1. Nutrigenomics: Using Genetic Clues to Personalize Nutrition
How many of you know about nutrigenomics?
NYSAND Annual Meeting & Expo May 21, 2016
Janet Zarowitz, MS, RD, CDN

2. Nutrigenomics!
The study of the effects of foods and food constituents on gene expression
Gene with a G!

3. Nutrigenomics
Building Upon What We Already Know Dovetailing With Established Science
Well Accepted
Diet and lifestyle choices can significantly affect our health
Poor 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 predispositions
I think we can we agree on these

4. Building Upon What We Already Know
Family History
Building Upon What We Already Know
Let’s go back to what we already know:
For a long time using family history for clues about potential health risks
Family history is an invaluable part of patient intake forms, covering cancers, heart disease, high blood pressure, diabetes, allergies, etc.
Family History provides clues to Potential for health and disease, looking for genetic trends

5. The same is true for Genetic Profile
Family History
Potential and Predisposition
NOT DESTINY
Talking about genes or a group of genes that can boost your risk of getting a disease vs. genes that always cause disease every time they are present. E.g. sickle cell, Tay-Sachs
The same is true for Genetic Profile

6. Role of Genetic Profile
In the Patient Care Process
Genetic profile “joins” the intake process, alongside:
Patient’s genetic profile provides new information that Dietitians can use in the intake and assessment process.
Family History
Signs and Symptoms
Medical History/Diagnoses
Lab Values, Biomarkers
Medications, Supplements
Diet, Cooking, Eating Environment
Lifestyle, Exercise, Self Care
Social Network, Supports
…to help figure out the patient puzzle

7. Genetic Profile Mapping a Person’s DNA
Individual’s genetic characteristics (DNA analysis) can:
Provide insight into potential for developing certain diseases
Offer clues to root causes of disease/symptoms
Help reduce guesswork in treating suboptimal health

8. Gene Expression
Epigenetics, or how genes are expressed is where Nutrition gets into the game.

9. Nature Meets Nurture Epigenetics - Where Genes Meet the Environment
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 Environment
Nature Meets Nuture.
The Environment (nurture) interacts with Genes (nature) and can change their expression.
Twin studies - twins raised apart - have been trying tease out nature and nuture
Twins - Danny deVito and Arnold Schwarzenegger
Big Business - Lily Tomlin and Bette Middler
**********************************
The environment, which of course includes diet and food, influences a network of chemical switches within our cells collectively known as the epigenome. - nova

10. 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 mix
Exercise, lifestyle, stress, aging, diseases
Prenatal, childbirth, early life experiences
Chemicals, toxins, radiation, pathogens, drugs ….. they all affect gene expression ….. the genome adapts to environmental factors
Nutrition is a Primary Environmental Factor
Epigenetics is the process by which specific chemical marks are selectively placed either on the genes or on the nucleosomes that regulate the way genes are expressed.
These marks constitute methylation, acetylation, phosphorylation, and ubiquitination processes that attach specific chemical marks to the genes as a result of environmental signals received by the genes. These marks can represent either “read here” or “silencing” messages for the genes.
The queen bee and worker bees have same genonome; queen bee’s epigenotype is determined by feeding of royal jelly and its nutritive factors!
KEY PAPER Transposable Elements: targets for Early Nutritional Effects on Epigenetic Gene Regulation, by Waterland and Jirtle in J of Molecular and Cellular Biology. — e\Epigenetic alterations at metastable epialleles are likely a mechanistic link between early nutrition and adult chronic disease susceptibility. (supplementation of mice with nutrients supporting methyl donors - b12, choline, betaine, folic acid, — yielded a different coat color in offspring
further exploration of epigenetic methylation of the genome
further work found that genistein, phytochemical found in soy , could also epigenetically alter the epigenome through altered methylation of the genes in the agouti mouse, thereby preventing obesity and diabetes.
This work has been followed by numerous studies confirming their observations and demonstrating that many phytochemicals found in specific plant foods can alter the epigenetic methylation of the genome and genetic expression into the phenotype.
The phytochemicals that have been found to influence epigenomic modification of histone proteins, methylation, and inhibitory RNAs include epigallocatechin gallate from green tea, genistein from soy, indole-3-carbinol, sulforaphane and phenylisothiocyanate from cruciferous vegetables, lycopene from tomatoes, curcumin from turmeric, and resveratrol from grape and peanut skins.

11. Intergenerational Transmission
We know genes can be inherited, but did you know that Genetic expression is also be inherited - actually passed down to the next generation - without changing the DNA?
So the nutrition of their parents/grandparents (genomic imprinting) affects them too — genetically.
But the altered expression of these genes is also potentially reversible! ********************************
Current Topics in Medicinal Chemistry. 2016;16(7):
Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins.
Declerck K, Vel Szic KS, Palagani A, Heyninck K, Haegeman G, Morand C, Milenkovic D, Berghe WV1.
Abstract
Nowadays, epigenetic mechanisms involving DNA methylation, histone modifications and microRNA regulation emerge as important players in cardiovascular disease (CVD). Epigenetics may provide the missing link between environment, genome and disease phenotype and be responsible for the strong interindividual variation in disease risk factors underlying CVD. Daily diet is known to have a major influence on both the development and the prevention of CVD. Interestingly, the dietary lifestyle of our (grand)parents and of us contributes to CVD risk by metabolic (re)programming of our epigenome in utero, after birth or during life. In contrast to genetic mutations, the plasticity of CVD related epigenetic changes makes them attractive candidates for nutritional prevention or pharmacological intervention. Although a growing number of epidemiologic studies have shown a link between the ingestion of nutritional polyphenols and cardiovascular health benefits, potential involvement of epigenetic mechanisms has been underexplored. In this review, we will give an overview of epigenetic alterations in atherosclerosis, with the focus on DNA and histone modifications by chromatin-modifying proteins. Finally, we illustrate that cocoa flavanols and other classes of dietary molecules may promote cardiovascular health by targeting multiple classes of chromatin writer-reader-eraser proteins related to histone acetylation-methylation and DNA methylation.
Expression of genes, turning them on and off, can be affected at different levels - DNA level, histone level
methylation turns off gene expression
DNA is supercoiled, tightly wrapped around proteins called histones, which are then covered with methyl chemical compounds.
histone modification - acetylation opens and deacetylation closes
DNA methylation - methylation of CpG islands in promoter region of genes
genomic imprinting - inherited change in DNA expression
-methylation -histone modulation -microRNA gene silencing
Most genes are transcribed into "messenger" RNA (mRNA) and, ultimately, into a protein product.
From Macmillan Publishers Ltd: : Qiu, J. Nature, 2006, 441, 143, copyright (2006)

12. Are Nutrition Professionals Already Practicing Epigenetics?
Dietary Polyphenols and Cancer Prevention
Eat Rainbow of Foods More Plant-based Foods
Tomatoes
Apples
Citrus
Turmeric
Garlic
Cinnamon
Broccoli
Cashews
Grapes
Tea
Are RDs already practicing Epigenetics?
This study looked at polyphenols in diet and their protective role against cancer
RDS for a long time promoted foods high in polyphenols - fruits, vegetables, herbs, spices, colors of the rainbow.
These foods can alter genetic expression which can then be inherited
further work found that genistein, phytochemical found in soy , could also epigenetically alter the epigenome through altered methylation of the genes in the agouti mouse, thereby preventing obesity and diabetes.
This work has been followed by numerous studies confirming their observations and demonstrating that many phytochemicals found in specific plant foods can alter the epigenetic methylation of the genome and genetic expression into the phenotype.
The phytochemicals that have been found to influence epigenomic modification of histone proteins, methylation, and inhibitory RNAs include epigallocatechin gallate from green tea, genistein from soy, indole-3-carbinol, sulforaphane and phenylisothiocyanate from cruciferous vegetables, lycopene from tomatoes, curcumin from turmeric, and resveratrol from grape and peanut skins.
As a consequence of the advancing knowledge concerning the role of dietary and nutrient factors in the alteration of the epigenome, there is increasing evidence that demonstrates the important role of diet in altering genetic expression through specific epigenetic mechanisms, including histone modifications, DNA methylation, non-coding RNA expression, and chromatin remodeling. These factors help to mechanistically define why individuals may have vastly different responses to dietary signals and underpin the concept that there is no perfect diet for all people.
***********************
Effects of dietary polyphenols on the DNA methylation and histone modifications
Epigenetic changes that occur during carcinogenesis.
In cancers, tumor suppressor genes become “inactivated” while oncogenes are “activated”.
Epigenetic gene expression regulation is a complex process and several key enzymes play crucial roles.
DNA methyltransferase (DNMT) is responsible for transfer of methyl group to 5′-cytosine. Histone acetylases (HAT) and histone deacetylases (HDAC) are responsible for the acetylation and de-acetylation of lysine residues within histone tails, respectively. Because of these histone modifications, conformational changes in chromatin structure lead to changes in DNA accessibility for transcription regulators and polymerases.
Polyphenols can impact these enzymes in specific ways induces reversibility of epigenetic dysregulation in cancer cells.
Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression.
In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs.
Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies.
More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans.
Biochem Pharmacol Dec 15;80(12): doi: /j.bcp Epub 2010 Jun 26.
Cancer chemoprevention by dietary polyphenols: promising role for epigenetics.
Link A1, Balaguer F, Goel A.

13. Isolating Compounds & Epigenetics
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 expression
ssociated with changes in epigenetic mechanisms regulating gene expression, such as selenium and zinc, which intervene in the regulation of DNMT activity and play a key role in the one-carbon pathway and in the activation of most HDACs (Ho et al., 2011). High levels of various inorganic and organic forms of heavy metals have been also related to epigenetic effects, including chromium, arsenite,
lead, cadmium, copper and nickel (Cheng et al., 2012). Magnesium is other element that is able to modify epigenetic marks.
Another paper explaining - in terms of epigenetics— why foods/food components recommended by RDs, have a beneficial effect.
For example, dietary fiber — is fermented by beneficial bacteria in the colon which then produces buyrate, short chain fatty acid. Butyrate has a protective effect on gene expression
Nutrition supplements often utilize the active compounds as a more intensive therapy - such as curcumin, resveratrol, quercetin.
Dietary Manipulation of Histone Structure and Function, Barbara Delage and Roderick H. Dashwood
Annu Rev Nutr. 2008; 28: 347–366.

14. Epigenetics & Personalized Nutrition
“From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?”
Here’s an article from the — summarize/simplify
Journal Clinical of Epigenetics
“From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?”
Makes the case for personalizing nutrition to reduce inflammation, chronic disease and aging, according to each individual’s profile of particular genes.
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
Clinical Epigenetics, 2015 Mar: 7(1):33, vel Szic, Vidakovic, and Berghe

15. 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.

16. How I Started Testing Options
Reference integrativerd.org
Brought up the topic with my doctor about having the MTHFR test done. She gave me a take home/mail in finger prick kit.
When I wanted to have information about my full profile, I did the 23andme.

17. 23andMe Process Order at-home saliva kit through http://23andme.com
Mail-in
NYS workaround
Results ed within several weeks
Raw data 1000’s genes vs. few
Upload data file to third party websites for interpretive genetic reports, e.g., MTHFRSupport.com
When I did it all I got was the raw data — no health reports telling clinical significance from 23and me
(Several years ago 23andme was allowed to offer some health reports but then FDA prohibited them from doing it)
So I had to take the raw data and upload it to programs that would interpret its clinical significance
FDA just changed their position and will allow 23 to provide some health reports - how complete they will be is not known
It’s all evolving

18. Reading Genetic Reports
Understanding SNPs/Gene Variations
Single 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 change
To understand how to use Genetic Information and Reports I have to explain SNPs or single nucleotide polymorphisms.
*************************
A variation in a single DNA nucleotide or code (recipe) for a protein.
Most of the variation in people is due to SNPs
4 nucleotides make up DNA A = Adenine T = Thymine C = Cytosine G = Guanine
Adenine pairs with Thymine, Cytosine with Guanine.

19. What’s Their Relevance?
SNPs
What’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 risk
Genes 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, PhD
Resilience genes have been identified that can improve insulin sensitivity, increase antioxidant defense, improve detox of specific chemicals, enhance immune response to infectious organisms and improve metabolism of dietary fats and carbs, — how mutations can help people maintain good health in a suboptimal environment. Their expression/activity is sensitive to environmental, lifestyle and dietary factors.
may be a family of genes that imparts resilience/reduce physiological disturbances — keeps genes associated with disease risk from being expressed
can we identify resilience genes in people and personalize a program to optimize their expression?

20. Affecting the Body’s Ability to Do Work
SNPs
Affecting the Body’s Ability to Do Work
SNPs reflect the ability of the body to do work
Some SNPs reduce function, less often enhance function
More 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 requirements
Effects of these SNPs can be substantially mitigated with targeted nutritional approach - diet and supplementation
Metaphor - presentation by Dr. Ben Lynch - helps me understand SNPs.
if wheelbarrow is coded by a gene with a snp
he makes analogy of wheelbarrow
Think of the protein coded for by that gene as a wheelbarrow
And a wheel barrow is a tool designed to do work
If the wheelbarrow has a variation (like a gene has a SNP), maybe it’s a cracked handle, it can still perform the job, but you may have to be more careful when handling it.
tire flat - If the wheelbarrow wheel is also flat, not only will you have to be more careful when handling it, you may also only be able to move it slowly.
hole in container - On top of that, if the body of the wheelbarrow has a hole in it, some of its contents may fall out along the way.
So this wheelbarrow will still perform the work, but less efficiently.
Larger container - And there are situations where the wheelbarrow will be more efficient, for example if the container is larger than usual.
Similarly, if you have a SNP your body can still do the work, though it may be just less (most common) or more efficient.

21. Homozygous | Heterozygous
for each gene pair, SNP may occur in none, one or both copies of gene
on genetic reports “+” represents SNP
homozygous SNP “+/+” can have more significant health implications compared to milder heterogeneous genotype
Need to know about about homozygous and heterozygous SNPs for understanding genetic reports.
-/-
Homozygous “normal”
no SNPs
-/+
Heterozygous “variant” 1 SNP
+/+
Homozygous “variant” 2 SNPs

22. rsID Number or SNP ID identifies chromosomal locations
Reading Genetic Report -
Here’s a report from MTHFR Support which focuses on Genes involved with Liver Detoxification
1. rs ID - are Numbers used to identify the chromosomal locations of SNPs.
This is a very important reference point that’s used in research studies or between different reports
As you can see, there are multiple potential SNPs for each gene.
2. Under Your Results - you’ll see the hetero – or homozygosity that we discussed on the previous slide.
color coded -
Results in Green (no SNPs) or -/-
Yellow (1 SNP or heterozygous) or +/-, and
Red (2 SNPs or homozygous) or +/+

23. Nutritionally Relevant Genes
Well Researched
MTHFR C677T and A1298C folate and methylation
COMT Val/Met 158 methylation, mood and estrogen metabolism
We are going to look at SNPs in two well-researched nutritionally relevant genes, how to assess if nutrition strategy is warranted and what the nutrition protocol would be.
********************************
MTHFR - In the standard population, up to 50% have the likelihood of having 1 MTHFR mutation while 10-20% have 2 copies of the MTHFR mutations.
Esp prevalent in Italian and Mexican populations
COMT - COMT gene polymorphisms are VERY common.
A 2015 study published in Sleep Medicine Reviews highlights the fact that that 30% of people are homozygous (+/+) and 50% are heterozygous (+/-) for the COMT V158M allele.
DAO -

24. What is Methylation? Chemically Speaking
Methylation is a biochemical reaction in which a methyl group (CH3) is attached to a molecule, converting it to a different molecule
let’s look at methylation and then mthfr
*****************************

25. What is Methylation? Clinically Speaking
Methylation has vital roles in:
epigenetics and gene regulation (DNA methylation & histone acetylation)
neurotransmission
amino acid metabolism
DNA synthesis and repair
hormone detoxification
vitamin assimilation (including folate)
homocysteine clearance
cell membrane structure
Clinically Speaking
let’s look at methylation and then mthfr
****************************

26. Methylation Pathway SNPs
May Present As
loss of digestive integrity (rapid cell turnover), food intolerances
mood disorders, depression, anxiety, cognitive function deficits
neural tube defects
endocrine imbalance (estrogens), environmental toxin buildup (phase 2 liver)
cancer, e.g. colorectal, breast, lung (altered suppression of gene transcription)
So you can see how widespread health problems/symptoms can be if methylation is compromised.

27. Methylation Pathway SNPs
May Present As
cardiometabolic 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 immunity
Neural tube defects and folic acid
carnitine production - fatty acid transport an muscle energy)

28. So That’s Why We Had to Take Biochemistry!
Methylation Pathways
So that’s why we had to take biochemistry!
A few slides here about Methylation Pathways.
I hope I’m not tapping into any nightmarish recollections about your college biochem or organic chemistry courses.
You don’t have to memorize them!
I am not a biochemist either, but I’ll present 1 or 2 takeaways from each slide.
Pharmacologists develop new drugs based on biochemical pathways all the time.
As nutritionists, we work with functional foods.
These slides help explain how functional foods, nutrients and supplements work at a biochemical level.

29. Cycles of Methylation Pathway
Plus Krebs cycle
SAMe, Gluathione generation; phospholipids
Nitrogen removal
Neurotransmitters
Activates folate
This is the first of a series of charts developed by Dr. Amy Yasko, researchers and practitioner focusing on neurological issues, including autism.
Highlighted - 4 cycles that make up the methylation pathway.
Plus Krebs Cycle - generation of energy from proteins, CHO and fats - intersects with them.
Urea cycle - removal of nitrogenous waste
BH4 cycle - (tetrahydrobiopterin) - maintains levels of certain neurotransmitters in the brain, and regulation of the nitric oxide cycle;
Folate Cycle - folic acid is converted to the active form - 5 Methyl THF in the cells
Methionine Cycle - methionine ( a sulfur containing amino acide) is converted to SAMe (S−Adenosyl Methionine), which is a methyl donor for numerous reactions. In losing its methyl group, SAMe eventually is converted to homocysteine.
This cycle also produces glutathione, the body’s master antioxidant.
(Homocysteine is either converted back to methionine, or it enters the transsulfuration pathway to form other sulfur-containing amino acids.)
More than half of the population has SNPs affecting the methylation pathway.
Krebs cycle
fumarate
aspartate

30. Genes Code for Enzymes Gene Locations Genes
The blue boxes represent genes in the methylation pathway.
They code for enzymes.
Highlighted MTHFR and COMT, nutritionally relevant genes which I’ll be using as examples.
Genes

31. Enzymes Need Cofactors
Like Mg, Zn, Riboflavin, B12, B6
The purple ovals represent cofactors.
Enzymes need cofactors in order to function.
Cofactors of the methylation pathway include minerals like Magnesium, Zinc Iron, and B vitamins like Riboflavin, B6 and B12.
BH4 cycle - Tryptophan, tyrosine, and neurotransmitters: serotonin, dopamine, norepinephrine
So you see that SNPs in this pathway and inadequate cofactors may affect mood and cognitive function.
Folate cycle - active form of folate - 5 Methyl THF
So you see that SNPs in this pathway and inadequate cofactors may produce a reduced amount of the active form of folate.
Methionine cycle - methionine, SAMe, glutathione, homocysteine
So you see that SNPs in this pathway and inadequate cofactors may affect buildup of homocysteine levels and reduced methylation end products as well as reduced glutathione levels.
*************************
Folate functions as a coenzyme or cosubstrate in single-carbon transfers in the synthesis of nucleic acids (DNA and RNA) and metabolism of amino acids.
One of the most important folate-dependent reactions is the conversion of homocysteine to methionine in the synthesis of S-adenosyl-methionine, an important methyl donor and necessary for neurotransmitter synthesis
Another folate-dependent reaction, the methylation of deoxyuridylate to thymidylate in the formation of DNA, is required for proper cell division. An impairment of this reaction initiates a process that can lead to megaloblastic anemia, one of the hallmarks of folate deficiency
Folate is needed for proper cell division and RBC and WBC formation in the bone marrow
So a deficiency would affect all new cells, and in particular body systems with a rapid cell turnover rate and as we all know, for normal fetal development.
Genes
Cofactors

32. Nutrients Can Bypass SNPs
This is the last diagram! (also diagrams which show where environmental toxins block pathways)
Green boxes are nutrition supplements that can be added to support alternative pathways to bypass SNPs or mutations (blue boxes)
Nutrient bypass support in the methylation pathway includes 5-MTHF (folate), B12, methionine, SAMe, choline, DHA, phosphatidyl serine
Genes
Cofactors
Nutrient bypass support includes 5-MTHF (folate), B12,
methionine, SAMe, choline, DHA, phosphatidyl serine
Nutrient bypass support

33. MTHFR Gene Key Regulators of Methylation C677T & A1298C SNPs
Methylene 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)

34. Methylene Tetrahydrofolate Reductase
MTHFR Gene
C677T & A1298C SNPs
Methylene Tetrahydrofolate Reductase
Potential 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 levels
Both SNPs, if expressed, differ in their impact on health, but they share the same nutrition intervention.
change enzyme in diff way …leading to diff clinical problems
**********************
c677T
- +/- heterozygous SNP - Reduces enzyme function by 30%
+/+ homozygous SNP - Reduces enzyme function by 65-70%
MTHFR A1298C - enzyme functions at approx 30-45% of its normal rate
MTHFR - A1298C and MTHFR C677T - Compound heterozygous +/- heterozygous for both - Estimated at 50% loss of function

35. Making the Assessment Will Nutrition Strategy Help?
Take a holistic approach to determine if a nutritional strategy might help your patient with SNPs.
Look at all the clues.
YOUR DNA IS NOT YOUR DESTINY… it’s one factor

36. Look at Clues Holistically Treat the Person, Not the SNP
Making the Assessment
Look at Clues Holistically Treat the Person, Not the SNP
Take a holistic approach to determine if a nutritional strategy might help your patient with SNPs.
Look at all the clues.
Medical History/Diagnoses
Signs and Symptoms
Biomarkers
Dietary Intake
Special Requirements
Interfering Meds, Supplements
Environmental Toxins
Cigarette Smoking, Alcohol
Stressors - Emotional, Physical
AND Genetic Profile - SNPs

37. 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 syndrome
Weight 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, inflammation
(brush border of intestinal mucosal cells have enzyme that converts food bound folate to active form)

38. May Indicate Methylation Issues
Biomarker Clues
Of Undermethylation
Low Folate
Low B12
-Elevated Methylmalonic Acid -Elevated Homocysteine -Anti-parietal/Anti-intrinsic Factor Antibodies
-Elevated Homocysteine -Low RBC Folate Levels -High FIGLU in Urine
Elevated Methylmalonic Acid
Elevated Homocysteine
Anti-parietal/Anti-instrinsic Factor antibodies
******
Folate - RBC - less affected by recent dietary changes than plasma levels (RBC can be falsely low in alcoholism and pregnancy)
folate plasma levels best to do after fasting -can be affected by last meal
formiminoglutamic acid an intermediate metabolite in the conversion of L-histidine to L-glutamic acid (with the formimino group being transferred to tetrahydrofolate)
(B12 deficiency can decrease RBC folate)
see the charts from velszic article.
methylation status biomarkers - pg 13 from noland and wagner presentation
Methylmalonic Acid (functional B12)
• Folate
Vitamin B6 (serum)
also add lithium levels
The "FIGLU" test is used to identify deficiency of vitamin B12 or folate deficiency or liver disease.
The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load
Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.
Mutations in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making the enzyme formiminotransferase cyclodeaminase. This enzyme is involved in the last two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It also plays a role in producing one of several forms of the vitamin folate, which has many important functions in the body.
An intermediate metabolite in L-histidine catabolism in the conversion of L-histidine to L-glutamiate, with the formimino group being transferred to tetrahydrofolate; it may appear in the urine of patients with folic acid or vitamin B12 deficiency, or liver disease.
do urine test without histidine loading
use SAMe for anxiety
look up how methylation silences genes
May Indicate Methylation Issues
-Urinary estrogen metabolites panel - high hydroxyestrones, low methoxyestrones and ratios -Elevated Histamine -Anemias - megaloblastic or macrocytic

39. 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 drug; work with MD
Many use up methyl groups, others reduce absorption/production of nutrients.
**********************
acid blockers & antacids - deplete probiotics, suppress ability to make B12, production, reduce absorption of Ca, Mg, etc.
cholesterol-binding drugs - reduce absorption of folate and cobalamin from food
anti-seizure drugs*- deplete folate
estrogen drugs - birth control, menopause meds - “drug mugger” of folate
methotrexate* -“drug mugger” of folate
metformin -“drug mugger” of B12
sulfa-containing drugs - inhibit other enzymes in methylation pathway *don’t supplement with folate at same time or will negate effect of drug* ******************************************************
Medications that use up methyl groups - increase probability for increased need for methylation support
medications - metformin, methotrexate, antacids, acid blockers, proton pump inhibitors, corticosteroids, estrogen containing drugs and nitrous oxide. - Dr. Suzy Cohen - Drug muggers
supplements - niacin uses up methyl groups, green coffee bean extract is high in catchols and uses up methyl pathway nutrients fast
also things that use of nutrients required for methylation pathways
Environmental stressors - toxins in work-related or home environment increased need for detoxification, candida increased need to detox acetaldehyde
inflammatory medical conditions and need for more antioxidants (glutathione)
need for more methyl groups for detoxification, breakdown of histamines, candida, infections
high alcohol intake
stress
pregnancy, aging, growth spurts
lyme disease - uses up mgref re
if cant methylate properly have trouble eliminating poisons
if can’t methyl properly cant product C,Q 10 , carnitine, creatinine or ATP
if can't
Ref: Dr. Suzy Cohen, R Ph,

40. 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
Many use up methyl groups, others reduce absorption/production of nutrients.
**********************
acid blockers & antacids - deplete probiotics, suppress ability to make B12, production, reduce absorption of Ca, Mg, etc.
cholesterol-binding drugs - reduce absorption of folate and cobalamin from food
anti-seizure drugs*- deplete folate
estrogen drugs - birth control, menopause meds - “drug mugger” of folate
methotrexate* -“drug mugger” of folate
metformin -“drug mugger” of B12
sulfa-containing drugs - inhibit other enzymes in methylation pathway *don’t supplement with folate at same time or will negate effect of drug* ******************************************************
Medications that use up methyl groups - increase probability for increased need for methylation support
medications - metformin, methotrexate, antacids, acid blockers, proton pump inhibitors, corticosteroids, estrogen containing drugs and nitrous oxide. - Dr. Suzy Cohen - Drug muggers
supplements - niacin uses up methyl groups, green coffee bean extract is high in catchols and uses up methyl pathway nutrients fast
also things that use of nutrients required for methylation pathways
Environmental stressors - toxins in work-related or home environment increased need for detoxification, candida increased need to detox acetaldehyde
inflammatory medical conditions and need for more antioxidants (glutathione)
need for more methyl groups for detoxification, breakdown of histamines, candida, infections
high alcohol intake
stress
pregnancy, aging, growth spurts
lyme disease - uses up mgref re
if cant methylate properly have trouble eliminating poisons
if can’t methyl properly cant product C,Q 10 , carnitine, creatinine or ATP
if can't
Ref: Dr. Suzy Cohen, R Ph,

41. Environmental Stressor Clues
May Not Satisfy Methylation Requirements
Diet
-Low in leafy green vegetables and other folate-rich foods
-High in processed foods, many enriched with competing folic acid
-High alcohol intake
Environmental toxins
-Cigarette smoking
-Working or living near/with chemicals including household
Emotional or physical stress
-Injury, surgery, infection, pregnancy, aging

42. Genetic Clues - SNPs Clues suggest possibility -/- no SNPs -/+ one SNP
This report by PureGenomics clearly shows the SNPs in the methylation pathway (using the 23andme data)
In grey, you’ll see that this person is heterozygous for both MTHFR C677T and A1298C and it’s estimated that this person has about a 50% reduction in loss of function of this gene. This is very common.
That doesn’t mean that they the SNPs are expressed or that they are undermethylating.
nutrition recommendation for each genetic SNP
-/- no SNPs
-/+ one SNP
+/+ two SNPs

43. How Does it Add Up?
Clues Related to Possible Undermethylation + Methylation SNPs = Case for Nutrition Intervention
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 histamine
Postmenopausal woman on PPIs, borderline osteopenia
*Testing for Methylation SNPs - all young women prior to pregnancy
In summing up the clues I have just mentioned, here are a variety of clinical scenarios suggesting inadequate methylation. These patients would potentially benefit from genetic profile and nutrition intervention
estrogen drugs - birth control, menopause meds - “drug mugger” of folate
metformin -“drug mugger” of B12
acid blockers & antacids - deplete probiotics, suppress ability to make B12, production, reduce absorption of Ca, Mg, etc.
methotrexate* -“drug mugger” of folate
must work with doctor/ addl folate could negate drug

44. How Does it Add Up?
Clues Related to Possible Undermethylation + Methylation SNPs = Case for Nutrition Intervention
Family hx cardiovascular disease, blood clots, elevated homocysteine, low folate
Patient on cholesterol-binding med, brain fog, sleep difficulties, elevated methylmalonic acid
Teenager with anxiety, mood disorder, diet high in processed foods
Premenopausal woman, family hx breast cancer, imbalanced urinary estrogen metabolites (high hydroxyestrones, low methoxyestrones)
If you look back on the clues you will see that these are tip-offs to potential SNPs in MTHFR.
********************
cholesterol-binding drugs - reduce absorption of folate and cobalamin from food

45. Nutrition Intervention for MTHFR SNPs
Integrating Diet and Supplements
******Let’s go through this process for the well studied SNPs in the MTHFR gene - C677T and A1298C.
We’ll look at:
Gene Function and Potential Impact of SNPs
Then we’ll look at clues for Assessing Nutrition Intervention.
In addition to genetic SNPs, we’ll look at:
Symptoms/Diagnosis, Biomarkers, Lab Values, Medications, Diet, Environmental Stressors

46. Targeted Nutrition Support
for MTHFR C677T and A1298C SNPs
STRATEGY: BYPASS GENE BY ADDING ACTIVATED NUTRIENTS
Supplement - First support pathways with minerals and B vitamins except folate and B12
Then, 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 supplement 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 - Multivitamin containing vitamins and cofactors
Can also eat more foods/supplement with things that donate methyl groups - Betaine Anhydrous (Trimethylglycine) donates a methyl group for methylation. Beets and quinoa, and lamb, very high in Betaine. Betaine HCl is used for increasing acidity in the stomach and is also the form that is more capable of reducing homocysteine.
by pass MTHFR SNPs by supplementing with active, universally metabolized form of folate (5-mthf/Metafolin); up to 1000 mcg. (RDA of folate is 400 mcg.)
daily supplementation with 1.7 mg ribofvain, the cofactor for mthfr,
more than half of the population has snps affecting the methylation pathway.
FOLINIC ACID, which also is known as 5-formyl tetrahydrofolate, is naturally found in foods

47. Targeted Nutrition Support
for MTHFR C677T and A1298C SNPs
Limit synthetic folic acid which may compete with active form of folate
Diet - Limit processed foods enriched with folic acid
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, lamb

48. Why Diet May Not Be Enough
Using Supplements
Why Diet May Not Be Enough
Inability to convert vitamin form in food to bioactive form body requires; active form of nutrient can bypass affected gene
Assimilation 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 stability

49. Best Practices Addressing Methylation
Using Supplements
Best Practices Addressing Methylation
Begin with supplement with minerals & B vitamins except B12 & folate
Transition to multivitamin for foundational support of methylation path
With cofactors, vitamins, minerals of methylation cycle, highly bioavailable, active forms e.g., Puregenomics
Start slowly, one new supplement/dose at a time
Check B12 levels before giving folate
Concurrently address other issues - e.g. inflammation, GI problems
Work with the MD regarding certain medications, diagnoses
Puregenomics Multivitamin - was specifically designed by Dr Kelly Heim for Pure Genomics to address nutrient requirements of common genetic variations in the methylation pathway
It’s a foundational product
addition of targeted nutrients
nutrients in the most bioavailable form
800 mcg active folate - Metafolin (L-5-MTHF)
1000 mcg B12 as blend of adenosylcobalamin and hydroxycobalamin
activated B vitamins like P-5-P, riboflavin-5-phosphate, benfotiamine (thiamin with enhanced retention)
bioavailable nutrients - vitamins A, C, D, E, fully-chelated minerals and antioxidants
folate support cell division, cell division needs MG and K which Puregenomics Multivitamin does NOT have

50. Monitoring Nutrition Support
Follow-up - how pathways are “pushed” or driven; feelings of detoxification
Monitor dietary and lifestyle changes, supplement compliance, symptom changes (digestive, mood, sleep, pain), side effects
3-6 months revisit physiological biomarkers
(some people get jittery with folate or methyl B12 supplementation)

51. Assessing Nutrition Intervention for COMT
Neurotransmitters
Let’s go over one more example, COMT - part of BH4 pathway
I highlighted the serotonin, dopamine and norepinephrine that need the COMT enzyme and hence the COMT gene.
So you see that SNPs may affect mood and cognitive function.

52. COMT Gene Val/Met158 SNP
Another SNP with Nutritional Relevance in methylation pathway
Catechol-O-methyltransferase
Gene function: encodes catechol-O-methyltransferase enzyme
Enzyme function: metabolizes and detoxifies dopamine, norepinephrine, epinephrine and estrogens through methylation process

53. Catechol-O-methyltransferase
COMT Gene Val/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 stimulants
Dopamine, norepinephrine, epinephrine & estrogens may build up
May have greater impulsivity in behavior choice
Cognitive performance may be affected
Just like with MTHFR - have to look at all the clues — including the genetic profile, symptoms, potential biomarkers, etc.

54. Targeted Nutrition Support
STRATEGY: SUPPORT ALTERNATE METHYLATION PATHWAYS, SUPPORT LIVER, FOSTER RELAXATION & SLEEP
Support alternate pathways that bypass the COMT SNP
Diet – 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 - More cruciferous vegetables, garlic, onion, fruits, vegetables, nuts, herbs, spices
Diet - Organic foods and animal protein without raised without hormones or antibiotics, as much as possible
for COMT Val/Met 158 SNP

55. 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 load
Support 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 SNP

56. More Genes with Nutritional Relevance
Potential Impact of SNPs
DAO & HNMT - potential for histamine intolerance
HLA-DQ - potential for celiac disease 95% 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 BP when high Na intake
DAO - diamine oxidase - other dietary interventions include a low histamine diet, supplementation of DAO, mast cell stabilizers like quercetin, vitamin C, and anti-histamines.
HLA-DQ - cell surface receptor protein found on antigen presenting cells. - since a person with these SNPs only have the potential to have celiac disease, discuss with MD if a low gluten or gluten free diet might be worth trying, especially if they have symptoms but are undiagnosable
MTR A2756G - methionine synthase - methylates homocysteine to methionine; this SNP increases the efficiency of the MTR enzyme which increases demand for B12; without adequate b12 levels people with this SNP may exhibit higher homocysteine and reduced overall methylation potential.
Support includes multivit, folate and b12 - supplements and diet

57. More Genes with Nutritional Relevance
Potential Impact of SNPs
MTRR - may have slower B12 regeneration
CBS - may have reduction of intermediates required for transsulfuration and detoxification
TCN2 - delivery of B12 to cells may be limited
FUT2 - intestinal microbial diversity and bifidobacteria levels may be low; may also be protective of B12 status
MTRR A66G - mtr reductase - less efficient reactivation of used B12; reduced methylation status and may have low b12 levels; supplement with PureGenomics and B12
CBS C699T - cystathionine beta-synthase - converts homocysteine to cystathionine, a precursor of amino acid cysteine; SNP is an upregulation; may divert homocysteine from methylation pathway, reducing intermediates required to make glutathione and other sulfur containing derivatives; supplement with PureGenomics multivit and B6
TCN2 C776G - transcobalamin - encodes this protein which transports B12 from plasma to cells; may have noraml serum b12 levels but low intracellular levels. Elevated methymalonic acid and/or elevated homocysteine is common; supplement with Puregenomics multivit and higher dose of B12; more than 20 % of population has one or 2 SNPs.
FUT2 G772A - alpha -1,2-fucosyltransferase - limits b12 absorption, regulates gut microbiota and adhesion of microbes to intestinal mucosa; SNP associated with lower intestinal microbial diversity and lower bifidobacteria levels. Has PROTECTIVE effect on B12 status; supplement with probiotics and multivitamin

58. More Genes with Nutritional Relevance
Potential Impact of SNPs
GC - 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 triglycerides
BCOM1- may have limited β-carotene to Vitamin A conversion THIS PARTIAL LIST WILL CONTINUE TO GROW!
MTRR A66G - mtr reductase - less efficient reactivation of used B12; reduced methylation status and may have low b12 levels; supplement with PureGenomics and B12
CBS C699T - cystathionine beta-synthase - converts homocysteine to cystathionine, a precursor of amino acid cysteine; SNP is an upregulation; may divert homocysteine from methylation pathway, reducing intermediates required to make glutathione and other sulfur containing derivatives; supplement with PureGenomics multivit and B6
TCN2 C776G - transcobalamin - encodes this protein which transports B12 from plasma to cells; may have noraml serum b12 levels but low intracellular levels. Elevated methymalonic acid and/or elevated homocysteine is common; supplement with Puregenomics multivit and higher dose of B12; more than 20 % of population has one or 2 SNPs.
FUT2 G772A - alpha -1,2-fucosyltransferase - limits b12 absorption, regulates gut microbiota and adhesion of microbes to intestinal mucosa; SNP associated with lower intestinal microbial diversity and lower bifidobacteria levels. Has PROTECTIVE effect on B12 status; supplement with probiotics and multivitamin

59. Nutrigenomics Best Practices
Focus on well-researched, evidence-based nutritionally relevant SNPs
SNPs represent potential for suboptimal functioning – their expression not predetermined
A homozygous SNP (+/+) can have more significant health implications compared to milder heterogeneous genotype
Understand the gene’s role, related biochemical pathways

60. Keeping Nutrigenomics 2016 in Perspective
Providing Clues and Potential, Not Certainty
Genetic research and relevance of SNPs in its infancy
If multiple SNPs in a particular gene, impact may be more significant
Nutrigenomics is complementary with medical nutrition therapy, integrative nutrition approaches
Look at all the clues … do they validate each other?
Treat the patient not the SNP!

61. No SNP is an Island
Genes don't work in isolation — work synergistically
Chronic diseases affected by multiple genes; impact of single SNP, even if relevant, usually small
Body designed with “backup systems” — biochemical pathways overlap
May be compensatory genes in closely related pathways that support the body’s performance
Mix of positive and negative environmental factors that impact genes (and SNPs) and their expression is infinite

62. Plus Gut DNA!
Gut microbiome - second pool of person’s genetic material
100 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 biome
Gut bacteria (under their DNA instructions) respond to food just like human genes; their end products influence epigenetic expression Examples: gut bacteria’s response to dietary fiber and phytochemicals
RDs already address balance of gut ecology with diet, probiotics
Even more context to consider!
Consider the DNA from the microbes in our gut and their genetic expression!
NIH established the Human Microbiome Project

63. 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.
No, we can’t change our genetics but we can eat the right foods and take supplements to support our genetic predispositions.

64. Part of Functional Medicine Model
Nutrigenomics
Part of Functional Medicine Model
Health now recognized as more than absence of disease
Nutritional 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, PhD
DIFM - Dietitians in Integrative and Functional Medicine - is a growing Academy practice group
I wonder how many here today are members of DIFM?
************
defining these disturbances will not rely upon grouping and labeling common signs and symptoms, but rather will be informed by a systems approach to understanding how genetics, lifestyle and environment intersect with physiological function
This approach will help us optimize health, uncover subclinical health imbalances, understand chronic diseases and have better outcomes
health over a lifetime is not determined at conception by our dna

65. Future of Nutrigenomics

66. Present & Future Research
More Precise Predictability, Disease Prevention, Early Intervention, Confirmation
More information about gene function, nutritionally relevant SNPs, clinical implications
More research on effects of foods & nutrition supplements on gene expression
More 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 consumer

67. 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 presents

68. Resources DIFM - integrativeRD.org
DIFM list serve - Q & A’s with fellow RDs
Links to testing, books and websites
International Society of Nutrigenetics and Nutrigenomics (ISSN) relationship

69. Resources Dr. Amy Yasko – knowyourgenetics.com - neurological/autism
Dr. Ben Lynch: mthfr.net
mthfrsupport.com
Dr. Eric Balcavage – the methylationdoctor.com
SNPedia – snpedia.com
******
Yakso- her own protocols for autism - reducing excitotoxins, GABA:Glutamate, lithium, balance Ca:Mg (add mg) calcium opens up nerve channels and increases excitability
then short cut of methylation pathway - DHA, phosphatidylserine
Then long route of methylation pathway b12 then folate (don’t want to mask B12 deficiency)

70. Resources
NIH
National Center for Biotechnology Information ncbi.nlm.nih.gov/clinvar/
National Human Genome Research Institute genome.gov
Genetics Home Reference, US National Library of Medicine ghr.nlm.nih.gov
Genome magazine – genomemag.com
******
Yakso- her own protocols for autism - reducing excitotoxins, GABA:Glutamate, lithium, balance Ca:Mg (add mg) calcium opens up nerve channels and increases excitability
then short cut of methylation pathway - DHA, phosphatidylserine
Then long route of methylation pathway b12 then folate (don’t want to mask B12 deficiency)

71. 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.

72. Janet Zarowitz, MS, RD, CDN Integrative and Functional Nutritionist
Contact Me
Janet Zarowitz, MS, RD, CDN
Integrative and Functional Nutritionist