Academy Position Paper
Position of the Academy of
Nutrition and Dietetics:
Nutritional Genomics
Written by Kathryn M. Camp, MS, RD, CSP and Elaine Trujillo MS, RD.
Provided in the Journal of the Academy of Nutrition and Dietetics in
February 2014
Krystal Powell
NFS 4950: Senior Seminar
2-2-2015
“It is the position of the Academy of Nutrition and Dietetics that nutritional genomics provides insight
into how diet and genotype interactions affect phenotype. The practical application of nutritional
genomics for complex chronic disease is an emerging science and the use of nutrigenetic testing to
provide dietary advice is not ready for routine dietetics practice. Registered dietitian nutritionists need
basic competency in genetics as a foundation for understanding nutritional genomics; proficiency
requires advanced knowledge and skills.”
Science and technology are ever evolving and developing, deepening our understanding
of how dietary patterns and nutrients affect health maintenance and disease development.
Although not ready for routine dietetics practice, nutritional genomics provides insight into how
diet and genotype, which is the genetic makeup of a cell, interact to affect phenotype, the
expression of a genotype, such as eye color. Most chronic diseases, such as cancer, diabetes, and
cardiovascular disease are multigenetic and therefore genetic mutations are only partially
predictive of disease risk. Family history, risk factors, and biochemical parameters are influential
tools for personalizing dietary interventions. Because this is an emerging science, it is not closely
regulated by the United States. The application of nutritional genomics in a clinical practice
through the use of genetic testing requires an understanding, ability to interpret, and
communicate complex test results in which the actual risk of developing a disease is unknown.
This will require an evidence-based approach in the health benefits to individuals, rather than
cause harm. To personalize diets, genotyping alone will not be sufficient. An understanding of
how diet affects the phenotype will require technology that will reveal the processes of what is
happening from the DNA (deoxyribonucleic acid) through transcription and synthesis of proteins
to identification of metabolites that will tell us what has occurred in abnormal and normal
incidents. Repeating the same rigorous evidence will help translate these scientific discoveries in
to practical clinical application.
150 years after Mendel manipulated the color of flowers in peas discovering autosomal
recessive inheritance, 100 years after inherited traits called chromosomes were identified, 50
1
years after Watson and Crick described the double helix structure of genetic material, in 30 years
after the invention of the first DNA sequencing technology, the first full sequence of human
genome was completed and published in 2003. The Human Genome Project is an international
effort to draft the human genomes. It took 20 years from the start to completion and cost $3
billion. Since the completion of the human genome project, hundreds of genomes have been
sequenced from the tiniest bacteria to the largest mammal. In 2001 it cost approximately $95
million to sequence a human genome, with technological advances by 2013 it cost less than
$6,000. It is expected that as the cost continues to drop as integrating this technology into
standard medical practice will become more realistic. Translating genome sequencing into
therapies will require the ability to identify significant and clinically meaningful outcomes.
Within a living organism, there are genes which contain all of the biological information
needed to build and maintain that structure. These are responsible for protein formation and
metabolic function. Metabolic signals received from the nucleus, influenced by environmental
factors such as diet, hormones, and enzymes can turn genes on and off. Here is where the
exciting part of how a diet can affect gene expression and contribute or inhibit genetically
inherited diseases and disorders. Of the approximately 20,000 genes, most of these are the same
with in humans with less than 1% of the genes being different. The DNA sequence of an
organism is a genome. Polymorphs occur frequently and are natural variations in a gene, DNA
sequence, or chromosomes. Single nucleotide polymorphisms (SNP) are the most common type
of polymorphism. With an a segment of DNA, a SNP may replace thymine with cytosine which
could cause something as simple as a hair color change, or in other instances change the risk of
developing diseases or disorders of a specific source. Before that happens, the information in
the DNA must be transcribed to RNA. The messenger RNA leaves the nucleus into the
2
cytoplasm where translation occurs then it interacts with the ribosomes that read the messenger
RNA into codons that code for a particular amino acid each. From this process proteins are
formed.
Omics, as in genomics refers to the category of molecules and information being described,
studied, and measured. Nutritional genomics is the broad term used to encompass nutrigenetics,
nutrigenomics, and nutritional epigenomics, together are how nutrients and genes interact and are
expressed to reveal the outcomes of phenotypic diseases. The influence of genetic variables is
the nutrigenetics, the interactions between dietary/nutritional components is the nutrigenomics,
and influence of diet changes in the gene expression is the nutritional epigenomics. The genetic
studies dig even deeper into studying RNA transcripts, protein expression and low molecular
weight of the molecules found within the cells and biological systems. It has been found that
chronic diseases or genetic variants do not necessarily translate into an elevated risk of disease
development. Environmental factors such as air quality, physical activity, nutritional intake, and
tobacco smoking modified genetic expression and can influence the outcome of disease. Our
bodies are in a constant state of fighting for homeostasis. In doing so one event can set off a
chain reaction. If we were to compare our bodies to a balancing scale, when one side is deficient
then it affects the other side. This is evident in the balance of choline, folate, and methionine. A
choline deficient diet results in a reversible fatty liver with liver and muscle damage,
predominantly in premenopausal women who have a SNP in the phospatidylethanolamine Nmethyltransferase (PEMT) gene.
Coronary heart disease is one of the two leading causes of death in the United States,
causing the association between coronary heart disease and the SNP apolipoprotein E (apoE)
3
genotype to be widely investigated. ApoE is a protein involved in triglyceride and cholesterol
metabolize. There are 3 isoforms for apoE (E2, E3, and E4) where E3 is normal, E2 and E4 are
dysfunctional. Generally individuals that have the E2 allele have lower low-density lipoproteins
(LDL) cholesterol and those with the E4 allele have higher LDL than those with the E3
genotype. This causes the individuals with E4 alleles to have an increased risk of coronary heart
disease, especially if E4 carriers consume a diet high in LDL cholesterol.
Environmental exposures such as diet can affect the risk for developing conditions
including obesity. There are 20 single gene mutations that have been linked to severe obesity.
These gene variants can effect waist to hip ratio, waist circumference, and body mass index
(BMI). The children that are affected with these obesity related genes have a higher energy
intake which carry into adulthood. Carrying these genes increases the risk of obesity; however,
this can be modified by reducing caloric intake or physical activity. We should see in the near
future that therapeutic guidelines for the intervention of obesity based on genotypes will be a
viable approach. Classifying obese or obese prone patients into subtypes and then identify
different phases of weight loss such as long term or acute can affect their gene expression.
A group of low-risk prostate cancer patients participated in nutrigenomic testing after
declining traditional treatments participated in intensive nutrition and lifestyle intervention. It
was found that after 3 months, the men were exercising more than 3.6 hours per week,
consuming about 12% of their energy from fat, and for 4.5 hours per week were practicing stress
management. The risk factors for cardiovascular disease were improved, BMI was reduced, and
waist circumference was reduced as well as blood pressure and lipid levels. Not only were these
men healthier, their gene expression analysis detected 453 down-regulated transcripts and 48 up-
4
regulated transcripts after the intervention. Using nutritional intervention alone, no effects of diet
were found on the gene expression, showing that diet alone was not the only contributing factor.
Affecting cellular function and metabolism, diet can cause epigenetic changes that may
turn certain genes on or off. Epigenomics is the process that regulates how and when genes are
silenced and activated. The intake of too little or too much vitamin B-6, vitamin B-12, choline,
folate, and methionine effects one-carbon metabolism and has the potential to disrupt DNA and
histone methylation patterns. These have been linked to increased cancers. Direct dietary factors
may even extend across generations. Those that are prenatally exposed to famine such as during
war time or poverty had less DNA methylation of the maternally imprinted insulin like growth
factor to gene, which is a key factor in human growth and development compared with those
unexposed same gender siblings. For example those affected by a lesser quality of nutritional
intake during the mother's pregnancy due to reduced income that could be related to war type
efforts, those individuals were at a higher risk for developing chronic diseases such as type 2
diabetes, high cholesterol, schizophrenia, heart disease, and some cancers. This could be why
there are more known and diagnosed health concerns from those born during the World War II
era. The baby boomers may not just be diagnosed with more frequency, but because our
technology is more advanced showing the influence down to the DNA level due to the mother's
dietary habits while she was pregnant. Analyzing family history can provide information on
environmental exposures, genes, and behaviors. A positive family history of a disease or disorder
predicts risk and genetic variation. For example those with a family history of colorectal cancer
are at an increased risk of developing this disease. There is genetic testing for hereditary nonpolyposis colorectal cancer, Lynch syndrome as well as BRCA1 and BRCA2, which if present
shows an increase the probability of developing breast cancer. Testing for a single gene disorder
5
is gradually becoming part of the general practitioner medical testing. Some disorders and the
gene expression can be influenced by whether it is the paternal or maternal inherited alleles. For
example, if it is the paternal inherited allele it can cause obesity where as if that allele is
expressed from the maternal side it can cause neurodevelopmental disorders characterized by
severe mental retardation rather than obesity.
The social, ethical, and legal implementation for genetic testing fall into 3 categories being:
analytic validity referring to how accurately and reliable the tests are, the clinical utility referring
to the likelihood that the test will improve outcomes, and clinical validity referring to whether
the test is accurately detecting or predicting the presence of a disorder or disease. Currently there
are evidence-based recommendations for following genomic testing by the Center for Disease
Control (CDC) in newborn screening panels, BRCA1 & 2 for breast and ovarian cancers, human
epidermal growth factor receptor 2 mutation testing in invasive breast cancer, Lynch syndrome,
and human leukocyte antigen testing for abacavir sensitivity for HIV patients. Genetic test that
are classified into categories, in vitro diagnostic test and direct to consumer DTC testing which
are directly marketed to consumers. The DTC tests have been available for the past decade
online and are gradually declining in cost due to the improved testing technologies and lack of
regulation. A cheek swab containing DNA is mailed to the lab and results are returned either via
the telephone, mail, or can be posted online. A healthcare provider such as your family
practitioner is not typically involved in these tests nor in the interpretation of these. This could be
used is by persons that have been adopted, as it is possible to find out your generalized ethnic
heritage such as European, Mediterranean, or Native American Indian. Some of the DTC
nutrigenetic testing companies are also offering diets that are tailored to the discoveries in your
DNA testing. However due to lack of regulation, tests mislead consumers and provided
6
nutritional advice based primarily on known family and medical history rather than the scientific
discoveries. This raises questions as to whether or not the genetic data should be handled
explicitly by qualified medical practitioners. Currently regarding dietetics programs, there is no
requirements for proficiency in genetic knowledge.
There is a plan to introduce nutritional genomics education in undergraduate dietetics
curriculum as the evidence based science becomes more evident and prevalent. As we are
learning more there is always more to learn. Not only will need we need to be able to identify
and monitor medical risks, physiological changes, we will also need to be able to monitor
psychological changes as well. Nutritional genomics has the potential to be an all-encompassing
science that will touch into nearly every practice of medicine. As future dietitians, I believe it is
imperative that we have at the very least, a basic understanding of nutritional genomics as this is
where our future is taking us.
7
References
Camp K, Trujillo E. Position of the Academy of Nutrition and Dietetics: Nutritional Genomics.
Journal of the Academy of Nutrition and Dietetics. 2013; 114(2):299-312.
8