Biomedical Agriculture: A New Approach for Developing Crops for Health

Henry J. ThompsonCancer Prevention Lab

Colorado State UniversityFort Collins, CO 80523

henry.thompson@colostate.edu

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.

Colorado State University Crops for HealthTM

A Transdisciplinary Research & Training Program inBiomedical Agriculture

PreventionTherapy

Chronic disease• Obesity• Diabetes• Heart disease

• Cancer

FoodSupplements

Bioactive food components

Nutrients

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

Biomedical engagement

Overweight/Obesity

Diabetes-Type II

Cardiovascular Disease

Cancer

Glucose availability

Inflammation

Cellular oxidation

Plant Food-Health Conundrum

• The issue of botanical diversity.

• Not the right crop varieties (cultivars) in the supermarket Crops for Health

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

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

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

Food Chemical NomenclatureFoods Phytochemicals

(phytonutrients)

Matrix effects

Mammalian cells Gut microflora

Biological inert chemicals

Non-nutrient1000s

Individual chemicals

Bioactive Food ComponentsBAFC

Nutrients50

• Cannot be made• Required for normal cellular function• Absence results in disease

Targets

Drill Down Point: What are the nutrients

• 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

The Big Picture Vision• 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

JA Milner : NCI Road Map 2005

CSU-Credential Cultivars

BOTANICAL FAMILIES COMPARISON

Actinidiacae

Agaricaceae Chenopodaceae

CompositeaeConvolvulac

CruciferaeCucurbitace

Ericaceae Gramineae

Leguminosae Liliaceae

Musaceae Rosaceae Rutaceae

SolanaceaeUmbellifera

Vitaceae

Bot

anic

al F

amili

es

0 1 2 3Average Serving Per Day

Low FV

High FV

Diet

Nouveau Cuisine for Cancer Prevention

N= 118

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]

0.00 0.50 1.00 1.50 2.00 2.50

Actinidiaceae

Chenopodiaceae

Convolvulaceae

Cucurbitaceae

Graminae

Liliaceae

Rosaceae

Solanaceae

Vitaceae

n-a-day

17 family5 family

DAILY SERVINGS OF VEGETABLES AND FRUIT FROM EACH BOTANICAL FAMILY

Cruciferae

Rutaceae

• 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

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.

Plant Food-Health Conundrum

• The issue of botanical diversity.

• Not the right crop varieties (cultivars) in the supermarket: Crops for Health

Dry Bean

Apple

Potato

Created Equal?

VisionProvide consumers with crop varieties in the

food market for which we have evidence of enhanced human health benefits

Experimental Overview

• Chemical Analysis– Antioxidants and phytochemicals

• Cell Culture– Cell accumulation

• In Vivo Screening Bioassay– Mammary carcinogenesis

– Colon carcinogenesis

Genetic Classification Centers of Domestication

Epiphany: what’s the most efficient approach by which to discover

microbe or pest resistance?...why not health traits?

IR64

IAC

165

M20

2

Mor

ober

kan

Dom

Suf

id

Cyp

ress

Pokk

ali

Asw

ina

Swar

na

Inia

Toc

uari

Co 39 Patbyeo Gerdeh Dular Sadu-cho

Panicle/Seed Types in Current SNP set

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

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”

Colorado Cuisine Modular Diet

• Cultivar defined certification

Modular Unit (B,L,D)(credential certified)

• 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.

Obesity Trends* Among U.S. Adults

1992 1995

1998 2001

Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.