Building Actionable Nutrition Knowledge

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Building Actionable Nutrition Knowledge

• Rosemary L. Walzem RD, PhD, FACN
• Associate Professor of Nutrition
• Department of Nutrition Food Science
• Faculty of Nutrition
• Director Center for Nutrition, Health and Food
  Genomics
• Texas A M University

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Development of Nutrition
Empirical healing of some diseases by certain
foods
Deficiency diseases identified essential
nutrient concepts
Discovery, isolation, structure elucidation, and
synthesis
First Commercial Synthesis, 1933
1943, First RDA
Establishment of biochemical functions, dietary
requirements, commercial production
1500 BC 1880 1900 1920 1940 1960 1980 2000
Adapted from Guthrie Picciano
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Centurys Changing Top Ten Killers
Total Mortality
Total in 1900 1719 deaths / 100,000
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Disease
Pharmaceutical For Medical Treatment
Health Injury
Health Recovery by Secondary Care
Impaired Health
Health
Health Promotion
Food for nutrient supply
Malnutrition
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Leading Causes of Death for All Males and Females
A All Cardiovascular Diseases
B Cancer
Deaths in Thousands
D Chronic Obstructive Pulmonary Disease
E Pneumonia/Influenza
C Accidents
F Diabetes
National Center for Health Statistics and the
American Heart Association,
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Chronic Diseases Are Different

• Acute diseases
• Specific organisms
• Magic bullets
• Cause effect close in time
• Occur at all ages

• Chronic diseases
• Multifactorial
• Prevention
• Temporal disconnect
• Occur more frequently in older individuals

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Development of Nutrition
Empirical healing of some diseases by certain
foods
Deficiency diseases identified essential
nutrient concepts
Discovery, isolation, structure elucidation, and
synthesis
First Commercial Synthesis, 1933
1943, First RDA
Establishment of biochemical functions, dietary
requirements, commercial production
1955 Niacin Cholesterol
French Paradox, 1991
Recognition of health effects beyond prevention
of deficiency diseases new biochemical functions
1500 BC 1880 1900 1920 1940 1960 1980 2000
Adapted from Guthrie Picciano
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Many Compounds

• Carotenoids, Tocopherols, Flavonoids, Tannins,
  Glucosinolates, Indoles, Sulfides Thiols,
  Isothiocyanates, Phenols, Isoflavones, Saponins
• Prebiotics, Probiotics, Fibers
• Phytosterols, CLA, 1,3-DAG, DHA, EPA,
  Sphingolipids, Structured lipids
• Bioactive peptides, Arginine, Glutamine, N-Acetyl
  Cysteine

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Many Systems Processes

• Liver intestine
• Lipoprotein production metabolism
• Peripheral tissues
• Glucose, amino acid lipoprotein use
• Adipose hormone release
• Blood flow
• Vascular biology
• Responsiveness
• Permeability retention
• Immune function
• Disease resistance
• Systemic inflammation

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Many Modes of Action

• Chemical Antioxidant
• Biological Antioxidant
• altered enzyme activities e.g. lipoxygenase
• Altered Metabolism Signaling
• competition for enzyme systems
• grapefruit juice Ca channel blockers
• quercetin, estrogen SAM
• altered protein synthesis
• P-gp transmembrane protein cytotoxin efflux
• altered transport(ers)
• altered signaling though nuclear receptors
  messengers
• PPAR, FXR, LXR
• Eicosanoids, resolvins

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Disease
Health Injury
Health Recovery by Secondary Care
Impaired Health
Functional Diets For Disease Risk Reduction
Health Maintenance by Primary Care
Lifestyle Choices
Health
Health Promotion
Food for nutrient supply
Malnutrition
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• Nutrition is the science that interprets the
  relationship of food to the functioning of the
  living organism.
• R.L. Pike M.L. Brown, 1975

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Nutrition Foods in the 21st Century

• Driven by omic information
• Human
• Animal
• Microbial
• Plant
• Individualization of food choices
• Focus on health rather than simple disease or
  deficiency prevention

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Informatics

• Develop technology to measure everything
• Build a quantitative database
• Test hypotheses on database

Phenotype
Metabolites
Activity
Proteins
Complexity
Genes
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Metabolomics

• Resources Activities Needed
• Database development
• Computing power
• Model development
• Standardized analytical protocols
• Data integration storage
• Predictive tools
• Data visualization

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Practical Example

• Analysis of Plasma Lipids during an Oral Glucose
  Tolerance Test in Old Young Humans
• Subjects
• Group 1 healthy 20-40 yo
• Group 2 healthy 65 yo
• Protocol
• 12h fast
• Whole body DEXA scan
• MRS scan of liver and soleus muscle, fat
• 2h Oral GT test
• Blood taken _at_ -15, 0, 30, 60, 90 120 min

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Lipids

• An attractive target for Metabolomics
• Analytical platform well established
• Rigorous quantitation possible
• Metabolic pathways well known
• Unique capabilities
• Retains diet characteristics with ingestion
• Reflects further metabolism of dietary components
  as well as endogenous metabolism

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www.lipomics.com
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Fatty Acid Metabolism
EFAD
n6
n3
n7
SFA
n9
225
226
E/D6/RC
224
225
240
241
222
Elongase
203n9
204
205
D 5 Desaturase
203
204
220
221
202
202n6
203n3
Elongase
183
184
182
D 6 Desaturase

181
200
201
182n6
183n3
Elongase
161n7
181n9
D 9 Desaturase
180
Elongase
Diet
160
140
De novo synthesis Diet
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Interpreting Quantitative Data

E
Mass differences can be used to
estimate steady-state pathway flux
D6
E
D6
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Young Relative to Old
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Metabolomics to Enable Health Promotion

• Identify
• Metabolic defect/gain caused by diets or
  interventions
• Adverse drug reactions
• Global surrogate markers
• Pre-trial characterization of clinical
  populations
• Compliance monitoring
• Discover
• Pathways supporting systemic organ specific
  actions
• Global integration to predict outcomes
• Diagnostics
• Metabolic definition of state change of state
• Document efficacy
• Rational intervention design

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Thank You!