A photo Kenneth Setchell.

Kenneth D. Setchell, PhD

  • Director, Mass Spectrometry Lab
  • Professor, UC Department of Pediatrics



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 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, and he is now a tenured professor in the Department of Pediatrics at the UC College of Medicine. 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 soy foods 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:

  1. The development of chromatographic and mass spectrometry techniques for the isolation, purification, and separation, identification and measurement of steroids, bile acids and phytoestrogens.
  2. 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.
  3. 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 used in the formulation of feline diets. This work had major significance to the survival of this endangered species.
  4. 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.

Research Areas



Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis. Shi, T; Malik, A; vom Hofe, AY; Matuschek, L; Mullen, M; Lages, CS; Kudira, R; Singh, R; Zhang, W; Setchell, KD R; et al. Science Translational Medicine. 2022; 14.

Dietary Isoflavone Aglycons from Soy Germ Pasta Improves Reproductive Performance of Aging Hens and Lowers Cholesterol Levels of Egg Yolk. Setchell, KD R; Mourvaki, E; Clerici, C; Mattioli, S; Brecchia, G; Castellini, C. Metabolites. 2022; 12.

Serum Bile Acid Profiling and Mixed Model Analysis Reveal Biomarkers Associated with Pruritus Reduction in Maralixibat-Treated Patients with BSEP Deficiency. Zhao, X; Zhang, W; Vig, P; Kostrub, C; Setchell, KD R. Metabolites. 2022; 12.

Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study. Loomes, KM; Squires, RH; Kelly, D; Rajwal, S; Soufi, N; Lachaux, A; Jankowska, I; Mack, C; Setchell, KD R; Karthikeyan, P; et al. Hepatology Communications. 2022; 6:2379-2390.

Perinatal Morphine Exposure Leads to Sex-Dependent Executive Function Deficits and Microglial Changes in Mice. Smith, BL; Guzman, TA; Brendle, AH; Laaker, CJ; Ford, A; Hiltz, AR; Zhao, J; Setchell, KD R; Reyes, TM. eNeuro. 2022; 9.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery. Smith, BL; Hall, ES; McAllister, JM; Marcotte, MP; Setchell, KD R; Megaraj, V; Jimenez, KL; John Winhusen, T; Wexelblatt, SL. Journal of Perinatology. 2022; 42:1026-1031.

Cutting Edge: l-Arginine Transfer from Antigen-Presenting Cells Sustains CD4+ T Cell Viability and Proliferation. Crowther, RR; Schmidt, SM; Lange, SM; McKell, MC; Robillard, MC; Zhao, J; Haffey, WD; Wyder, MA; Greis, KD; Setchell, KD R; et al. Journal of Immunology. 2022; 208:793-798.

Test-dose pharmacokinetics guided melphalan dose adjustment in reduced intensity conditioning allogeneic transplant for non-malignant disorders. Chandra, S; Mizuno, K; Zhao, J; Davies, SM; Marsh, RA; Fukuda, T; Setchell, KD R; Vinks, AA; Mehta, PA. British Journal of Clinical Pharmacology. 2022; 88:115-127.

Risk Factors for Bile Aspiration and its Impact on Clinical Outcomes. Rosen, R; Lurie, M; Kane, M; DiFilippo, C; Cohen, A; Freiberger, D; Boyer, D; Visner, G; Narvaez-Rivas, M; Liu, E; et al. Clinical and Translational Gastroenterology. 2021; 12.

Bile Acid Profiling Reveals Distinct Signatures in Undernourished Children with Environmental Enteric Dysfunction. Zhao, X; Setchell, KD R; Huang, R; Mallawaarachchi, I; Ehsan, L; Dobrzykowski, E; Zhao, J; Syed, S; Ma, JZ; Iqbal, NT; et al. Journal of Nutrition. 2021; 151:3689-3700.

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