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Kenneth D. Setchell, PhD

Title

Director

Appointment

Professor of Pediatrics

Email

kenneth.setchell@cchmc.org

Phone

513-636-4548

Bio

Kenneth D. Setchell, PhD, joined the tenured faculty of the Department of Pediatrics, University of Cincinnati College of Medicine in 1984, having moved from the Clinical Research Centre of the Medical Research Council, (UK) where he previously held a tenured Scientific position. In 1973 he obtained a PhD Degree in steroid biochemistry from the University of London. He was then awarded a Fellowship from The Royal Society for post-doctoral studies at the Karolinska Institute in Stockholm, Sweden (1974-1975) in the application of mass spectrometry to clinical and biomedical problems specifically relating to the steroid hormone field. He returned to the United Kingdom to a scientific position in the Division of Clinical Chemistry at the Medical Research Council's Clinical Research Centre where he continued his research in the field of steroids, expanding into cholesterol and bile acid metabolism as it related to gastrointestinal diseases. His parallel research discoveries of the first mammalian lignans later led to the discovery of soy isoflavones in humans, their association with soy intake, and established his research in the area of bioactive plant constituents and human nutrition and disease.

In September 1984, Dr. Setchell moved to Cincinnati to become Director of a new Clinical Mass Spectrometry facility at Cincinnati Children's Hospital Medical Center where he is now a tenured Professor in the Department of Pediatrics. His research program is internationally recognized as a leader in several areas of research that established collaborations with other groups from England, Italy, Germany, France Sweden, Canada and Australia. He has consulted with pharmaceutical and food companies, and to industries involved in clinical and biochemical research. Dr. Setchell cites >200 scientific publications and has presented over 250 papers at National and International symposia, while serving on National and International committees and Editorial Boards of International journals. Dr. Setchell was awarded the 1997 Gilbride award by the Canadian Liver Foundation for his contributions to the diagnosis and treatment of liver disease. He received awards from the AOCS at the 3rd International Symposium on the "Role of Soy in Preventing and Treating Chronic Disease" in 1999 for his outstanding contributions to increasing understanding and awareness of the health benefits of soyfoods and soybean constituents, and from North American Menopause Society (NAMS) 2000 annual award for his research on soy and women's health. He received the Roche 2003 International Award for Innovative Research in Human Nutrition for his discoveries of classes of phytoestrogens and the 2004 Adolf Windaus Prize for research on bile acids and the discovery of genetic defects in the cholesterol-bile acid pathway causing liver disease.

Some of his most significant research contributions include the following:

The development of chromatographic and mass spectrometry techniques for the isolation, purification, and separation, identification and measurement of steroids, bile acids and phytoestrogens.
Dr. Setchell and his group were the first to identify lignans and isoflavones in human urine and blood and his studies went on to show that flaxseed and soy protein are the richest dietary sources of these two classes of bioactive ingredients. His proposals that these dietary plant estrogens may be beneficial in the prevention of many hormone-dependent diseases, and his supporting studies led to a widespread interest in phytoestrogens and in the utilization of flax and soybeans as functional foods. He is focused on the role that early dietary exposure to phytoestrogens may play in preventing hormone-related diseases later in life. His group is internationally recognized as one of the leaders in the field of phytoestrogen research.
The identification that diet was a major factor in the infertility and development of liver disease in the captive cheetah population of North American zoos and that this was due to the presence of phytoestrogens from soy meal use din the formulation of feline diets. This work had major significance to the survival of this endangered species.
The discovery of six genetic defects in pathway for bile acid synthesis from cholesterol and which are manifest as progressive neonatal cholestasis. These discoveries explain some of the cases of idiopathic neonatal cholestatic syndromes and account for 2-5% of pediatric liver diseases. These conditions are fatal if untreated, and he showed that oral bile acid therapy successfully reverses the biochemical and histological abnormalities circumventing the need for a liver transplantation, the only alternative treatment. His research group is now an established International center for the diagnosis and treatment of liver disease due to these specific genetic defects in cholesterol and bile acid synthesis and is referred patients from all around the world.

Awards and Honors

2004 Adolf Windaus Prize 2004 for outstanding accomplishments in the field of bile acid research related to the discovery of six genetic defects in bile acid synthesis causing fatal liver disease in infants and children and developing a therapeutic strategy for improving and reversing the liver injury, 2004
Roche 2003 International Award for Innovative Research in Human Nutrition, 2003
North American Menopause Society / Genisoy 2000 Award for outstanding work in the area of soy and women's health, 2000
American Oil Chemists Society Award at the "Third International Congress on the Role of Soy in Preventing and Treating Chronic Diseases" in Washington DC, for distinguished research into soy and phytoestrogens, 1999
Gilbride Professorship from the Canadian Liver Foundation for significant contributions to research in pediatric liver disease, 1996
European Post-Doctoral Research Fellowship of the Royal Society, 1973 -1974

Publications, Most Recent

Lephart ED, SETCHELL KDR, Lund TD (2005) Phytoestrogens: hormonal action and brain plasticity.Brain Res Bull 65:193-198.

Setchell, KDR, Brzezinski A, Brown NM, Desai PB, Melhem M, Meredith T, Zimmer-Nechimias L, Wolfe B, Cohen Y, Blatt Y Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women.J Agric Food Chem 2005; 53(6):1938-1944.

Setchell KDR. Adolf Windaus Prize Lecture 2004: Defects in Bile Acid Synthesis – Specific and treatable causes of metabolic liver disease. In: Proceedings of the XVIII International Bile Acid Meeting – Bile Acid Biology and its Therapeutic Implications. Stockholm, June 18-19, 2004. Kluwer Academic Publishers, Lancaster, England.

Setchell KDR, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, Wolfe B, Nechemias L-Z, Brown N, Baraldi G, Lund TD, Handa RJ, Heubi JE. S-Equol, a potent ligand for estrogen receptor-beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by intestinal bacterial flora.American Journal of Clinical Nutrition 2005; 81:1072-1079.

Messina M, Erdman J, Jr., Setchell KD (2004) Introduction to and perspectives from the Fifth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease.J Nutr 134:1205S-1206S.

Lephart ED, Setchell KDR, Handa RJ, Lund TD. Behavioral Effects of Endocrine-disrupting Substances: Phytoestrogens.Ilar J 2004; 45:443-454.

Lephart ED, Porter JP, Lund TD, Bu L, Setchell , KDR, Ramoz G, Crowley WR (2004) Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats.Nutr Metab (Lond) 2004; 1:16.

Setchell KDR, O'Connell NC. Disorders of bile acid synthesis and metabolism. In: Pediatric Gastrointestinal Disease 4th Edition (Walker, Goulet, Kleinman, Sherman, Schneider, Sanderson Eds) B.C. Decker Inc., Hamilton, Ontario, Canada, 2004; pp 1138-1170.

Setchell KDR, O'Connell N, Brunetti G, Tauschel H-D. Bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) and Ursofalk capsules measured by plasma pharmacokinetics and biliary UDCA enrichment.Alimentary Pharmacology & Therapeutics 2005; 21:709-721.

Thigpen, JE, Setchell KDR, Saunders HE, Haseman JK, Grant MG, Forsythe DB. Selecting the appropriate rodent diet for endocrine disruptor research and testing studies.ILAR 2004; 45: 401-414.

Bove KE, Heubi JE, Balistreri WF, Setchell KDR. Bile acid synthetic defects and liver disease, a review.Pediatric Developmental Pathology 2004; 7:315-334.

Erdman JW, Badger TM, Lampe JW, Setchell KDR, Messina M. Not all soy products are created equal: Caution needed in the interpretation of research results.American Journal of Clinical Nutrition 2004; 134:1229S-1233S.

Setchell KDR, Brzezinski A, Brown NM, Desai PB, Meredith T, Zimmer-Nechmias L, Wolfe B, Cohen Y, Blatt Y. Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women. Journal of Agricultural Food Chemistry 2005; 53:1938-1944.

Bucuvalas JC, Setchell KDR. Bile acid metabolism during development. In: Fetal and Neonatal Physiology 3rd Edition (eds: RA Ploin, Fox WW, Abman SH) Saunders 2004; pp1179-1185.

Lund TD, Munson DJ, Haldy ME, Setchell KDR, Lephart ED, Handa RJ. The phytoestrogen equol acts as an anti-androgen to inhibit prostate growth and hormone feedback.Biology of Reproduction 2004; 70:1188-1195.

Smith JL, Lewindon PJ, Hoskins AC, Pereira TN, Setchell KDR, O'Connell N, Shepherd RW, Ramm GA. Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis.Hepatology 2004; 39:1673-1682.

Lydeking-Olsen E, Beck Jensen J-EB, Setchell KDR, Holm-Jensen T. Soymilk or progesterone for the prevention of bone loss: A 2-year randomized placebo-controlled trial.European Journal of Nutrition 2004; 43:246-257.

Vilca Melendez H, Rela M, Setchell KDR, Murphy GM, Heaton ND. Bile acid analysis: A tool to assess graft function in human liver transplantation.Transplant International 2004; 17:286-292.