding. While further research is needed, this herb may have some efficacy in alleviating cold symptoms and duration, especially if treatment is started with appropriate doses as soon as signs of infection appear and continued for about 2 weeks. Echinacea appears to be safe when orally administered.
Based on presentations by June McDermott, MS Pharm, MBA, FASHP, clinical assistant professor, School of Pharmacy, University of North Carolina, Chapel Hill; and Mary Hardy, MD, medical director, Cedars-Sinai Integrative Medicine Medical Group, Cedars-Sinai Hospital, and associate clinical professor of medicine, University of Southern California, Los Angeles.
S44
Supplement to the Journal of the American Phannaceutical Association
Can Ginkgo Cause Bleeding Episodes? Studies have shown ginkgo may be useful for ordinary agerelated memory loss and may improve memory and mental function in younger people. Some research also supports a role for ginkgo in the treatment of Alzheimer's disease and other forms of dementia. However, pharmacists· need to caution ginkgo users that this herb can increase the risk of bleeding, particularly if used with other anticoagulation agents. Ginkgo has anticoagulant actions because it inhibits plateletactivating factor and stabilizes capillary permeability. McDermott discussed several case reports on bleeding episodes associated with ginkgo use, including subdural hematoma (i.e., bleeding in the skull) and hyphema (i.e., spontaneous bleeding into the iris chamber). Because of ginkgo's "blood-thinning" effects, this product should not be used in combination with anticoagulants such as warfarin, heparin, or aspirin. Caution also is warranted in patients with risk factors for bleeding episodes, such as those with hypertension or diabetes.
Does Garlic Lower Cholesterol? Dr. Hardy explored evidence regarding the cardiovascular benefits of garlic. One of the oldest described plants in the world, garlic has long been used in traditional medicine to enhance the immune system and improve circulation. Garlic contains a number of volatile sulfur-containing oils, including alliin, which is converted into allicin when garlic is crushed or broken. Allicin is one of the most important biologically active compounds in garlic. Commercial garlic preparations vary in their allicin content and are often standardized to their alliin content. Much recent investigation has focused on the ability of garlic to lower levels of cholesterol and triglycerides. A recent meta-analysis of 13 trials found that garlic reduced total cholesterol concentrations significantly more than placebo, for a weighted mean difference of 15.7 mgldL (P<.OI).2 Dr. Hardy concluded that garlic does reduce total blood cholesterol levels, but this effect appears to be modest.
September/October2001 Vol. 41, No.5, Suppl. 1
Issues and Controversies in Botanical Medicine
Do Soy Products Affect Breast Cancer Risk? McDermott reviewed tudie examining the effects of soy products on breast cancer ri k. She explained that phytoestrogens are estrogen-like sub tance found in orne plants and are classified as either isoflavones or lignans. Soy is an abundant source of isoflavones, particularly genistein. Genistein binds to and stimulates human estrogen receptors, but not as strongly as estrogen. When estrogen concentration are high, as in premenopausal women, genistein may partially block the hormone's effects. When estrogen concentrations are low, as in postmenopausal women, genistein can enhance estrogen's effects. Asians, whose diets are high in soy, have much lower rates of cancer of the breast, endometrium, colon, and prostate than Americans. Several studies have been conducted to investigate the possible protective benefits of soy against breast cancer. For example, a meta-analysis of nine epidemiologic studies found a modest reduction in breast cancer risk associated with high soy intake during the premenopausal years, but not after menopause. Studies have not found soy to be harmful in the postmenopausal years. In fact, soy contains other anticancer compounds that may continue to provide benefits after menopause. McDermott concluded that soy appears to be effective and safe, but recommended dosages of no more than 100 mg of isoflavones daily (Table 1). She also advised consuming phytoestrogens in whole soy foods rather than from dietary supplements.
Is Black Cohosh Safe and Effective for Menopause Symptoms? Black cohosh, Cimicifuga racemosa, is an indigenous North American plant with a long history of traditional use. Although the mechanism of action of black cohosh has not been fully elucidated, triterpene glycosides or saponins are thought to be the main active constituents. Most clinical trials have been conducted using a proprietary formula, Remifemin, standardized to contain 1 mg triterpene glycosides. A series of open clinical studies have shown good efficacy of black cohosh in relieving menopausal symptoms, such as hot flashes, with little or no toxicity. Because black cohosh is a phytoestrogen, concern has been raised about its possible effects on breast and endometrial cancer. However, in vitro and clinical studies have demonstrated a good safety profile for this herb. For example, black cohosh was found not to stimulate growth of an estrogen-dependent breast cancer cell line. In fact, the product was found to increase the inhibitory
PATIENT CARE
effects of tamoxifen, an anti-estrogen. Based on clinical experience and the few controlled studies available, black cohosh appears to be an effective treatment for menopausal complaints, especially for women who cannot or do not wish to use estrogen replacement therapy.
Is Chocolate a Health Food? Chocolate contains many biologically active constituents, including flavonoids, alkaloids, methylxanthines (e.g., caffeine, theobromine), and phenols. Flavonoids in chocolate, which have very potent antioxidant activity, have been found to decrease the lipid oxidation of low-density lipoprotein cholesterol while raising high-density lipoprotein cholesterol concentrations. Catechin, a phenol found in chocolate, is a potent antioxidant that is believed to be responsible for many of the beneficial effects of green and black tea. Dark chocolate has a particularly high concentration of catechin, and is a better source than milk chocolate or black tea. Chocolate also contains constituents that bind to the cannaboid receptor. However, they are not present in sufficient concentrations to be psychoactive. While few studies have investigated the clinical benefits of chocolate, an analysis of 7,841 subjects enrolled in the Harvard alumni health study (an ongoing study of men who entered Harvard University between 1916 and 1950) yielded interesting results. In this study, candy consumers lived an average of almost 1 year longer than nonconsumers, an effect observed up to 95 years of age. 3 The authors postulated that the antioxidant phenols in chocolate could have contributed to this effect on longevity. To the delight of the audience, the speakers concluded that although data remain sparse, moderate chocolate intake appears to confer some health benefits.
Summary • Echinacea may reduce the duration of the common cold, but most studies do not show a significant preventive effect. • Pharmacists should caution patients that gingko can increase the risk of bleeding events, especially when used in combination with other anticoagulants. • Garlic has a modest cholesterol-lowering effect. • Soy and black cohosh are well tolerated and do not appear to increase breast cancer risk. • Moderate intake of chocolate may have some healthful benefits.
References 1. Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing
Table 1. Isoflavone Content of Selected Foods Food
Isoflavone Content (mg)
Tofu (4 oz)
35-40
Soy milk (8 oz)
35-40
Cooked soybeans (1/2 cup)
35
Vol. 41, No.5, Suppl. 1
September/October 2001
and treating the common cold. Cochrane Database Syst Rev. 2000;(2):CD000530. 2. Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med.2000;133:420-9. 3. Lee 1M, Paffenbarger RS Jr. Life is sweet: candy consumption and longevity. BMJ. 1998;317:1683-4.
Supplement to the Journal of the American Pharmaceutical Association
S45
Issues and Controversies in Botanical Medicine A growing number of scientific studies are being conducted on natural products, allowing more objective examination of their safety and efficacy.
Although the use of herbal remedies is becoming more mainstream in the United States, important questions and controversies remain about the safety and efficacy of many of these products. In this session, June McDermott, MS Pharm, MBA, and Mary Hardy, MD, reviewed the scientific evidence about the use of several popular natural products and explored current issues regarding their safety and efficacy.
Does Echinacea Prevent the Common Cold? Echinacea, which is believed to stimulate the immune system, is one of the most commonly used herbal products. McDermott began the session with a review of studies that investigated the efficacy of echinacea for preventing and treating the common cold. Several double-blind, placebo-controlled studies indicate that echinacea may be beneficial for reducing the symptoms and duration of the common cold. However, evidence supporting the u e of echinacea for preventing colds is weaker. A meta-analysis of 16 trials (8 studying prevention and 8 tudying treatment) surveying a total of 3,396 patients found that, overall, echinacea appears to be more effective than placebo for treating the common cold. 1 However, the authors concluded that additional scientific evidence is required to support this finding. While further research is needed, this herb may have some efficacy in alleviating cold symptoms and duration, especially if treatment is started with appropriate doses as soon as signs of infection appear and continued for about 2 weeks. Echinacea appears to be safe when orally administered.
Based on presentations by June McDermott, MS Pharm, MBA, FASHP, clinical assistant professor, School of Pharmacy, University of North Carolina, Chapel Hill; and Mary Hardy, MD, medical director, Cedars-Sinai Integrative Medicine Medical Group, Cedars-Sinai Hospital, and associate clinical professor of medicine, University of Southern California, Los Angeles.
S44
Supplement to the Journal of the American Phannaceutical Association
Can Ginkgo Cause Bleeding Episodes? Studies have shown ginkgo may be useful for ordinary agerelated memory loss and may improve memory and mental function in younger people. Some research also supports a role for ginkgo in the treatment of Alzheimer's disease and other forms of dementia. However, pharmacists· need to caution ginkgo users that this herb can increase the risk of bleeding, particularly if used with other anticoagulation agents. Ginkgo has anticoagulant actions because it inhibits plateletactivating factor and stabilizes capillary permeability. McDermott discussed several case reports on bleeding episodes associated with ginkgo use, including subdural hematoma (i.e., bleeding in the skull) and hyphema (i.e., spontaneous bleeding into the iris chamber). Because of ginkgo's "blood-thinning" effects, this product should not be used in combination with anticoagulants such as warfarin, heparin, or aspirin. Caution also is warranted in patients with risk factors for bleeding episodes, such as those with hypertension or diabetes.
Does Garlic Lower Cholesterol? Dr. Hardy explored evidence regarding the cardiovascular benefits of garlic. One of the oldest described plants in the world, garlic has long been used in traditional medicine to enhance the immune system and improve circulation. Garlic contains a number of volatile sulfur-containing oils, including alliin, which is converted into allicin when garlic is crushed or broken. Allicin is one of the most important biologically active compounds in garlic. Commercial garlic preparations vary in their allicin content and are often standardized to their alliin content. Much recent investigation has focused on the ability of garlic to lower levels of cholesterol and triglycerides. A recent meta-analysis of 13 trials found that garlic reduced total cholesterol concentrations significantly more than placebo, for a weighted mean difference of 15.7 mgldL (P<.OI).2 Dr. Hardy concluded that garlic does reduce total blood cholesterol levels, but this effect appears to be modest.
September/October2001 Vol. 41, No.5, Suppl. 1
Issues and Controversies in Botanical Medicine
Do Soy Products Affect Breast Cancer Risk? McDermott reviewed tudie examining the effects of soy products on breast cancer ri k. She explained that phytoestrogens are estrogen-like sub tance found in orne plants and are classified as either isoflavones or lignans. Soy is an abundant source of isoflavones, particularly genistein. Genistein binds to and stimulates human estrogen receptors, but not as strongly as estrogen. When estrogen concentration are high, as in premenopausal women, genistein may partially block the hormone's effects. When estrogen concentrations are low, as in postmenopausal women, genistein can enhance estrogen's effects. Asians, whose diets are high in soy, have much lower rates of cancer of the breast, endometrium, colon, and prostate than Americans. Several studies have been conducted to investigate the possible protective benefits of soy against breast cancer. For example, a meta-analysis of nine epidemiologic studies found a modest reduction in breast cancer risk associated with high soy intake during the premenopausal years, but not after menopause. Studies have not found soy to be harmful in the postmenopausal years. In fact, soy contains other anticancer compounds that may continue to provide benefits after menopause. McDermott concluded that soy appears to be effective and safe, but recommended dosages of no more than 100 mg of isoflavones daily (Table 1). She also advised consuming phytoestrogens in whole soy foods rather than from dietary supplements.
Is Black Cohosh Safe and Effective for Menopause Symptoms? Black cohosh, Cimicifuga racemosa, is an indigenous North American plant with a long history of traditional use. Although the mechanism of action of black cohosh has not been fully elucidated, triterpene glycosides or saponins are thought to be the main active constituents. Most clinical trials have been conducted using a proprietary formula, Remifemin, standardized to contain 1 mg triterpene glycosides. A series of open clinical studies have shown good efficacy of black cohosh in relieving menopausal symptoms, such as hot flashes, with little or no toxicity. Because black cohosh is a phytoestrogen, concern has been raised about its possible effects on breast and endometrial cancer. However, in vitro and clinical studies have demonstrated a good safety profile for this herb. For example, black cohosh was found not to stimulate growth of an estrogen-dependent breast cancer cell line. In fact, the product was found to increase the inhibitory
PATIENT CARE
effects of tamoxifen, an anti-estrogen. Based on clinical experience and the few controlled studies available, black cohosh appears to be an effective treatment for menopausal complaints, especially for women who cannot or do not wish to use estrogen replacement therapy.
Is Chocolate a Health Food? Chocolate contains many biologically active constituents, including flavonoids, alkaloids, methylxanthines (e.g., caffeine, theobromine), and phenols. Flavonoids in chocolate, which have very potent antioxidant activity, have been found to decrease the lipid oxidation of low-density lipoprotein cholesterol while raising high-density lipoprotein cholesterol concentrations. Catechin, a phenol found in chocolate, is a potent antioxidant that is believed to be responsible for many of the beneficial effects of green and black tea. Dark chocolate has a particularly high concentration of catechin, and is a better source than milk chocolate or black tea. Chocolate also contains constituents that bind to the cannaboid receptor. However, they are not present in sufficient concentrations to be psychoactive. While few studies have investigated the clinical benefits of chocolate, an analysis of 7,841 subjects enrolled in the Harvard alumni health study (an ongoing study of men who entered Harvard University between 1916 and 1950) yielded interesting results. In this study, candy consumers lived an average of almost 1 year longer than nonconsumers, an effect observed up to 95 years of age. 3 The authors postulated that the antioxidant phenols in chocolate could have contributed to this effect on longevity. To the delight of the audience, the speakers concluded that although data remain sparse, moderate chocolate intake appears to confer some health benefits.
Summary • Echinacea may reduce the duration of the common cold, but most studies do not show a significant preventive effect. • Pharmacists should caution patients that gingko can increase the risk of bleeding events, especially when used in combination with other anticoagulants. • Garlic has a modest cholesterol-lowering effect. • Soy and black cohosh are well tolerated and do not appear to increase breast cancer risk. • Moderate intake of chocolate may have some healthful benefits.
References 1. Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing
Table 1. Isoflavone Content of Selected Foods Food
Isoflavone Content (mg)
Tofu (4 oz)
35-40
Soy milk (8 oz)
35-40
Cooked soybeans (1/2 cup)
35
Vol. 41, No.5, Suppl. 1
September/October 2001
and treating the common cold. Cochrane Database Syst Rev. 2000;(2):CD000530. 2. Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med.2000;133:420-9. 3. Lee 1M, Paffenbarger RS Jr. Life is sweet: candy consumption and longevity. BMJ. 1998;317:1683-4.
Supplement to the Journal of the American Pharmaceutical Association
S45