Obesity, Nutrition, Nutrigenonmics – OH MY!

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Obesity, Nutrition, Nutrigenonmics OH MY!
Karen L. Edwards, Ph.D. Director, UW Center for
Genomics and Public Health Department of
Epidemiology and Institute for Public Health
Genetics School of Public Health and Community
Medicine University of Washington
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Objectives

• Be familiar with the evidence for genetic
  influences on obesity
• Be able to define nutrigenomics
• Understand current limitations of nutrigenomic
  testing

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Outline

• Background
• Genetics of Obesity
• Animals
• Humans
• Environmental effects
• Nutrigenomics
• Why the interest?
• Current products and examples
• Why the concern?
• Moving from promise to practice
• 5. Summary and Conclusions

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Public Health Importance

• Mortality
• Increased risk of premature death
• Morbidity
• Diabetes, Heart disease, Hypertension, some
  Cancers, Breathing Problems, Ischemic Stroke,
  Arthritis, and Reproductive Complications
• Prevalence
• 59 million (30) Americans are obese (BMIgt 30)
• Rates are increasing faster than ever (epidemic
  proportions)

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Risk Factors for Obesity

• Diet high calorie and low nutrient dense foods
• Physical Inactivity
• Age
• Socioeconomic status
• Certain medical conditions and medications
• Race
• Smoking cessation
• Family History
• Genetic susceptibility

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Evidence for Genetic Influences on Obesity
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Evidence for genetic influences Humans

• Familial aggregation
• - familial clustering of obesity in families
• Twin Studies
• - greater concordance among MZ twins compared to
  DZ twins
• Family Studies
• - variety of statistical models consistent with
  genetic influences

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The Search for Obesity Susceptibility Genes
I found one! I found one!
Kenneth M. Weiss Joseph D. Terwilliger nature
genetics volume 26 October 2000
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Candidate Genes and Single Gene Disorders
Chromosomal Location
Image adapted from Loos, R. J. and C. Bouchard
(2003). J Intern Med 254(5) 401-25.
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Genetics of Human Obesity

• Common form(s) of obesity are likely due to
  complex interactions between genes and
  environment
• - body fat pattern
• - appetite regulation
• - other pathways
• Rare monogenic forms do not account for majority
  of cases

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Trends in Obesity
From the CDC website BRFSS Trends Data
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Trends in Obesity
From the CDC Website NHANES Study Data
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Trends in Obesity
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Nutrigenomics

• Integrates genomics and nutrition
• Goal Improving health and preventing disease
  through tailored diet and lifestyle
  prescriptions

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Nutrigenomics Magic, Myths and Maybes
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Nutrigenomics vs. Nutrigenetics

• Nutrigenomics
• Nutrigenomics refers to the application of
  genomics in nutrition research, enabling
  associations to be made between specific
  nutrients and genetic factors, e.g. the way in
  which food or food ingredients influence gene
  expressionNutrigenomics should facilitate
  greater understanding of how nutrition affects
  metabolic pathways and how this process goes awry
  in diet-related diseases. Chadwick R. (2004)
  Proceedings of the Nutrition Society 63161-166.

• Nutrigenetics
• Nutrigenetics is the study of individual
  differences at the genetic level influencing
  response to diet. These individual differences
  may be at the level of single nucleotide
  polymorphisms rather than at the gene levelIt is
  envisaged that nutrigenetics may lead to
  individualized dietary advice. Chadwick R.
  (2004) Proceedings of the Nutrition Society
  63161-166.

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Nutrigenomics vs. Nutrigenetics

• Nutrigenomics
• Nutrigenomics attempts to study the genome-wide
  influences of nutritionand aims to identify
  the genes that influence the risk of diet-related
  diseases on a genome-wide scale, and to
  understand the mechanisms that underlie these
  genetic predispositions. Muller M Kersten S.
  (2003) Nature Reviews Genetics 4315-322.

• Nutrigenetics
• Nutrigenetics examines the effect of genetic
  variation on the interaction between diet and
  disease or on nutrient requirements. Genetics has
  a pivotal role in determining an individuals
  risk of developing a certain disease. Muller M
  Kersten S. (2003) Nature Reviews Genetics
  4315-322.

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Nutrigenomics vs. Nutrigenetics

• Nutrigenetics
• Nutrigenetics embodies the science of
  identifying and characterizing gene variants
  associated with differential responses to
  nutrients, and relating this variation to disease
  states. Mutch D, et al. (2005) FASEB Journal
  191602-1616.
• Nutrigenetics examines the effect of genetic
  variation on the interaction between diet and
  exercise. This includesgene variants associated
  with, or responsible for, differential responses
  to nutrients. Ordovas J Mooser M. (2004)
  Current Opinion in Lipidology 15101-108.

• Nutrigenomics
• Nutrigenomics describes the use of functional
  genomic tools to probe a biological system
  following a nutritional stimulus that will permit
  an increased understanding of how nutritional
  molecules affect metabolic pathways and
  homeostatic control. Mutch D, et al. (2005)
  FASEB Journal 191602-1616.
• Nutrigenomics focuses on the effect of nutrients
  on the genome, proteome, and metabolome. Ordovas
  J Mooser M. (2004) Current Opinion in
  Lipidology 15101-108.

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Nutrigenomics Nutrigenetics Two Sides of a Coin

• Mutch D, et al. (2005) FASEB Journal 191602-1616.

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Nutritional Genomics

• The study of how different foods can interact
  with particular genes to increase the risk of
  diseases
• such as type 2 diabetes, obesity, heart disease
  and some cancers
• Goal Use of personalized diets to prevent or
  delay the onset of disease and optimize and
  maintain human health

http//nutrigenomics.ucdavis.edu/pressarticles.htm
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Nutritional Genomics

• van Ommen B. (2004) Nutrition 204-8.

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Why the interest?

• Improve health of populations
• United States
• Globally
• Improve athletic performance
• Weight loss
• Potential economic impact
• Functional food and dietary supplements is
  currently a 40 billion industry
• The focus on nutrigenomics could mean an 80
  billion dollar industry in 7-10 years

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What is the evidence?

• Single Gene Disorders
• PKU
• Lactose intolerance
• Complex conditions
• Genes involved in susceptibility to complex
  diseases have been identified
• Nutritional environment modifies the expression
  of genes
• Metabolism of nutrients may vary by genotype,
  ultimately affecting health

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What is the public health implication?

• Can we use this information along with our
  increasing knowledge of the genetics of obesity
  for public health applications?
• Obesity epidemic

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Direct to Consumer Marketing

• Health Clubs
• Vending Machines
• Internet
• Retail stores

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On the internet
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Weight Loss
DNA Diet Builds Customized Weight-Loss
Plan One-size-fits-all diets could be a thing of
the past. NBC station KNSD in San Diego reported
that a handful of bio-tech companies are
promising a high-tech recipe for losing weight
and eating better. The newest weight-loss plan is
a customized diet based on your DNA. The DNA
diet is a personalized meal plan that claims to
be based on your unique genetic
blueprint. Katzin claims that based on your DNA
profile she can determine whether someone should
increase the amount of folic acid, B-6 or B-12,
for example. So, we would choose foods that are
rich in those supplements. interprets the
data and makes a customized meal plan. Her
suggestions range from taking more vitamins to
eating more meat.
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Diet Design, One Pair of Genes at a Time
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Currently in the United States, no regulations
are in place for evaluating the accuracy and
reliability of genetic testing. Most genetic
tests developed by laboratories are categorized
as services, which the Food and Drug
Administration (FDA) does not regulate. This lack
of government oversight is particularly
troublesome in light of the fact that a handful
of companies have started marketing test kits
directly to the public. Some of these companies
make dubious claims about how the kits not only
test for disease but also serve as tools for
customizing medicine, vitamins, and foods to each
individual's genetic makeup. (doegenomes.org)
Genetic testing to identify alleged risk factors
that have no proven corrective measures is simply
a waste of money. As noted by Helen Wallace,
Ph.D., Deputy Director of GeneWatch UK "For most
people, tailoring your diet to your genetic
make-up is about as scientific as tailoring your
diet to your star sign."
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Sciona

• International company previously based in the UK
• Personalized health and nutrition recommendations
  
• Products were available through retail stores
• GeneWatch UK called on retail stores to stop
  offering these tests
• Currently based in Boulder, Colorado
• Launching a campaign in 4 test markets
• Partnerships with retail stores and local health
  care system

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In store sales
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• Lund Foods CEO plan is to create a link
  between the evaluations performed by Sciona and
  his stores food experts, which have long
  provided consumers with diet and nutritional
  advice and information.
• Today Food Editor The idea, which is a good
  one, is to help shoppers understand what they can
  do in their daily food choices to either maintain
  their good health or help correct certain genetic
  defects that the test may have identified.

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Heart Health

• Analyzes thirteen of your genes that may play an
  important role in determining how your body
  manages overall heart health
• assesses nine key diet and lifestyle action
  areas

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Bone Health

• Analyzes four of your genes that may play an
  important role in determining how your body
  manages overall bone health
• ..assesses seven key diet and lifestyle action
  areas

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Insulin Resistance

• Analyzes five of your genes that may play an
  important role in determining how your body
  manages overall insulin resistance
• ..assesses five key diet and lifestyle action
  areas

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Genetic Assessment for Antioxidant and
Detoxification

• Analyzes six of your genes that may play an
  important role in determining how your body
  manages overall antioxidant/ detoxification
  health
• ..assesses four key diet and lifestyle action
  areas

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Inflammation Health

• Analyzes six of your genes that may play an
  important role in determining how your body
  manages inflammation
• ..assesses four key diet and lifestyle action
  areas

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Consumer Demand?

• Sciona claims to have sold 10,000 kits in Europe,
  Asia and the US
• Current use is likely limited to those who can
  afford to pay
• HealthSyles Survey indicates that only 14 of US
  population are aware of these tests, and only
  0.6 have used a test
• - age and income are associated with awareness
• (Goddard et al., GIM 20079510-7)

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Why the Concern?
Currently in the United States, no regulations
are in place for evaluating the accuracy and
reliability of genetic testing. Most genetic
tests developed by laboratories are categorized
as services, which the Food and Drug
Administration (FDA) does not regulate. This lack
of government oversight is particularly
troublesome in light of the fact that a handful
of companies have started marketing test kits
directly to the public. Some of these companies
make dubious claims about how the kits not only
test for disease but also serve as tools for
customizing medicine, vitamins, and foods to each
individual's genetic makeup. (doegenomes.org) Gen
etic information is unlike other health
information, in that it also provides information
about your family members Genetic testing to
identify alleged risk factors that have no proven
corrective measures is simply a waste of money.
As noted by Helen Wallace, Ph.D., Deputy Director
of GeneWatch UK "For most people, tailoring your
diet to your genetic make-up is about as
scientific as tailoring your diet to your star
sign."
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Buyer Beware
A recent report by the Government Accountability
Office highlighted a few of the concerns with
four examples of DTC nutrigenomic tests. The GAO
report raised concerns that the tests may mislead
consumers by making unsound and
ambiguous predictions about health risks. In
addition, the test results frequently include
recommendations for the consumer to purchase
dietary supplements that may be
significantly overpriced compared with similar
products available through a supermarket or
pharmacy and that may, in fact, be harmful for
some individuals.
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Potential Benefits

• Increased focus on a healthy diet and lifestyle
• Motivate positive behavior change
• Increased awareness of risk of certain conditions
• Improved health and quality of life
• Focus on prevention
• Decreased morbidity and premature mortality
• Reduced health care costs
• Identify subgroups who might be particularly
  responsive or resistant to environmental
  (dietary) intervention
• Better understanding of the mechanisms involved
  in disease susceptibility

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Potential Harms

• Attention is drawn away from other modifiable
  risk factors
• Decreased use of other services
• False sense of security
• Focus on specific nutrients/foods
• Ineffective or harmful
• Misleading claims
• Dilute or contradict public health messages

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Potential Harms, cont.

• Increased costs associated with personalized
  diets and designer foods
• Targeting vulnerable populations
• Concerns surrounding confidentiality, insurance
• Biobanking of samples, informed consent
• Unintended consequences

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From Promise to Practice

• Consistent evidence
• Evidence for clinical utility added value
• Understand how information is used
• Culturally specific translation
• Thoughtful integration based on evidence
• Holistic approach
• Address ELSI issues prior to integration
• Access to services and treatment

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Summary

• Potential is exciting
• Range of opinions regarding readiness of current
  applications
• Many parallels to pharmacogenomics
• Dr. Arno Motulsky the total promise of PGX is
  often overstated and is unlikely to lead to a
  revolution in therapeutics
• May provide benefits to some individuals, but
  probably not as broadly as currently predicted

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Conclusions

• Obesity is influenced by both genes AND
  environment
• Obesity is associated with poverty, SES and
  education
• Diet is important
• High-fat energy-dense foods are often the
  cheapest options for the consumer
• Health foods cost more
• Nutrigenomic testing is not ready for prime time

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UW Center for Genomics and Public Health
http//depts.washington.edu/cgph Funded as part
of the ASPH/CDC/ATSDR cooperative
agreement Office of Genomics and Disease
Prevention Centers for Disease Control and
Prevention