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

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. "Appendix K: Protoype Focused Monograph: Review of Anti-Androgenic Risks of Saw Palmetto Ingestion by Women." 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

Substance

Study Design

Results and Conclusions

Inhibition of enzymes

Saw palmetto, extract of fruit

5-α-reductase from human prostate (obtained from patients undergoing surgery for BPH)

Addition of any of 4 extracts inhibited 5-α-reductase. IC50 values: 5.6 μg/mL (Permixon), 7.0 μg/mL (Talso, presumed to be the same as Talso uno), 31 μg/mL (Strogen forte), 40 μg/mL (Prostagutt, presumed to be the same as Prostagutt uno)

For comparison, IC50 for finasteride: 1 μg/mL (Rhodes et al., 1993).

Saw palmetto, extract of fruit (Permixon)

Cells in culture: human foreskin fibroblasts (from healthy infants or adults)

Addition of extract inhibited steroid 5-α-reductase (conversion of testosterone to DHT) and 3-α-hydroxysteroid dehydrogenase (conversion of DHT to androstanediol) in assays using intact cells.

Addition of extract inhibited binding of [3H]-DHT to androgen receptor(s) in cytosolic, nuclear, and whole cell fractions.

Addition of extract inhibited binding of [3H]-methyltrienolone (R1881) to cytosolic components of rat prostate (Sultan et al., 1984).

Extract of fruit (Permixon)

Cells in primary culture:

Human prostate epithelial cells: from subjects with PBH (IC50 = 40 μg/mL); from subjects with prostate adenocarcinoma (IC50 = 90 μg/mL)

Human prostate fibroblasts: from subjects with PBH (IC50 = 200 μg/mL); from subjects with prostate adenocarcinoma (IC50 = 70 μg/mL)

Addition of extract inhibited metabolism of [3H]-testosterone (0.1 μM) to all metabolites (DHT, androst-4-ene-3,17-dione, 5-α-androstane-3,17-dione).

By comparison, finasteride inhibited metabolism of [3H]-testosterone (0.1 μM) to DHT and 5-α-androstane-3,17-dione (IC50 = 20–40 ηM for fibroblasts; IC50 = > 100 ηM for epithelial cells),

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472
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)