Biomedical Agriculture: A New Approach for Developing Crops for Health

1. Biomedical Agriculture: A New Approach for Developing Crops for Health Henry J. Thompson Cancer Prevention Lab Colorado State University Fort Collins, CO 80523 henry.thompson@colostate.edu

2. To meaningfully reduce the physical, psychosocial, and economic consequences of chronic diseases such as obesity, diabetes, heart disease and cancer through: • Identification, development, and production of food crop varieties that show maximum human health benefit while retaining marketability in the global arena. • Development of the tools and techniques require to understand how these food crops prevent chronic disease. • Dissemination of knowledge to the global community to promote long-term healthy lifestyle changes.

4. Food Supplements Prevention Therapy Colorado State University Crops for HealthTMA Transdisciplinary Research & Training Program inBiomedical Agriculture Chronic disease • Obesity • Diabetes • Heart disease • Cancer Bioactive food components Nutrients

5. Potential disease-preventive mechanisms of vegetables and fruit • Antioxidant activity (effector activity or marker?) • Antibacterial, antiviral, and anti-inflammatory activity • Modulation of detoxification enzymes • Stimulation of the immune system • Decrease in platelet aggregation • Alteration in cholesterol metabolism • Modulation of steroid hormone concentrations and hormone metabolism • Blood pressure reduction

6. Biomedical engagement Overweight/Obesity Glucose availability Diabetes-Type II Inflammation Cardiovascular Disease Cellular oxidation Cancer

7. Plant Food-Health Conundrum The issue of botanical diversity. Not the right crop varieties (cultivars) in the supermarket Crops for Health

8. Epidemiological Evidence • Strong inverse relationship between cancer incidence and VF intake • World Cancer Research Fund, American Institute for Cancer Research (1997) Food, nutrition and the prevention of cancer: a global perspective. • Evidence strongest for colon cancer • Concept challenged Schatzkin , New Engl. J. Med. 342:1149-55, 2000 • For breast cancer, the relationship is moderately strong (WCRF:1997) • Smith-Warner: JAMA 285: 769-776, 2001; Riboli JAMA 2004 No effect • Publications in 2002-2007 are mixed • Reports of protection (lung and ovarian cancer) and lack of association (breast and bladder cancer) • No reports of a positive association

9. Why the variability in study conclusions? • No effect: variation and chance • Measurement errors: VF intake • There is a threshold that VF intake must exceed for protection • Only certain VF matter: botanical family • VF can be protective • but not all individuals benefit from increased VF

11. Food • A collection of chemicals produced (synthesized) in a biological context • Propagation of that plant species • For people: food is simply a collection of chemicals that can be ingested

12. Food Chemical Nomenclature Foods Phytochemicals (phytonutrients) Bioactive Food Components BAFC Biological inert chemicals Nutrients 50 Non-nutrient 1000s Cannot be made Required for normal cellular function Absence results in disease Individual chemicals Matrix effects Targets Mammalian cells Gut microflora

13. Macronutrients Protein (4) Essential amino acids Non essentail amino acids Carbohydrate (4) Available Mono,di, oligo Starch Unavailable Fiber Soluble Insoluble Fat (9) Essentail (omega-6 vs 3) Nonessential *Water Micronutrients Vitamins Fat soluble Water soluble Minerals Macro Trace elements Drill Down Point: What are the nutrients

18. The Big Picture Vision JA Milner : NCI Road Map 2005 CSU-Credential Cultivars • ID America’s favorite 20 crops • Understand crop origins and breadth of each crop’s genetic diversity • Select cultivars from each crop for evaluation • Identify the most cancer protective cultivars • Define a cultivar-based diet of menus and recipes • Evaluate in women at high risk for breast cancer or its recurrence • Ultimate goal: a “certifiable disease prevention diet” JA Milner : NCI Road Map 2005

19. BOTANICAL FAMILIES COMPARISON Vitaceae Umbellifera Solanaceae Rutaceae Rosaceae Musaceae Diet Liliaceae Botanical Families Leguminosae Gramineae Low FV Ericaceae Cucurbitace High FV Cruciferae Convolvulac Compositeae Chenopodaceae Agaricaceae Actinidiacae 0 1 2 3 Average Serving Per Day

20. Nouveau Cuisine for Cancer Prevention N= 118

21. RESEARCH QUESTION • When vegetable and fruit (VF) intake is high what has a greater effect on levels of oxidation • focus on botanical families: powerful phytochemicals [Five family diet] • diverse number of VF with many many chemicals of varied activity [Seventeen family diet]

22. DAILY SERVINGS OF VEGETABLES AND FRUIT FROM EACH BOTANICAL FAMILY • 5 Family • Cruciferae • Chenopodiaceae • Liliaceae • Rutaceae • Solanaceae • 17 Family • Chenopodiaceae Ericaceae • Cruciferae Graminae • Liliaceae Leguminosae • Rutaceae Musaceae • Solanaceae Rosaceae • Actinidiaceae Umbelliferae • Agaricaceae Vitaceae • Compositae Curcurbitaceae • Convolvulaceae Rutaceae Cruciferae

24. LESSONS LEARNED • Diet is a powerful chemical tool box. • You can cause rapid and at times dramatic shifts in the chemicals to which your cells are exposed. • What you eat can make a difference in the body’s microenvironment.

25. Plant Food-Health Conundrum The issue of botanical diversity. Not the right crop varieties (cultivars) in the supermarket: Crops for Health

26. Created Equal? Dry Bean Apple Potato

27. Vision Provide consumers with crop varieties in the food market for which we have evidence of enhanced human health benefits

28. Experimental Overview • Chemical Analysis • Antioxidants and phytochemicals • Cell Culture • Cell accumulation • In Vivo Screening Bioassay • Mammary carcinogenesis • Colon carcinogenesis

29. Genetic Classification Centers of Domestication

31. Epiphany: what’s the most efficient approach by which to discover microbe or pest resistance?...why not health traits?

32. Panicle/Seed Types in Current SNP set Moroberkan Dom Sufid IAC 165 Inia Tocuari Cypress Swarna Aswina Pokkali M202 IR64 Co 39 Patbyeo Gerdeh Dular Sadu-cho

33. Health and Supplements • Nutrient supplements • Original concept: developed to prevent deficiency diseases • Contemporary use: if some is good, more is better • BAFC supplements • Drug concept: intervene in disease processes to prevent disease • Evidence of health benefit: limited • Evidence of harmful effects: growing

34. The Big Picture Vision • ID America’s favorite 20 crops • (Crops of International Importance) • Understand a crop’s origins and genetic diversity • Select cultivars from each crop for evaluation • Identify the most cancer protective cultivars • Define a cultivar-based diet of menus and recipes • Evaluate clinically • Ultimate goal: • CSU: “certifiable disease prevention diet”

35. Colorado Cuisine Modular Diet Cultivar defined certification

36. Macronutrient composition Protein 20%kcal Fat 30% (10/10/10) Carbohydrate 50% kcal 15% kcal as fiber Breakfast: 300 kcal 60 kcal Pr=15g 90 kcal Fat=10g 150 kcal CHO=37g Botanical Diversity 18 Families Each module: at least 3 botanical families At least 0.5 servings per family The serving sizes: 1 medium piece of fruit, ½ cup fruit or vegetable (raw, cooked, canned or frozen), 1 cup leafy green salad, ¼ cup dried fruit, ¾ cup or 6 oz. 100% fruit or vegetable juice, ½ cup cooked or canned dried peas or beans. Modular Unit (B,L,D)(credential certified)

38. Obesity Trends* Among U.S. Adults 1992 1995 1998 2001 Source: Mokdad A H, et al. J Am Med Assoc1999;282:16, 2001;286:10.