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Dietary Supplements: A Framework for Evaluating Safety (2005)
Institute of Medicine (IOM)

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. "Appendix J: Prototype Focused Monograph: Review of Liver-Related Risks for Chaparral." Dietary Supplements: A Framework for Evaluating Safety. Washington, DC: The National Academies Press, 2005.

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Dietary Supplements: A Framework for Evaluating Safety

verse environment for the growth of other plants, resulting in a monoculture in some areas (Schultz and Floyd, 1999). One remarkable feature of the chaparral bush is the complex resinous coating on the leaves that serves as a chemical defense against grazing by herbivores and against attack by insects. The chemicals in the resin find their way into the desert soil surrounding the chaparral plant and discourage growth by other plant species, thus effectively reducing competition for water and nutrients (Mabry et al., 1977).

Chaparral is formally known as Larrea tridentata (Sessé and Moc. ex DC.) Coville (synonymous with Larrea mexicana Moric.) of Zygophyllaceae (McGuffin et al., 1997). Historically, the dry leaves, green stems, and fine twig tips of chaparral were used for various ailments. Since about 1969, these same plant components have been used as dietary supplements. Various forms have been available: dried plant material for making teas (water extracts), aqueous-alcoholic extracts or tinctures, and tablets or capsules containing ground, dried plant material. During the past 10 years, chaparral products have not been as readily available as in the past; however, each of these forms is currently available in the U.S. marketplace in varying degrees.

B. Individual Components

Table A contains a list of the components of primary interest in chaparral (i.e., present in leaves, stems, and twigs). Some components of chaparral are common in other plants and are widespread in the human diet. The major components of the resinous coating of chaparral are lignans (Mabry et al. 1977; Sakakibara et al. 1976) which can comprise up to 80 percent of some extracts of chaparral, such as methanol extracts of green leaves or green stems (Hyder, 2001). Lignans are low-molecular-weight plant products made up of phenylpropanoid dimers or trimers. Mature chaparral leaves contain lower amounts of lignans than new leaves (Gisvold and Thaker, 1974). The major lignan in chaparral is nordihydroguaiaretic acid (NDGA) (Downum et al., 1988), which is a derivative of guaiaretic acid and is a catechol having two hydroxyl groups on each of the two phenol rings. NDGA comprises approximately 10 percent of the dry leaf weight, but may be as much as 15 percent in some instances (Obermeyer et al., 1995). NDGA comprises approximately 50 percent of the phenolic resin extracted from the external surface of the leaves (Botkin and Duisberg, 1949; Mabry et al., 1977; Sakakibara et al., 1976). Chaparral also contains guaiaretic acid and other substituted guaiaretic acid derivatives (Table A). Other lignans in chaparral are classified as furanoid lignans and 1 aryl tetralin lignans. The latter are structurally related to podophyllotoxins.

Chaparral contains flavonoids as non-water-soluble aglycones, as wa-

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386
Front Matter (R1-R20)
Executive Summary (1-18)
1 Introduction and Background (19-42)
2 Approaches Used by Others and Existing Safety Frameworks (43-84)
3 The Framework (85-125)
4 Categories of Scientific Evidence--Human Information and Data (126-155)
5 Categories of Scientific Evidence--Animal Data (156-174)
6 Categories of Scientific Evidence--Information About Related Substances (175-216)
7 Categories of Scientific Evidence--In Vitro Data (217-234)
8 Interactions (235-246)
9 Vulnerable Groups and Prevalance of Use (247-252)
10 Scientific Principles for Integrating and Evaluating the Available Data (253-268)
11 Applying the Framework: Case Studies Using the Prototype Safety Monographs (269-291)
12 Factors Influencing Use of the Safety Framework (292-296)
13 Findings and Recommendations (297-306)
Appendix A: Existing Frameworks or Systems for Evaluating the Safety of Other Substances (307-315)
Appendix B: Scope of Work and Comments to Initial July 2002 Framework (316-321)
Appendix C: Plant Family Information (322-355)
Appendix D: Chaparral: Prototype Monograph Summary (356-362)
Appendix E: Glucosamine: Prototype Monograph Summary (363-366)
Appendix F: Melatonin: Prototype Monograph Summary (367-371)
Appendix G: Chromium Picolinate: Prototype Monograph Summary (372-375)
Appendix H: Saw Palmetto: Prototype Monograph Summary (376-379)
Appendix I: Shark Cartilage: Prototype Monograph Summary (380-384)
Appendix J: Prototype Focused Monograph: Review of Liver-Related Risks for Chaparral (385-449)
Appendix K: Protoype Focused Monograph: Review of Anti-Androgenic Risks of Saw Palmetto Ingestion by Women (450-477)
Appendix L: Acknowledgements (478-480)
Appendix M: Biographical Sketches of Commitee Members (481-488)
Index (489-506)