Nutrigenomics - PowerPoint Presentation

Slide1

Nutrigenomics:Using Genetic Clues to Personalize Nutrition

Janet Zarowitz, MS, RD, CDN

NYSAND Annual Meeting & Expo

May 21, 2016Slide2

Nutrigenomics!

The study of the effects of foods and food constituents on gene expressionSlide3

Nutrigenomics

Building Upon What We Already KnowDovetailing With Established Science

Well Accepted

Diet and lifestyle choices can significantly affect our healthPoor eating habits can prevent achieving genetic potential and optimal health

Certain nutrients needed to promote normal replication of DNA for normal growth and healing

Evolving Evidence

Specific foods and supplements can support

our own unique genetic

predispositionsSlide4

Family History

Family History

provides clues to

Potential

for health and disease, looking for genetic trends

Building Upon What We Already KnowSlide5

Family History

The same is true for Genetic Profile

NOT DESTINY

Potential and PredispositionSlide6

Role of Genetic Profile

In the Patient Care Process

Genetic profile “joins” the intake process, alongside:

…to help figure out the patient puzzle

Family History

Signs and Symptoms

Medical History/Diagnoses

Lab Values, Biomarkers

Medications, Supplements

Diet, Cooking, Eating Environment

Lifestyle, Exercise, Self Care

Social Network, SupportsSlide7

Genetic ProfileMapping a Person’s DNA

Individual’s genetic characteristics (DNA analysis)

can:Provide insight into

potential for developing certain diseasesOffer clues to root

causes of disease/symptomsHelp reduce

guesswork

in treating

suboptimal

healthSlide8

Gene Expression

Epigenetics, or how genes are expressed is where Nutrition gets into the game.Slide9

Nature Meets Nurture

Once nurture seemed clearly distinct from nature.

Now it appears that our diets, lifestyles & other environmental factors can change the expression of our genes.

Epigenetics

-

Where Genes Meet the EnvironmentSlide10

Epigenetics - Beyond The Gene

Environmental factors affect gene expression (without changing DNA)

Environmental factors

turn genes “on” or “off”

Food, nutritional deficiencies/excess, breast/bottle feeding, GI microbial mixExercise, lifestyle, stress, aging, diseases

Prenatal,

childbirth, early life experiences

Chemicals, toxins, radiation, pathogens, drugs

….. they all affect gene expression

…..

the genome adapts to environmental factorsSlide11

Intergenerational Transmission

From Macmillan Publishers Ltd: : Qiu, J. Nature, 2006, 441, 143, copyright (2006)Slide12

Are Nutrition Professionals Already Practicing Epigenetics?

Biochem Pharmacol. 2010 Dec 15;80(12):1771-92. doi: 10.1016/j.bcp.2010.06.036. Epub 2010 Jun 26.

Cancer chemoprevention by dietary polyphenols: promising role for epigenetics

.Link A1,

Balaguer F, Goel A.

Dietary Polyphenols and Cancer Prevention

Eat

Rainbow

of

Foods

More

Plant-based Foods

Tomatoes

Apples

Citrus

Tu

r

meric

Garlic

Cin

n

amon

Broccoli

Cashews

Grapes

TeaSlide13

Isolating Compounds & Epigenetics

Dietary Manipulation of Histone Structure and Function, Barbara Delage and Roderick H. Dashwood

Annu Rev Nutr. 2008; 28: 347–366.

Diet and Supplements

Dietary fiber

- gut bacteria ferment dietary

fiber

,

produce

butyrate, which mediates epigenetic process in

gut

associated immune system - GALT

Phytochemicals

-

gut bacteria metabolize

phytochemicals

into

products

that

have epigenetic effects

Minerals

- associated with changes in epigenetic mechanisms regulating gene

expressionSlide14

Epigenetics & Personalized Nutrition

Personalizing Nutrition

affect epigenetic mechanisms - methyl donors, phytochemicals, fatty acids, vitamins

modulate genes involved in inflammatory diseases

modulate genes encoding absorption, distribution, metabolism, & excretion proteins

“From inflammaging to healthy aging by dietary lifestyle choices:

is epigenetics the key to personalized nutrition?”

Clinical

Epigenetics, 2015 Mar: 7(1):33,

vel

Szic

,

Vidakovic

, and

Berghe

Slide15

How To Put This Into Practice, Today?

Epigenetic Nutrition Strategy

Using new genetic info, RDs can ….

design customized nutrition therapies and lifestyle changes for healing — above and beyond symptom management.Slide16

How I StartedTesting Options

Reference

integrativerd.orgSlide17

23andMe Process

Order at-home saliva kit through http://23andme.com

Mail-in NYS workaround

Results emailed within several weeksRaw data 1000’s genes vs. few

Upload data file to third party websites for interpretive genetic reports, e.g., MTHFRSupport.comSlide18

Reading Genetic Reports

Understanding SNPs/Gene VariationsSingle nucleotide polymorphisms - “snips”Most variations “typos” - switching one letter in gene’s sequence to another (switching

nucleotide)We all have SNPs

A person’s genome (and their SNPs) do not changeSlide19

SNPsWhat’s Their Relevance?

Some SNPs change the gene’s “instruction manual” - encoding a protein with altered shape, activity, stability and/or abundance

Only certain SNPs are associated with difference in molecular function significant enough to effect clinical

measurements or disease riskGenes that encode different enzymes (e.g., MTHFR) prone to common mutations or SNPs

Innovative view: “What if DNA mutations are not always the markers of disease, but rather — under the right set of circumstances — markers for resilience?” - Eric Schadt, PhD and Stephen Friend, MD, PhDSlide20

SNPs

Affecting the Body’s Ability to Do WorkSNPs reflect the ability of the body to do workSome SNPs reduce function, less often

enhance functionMore than half

population has SNPs that reduce activity of one or more enzymes by up to 70%Some SNPs directly affect nutrient assimilation

and nutritional requirementsEffects of these SNPs can be substantially mitigated with targeted nutritional

approach

- diet and supplementationSlide21

Homozygous | Heterozygous

for each gene pair,SNP may occur in none, one or both copies of geneon genetic reports “+” represents SNP

homozygous SNP “+/+” can have more significant health implications compared to milder heterogeneous genotype

-/-

-/+

+

/+

Homozygous “variant”

2 SNPs

Heterozygous “variant”

1 SNP

Homozygous “normal”

no SNPsSlide22

SNP ID

rsID Number

or SNP ID

identifies chromosomal locationsSlide23

Nutritionally Relevant Genes

Well ResearchedMTHFR C677T and A1298C

folate and methylation

COMT Val/Met 158 methylation, mood and estrogen metabolism

Slide24

What is Methylation?

Methylation is a biochemical reaction in which a methyl group (CH3) is attached to a molecule, converting it to a different molecule

Chemically SpeakingSlide25

What is Methylation?

Methylation has vital roles in:

epigenetics and gene regulation

(DNA methylation & histone acetylation)neurotransmission

amino acid metabolismDNA synthesis and repair

hormone detoxification

vitamin assimilation (including folate)

homocysteine clearance

cell membrane structure

Clinically SpeakingSlide26

Methylation Pathway SNPs

May Present Asloss of digestive integrity (rapid cell turnover), food intolerances

mood disorders, depression, anxiety, cognitive function deficits

neural tube defectsendocrine imbalance (estrogens), environmental toxin buildup (phase 2 liver)

cancer, e.g. colorectal, breast, lung (altered suppression of gene transcription)Slide27

Methylation Pathway SNPs

May Present Ascardiometabolic

syndrome (with homocysteine buildup)chronic inflammatory diseases (less glutathione production)

impaired thyroid function (less T4 to active T3 conversion)

impaired fertility (male and female)fatigue (reduced CoQ10 and carnitine production)general poor overall health and immunitySlide28

So That’s Why We Had to Take Biochemistry!

Methylation PathwaysSlide29

Cycles of Methylation Pathway

fumarate

Krebs

cycle

aspartate

Plus Krebs cycle

Activates

f

olate

N

eurotransmitters

Nitrogen removal

SAMe

,

G

luathione

generation; phospholipidsSlide30

Genes Code for Enzymes

Genes

Gene LocationsSlide31

Enzymes Need Cofactors

Cofactors

Genes

Like

Mg

, Zn,

Riboflavin

, B12, B6Slide32

Nutrients Can Bypass SNPs

Nutrient bypass

support

Genes

Cofactors

Nutrient bypass support includes 5-MTHF (folate), B12,

methionine, SAMe,

choline, DHA, phosphatidyl serineSlide33

MTHFR GeneC677T & A1298C SNPs

Key Regulators of MethylationMethylene Tetrahydrofolate Reductase

Gene function:

encodes Methylene Tetrahydrofolate Reductase enzyme

Enzyme function

:

converts

folic

acid

and

5,10-methylene

THF

to

active

form of

folate

(5-MTHF)Slide34

MTHFR GeneC677T & A1298C SNPs

Methylene Tetrahydrofolate ReductasePotential impact

of reduced enzyme function of these SNPs:

Reduced conversion of Folate to ACTIVE form, needed for methylation and as coenzyme or cosubstrate in synthesis of DNA, RNA & amino acids

C677T - associated with cardiovascular problems

reduced conversion of homocysteine to methionine;

also

associated with increased male infertility and sperm DNA alteration

A1298C - associated with neurological/cognitive problems

reduced production of tetrahydrobiopterin (

BH4)

,

integral

cofactor in nitric oxide & neurotransmitter synthesis; does

not

affect homocysteine levelsSlide35

Making the Assessment

Will Nutrition Strategy Help?

YOUR DNA IS NOT YOUR DESTINY

…

it’s one factorSlide36

Making the Assessment

Look at Clues Holistically Treat the Person, Not the SNP

Medical History/Diagnoses

Signs and Symptoms

BiomarkersDietary IntakeSpecial Requirements

Interfering Meds, Supplements

Environmental Toxins

Cigarette Smoking, Alcohol

Stressors - Emotional, Physical

AND Genetic Profile - SNPs Slide37

Symptom/Diagnosis Clues

Of Undermethylation

Digestive issues, bloating, IBS, constipation/diarrhea, poor nutrient absorption, food intolerances

Excessive histamine response, itchiness, stomach pain, histamine intolerance

Cardiometabolic syndromeWeight changes, impaired thyroid

Brain fog, sleep difficulties, neurological problems, anxiety, mood disorders, autism

Getting sick often, lowered immunity, cancer

Peripheral neuropathy, dementia

Fatigue, joint pain, inflammationSlide38

Biomarker Clues

Of Undermethylation

-Elevated Homocysteine

-Low RBC Folate Levels-High FIGLU in Urine

-Elevated

Methylmalonic

Acid

-Elevated Homocysteine

-Anti-parietal/Anti-intrinsic Factor Antibodies

Low Folate

Low B12

-Urinary estrogen metabolites panel - high hydroxyestrones, low methoxyestrones and ratios

-Elevated Histamine

-Anemias - megaloblastic or macrocytic

May

Indicate Methylation IssuesSlide39

Nutrient Requirement Clues

Drugs Interfere with Folate – Absorption/Availability

-

antacids, H2 blockers, proton pump inhibitors

-bile acid sequestrants/cholesterol-binding drugs-NSAIDS

-anti-seizure drugs

*

-sulfa drugs - antibiotics

-

estrogen drugs - birth control, menopause meds

-methotrexate

*

- chemotherapy

*

folate

may negate effect of

dru

g; work with MD

Ref: Dr. Suzy Cohen, R Ph,

www.suzycohen.comSlide40

Nutrient Requirement Clues

Drugs Interfere with B12 – Absorption/Availability

-metformin

-colchicine (gout)

-antacids, H2 blockers, proton pump inhibitors-bile acid sequestrants/cholesterol-binding drugs

-

anti-seizure

drugs

-sulfa drugs - antibiotics

-

estrogen drugs - birth control, menopause meds

-

methotrexate

- chemotherapy

Ref: Dr. Suzy Cohen, R Ph,

www.suzycohen.comSlide41

Environmental Stressor Clues

Diet-

Low in leafy green vegetables and other folate-rich foods-High in processed foods, many enriched with competing folic acid

-High alcohol intakeEnvironmental toxins -Cigarette smoking

-Working or living near/with chemicals including householdEmotional or physical stress -Injury, surgery, infection, pregnancy, aging

M

ay Not Satisfy M

ethylation Requirements

Slide42

Genetic Clues - SNPs

nutrition recommendation

for each genetic SNP

-/+ one SNP

+/+ two SNPs

-/- no SNPs

Clues suggest possibilitySlide43

How Does it Add Up?

Woman trying to get pregnant, long-time on oral contraceptives *Type 2 Diabetic on metformin, vegetarian

Patient with IBS, abdominal bloating, food intolerances/limited diet, elevated histaminePostmenopausal woman on

PPIs, borderline osteopenia*Testing for Methylation SNPs - all young women prior to pregnancy

Clues Related to Possible Undermethylation+ Methylation SNPs = Case for Nutrition InterventionSlide44

How Does it Add Up?

Family hx cardiovascular disease, blood clots, elevated homocysteine, low folatePatient on cholesterol-binding

med, brain fog, sleep difficulties,

elevated methylmalonic acidTeenager with anxiety, mood disorder, diet high in processed foodsPremenopausal woman, family

hx breast cancer, imbalanced urinary estrogen metabolites (high hydroxyestrones, low methoxyestrones)

Clues Related to Possible Undermethylation

+ Methylation SNPs = Case for Nutrition InterventionSlide45

Nutrition Intervention for MTHFR SNPs

Integrating Diet and SupplementsSlide46

Targeted Nutrition Support

for MTHFR C677T and A1298C SNPsSTRATEGY: BYPASS GENE BY ADDING ACTIVATED NUTRIENTS

Supplement - First support pathways with minerals and B vitamins

except folate and B12Then, bypass MTHFR gene — greater need for folate, active form

Diet - More folate-rich foods: liver, spinach, kale, other green leafy vegetables, asparagus, cauliflower, Brussels sprouts, broccoli, beets, lentils, legumes, papaya

Supplement

– Transition to s

upplement

with

5-MTHF/

Metafolin

,

active

,

universally

metabolized folate

Increase vitamins and

cofactors

needed by folate

Diet

- More

foods

rich in B12, riboflavin, B6, Mg, Zn, Cysteine

Supplement

-

M

ultivitamin

containing vitamins and cofactorsSlide47

Targeted Nutrition Support

for MTHFR C677T and A1298C SNPsLimit synthetic folic acid which

may compete with active form of folate

Diet - Limit processed foods enriched with folic acid

1998 - folic acid fortification required in grain products - breads, cereals, flours, corn meals, pastas, rice, etc.Supplement - Do not take folic acid supplements or multivitamins with it

(most have it

)

Diet

- More foods good methyl donors, e.g. beets, quinoa, lambSlide48

Using Supplements

Why Diet May Not Be EnoughInability to convert vitamin form in food to bioactive form body requires; active form of nutrient can bypass affected geneAssimilation is compromised requiring greater amount of specific nutrients than the “average” person

Nutritional deficiencies of folate, B12 and zinc may alter epigenetic methylation and reduce genomic stabilitySlide49

Using Supplements

Best Practices Addressing MethylationBegin with supplement with minerals & B vitamins except B12 & folate

Transition to multivitamin for foundational support of

methylation pathWith cofactors, vitamins, minerals of methylation cycle, highly bioavailable, active forms e.g., Puregenomics

Start slowly, one new supplement/dose at a timeCheck B12 levels before giving folateConcurrently address other issues - e.g. inflammation, GI problemsWork with the MD regarding certain

medications,

diagnosesSlide50

Monitoring Nutrition SupportFollow-up

- how pathways are “pushed” or driven; feelings of detoxificationMonitor dietary and lifestyle changes, supplement compliance, symptom changes (digestive, mood, sleep, pain), side effects3-6 months revisit physiological biomarkersSlide51

Assessing Nutrition Intervention for COMT

NeurotransmittersSlide52

COMT GeneVal/Met158 SNP

Another SNP with Nutritional Relevancein methylation pathwayCatechol-O-methyltransferase

Gene function: encodes catechol-

O-methyltransferase enzyme

Enzyme function: metabolizes and detoxifies dopamine, norepinephrine, epinephrine and estrogens through methylation processSlide53

COMT GeneVal/Met158 SNP

Catechol-O-methyltransferase Potential impact of reduced enzyme function of this SNP

Patient may feel excessive stimulation - alertness, wakefulness, sleeplessness, restlessness — norepinephrine, epinephrine are stimulantsDopamine, norepinephrine, epinephrine & estrogens may build up

May have greater impulsivity in behavior choiceCognitive performance may be affectedSlide54

Targeted Nutrition Support

STRATEGY: SUPPORT ALTERNATE METHYLATION PATHWAYS, SUPPORT

LIVER,

FOSTER RELAXATION & SLEEP

Support alternate pathways that bypass the COMT SNPDiet – More foods rich in B12

Supplement

-

Multivitamin

with B

vitamins

(

adenosyl

/

hydroxycobalamin

)

Avoid COMT inhibitors - caffeine, green tea, quercetin

Support Liver (detoxification including estrogen detox)

Diet

-

M

ore

cruciferous vegetables, garlic, onion,

fruits

,

vegetables

, nuts,

herbs

,

spices

Diet

-

O

rganic

foods and animal protein without raised without hormones or antibiotics, as much as possible

for COMT Val/Met 158 SNPSlide55

Targeted Nutrition Support

Support Liver & Detox (con’t)Supplement - DIM (diindolylmethane)

Lifestyle - Moderate alcohol, no smoking, less toxic household cleaners, beauty and hair

products, reduce toxic loadSupport Sleep & Relaxation - alternate pathways/bypass COMT SNP

Diet - Foods rich in magnesium Supplement - Magnesium at bedtime

Lifestyle

– Incorporate

yoga

, meditation, breathing exercises,

etc.

,

promote

relaxed mood

Lifestyle

-

Follow

sleep hygiene

principles

,

support

sleep

quality/quantity

* Work closely with MD if patient has mood disorder/cognitive diagnosis

for COMT Val/Met 158 SNPSlide56

More Genes with Nutritional Relevance

Potential Impact of SNPsDAO & HNMT

- potential for histamine intolerance

HLA-DQ - potential for celiac disease95% with celiac disease have SNP in HLA-DQ2 gene;

most remaining 5% have SNP in HLA-DQ8 gene

CYP1A2

- may be fast or slow metabolizer of caffeine

ACE

-

may have increased risk high

B

P when high Na intakeSlide57

More Genes with Nutritional Relevance

Potential Impact of SNPsMTRR - may have

slower B12 regeneration

CBS - may have reduction of intermediates required

for transsulfuration and detoxificationTCN2 - delivery of B12 to cells may be limited

FUT2

-

intestinal microbial diversity and

bifidobacteria

levels may be low;

may

also be

protective

of B12 statusSlide58

More Genes with Nutritional Relevance

Potential Impact of SNPsGC - may have increased risk of suboptimal

Vit D status

TCF7L2 - may have increased risk of type 2 diabetes

NOS3 - may have higher circulating levels of triglyceridesBCOM1

-

may have limited

β

-carotene to Vitamin A conversion

THIS PARTIAL LIST WILL CONTINUE TO GROW!Slide59

NutrigenomicsBest Practices

Focus on well-researched, evidence-based nutritionally relevant SNPsSNPs represent potential for suboptimal functioning –

their expression not predeterminedA homozygous SNP (+/+) can have more significant health implications compared to milder heterogeneous genotype

Understand the gene’s role, related biochemical pathwaysSlide60

Keeping Nutrigenomics 2016 in Perspective

Providing Clues and Potential, Not CertaintyGenetic research and relevance of SNPs in its infancyIf multiple SNPs in a particular gene, impact may be more significant

Nutrigenomics is complementary with medical nutrition therapy, integrative

nutrition approachesLook at all the clues …

do they validate each other?Treat

the patient not the SNP!Slide61

No SNP is an IslandGenes don't work in isolation

— work synergisticallyChronic diseases affected by multiple genes; impact of single SNP, even if relevant, usually small

Body designed with “backup systems” — biochemical

pathways overlapMay be compensatory genes in closely related pathways that support the body’s performanceMix of positive and negative environmental factors that impact genes (and SNPs) and their expression is infiniteSlide62

Plus Gut DNA!Gut microbiome -

second pool of person’s genetic material100 trillion bacteria in gut have their own DNA!(10x more than 10 trillion human cells in body)

Foods we eat influence composition of individual’s gut biomeGut bacteria (under their DNA instructions) respond to food just like

human genes; their end products influence epigenetic expressionExamples: gut bacteria’s response to dietary fiber and phytochemicalsRDs already address balance of gut ecology with

diet, probioticsSlide63

Nutrigenomics - A New Tool

Using Genetic Clues to Personalize Nutrition Counseling

Nutrigenomics provides an exciting new

tool for Registered Dietitians

to

personalize nutrition care by matching diet and lifestyle with a client’s genotype and biochemical individuality…to optimize health.Slide64

Nutrigenomics

Part of Functional Medicine ModelHealth now recognized as more than absence of diseaseNutritional imbalances characteristic of chronic disease

Concept of multiple diseases existing independently from one another is

being replaced by understanding that origins of illness can often be traced to the same physiological disturbances and common underlying pathways - adapted from Jeffrey Bland, PhDSlide65

Future of NutrigenomicsSlide66

Present & Future Research

More Precise Predictability, Disease Prevention, Early Intervention, Confirmation

More information about gene function, nutritionally relevant SNPs, clinical

implicationsMore research on effects of foods & nutrition supplements on gene expressionMore specific biomarkers (various stages of pre, early and full disease onset) that reflect gene expression/genetic differences

Growth of genetic profile databases, related health profiles Understanding of multiple SNPs in multiple genes that collectively influence

likelihood

of developing common and complex diseases

Mechanisms of gene expression transfer between generations & health implications

New direct reporting to consumerSlide67

Future of Nutrigenomics

…will evolve from providing clues to underlying root causes to offering better predictive tools

…will ready us for the earliest nutrition intervention to treat disease if it occurs, in a precise, targeted way

…will evolve as a framework to design and prioritize personalized diet and lifestyle plans for optimal health and preventive strategies before disease presentsSlide68

ResourcesDIFM -

integrativeRD.org DIFM list serve - Q & A’s with fellow RDsLinks to testing, books and websites International Society of

Nutrigenetics and Nutrigenomics (ISSN) relationshipSlide69

Resources

Dr. Amy Yasko – knowyourgenetics.com - neurological/autism

Dr

. Ben Lynch: mthfr.netmthfrsupport.com

Dr. Eric Balcavage – the methylationdoctor.com

SNPedia

– snpedia.comSlide70

Resources

NIHNational Center for Biotechnology Information ncbi.nlm.nih.gov/clinvar

/

National Human Genome Research Institute genome.gov

Genetics Home Reference, US National Library of Medicineghr.nlm.nih.gov Genome magazine – genomemag.comSlide71

Definitions

Genome - The sum total of all the genetic information in an organism; its instruction book—the blueprint that directs the development and functioning of human beings and other organisms.Genomics - The study of genes and their function.

Nutrigenetics - Focuses on the impact the changes in our genes (also referred to as polymorphisms) have on our potential health path,

which is strongly influenced by food, nutrition, stress, and toxins.

Nutrigenomics - Concentrates on the impact of diet and lifestyle factors, such as food, nutrition, stress, and toxins on gene expression.

Nutritional Epigenomics -

Focuses on the

changes in gene expression influenced by modifications to DNA and its associated proteins without changing the nucleotide sequence of DNA

, where the genetic information is stored. These epigenomics changes affect gene expression and can also be inherited.Slide72

Contact Me

Janet Zarowitz, MS, RD, CDNIntegrative and Functional Nutritionist

www.mysupplementRD.com

Janet@mysupplementRD.com

914-222-3919