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The Nutrigenomics Guidebook

The Nutrigenomics Guidebook April L. Ward -Hauge MS, NP, BCIM

April L. Ward-Hauge MS, NP, BCIM

“The person who says it cannot be done should not interrupt the person doing it”

Chinese proverb

Biochemical nutrigenomics is an evolving science. As such, we do not have the advantage of two or more decades of “Double blind placebo controlled” studies to lead our way. Nevertheless, we do have chemistry pathways that have been well characterized. We are also privileged to have a core group of scientists and physicians wh o are willing to accept the overwhelming responsibility of devising and implementing highly intricate protocols. Their steadfast dedication has led many considerably ill and “incurable” patients through a maze of biochemical pathways toward health and rec overy.

In truth, absolutely n othing in life is static; it is a constantly changing continuum. Therefore, we will undoubtedly modify a variety of treatment strategie s throughout the following decades . The key is in finding the right balance for each in dividual’s needs. Rather than strictly adhering to a single theory, I have chosen what I believe are the best principles from each scientific trailblazer. I thank God for such outstanding thinkers and mavericks. And while the list is certain ly much long er, the following physicians and scientists have inspired this guidebook.

Russell Blaylock MD

Andrew Cutler, PhD

Madeleine Cunningham PhD

Richard Deth, PhD

Max Gerson MD

Nicholas Gonzalez MD

Linda Isaacs MD

Jill James PhD

Nancy Mullan MD

John Olney PhD

M artin Pall PhD

James Roberts MD

William Shaw PhD

Susan Swedo, MD

Richard Van Konynenburg, PhD

Rosemary Waring, PhD

Amy Yasko PhD, NHD

In a world in which survival of the fittest makes the difference between happiness and success versus desperation and fut ility, we now have hope for the millions who have been cast aside. This handbook is dedicated to the scientists and practitioners who envisioned a future where everyone has the opportunity to live their lives to their fullest potential. Let it not be sai d that recovery wasn’t possible; only feared, distrusted, or unheeded.

Index

Acknowledgements

2

Surviving change

6

Part 1: The Protocol

Introduction

8

Definitions

9

SNP Test Examples

11

Protocol Steps

15

General Support

23

Lifestyle Factors

25

Part 2: The SNPs

The Enzy me Defects & Mutations

28

ACAT & The Citric Acid Cycle/Kreb’s Cycle

30

High Ammonia

38

Second Priority Mutations

44

M ethyl Donor Status

53

The Folate Trap

59

Part 3: DNA Is Not Destiny

Nutrigenomics & Epigenetics

61

Genetic Testing & SNPs

64

DNA is Not Destiny: The Agouti Mice

66

The Methylation Commun ity & Your Body Chemistry

67

S implified Diagrams

68- 69 & 72

Part 4: The Cycles

The Energy Cycle (CAC)

74

The Waste Cycle (Urea)

76

S ummary of the Cycles

78

BH4 Cycl e

79

The Fa rming region (folate)

81

Methyl Donors & Ammonia Provokers

83

Lipid Donors

83

SAM’s Industry (Methionine)

84

The Bad Boys: Free Radicals

85

Review

88

Disorders relat ed to poor methylation

89

Part 5: Neurotransmitters/Neurotalkers

Neurotransmitters

90

The E xcitatory NT’s

91

The Inhibitory NT’s

93

Part 6: Detoxification

Detox 101

95

Methods for easing detox symptoms

96

Coffee & Juice, anyone?

98

Common Pit falls

98

Common signs & symptoms of detox

100

Urine & Stool Testing

101

Part 7: Nervous System Dominance

Parasympathet ic Nervous System (PNS)

104

Sympathet ic Nervous System (SNS)

107

Balanced or Mixe d

109

SNS vs. PNS Table

111

Part 8 : Dietary Components

Dietary st rategies for children (& adults!)

113

Excitotoxins

117

Tips f or removing Glutamates

122

Sulfu r/Sulfites & Thiols

124

Phenols

128

Pesticides & The Dirty Dozen

132

How to make supplements

133

Part 9 : Miscellaneous

Immune Factors

136

Stoma ch Acid & H. Pyl ori

137

Streptococcus & PANDAS

139

Herpes Viru s

142

Drs. Yasko & Van Konynenburg’s Basic Methylat ion Support

143

Frequently asked Questions (GcMAF, BH4, & RNA )

145

Part 10: Definitions & References

Definitions

149

Clinic Questions

157

Resources & Bibliography

158

Disclaimer : The information and suggestions included with in this nutrigenomi cs guidebook are not intended as a substitution for your physician’s recommendations . Furtherm ore, the content withi n is meant as a brief overview rather than a comprehensive didactic regarding the vas t yet evolving scientific fields of nutrigenomics, epigenetics, and biochemical medicine. The reader is fully encouraged to seek additional knowledg e thro ugh all available methods .

The New Survivor

While America was ensnared in the ever- popular series known as “Survivor,” my husband and I went on some expeditions of our own, only ours weren’t nearly as glamorous and there was never any promise of a huge reward, only debt. I would listen in fascination as staff members and colleagues would discuss whether Jessie and Ethan were going to win this week and whether they could make it through Africa. They seemed to know all about their lives, from the mu ndane to the exciting. I, on the other hand, had spent the entire night either cooking everything from scratch or researching the new findings within the methylation pathway, courtesy of Jill James, PhD. How could everyone be so vacuous? I often felt that a REAL challenge would be to have these couples travel around the world with autistic children. Now THAT would be a challenge worthy of great praise! I can see it even now, Jessie and Ethan in the peak of youthfulness, dragging an amazingly energetic c hild from place to place, in between meltdowns that rival Big Time Wrestling, while passersby disgustedly shake their heads at them for being such incredibly inept, weak parents. Anyone can see that if they just learned to discipline him, he’d be fine.

W hile I didn’t understand it then, I do now. It’s obviously escapism at its best (worst?). Americans need to hide from the reality of their lives and even while I regularly daydreamed about doing the same, I couldn’t have lived with myself. While my days were filled with dispensing advice and problem - solving issues for my patients, my nights were filled with constant terror. I studied impossible subjects, some of which I had never heard of, and they weren’t coming easily. When you’ve seen “Methylentetra hydrofolate reductase” for the tenth time, it’s really no better than the first time. Nor did it ease my mind when I queried all of my physician colleagues while they stared uncomprehendingly at the diagrams and charts. Yet, like many parents and patient s before me, I was determined! Even so, I had no idea that it would take 3 years of intensive research in order to comprehend and connect fields as diverse as biochemistry, genetics, and nutrigenomics as well as metabolic and mitochondrial medicine. The main reason this personalized guidebook exists is to make it easier for others.

Nevertheless, as you’ve probably suspected, it won’t be simple or easy and many inquire about surviving such an experience. While I haven’t found anything that p rovides a n easy route to salvation, I can assure you that it can be done; it simply has to be done gradually. In an age of ATMs, iPhones, texting, and TiVo , I fully realize that human nature dictates healing and redemption must occur straightaway. Most have suffered with chronic illness or struggled to manage career, family, home, an d a special needs child for too many years. I truly understand. I’ve been there myself, and sometimes, I’m still there. And it is often overwhelming!

As a patient of mine often says When I feel the need to stick a serving fork in my husband’s eye just because the sound of his breathing drives me into an irrational frenzy, I realize that I need some distance from the strain ”. Subsequently, it’s important to recognize that we all have our own style of coping. While some are in complete denial, others must take the “bull by the horns” and “fix this NOW!However, she did learn that once she cooled down and talked to him about it, explaining that she was going to purchase a rifle and perch atop the nearest clock tower, he came through and made the next load of peanut butter balls or laundry. I f I can impart anything here it’s that you must communicate! Oftentimes, m en retreat into silence, denial and oblivion. We women are a force to be reckoned with yet we must include our partners in the bargain. Despite your anger and resentment, your partner is completely unawa re that he’s letting you down. He honestly isn’t dumb or malicious; he just hasn’t thought it all thr ough and feel s ju st as lost as you do.

In the end, this program takes time. Generally, I’ve found that when you try to rush through , you will often hit a wa ll that takes you back much farther, which is terribly demoralizing . Work as a team, b e good to yourself , find hu mor through the darker times, and support each other. In doing so, you will have a far richer reward than the TV series of survivors, despite the greater sacrifice. Ultimately, y ou will have regained your health and wellbeing or something even more incredible, a healthy child who loves you more than anything in the world.

With love and appreciation to my husband, Sten, and our beautiful children . You have

With love and appreciation to my husband, Sten, and our beautiful children . You have taught me what’s most important in life.

This guidebook is also dedicated to a dear friend, Rich Van Konynenburg PhD. Rich was instrumental in leading me to methylation medicine and he tirelessly guided thousands of patients with complex neuroimmune disorders. He dedicated his life to helping others and provided some of the editing cri tiques throughout this guidebook. His death in the fall of 2012 came as a great shock to many. He will be deeply missed.

To live in hearts we leave behind Is not to die Thomas Campbell

Part 1: The Protocol

Part 1 : The Protocol Introduction Welcome to y our personalized nutrigenomics guidebook ! In order

Introduction

Welcome to y our personalized nutrigenomics guidebook ! In order to make this process less overwhelming, I’d like you to think of this book as a work in progress so that you can address one portion at a time. This guidebook reviews the evolving field of nutrigenomics as it specifically pertains to you. It also outlines the genetic makeup of your methylation pathway , which is one of the most important systems in the human body. The genetic testing allows for a personalized treatment plan that is founded upon the characteristic defects, or typos, found throughout your genetic code. There are also some general recommendations that are based on your medical history, health problems, and biochemical testing in order to narrow down an extensive list of supplements. In developing this guidebook, I hope to assist you in better understanding and streamlining your own nutrigenomics program.

The objective of nutrigenomics medicine is to provide the nutrients that each person requires for optimal health. An individual’s idea l nutrients are established by evaluating their genetic blueprint, or DNA. For the sake of simplicity, it may help to think of your genes as a series of piano keys. Each key is unique and makes a different sound, yet they are all necessary for making music. Even when several keys are broken you may still be able to play music, though the melody won’t sound the same and depending upon the song, these failings may or may not make a difference. However, if you are to play in a symphony, you will have three options:

1. You can ignore the differences , playing music that is off key ,

2. You can try to use the black keys instead, to bypass the changes, or

3. You can address the problems and call a piano service to fix them.

In treating genetic vulnerabilities we have similar options:

1. You can ignore the problem and live with poor health,

2. You can change your diet to eliminate some of the toxic triggers, thereby skirting around some of the

damaged genes, or

3. You can address the faulty genes at their root cause, applying specific nutrients, RNA, nucleotides, and

other genetic reinforcements.

In choosing the last two options, you achieve a balance that allows your body chemistry to work more efficiently. This also targets the root cause rather than simply applying Band- Aids with various therapies and medications. This can be achieved through diet and supplementation yet it is much more challenging when only using the diet to meet these needs. For instance, anyone with an MTHFR C677T defect, known for contributing to bl ood clots, colon cancer, heart disease and dementia, requires the more active form of folate to address this vulnerability. Nevertheless, if you eat foods that are rich in these active versions (eggs & spinach) while consuming even more foods with the pla in type (almost everything!), both kinds of folate compete with each other in order to latch onto various sites on each cell. Ultimately, the dominant version wins and since plain folate is so prevalent in the food supply, it is usually the less preferred folate that succeeds. Even so, you will overcome this disparity more successfully when eating and supplementing with the active form of folate. In doing so, you achieve a balance that allows this area of the methylation pathway to work more efficiently. You will also target the root cause rather than applying Band - Aids with blood pressure and cholesterol medications. Welcome to individualized medicine of the 21 st Century!

Basic Definitions

Allele : Alternate versions of a gene

B iomolecular Nutrigeno mics : This field of study incorporates the tenets of nutrigenomics while taking this a step further by analyzing the chemical pathways that are affected by specific, single site base changes (SNPs). It then utilizes a combination of nutrients, foods, nucleotides, and natural RNAs to bypass mutations and restore proper pathway function.

Call Letters: Examples are A, C, G, T

DNA (Deoxyribonucleic acid): An acid that carries each person’s genetic code, making them unique & can replicate on its own. This double- stranded chemical blueprint or instruction manual codes for everything

a plant or animal does such as growing and dividing and deciding how and when to die. DNA is normally

very stable and has error detection and repair mechanisms. It remains in the cell’s nucleus and can make

good copies of itself through transcription. S cientists now believe that our DNA only accounts for approximately 35% of health & disease outcomes while stress and environmental factors have a far greater influence on illness, recovery, and durability than previously understood.

Defect : A mutation that occurs in less than 1% of the population.

Epigenetics: Simply explained, this is the study of how the environment and/or methylation pathway influences gene function and gene expression. Epigenetics is multifactorial and evaluates the environmental impact of diet, supplementation, infection, stressors, and medical treatment as well as pollution and other toxic exposures on health status and disease outcomes. One of the most intriguing aspects of this evolving field of science is the fact that many other issues impact genetic expression without actually altering the genetic configuration.

Heterozygous: Having one allele, otherwise known as a partial defect.

Homozygous : Having both alleles, otherwise known as having a complete defect.

Human Genome: The human genome is a string of over 3 billion chemical letters that spell out every inherited trait. Alt hough the letters of all our genomes are virtually identical and have little variation, more and more frequently, nature gets a letter wrong, similar to a typo (SNP).

Nutrigenomics : Simply put, it is the study of how the food we eat, and the nutrients therein, impact our health. This is largely based upon our own unique genetic blueprint. Nutrigenomics has potential for preventing, mitigating, or treating chronic disease, and certain cancers, through small but highly informative dietary changes. Chronic diseases (and some types of cancer) may be preventable, or at least delayed, by balanced, sensible diets.

A dapted by the National Center of Excellence in Nutritional Genomics at UC Davis, “Nutritional

genomics.”

Methylation: An intricate process that is necessary for survival and occurs when your body takes one substance and turns it into another. Methylation is a chemical exchange that occurs between enzymes, amino acids, proteins, and other molecules to maintain cell function. This pathway regulates gene expression, allowing beneficial genes to function while keeping less desirable genes at bay. It also

provides the backbone for the immune system, DNA, RNA, cellular repair, detoxification, hormone regulation, and communication between the cell s and organ systems by way of neurotransmitters.

Methylation pathway : The expanded version of this pathway is based on The Yasko Theory of neurodegenerative and autoimmune disorders. As depicted in the diagram, it includes the Kreb, Urea, BH 4, Folate, and Methionine Cycles. Most scientists and medical practitioners are familiar with at least two of these, The Folate and Methionine Cycles of the methylation process. This pathway acts as a series of interconnected cycles that enable the highly complex biochemical process of methylation to occur.

Nucleotides: These are molecules that form critical sections of RNA and DNA. Many are also involved in enzyme reactions throughout the body as well as cell communication and the production of chemical energy .

Mutation: Defects in the genome that are rarer and found in less than 1% of the population.

Single Nucleotide Polymorphism (SNP): Pronounced “Snip,” an SNP is a variation or typo in one of the 3 billion chemical letters that make up the human genome. Scientists call these genetic misspellings SNPs, which often occur as variations at a single site in DNA. In fact, an SNP is the most frequent variation in the human genome & there is about 5- 10 million of them, although not all of these disparities contribute to disease. SNPs do not cause disease by themselves but influence a person’s susceptibility to specific environmental and/or nutritional factors that increase disease risk. Currently, scientists are using them to diagnose medical disorders, craft sup erior medications, and tailor treatment regimens that circumvent such mutations.

RNA (Ribonucleic acid): A single - stranded molecule that transmits the genetic messages from DNA (which is double stranded), to the cells and is essential for protein production and transfer. This simply means that RNA transcribes and then delivers genetic messages. RNA is also considered a “fundamental mechanism for controlling the flow of genetic information”, as it influences gene expression. In 2006, two scientists (Craig Mello & Andrew Fire) were awarded the Nobel Prize in medicine for their discovery that RNA impacts gene silencing and gene expression. In fact, a mutation in a smaller type of RNA, known as micro RNA, often leads to diabetes.

Color coding :

- / - Green, n o defect +/+ Red, complete defects +/ - Yellow, partial defect

Examples of Genetic Profiling Systems

Gene Name

Variation

Result

Call

COMT

V158M

-/-

G

COMT

H62H

-/-

C

COMT

61

-/-

G

VDR

Taq

+/-

Hetero

VDR

Fok

-/-

C

MAO A

R297R

-/-

G

ACAT

1-02

-/-

G

ACE

Del16

-/-

NO DELETION

MTHFR

C677T

+/-

Hetero

MTHFR

3

-/-

C

MTHFR

A1298C

-/-

A

MTR

A2756G

-/-

A

MTRR

A66G

-/-

A

MTRR

H595Y

-/-

C

MTRR

K350A

-/-

A

MTRR

R415T

-/-

C

MTRR

S257T

-/-

T

MTRR

11

-/-

G

BHMT

1

-/-

A

BHMT

2

+/-

Hetero

BHMT

4

+/-

Hetero

BHMT

8

-/-

C

AHCY

1

-/-

A

AHCY

2

-/-

T

AHCY

19

-/-

A

CBS

C699T

-/-

C

CBS

A360A

+/-

Hetero

SUOX

S370S

-/-

No Support Needed

SHMT

C1420T

+/-

Hetero

NOS

D298E

+/-

Hetero

34-year-old male with a history of chronic strep, boils, and adrenal fatigue. The latter developed after a sustained period of considerable stress and resolved with basic support after 4 months. With the exception of the SHMT, this is generally considered a “clean” genetic profile with mostly minor SNPs

Gene Name

Variation

Result

Call

COMT

V158M

+/-

Hetero

COMT

H62H

+/-

Hetero

COMT

61

+/-

Hetero

VDR

Taq

+/+

T

VDR

Fok

-/-

C

MAO A

R297R

-/-

G

ACAT

1-02

-/-

G

ACE

Del16

-/-

NO DELETION

MTHFR

C677T

+/-

Hetero

MTHFR

3

-/-

C

MTHFR

A1298C

-/-

A

MTR

A2756G

-/-

A

MTRR

A66G

-/-

A

MTRR

H595Y

-/-

C

MTRR

K350A

-/-

A

MTRR

R415T

-/-

C

MTRR

S257T

-/-

T

MTRR

11

-/-

G

BHMT

1

-/-

A

BHMT

2

+/+

T

BHMT

4

+/+

C

BHMT

8

-/-

C

AHCY

1

+/-

Hetero

AHCY

2

+/-

Hetero

AHCY

19

+/-

Hetero

CBS

C699T

-/-

C

CBS

A360A

+/-

Hetero

SUOX

S370S

-/-

No Support Needed

SHMT

C1420T

+/-

Hetero

NOS

D298E

-/-

G

4 year old male with Autism & PANDAS—2 year recovery process with great success

Gene Name

Variation

Result

Call

COMT

V158M

+/-

Hetero

COMT

H62H

+/-

Hetero

COMT

61

-/-

G

VDR

Taq

+/-

Hetero

VDR

Fok

+/-

Hetero

MAO A

R297R

+/+

T

ACAT

1-02

-/-

G

ACE

Del16

-/-

NO DELETION

MTHFR

C677T

-/-

C

MTHFR

3

-/-

C

MTHFR

A1298C

+/-

Hetero

MTR

A2756G

+/-

Hetero

MTRR

A66G

+/-

Hetero

MTRR

H595Y

+/-

Hetero

MTRR

K350A

+/-

Hetero

MTRR

R415T

-/-

C

MTRR

S257T

-/-

T

MTRR

11

+/-

Hetero

BHMT

1

+/-

Hetero

BHMT

2

-/-

C

BHMT

4

-/-

A

BHMT

8

+/-

Hetero

AHCY

1

+/-

Hetero

AHCY

2

+/-

Hetero

AHCY

19

+/-

Hetero

CBS

C699T

+/-

Hetero

CBS

A360A

-/-

C

SUOX

S370S

-/-

No Support Needed

SHMT

C1420T

-/-

G

NOS

D298E

+/-

Hetero

46 year old female with Multiple Sclerosis and severe Multiple Chemical Sensitivity (MCS)—3 year recovery process with great success.

Example of recent test results with new VDR report & the ACE is no longer included

Gene Name

Variation

Result

Call

COMT

V158M

-/-

G

COMT

H62H

-/-

C

COMT

61

-/-

G

VDR

Taq

Tt

Hetero

VDR

Fok

FF

C

MAO A

R297R

+/-

Hetero

ACAT

1-02

+/-

Hetero

MTHFR

C677T

+/-

Hetero

MTHFR

3

-/-

C

MTHFR

A1298C

+/-

Hetero

MTR

A2756G

-/-

A

MTRR

A66G

+/+

G

MTRR

H595Y

-/-

C

MTRR

K350A

-/-

A

MTRR

R415T

-/-

C

MTRR

S257T

-/-

T

MTRR

11

+/-

Hetero

BHMT

1

+/+

T

BHMT

2

-/-

C

BHMT

4

-/-

A

BHMT

8

+/-

Hetero

AHCY

1

+/-

Hetero

AHCY

2

+/-

Hetero

AHCY

19

+/-

Hetero

CBS

C699T

+/-

Hetero

CBS

A360A

-/-

C

CBS

N212N

-/-

C

SUOX

S370S

-/-

No Support Needed

SHMT

C1420T

-/-

G

NOS

D298E

+/+

T

32 year old female with history of breast cancer & gut issues who recently began treatment

VDR Taq:

VDR Taq tt = - / - (green, no defect) tolerates fewer methyl donors VDR Taq TT = +/+ (red, complete defect) tolerates more met hyl donors VDR Taq Tt = +/ - (Yellow, partial defect)

VDR Fok :

VDR Fok FF = - / - (Green, no defect) VDR Fok ff = +/+ (red, full defect) VDR Fok Ff = - /+(Yellow, partial defect)

Protocol Steps You may be ahead with the methylation support and that’s okay. However, if

Protocol Steps

You may be ahead with the methylation support and that’s okay. However, if you aren’t adequately supported prior to starting these cycles up, the “clean up” will often be much more difficult. It can be compared to not warming up prior to a long run — you might be okay but then again, you could also tear a ligament or tendon. The methyl grou ps are very powerful supplements and as such, will initiate some detox or “start - up” symptoms. The goal is to layer in a solid foundation so that we can allow the methyl groups to do what they do best— allow you to produce the different troops necessary for your immune system and body chemistry while naturally filtering out toxins.

Since your genes will never change, most will require some form of lifelong support. Still, very few require substantial supplementation. For example, once recovered, a chil d with autism may require 10 main supplements to support his lifelong genetic defects while a 72 year old with ALS will require much more.

Step one: Layering in The Foundation Nervous system dominance is an integral part in establishing the treatment process A). Remove or limit triggers: Processed foods contain excitotoxins, dyes, and toxic preservatives. It is also crucial to remove obvious food allergies. Please see pages on excitotoxins for more information. This is simply defined and discussed in detail.

B). Begin general support: Provide a good foundation for your nervous system type and begin nutritional support. Though life- threatening reactions would be extremely rare (and to my knowledge, unheard of), moving too quickly can result in more intense symptoms of detox. In a perfect world, a handful of supplements would effectively treat everything that ails us. Alas, the human body is a highly complex system and as such, requires many highly specific chemicals and nutrients, particularly once this remarkable machine has broken down. Much like a mirage, conventional medicine strives to find that “one size fits all” healing tonic that we all hope to see one day, yet realize is as impossible as it is impractical. Conversely, many alternative practitioners believe that every single piece of the puzzle must be fully addressed before one might reasonably expect health and recovery. Having practiced both styles of medicine, I believe in the art of compromise .

In the past 20 years, I have seen time and time again that in addressing the root cause of prevailing health issues, the body has a remarkable capacity for healing itself. And, though treating every single component may be ideal, in crafting a treatment program based on each person’s health background and genetic foundation as well as some of the similarities faced in chronic disease, I believe that we have an opportunity to streamline a highly individualized and successful regimen. Please be aware that despite its’ comprehensive appearance, this framework includes the bare minimum of basic supports. There are many more supplements that are highly recommended, and which are often based on the genetic and biochemical testing as well as your overall health issues. I encourage you to consider them in your regimen, if even in smaller doses. For instance, if there are sign ificant issues with immunity the n it is important to have some immune supports on board.

C.) Organ support: This is critical for several reasons; first & foremost, most chronically ill children and adults have less than optimal organ function and the liver, kidneys, pancreas, and adrenals are most challenged. Since detox requires ideal organ activity for filtering wastes and toxins, it is vital to have this support on board. Though the RNAs are especially advantageous, there are also less expensive options available below under practical supports.

Ideal organ support : (This may vary depending on nervous system dominance)

Liver

Kidney

Pancreas

Adrenal (this will depend on the nervous system type) *RNA support (even 2- 3 x week is beneficial).

Examples of practical supports: (This may vary depending on nervous system dominance)

Ora Kidney $14.50/100 caps

Ora Liv $8.95/100 caps

Ora Pancreas $12.50/90 caps

Ora Adren 80 $11.50/100 caps

VDR/Fok + pancreatic support $41.95/90 caps

In providing organ support, most will experience some milder detox symptoms. This is due to the fact that normally, those with chronic disease are not able to process and filter toxins, chemicals, and wastes optimally and the extra support allows for more efficient house cleaning. With this in mind, it is wise to start out with a sprinkle and gradually increase the dose over several week s’ time.

Step Two: Win the war with the gut A). Address Gu t Issues: See for future consideration, depending on genetic testing This especially relates to the SHMT & ACAT defects, as these are priority mutations. However, the overwhelming majority of those plagued with chronic illness typically have several defects leading to gut problems. For many, these are the most important mutations to target since bacteria release ammonia and other wastes. The more ammonia your gut bugs make, the more waste you will have in the entire system, especially for those with the CBS and/or NOS defects. Nevertheless, genetic variations aside, the ensuing inflammation and leaky gut issues often lead to autoimmune and neurological activation, causing widespread complications.

For those who have used birth control pills, hormone replacement, steroids (prednisone/hydrocortisone), antibiotics, and/or antacid medications, the gut environment is often rife with harmful bacteria, yeast/fungus, and parasites due to the hormonal imbalances and collateral damage instigated by such ubiquit ous regimens. Furthermore, if you cannot absorb the necessary vitamins, minerals, and amino acids, you lack the fuel required for every other body system, particularly those that have high requirements such as the brain, heart, bone marrow and nerves. Add in the surfeit of processed starchy carbohydrates, sugars, saturated fats and calorie rich - nutrient devoid diets most consume and you have a recipe for disaster. For anyone troubled with irritable bowel syndrome, inflammatory bowel disease, chronic constipation, diarrhea, bloating, belching, acid reflux, nausea, abdominal pain, and/or “sensitive” stomachs, it is almost certain that one or more of the following defects are present: BHMT, AHCY, SHMT, ACAT, and/or the MTHFR A1298C, however, ACAT support should always come first with focus on the SHMT as a close second. If these defects are not present, you are fortunate although mutations notwithstanding, gut support is almost universally central for the road to recovery, regardless of the disease or disorder.

To learn more

Dr. Amy Yasko PhD, NHD http://www.dramyyasko.com/resources/webisodes/assessment - of - metals - microbes - as - a - f unction - of - nutrigenomic - profiling/

Dr. Nancy Mullan & Amy Yasko PhD: How bacterial Imbalances May predispose to Seizure Disorder http://nancymullanmd.com/ asd/wp - content/uploads/2011/10/Yasko - Mullan_Seizure_Article (may need to copy & paste)

Dr. Nancy Mullan MD & Amy Yasko PhD: Gastrointestinal disorders and Neurotransmitter imbalances http://nancymullanmd.com/asd/wp - content/uploads/2012/07/Gastrointestinal_Balance_and_Neurotransmitter_Formation (may need to copy & paste)

I have included this information to demonstrate the proper use of probiotics. They must be rotated every 2- 3 weeks for best outcomes. I have highlighted the top choices below in yellow. Although for those who are more sensitive, it is important to consider starting with smaller doses to avoid a significant die off reaction.

Gut Health: Probiotics & Enzymes

Key beneficial organisms:

Bifidobacteria

Acidophilus

Plantarum

Helpful Hints

For those that cost more use them for a week instead of 2- 3 weeks and rotate the less expensive versions in sooner to stretch t hem out longer.

To adjust to them, start at 1/8 to 1/4 of the ideal dose and gradually increase to 1/2 to 1 capsule every night, rotating to a new probiotic every 2 - 3 weeks.

You can use 1/2 the dose for most of them in order to save money.

To date, I have not found less expensive probiotics, particularly for the quality, than Holistic Health’s. However, feel free to use any brands you prefer.

All probiotics cause die off reactions. This means that bad bugs and yeast will release toxins and waste as they die off & for some, this can lead to uncomfortable symptoms. Start low, sometimes at a sprinkle & move up as tolerated.

Please keep in mind that if you’ve taken a sprinkle of probiotics yet still reacted significantly to them, it might be helpful to get a comprehensive stool test. If any of the good organisms are found in high amounts (3- 4+), particularly when you’ve not replaced them before as probiotics, they may be acting as harmful bacteria.

Some of the brands not made by HHI may be on sale at their company websites.

Examples of good broad- spectrum probiotics on Holistic Health’s Website:

http://www.holisticheal.com/supplements/probiotics

SupremaDophilus

: (*Multiple flora) Start low at a small sprinkle as this is a very effective, potent combo,

particularly for the price @ $14.85/60 Caps

Lactobacillus:

(L. Plantarum, L. Salivarius, L. Rhamnosus). $26.95/100 Caps. Start at a sprinkle to ¼ cap

& gradually increase to ½ to 1 cap daily.

Lactobacillus Acidophilus

: (Lactobacillus blend) ¼ to ½ cap twice a day. $7.95/100 Caps

Gut Health

:

( L Reuteri) Start at ¼ chewable daily & move up to 1 tab as tolerated. $29.99 (particularly

helpful with H. Pylori)

 

 

Ultra dairy Digest : Assists with digesting dairy and provides beneficial flora. $12.40/60 Caps. To take

with any dairy or as a probiotic.

 

NutriClean Probiotics

: (Multiple strains plantarum, Rhamnosus, Bifido, etc. ). Start at ¼ dose. $39.95/30

tabs.

Yeast Away: (L. Acidophilus, L. Rhamnosu s, L. Casei & Cellulase). ¼ to ½ cap twice daily. This is intended as a more intensive yeast/bad flora cleansing & is best used in conjunction with a low yeast diet; however, it may also be used as a nighttime probiotic. $23.95/48 Caps.

Candisol: Not a probiotic but destroys bacterial cell wall as well as Fungal/yeast so that good flora can take over more effectively. $24.99 for 40 caps. You will need to add in good flora to take the place of those dying off!

Florastor : (S. Boulardi) Start with ¼ Cap daily with goal of ½ to 1 cap. $49.95/50 Caps.

Paradex: Parasites and bacteria. May see more extreme “die off” so start sow and go slow. $17.95 for 90 caps

*The multiple Flora in Suprema include: L. Acidophilus, L. Rhamnosus, L. Bulgaricus, L. longum, L. Bifidum, L. Salivarius, L. Plantarum, & Bifidobacteria.

The two most frequently recognized probiotics include lactobacillus, which is found in the small intestine and bifidobacteria, which resides in the large intestine.

Normally, probiotics should be taken with water on an empty stomach to avoid higher gut acid, which could easily disable the good flora you are trying to introduce. Typically, nighttime is best though anytime you’ve had an empty stomach for at least 2- 3 hours is acceptable. Its also best to space these apart from antibiotics or natural anti - bacterial herbs and supplements since these can kill off the probiotic’s good bacteria as well. Generally, you should always rotate several different strains (4- 6) so that your bad stomach bugs do not acclimate to them. Use each for 2- 3 weeks and then rotate to another probiotic/flora balancer. Always start at a sprinkle or 1/8 to 1/4 of the dose that it says on the label. For some, the die off can be significant and many will experience some mild gas, bloating, nausea, or possibly, diarrhea, especially if the starting doses are too high or you increase them too quickly.

Of course, it is most beneficial to limit sugars, carbs, & yeast when doing so and be aware that you may crave these foods w hile on probiotics. This is owing to the theory of survival of the fittest as the bad guys struggle to stay alive and stimulate your appetite. You often begin to crave the very substances that keep them alive & multiplying so it’s best to be prepared, having better choices for snacks and meals available in order to avoid this temptation.

Digestive Enzymes:

The HHI Super digestive enzymes are a great product & can easily be used 1/3 to ½ cap with meals as most people tolerate this quite well. However, it should be started at lower doses such as 1/8 cap or a sprinkle, especially for children & those with chronic gut issues. Even then, some people find that they cannot tolerate this product due to the higher focus on pancreatic enzymes for better digestion. This may be related to H. Pylori gut infections and/or very low stomach acid. In this case, consider the digestive enzyme you can tolerate. One alternative for very sensitive stomachs is Serenaid. SDE $18.95/100 Caps or Serenaid $51.90/180.

Helpful w ebsites:

1). Digestive enzymes, probiotics, etc.

http://www.ei- resource.org/treatment - options/treatment - information/probiotics- and- prebiotics/

http://www.enzymestuff.com/digestion.htm

2). Nutricology Pancreatic enzymes:

Pork Pancreas Natural Glandular $178.27/720 Caps Please also see the below for a less expensive alternative (same product, different packaging)

http://www.allergyresearchgroup.com/Pancreas- Pork- Natural- Glandular- 720- Caps- p - 181.html

Nutricology Pancreas Product: (Can be obtaine d at Amazon for $72 - $75 for 720 Caps! Or $10/60 - 90 c aps. http://www.amazon.com/s/ref=nb_sb_noss?url=search - alias%3Dhpc&field -

keywords=nutricology+pancreatic+enzymes+720

or smal ler bottle of 90 caps http://www.amazon.com/Nutricology - Pancreas - Lamb - Vegicaps - 90 - Count/dp/B00125Z9ZI/ref=sr_1_2?ie=UTF8&qid=1348189099&sr=8 - 2&keywords=nutricology+pancreatic+enzymes

or Nutricology Pancreas Product: (Can also be obtained at Allstar Health for $74- $80/720 Caps!)

http://www.allstarhealth.com/f/nutricology- pancreas_natural_glandular_(pork).htm

Step Three: Repairing Your Body Chemistry

A). Methylation Support: This refers to the active versions of folate and B- 12 as well as other methyl groups and/or nutrients that will provide the necessary foundation for this pathway and its’ supporting chemistry cycles. Much of this is based on your genetic make- up, however, it is important to focus on the most critical issues and each person’s ability to tolerate methyl, sulfur, & lipid donors.

Order for treating health issues & defects:

Evaluating the nervous system’s style or “dominance” is a key factor in the initial process. This will allow for a more targeted regimen, based on your individual needs.

1. Layering in a foundation of very basic supplements & support: general minerals, vitamin B’s & B - 12,

digestive enzymes, probiotics, antioxidants, essential fatty acids, etc.

2. Gut Health is critical. Since most chronically ill adults & children have at least 1- 2 (if not 3- 4!) enzyme defects that affect the gut and digestion, the gut is always a factor. Gut bugs tend to harbor metals and many of them off gas ammonia and hydrogen sulfide, a poisonous sulfur byproduct. You can repeatedly clean up the gut yet if you have not addressed the underlying genetic contributions (SHMT, ACAT, MTHFR A1298C, VDR Fok, AHCY, & BHMT) it will almost always resurface.

3. SHMT defect (Steals everything away from the system & causes gut issues as well as poor healing/recovery).

4. ACAT defect (Oxalates, cholesterol, mitochondrial issues, & severe gut dysbiosis)

5. CBS /NOS defects (drains everything through the transsulfuration pathway = liver, kidney, & urea cycle

dysfunction). Initially, targeting the gut bacteria is often more essential than fully addressing a CBS up - regulation. Many individuals have ammonia and sulfide producing bacteria with in the gut and this n oxious waste requires an escape route. Still, the CBS/NOS combination is often a significant issue and is important to address early on.

6. MTHFR A1298C & MTHFR C677T: The A1298C is the more critical defect in autism and other neurological disorders whereas the MTHFR 3 & C677T (& ACE/NOS) are paramount for treating vascular

diseases, such as heart disease, strokes, and clotting disorders. The MTHFR A1298C caps are critical for liver, gut, & BH4 support. Please consider that SAMe is only recommended for those who do not have the COMT +/+, although very low doses may be tolerated.

7. BHMT, also known as the “ Shortcut” through the system. You need to have the short - cut working prior to most other defects, particularly the MTR/MTRR defects, also known as the “ Long Way Ho me. ” Many have noted that ADHD symptoms intensify with this defect as well as opening up this region, until the MTR/MTRR is at least partially addressed.

8. MTR/MTRR or Long Route, which is essential for getting around the methylation pathway as it converts homocysteine into the critical methyl group known as methionine.

9. Other Defects: Many others may need some management yet do not require as intensive focus. Pending the health issues and overall risks, enzymes such as the MTHFR’s, COMT, NOS, ACE, MAO A and VDR Taq & Fok often require some support since they contribute to heart, neurological & gut issues as well as mood swings, volatility, and increased stress with cortisol depletion.

Example of Basic Methylation cycle support : Please do not start any of the following unless reviewed with your practitioner

Methylmate A (alternative is lecithin & Phosphatidylcholine )

Methylmate B (active folate)

Methyl and/or Hydroxy B12

SHMT spray

MTHFR A1298C (Liver & BH4 support) capsule ( critical for most, discuss with your health provider )

B). Soothing the “Detox” & “Start -up” Symptoms: By this I mean supporting the body and mind to function reasonably well despite a hefty “Spring- cleaning”. As I mentioned previously, no one should feel horrible or remain bedridden in order to target their methylation and biochemistry issues. There are supplements & RNAs that can help with this process and depending on your resources and sen sitivity to various treatments; it is wise to utilize them whenever possible.

treatments; it is wise to utilize them whenever possible. C). Det oxification of heavy metals &

C). Det oxification of heavy metals & virus:

For some, heavy metals, virus and other toxins and pathogens are a significant factor. As you move through the program layering in the foundation and methylation supports, many supports will aid in the release of considerable amounts of mercury, aluminum, virus, and other harmful substances. Still, some have a much higher toxic burden than others and will require more aggressive measures.

Rather than utilizing chelation, I prefer to apply less intensive measures that will generally accomplish this goal. Since only a small percentage of patients require more hard- hitting methods, I prefer to use the following measures (if necessary) in the final stages of the program. I do not ascribe to the theory that we must rid our bodies of every toxin. While this is possibly the most ideal method for combatting chronic illness in some circumstances, it is not necessary in many cases. Furthermore, this requires a much longer treatment process and is extremely challenging for m any to tolerate.

Nevertheless, if you have rigorously worked through the protocol and find that you have not reached your goal, this is the time to consider:

Natural chelating agents such as Malic acid, Horsetail, Alpha lipoic (in those without the CBS/MTRR defect s), and low dose EDTA.

Immune Factor Therapy (transfer factors): IMF 1- 10, which address specific viruses such as Epstein Barr, HSV, HPV, and MMR as well as bacteria including strep, staph, e. coli, and clostridia. These are listed at the end of this guidebook. (Chisolm Biological Laboratory 1- 800- 664- 1333)

Metals I - VI RNA, which address metals, toxins such as aluminum, and virus. For example, Metals IV appears to be most beneficial for adults, particularly those with CFS/ME.

Step Four: Maintenance and fine-tuning

A). Moving on: It’ s important to determine which treatments are temporary and only required for initial support and healing vs. those which are essential for life long health and well- being. Many of these will correlate wit h complete blocks, or full typos in your genetic code while some may be vital supports for partial blocks that lead to substantial illness or disability. Most will require anywhere from 10- 15 nutrients for maintenance. Still, some will be indispensible, others will no longer be vital, and many others will only be needed as issues arise.

B). Nerve Repair: Depending on your health problems, this is the stage that nerve repair is highly beneficial. Many of the myelin (nerve) repair supplements (Nerve Coat RNA, ashwaganda, sphingolin, & spirulina) are used for a period of 6 to 24 months, yet are not lifelong supplements.

C). Gut Health: While some supplements may be needed for lifelong gut health (digestive enzymes & probiotics), others such as the natural antibiotics, will only be used as needed to prevent the recurrence of chronic bacterial/yeast infection.

D). Reflection: This is the period of time where re- evaluation takes place. Now that the critical issues are behind you, there is more time t o focus on less pressing issues. For example, once recovered from Parkinson’s, some have decided to focus on digestive problems. And, a child who has recovered from autism may have residual ADD issues that his or her parents wish to address.

Attention: This is not an immediate process. The body requires time to replenish methylation requirements and adjust to so many changes; oftentimes 6 months to a year.

Tips that make the protocol easier and more comfortable

1) . Starting multiple supplements: You don't want to add in sev eral things at once that can cause issues.

W

hen you have s everal recommendations, it means you should start them one by one and gradually layer them

in

to your regimen, using very small doses to start. You also should not, and wil l not, be expected to have most of

the first stage supplements in process on your first follow - up appointment, so please do not race to do so.

2). Stopping & restarting : Caveat, if you ever stop any of these supplements and restart them later, you should start them at the lower doses again, unless it has only been a couple of days.

3). Lower doses: Many of the doses I have suggested are reduced in order to stretch the product out, thus reducing overall cost. Since you will undoubtedly be taking many supplements for the next couple of years, it makes sense to use the lowest amount that is helpful to you. However, if you find several that work quite well at higher doses and they do not conflict with other critical supports and you can afford t hem, feel free to increase them. Having helped family & friends, I have a keen understanding of how much everything costs and how labor intensive things can get so my goal is always to reduce the strain whenever possible both financially and physically.

4). The protocol steps: Yes, there are definitely a lot of steps in this protocol! I often daydream that in the future, scientists will be able to streamline this protocol so well, that we will have a Jetson’s like existence, moving down the conveyor belt of l ife while we pop our easy meals and treatments in as though they are chocolate chips! In the meantime, we have this “streamlined” version and it is truly the best that I can do to remain as true to the original process as possible. Without a doubt, there is much value in following all of the original recommendations for this program. And, in a perfect world we would all so. However, in the real world

of ever piling bills, other family member’s needs, and dwindling resources, I understand all too well how impossible it is to obtain every single test and treatment while researching every bit of information, particularly when one is ill. With this in mind, the basic steps are just that, basic. Please do the best that you can to follow them as much as you can, finding your own compromise.

5). How long will this take? This will vary, depending on the severity of your illness as well as how long you or your child has struggled with chronic health issues. Nevertheless, the average person can expect to be on this program approximately 3 years from start to finish. For those like myself who wish to take as much time as is needed in order to keep children in school throughout the process (and maintain sanity), it will take longer. For those who have exce llent resources and family support and are not overly concerned with children staying in school or going to work themselves and wish to speed up the process, you can expect to devote 1 to 2 years to becoming well. Since this is certainly not a quick fix, I believe much of this is a commitment to a new lifestyle change rather than a temporary way of life.

Notes:

Example of General Support Unless otherwise contraindicated, the following supports are ofte n beneficial. Nevertheless,

Example of General Support

Unless otherwise contraindicated, the following supports are often beneficial. Nevertheless, each regimen should be based on your unique health history, sensitivities, and nervous system requirements as well as methylation pathway dysfunction.

1). MTHFR A1298C + Liver & BH 4 support start at a few crumbs per day and very gradually, go up over several weeks’ time (generally 4- 6 weeks). The goal is ½ to 1 capsule daily ($54.95/60 caps & $29.95/30 caps). This is whether you have the MTHFR A1298C defect or not.

2). Black Bear Spray or Get B 12 Spray Start at 1 - 2 sprays per day and very gradually work up to 3 - 5 sprays once or twice daily. A tip for adults who develop headaches with wine, it is very likely that you are sensitive to sulfites and the Black Bear Spray would be even more beneficial for you (as well as limiting alcohol & sulfur). $12.95/$29.95 bottle

3).*GABA Balance to start at ¼ cap or less at night first (can cause very mild sedation) but is a great way to instill calming and reduce anxiety during the day & help with sleep disturbances at night. Best to sta rt low at ¼ cap and work up to ½ to 1 capsule in the AM and 1- 2 capsules at night depending on how you respond. ($17.50 /90 caps). This is not to be used with sedatives, sleeping pills, or alcohol.

*When the Glutamate/GABA (Calm Down Spray) spray comes out, this may be a better option for daytime.

4). Co Q 10 Spray is often much more readily tolerated than the capsules for those who are sensitive to methyl donors. Start at 1 spray per day and slowly work up to 3- 5 sprays daily. ($19.95 bottle w/CoQ 10, L- Carnitine, Vit E, & Ribose). For those taking statin (cholesterol drugs), it is paramount to take at least 3- 5 sprays.

5). Ultimate B is a very specific combination of B vitamins, which REALLY limits the dose of Vit B 6 and P5P since many cannot utilize or tolerate this as well, particularly those with the COMT & CBS defects. Some may not tolerate this combination of B vitamin supports. Proceed slowly and see how you do. *Start very slowly and watch behavior, energy level, mood/irritability, etc., for self or child. Start a small sprinkle daily for 3- 5 days before slowly going up. The goal is ½ to 1 capsule daily. ($41.95/60 caps).

6). Resveratrol is an excellent antioxidant, recommended by conventional & alternative practitioners alike and can take the place of Grape Seed Extract. Take ½ to 1 cap daily. Can purchase at Trader Joes for $15/60 caps or at HHI.

7). Minerals: (This will vary considerably) Potassium 99mg daily, Liquid Zinc at 1 drop daily & Magnesium citrate ½ to 1 cap/tab daily. If y ou have not previously tolerated any of these, please discuss this with your healthcare provider. This suggests a propensity toward Sympathetic vs. Parasympathetic nervous system dominance.

8). Special Digestive Enzymes (SDE) & Pancreatic enzymes Highl y recommended for anyone with gut issues or nutritional deficiencies and/or the genetic results are known. SDE are very necessary for those with the SHMT, ACAT, BHMT, AHCY, and/or VDR FOK defects. If you

cannot even tolerate tiny doses to start, try Seren A id digestive enzymes instead, also at small doses. Most people tolerate either of these quite well, however, a small percentage of those with chronic gut inflammation or specific bacteria pathogens may have cramping, pain, or more acid reflux. The enzyme known as SerenAid may be a better option for sensitive guts. SDE ($18.95 100/caps) ¼ cap with meals and gradually work up to ½ cap to 1 cap with meals yet may need to adjust based on CSA results. Also see Nutricology Pancreatin support.

9). Bionativus trace minerals Especially necessary for those with nutritional deficiencies, leaky gut issues, and those who drink filtered or bottled water as oftentimes, the essential minerals are vastly depleted. It is also helpful for the ACE defect. 1- 5 drops in every glass or water bottle throughout the day. ($9.95/bottle).

Other very helpful basic supports include :

Cell food — ideal for extra mineral support at 1 drop daily in juice/water.

Pycnogenol — an antioxidant that offsets excitotoxin damage. 1 Cap daily.

Lit hium orotate— if low on testing this mineral is substantially important for mood, B12 transport, & glutamate balance. Not to be mistaken for lithium carbonate, used in many mental health disorders. Take ¼ cap daily and periodically check levels. Especial ly helpful for those with COMT ++ & MTR 11 enzyme defects.

Vit D 3— either the HHI Vit D spray or Carlson’s brand (you need a bit of the herb Rosemary with Carlson’s for absorption).

Vit C with Rose hips or Ester C. 1 tablet daily (500 - 1,000 mg daily).

RNAs— Stress Foundation, Nerve Calm, & the General Health Foundation are excellent for lessening the added stress that natural detox also places on the body in addition to reducing the overall inflammation commonly found in chronic autoimmune or neurological diseases. If you can afford these, I HIGHLY recommend them & taking 2- 4 drops once or twice a day instead of ¼ dropper. This is a very reasonable dose for many & drastically reduces the cost. (All RNAs, except Bowel inflammation Plus, are $85 bottle & typically last 2 - 3 months, yet will last much longer if using smaller doses. Many patients have them for 4- 6 months).

Notes:

Lifestyle Factors & Key issues: *The following are the most important issues to address as

Lifestyle Factors & Key issues:

*The following are the most important issues to address as soon as you can :

Dietary changes: Reducing neurological irritation and achieving Glutamate/GABA bal ance is critical!

1). Excitotoxins: The more excitotoxins you have coming into your body will only serve to undo many of the helpful measures you’ve already implemented as well as those below. Therefore, I highly recommend a gluten (wheat, rye, barley ), casein (* dairy), & soy free diet. See the attached sheets/PDF regarding dietary guidance. In the end, you can only do the best that you can so if finances do not permit this, simply avoid these foods as much as possible. Eat fresh, whole foods with ve ry few processed meals or snacks in order to limit toxic ingredients due to the hidden chemicals and sources of MSG (also known as “natural flavors, citric acid, hydrolyzed protein, xanthan gum, etc. ). Additionally, due to the hybrid techniques utilized b y Monsanto & other food corporations, with few exceptions , wheat is 30% MSG. This does not include the typical additives and/or hidden ingredients added in for flavor. Aside from acting as a common allergen, it is an abundant excitotoxin and highly disco uraged. Buckwheat (a berry, not actually wheat), quinoa, millet, amaranth, and grains such as basmati brown rice are abundant and much better alternatives.

* Dairy: This is a controversial subject, especially within the dairy industry, yet if you read the information regarding this issue in the Excitotoxins (MSG) handout you will see that not all milk is created equally. Alpha 2 dairy (jersey & Guernsey cow’s milk, goat & sheep’s milk and cheese) is compatible with most digestive & immune systems.

Please consider that while fermented foods are exceptional for those with healthy digestive tracts, anyone with inflammatory bowel disease and other disorders contributing to leaky gut issues typically do not do well with fermented foods such as Kombucha, Bragg’ s amino acids, miso, etc., due to the naturally occurring yet exceptionally high levels of glutamates in such products.

Despite the higher sulfur level for those with the CBS and/or SUOX defects, cruciferous vegetables are extremely important for increa sing the phase I & phase II liver detoxification. This is the main reason behind their beneficial effects in treating cancer and chronic autoimmune and neurological disorders. While those with the CBS & SUOX defects may need to reduce their portion sizes (and increase their doses of molybdenum), kale, cabbage, broccoli, brussel sprouts, bok choy, collard greens, & cauliflower, are all good sources. Pick a few that you can live with on a regular basis and work toward integrating them into your diet. There are no absolutes here, just do your best.

2). Deodorants: Use natural Deodorants to remove heavy aluminum exposure: good deodorants include: 1). Herban Cowboy, 2). Every Man Jack, and 3). Bubble & Bee’s Pit Putty (Lemongrass or Spearmint coconut are ex cellent). It often takes 4- 6 weeks to adjust to NOT using the heavy aluminum deodorant so you will probably sweat more until your body adapts. It is also better to use one of the above as a base layer prior to adding the commercial deodorants. You will still have less toxin absorption and this is an option for those who do not adapt as well to the natural alternatives. Remember, it doesn’t need to be all or nothing. Compromise is almost always possible.

3). Oxygen & Sunshine : Try to air out the room you spend the most time in by cracking or opening the window whenever possible. Staying indoors eliminates a fresh oxygen supply and the less oxygen you receive, the

greater the risk for cell mutations, such as those leading to cancer. Also, sunshine is imperative so having at least 10- 15 minutes of sun exposure twice a day is optimal (if tolerated).

4). Continue organic fresh fruits and vegetables as pesticides wreak havoc on an already burdened system. See the “Dirty Dozen List” in order to focus on the most heavily contaminated so that you can reduce your grocery bill.

http://www.organic.org/articles/showarticle/article- 214

5). Sodium: Work toward reducing salt intake and using either “Natural, Himalayan salt” or pure “Sea salt” since table salt is rife with aluminum in order to prevent it from caking. Be aware that sea salt does not contain iodine as table salt does.

6). Water bottles : The concern is with leaching that occurs from plastics and aluminum bottles. Kleen canteen is probably the best re - useable water bottle available. It is unlined stainless steel and does not contaminate your water. Glass is optimal yet not terribly convenient for an “on the go” lifestyle. The stainless steel Camel Back containers are also ok. Likewise, it is best to store m ost wet foods in glass containers. Avoid using plastic containers in the microwave!

7). Microwaves : Please avoid using the microwave for cooking or reheating. There are many reasonably “quick” alternatives such as using a toaster oven (which also broils, brakes, & warms) or using a teakettle for hot water.

8). Establishing nervous system dominancesee the Nervous System attachment sent with this packet.

9). Cooking pots & pans : Avoid aluminum and Teflon or similar coatings and stick to cast iron or stainless steel as much as possible. Baking and broiling are optimal as opposed to grilling or pan - frying .

10). Optimize Nutrients: There are many methods for making simpler foods yet “doctoring” them up to boost the nutritional value. For instance, adding ground flax, quinoa, amaranth, millet, or pure buckwheat flour to your baked goods and Chipati’s or pre- mixed waffle & pancake batter, reduces the glycemic index and un healthful aspects of the refined, white rice & sorghum flours they generally use in GF/CF/SF mixes. Of course, with children, you want to start very gradually, adding in 1 tablespoon at a time to allow your child to adjust to them. Otherwise, they won’t l ike the changes. Quinoa is particularly rich in protein and minerals, yet tends to have a very strong flavor. Oftentimes, a ¼ cup is more than enough and you can also add in ground flax seed meal or chia seeds for omega 3 fats and moisture. You can also do this with pizza crust mixes or other baking mixes. Be creative, work toward making this fit your own family meals.

You can also grind up spinach, zucchini, squash, or carrots into GF/CF pizza sauce to have an added boost of vitamins and minerals. You can also do this for pasta when making spaghetti or Mac & cheese. When you add a little at a time, most kids do not notice very finely ground carrots or zucchini (take skin off zucchini for Mac & Cheese). The mini food processors make this much simpler and are much less expensive and cumbersome to use than the regular processors.

I highly recommend making up large batches and freezing them for simplicity. You can also do this with lentils, basmati brown rice, chipati’s, chicken, and casseroles as well as pizzas, meatballs, hamburger patties, stir- fry, meatloaf, and many more dishes. This reduces the stress of coming up with a healthful dinner on those busier nights. All of these dishes have the added bonus of hiding vegetables well. Please see the Dietary Strategies section for more detail.

11). Logbook : I t is always better to use smaller doses whenever possible, particularly as you begin to layer in multiple supplements. The goal is to use the least number of supports (including doses) as possible, in order to achieve the best outcome.

It is also important to maintain a basic monthly logbook of your current symptoms, rating them from 0- 10 (Zero is the least amount of discomfort and ten is the worst). This allows you to evaluate progress, or la ck thereof, as well as monitoring the effects of new supports. The example below allows for a quick review and does not require a significant amount of time. Still, it allows one to monitor patterns that develop or to quickly spot significant changes with in each month. For example, you may start 3- 4 supplements in micro doses and begin to have diarrhea or insomnia several weeks later. Without the logbook, you may not realize this is related to the new supports . Conversely, you may not realize that your daytime naps have ceased or that you no longer have nighttime anxiety. Please see the following example.

10/ 20/12 (The below log assumes you have done this previously so that you have a comparison)

Fatigue 6 (was 8/10) Dizziness 6- 7 (was 0/10) Anxiety 4- 5 (was 9/10) Depression 6- 8 (same) Muscle weakness 6 - 8 (was 3/10) Gut pr oblems 2 (wa s 7/10) Sleepiness 4- 5 (was 8- 9/10) Energy 4- 5/10 (was 2- 3/10) Anxiety 8/10 (was 4- 5/10) Stims or perseveration 3 (was 7/10)

Switched to new supplements (niacin, ribo, benfo) Reduced active folate as suggested Seems better with RNA Hasn’t changed Seems worse/better with less protein Seems better w ith digestive enzymes But still unable to nap Slightly more energy (but not able to leave house) Worse with new supplements Much better with Benfotiamine and Anxiety RNA

Supplements to generally avoid: Tylenol/Acetaminophen, Copper, iron, taurine, *calcium, plain folate & folic acid, glycine, glutathione, and “chelated minerals” as these mineral versions often contain one of the following:

aspartic acid/aspartame, glutamic acid/glutamate/Monosodium glutamate(MSG), which are all excitotoxins. * Those who are parasympathetic Dominants will probably require calcium, as will those who are in stage 2 -3 of the program (once excitotoxicity is well regulated)

Comfort measures for most detox symptoms : (These will vary considerably based on nervous system dominance and individual needs). Examples include GABA Balance, Benfotiamine (synthetic B1), and mag citrate/malate for anxiety, OCD, and depression as well as soothing detox symptoms. *RNAs such as: 1). General Inflammation Support RNA, 2). Anxiety RNA, 3). Nerve Calm, RNA, & 4). Stress Foundation RNA are also highly helpful for detox stress reactions & are typically well tolerated. *As mentioned, the RNAs will often last for at least 3- 4 months and the mutation specific RNAs will last even longer at 4- 6 mos.

Follow-up : 4- 6 weeks or sooner, if necessary. Since there are many supports to initiate or increase, it will be an important time to monitor your responses in order to determine what is most effective for you.

GOALS : General body chemistry and nervous system support. The above nutrients, supports, digestive enzymes, and probiotics will help immensely with establishing a good foundation. In the future, we can address the most significant methylation defects and vulnerabilities so that your symptoms are considerably lessened.

Considerations: The above recommendations are based on the current scientific understanding of biomolecular nutrigenomics and should never be used in place of your specialist or primary care provider’s recommendations for medical testing, treatment, and/or follow up care. Moreover, the science of nutrigenomics and biochemistry is an evo lving field and as such, there are few absolutes in the healing process. As we move forward, we will undoubtedly re - evaluate your regimen in order to tailor the treatments to your individual needs.

Part 2: The SNPs

Part 2: The SNPs The defects : Caveat: It is best not to add in several

The defects :

Caveat: It is best not to add in several things at once that can cause detox. When you have several recommendations, it is prudent to start them one by one, layering them into your regimen gradually. Furthermore, having a solid foundation is critical for your body chemistry as well as any genetic factors.

SHMT Serine Hydroxymethyltransferase “Stop! Dead End Road” Priority mutation # 1

SHMT This is a priority mutation! You want to address SHMT first, before ANY other defects. Out of all of the recommendations, this is most critical. When you address gut inflammation and bacteria, you will generally induce detox. Still, this will also depend on how significant your gut issues are as well as the bacterial load. This is due, in large part, to the metals and ammonia and other toxic waste that are released as bacteria die. Since bacteria tend to cleave to aluminum, you may have considerable dumping during treatment and subsequent detoxification. *Virus tends to hold onto heavy metals.

Normally folate is converted into its active version through the Little Motherflipper, (AKA MTHFR C677T). Shortly afterward, it departs for the SHMT enzyme in order to complete the exchange. Once the SHMT does its job, the active folate can happily pass through the MTR/MTRR into SAM ’s Corporation, our major work tag producer. Unfortunately, an SHMT defect often traps this precious commodity. Why is this important? Once it travels through the SHMT, you are capable of making new RNA and DNA, which are critical for making you distinc tively you! Nevertheless , once the fields are properly planted, this active folate travels through the farming region to the “Long Way Home” (MTR/MTRR) where it supplies the required work tags for the entire system. This juncture utilizes methyl groups to produce methylcobalamin. Methyl B - 12 then converts homocysteine into methionine, which is required for SAM. Without these tags, the community is forced to rely upon considerably less industrious regions such as the “Short - cut” (BHMT). The short cut al so converts homocysteine into methionine yet does not require folate or B - 12 to do so.

Moreover, defects within The Little Motherflipper and/or MTR/MTRR often allow homocysteine (HCY) levels rise. HCY is similar to the chain gangs of old in that it act s as a good source of work tags. Nonetheless, if left unchecked, it can cause substantial damage throughout the body just as a group of prisoners might wreak havoc upon the good citizens within an unsuspecting village.

As for any gut issues, you will address many of them by targeting the SHMT as well as using digestive enzymes to break down fatty acids, starches, and proteins. When you are unable to efficiently break these down, toxic fatty acids may build up to harmful levels. This can damage the mitochondria, which are the energy factories of each cell. Probiotics are also critical as they introduce new and beneficial bacteria into the gut. If you destroy the bad bacteria without having some good organisms ready to step up and take their place, other more resistant bugs will begin to multiply. This defect provides many answers for those with chronic gut issues, poor wound healing, and/or recurrent bacterial infections. Many have recurrent strep infections, boils, acne, and/or chronic bowel inflammat ion and infections.

Labs: Monitor homocysteine levels, which are also a good indication of folate or B- 12 deficiency.

Treatment recommendations a). * SHMT Spray to start at 1 spray and gradually increase to 4 - 5 sprays over several months time (or, as tolerated). Consider that as bacteria die, they release aluminum and ammonia so you do not want to do this quickly or you may have a huge load in the system. Consider diluting the spray at ¼ concentrated SHMT and ¾ Distilled water and begin 1 spray of this mix to see how you tolerate it first. b). Bowel Inflammation RNA at only 1 drop to start due to detox potential — you may also consider diluting this with distilled water to see how you do on less concentrated versions first. c). * SHMT/AHCY Caps: For those with full SHMT defects, you may wish to consider this combo support or a variation thereof, such as nucleotides, lactoferrin, low dose folinic, and/or hydroxy B- 12). For the combo support, start approx 8- 10 weeks after the above supplements have been initiated, with at least a couple of weeks in between them. Start with a few crumbs and move up to ¼ cap, depending on how sensitive you normally are (& how you tolerated the others). Gradually work up to 1 capsule, though ideally it’ s best in two divided doses such as ½ capsule in AM and PM. d). Consider SHMT RNA if significant medical issues (discuss with your practitioner).

significant medical issues (discuss with your practitioner). ACAT Acetyl - Coenzyme A acetyltransferase “A bad Gut

ACAT Acetyl - Coenzyme A acetyltransferase “A bad Gut & Oxalates” Priority mutation # 2

Although this mutation is fairly unc ommon, it significantly impacts the Energy Cycle (citric acid cycle) and mitochondrial function. The influences are wide and far ranging and include bile salt production, cholesterol, fatty acids, and the processing of oxalates. Notwithstanding a partial or full defect, m any have a “functional” variation due to the impact of aluminum, heavy metals, and toxins as well as other defects that impact this area such as the NOS, MTHFR, & CBS. Upon viewing the methylation community diagram, it is important to n ote that the energy cycle is closely connected to each sequence, yet it is intimately linked to both the waste cycle and SAM’s Corporation.

Since the energy cycle is essential for processing and converting all dietary nutrients (glucose, fats, proteins) into useable forms of energy, a breakdown anywhere down the line might trip an internal alarm. This is analogous to your car’s “low fuel” gauge . Just as any industry processes coal, gas, or oil for energy production, your body must have the essential nutrients in order to properly function. If you visualize the energy cycle as a clock, each hour represents an area in which one nutrient or substance converts into a more compatible form of energy. Depending on digestive function, diet, rate of absorption, and the presence of any genetic quirks, a problem might occur at any point within the device . This may lead to significant chemical imbalances within your body chemistry as well as mitochondrial dysfunction or disorders.

The ACAT plays a key role in creating bile salts, which is crucial for cholesterol and other membrane lipid balances. While we tend to view cholesterol and other fats as the “bad guys” in the war against disease, these compounds are critical for general health and wellbeing. Whether it’s the coating surrounding a nerve, cell, or organ, cholesterol is essential in its production. Think of your home’s electrical wiring and the thick, plastic or rubber coating normally found protecting it. An exposed wire is vulnerable and may “short out,” so that the impulse isn’t transmitted. Similarly, the body’s nervous system requires the protection afforded from a nice, thick fatty coating or fundamental connections may never be made. An exposed nerve may lead to a misfire, which is often the sourc e behind the early symptoms found in neuroimmune disorders. This often includes signs such as tremors, muscle fasciculations, weakness, and fatigue as well as word groping and poor concentration and retention. Without cholesterol, you also cannot make several vital hormones, including, your sex hormones (estrogen & testosterone) or insulin. Therefore, low cholesterol levels are not as beneficial as one would initially think.

Finally, if a chronically ill person has had heavy aluminum or other toxic ex posures along with a partially functioning ACAT, energy production is likely to stall to a near standstill. Moreover, as outlined in the energy cycle, other problems may include:

1. More B - 12 depletion, which has ramifications throughout the entire system.

2. Cholesterol & fatty acid imbalances, often leading to toxic fatty acid buildup & high cholesterol.

3. Decreasing bile salts & increased taurine production as well as poor cell wall function since they all rely on the proper breakdown of cholesterol through the ACAT.

4. Poor breakdown of fats, carbohydrates, & proteins to fuel other cells, nerves, tissue, & organs.

5. Rising oxalate levels that may cause painful urination and bladder & kidney stones.

6. Co Q - 10 reduction, which is also necessary for mitochondrial function & energy.

7. Limited energy for the Waste Facility & SAM’s Corp. due to less conversion of methionine to SAMe. In having over 400 methylation functions, SAMe is critical for the entire community.

As the energy factories of each cell, mitochondrial damage has significant implications. In fact, anything that demands more energy, including the gut and the brain, are particularly vulnerable. Significant blocks may limit the availability of bile salts; hence the digestive process is doubly burdened. This provides a valid reason for many unexplained digestive problems, while explaining poor growth & development as well as failure to thrive. Well - studied t oxins such as aluminum, lead, mercury, and MSG also greatly impact this factory. This is one reason those with known mitochondrial disorders are discouraged from eating foods with pesticides, MSG, and aluminum. Ultimately, anyone with multiple risk factors is especially prone to mitochondrial dysfunction.

Labs: monitor for oxalates, high taurine, MMA, and/or methionine levels as well as low cholesterol. Ethanolamine and the *branched chain amino acid (BCCA), isoleucine may be elevated on urine amino acids testing.

*If other BCCA’s such as valine and leucine are also elevated, consider clostridia.

Treatment Examples: (This will also depend on gut issues & nervous system balance)

1. Adenosylcobalmin (particularly if MMA levels are high)

2. Bile salts (Cholacol or Ox bile powder/tabs)

3. Policosanol (membrane balance & fluidity)

4. Pancreatic enzymes (Nutricolog y & special digestive enzymes)

5. Vitamin K

6. Vitamin E

7. Lactoferrin (While lactoferrin has a trace amount of dairy, it does not generally contain the milk protein known as casein).

8. Nucleotides

9. Co Q 10

The following may also be required yet if nervous system type is evident, it would be prudent to supplement accordingly.

1. Benfotiamine (synthetic thiamin)

2. Riboflavin

3. Pantothenic acid

4. Extremely low dose Alpha lipoic Acid (avoid if MTRR 11 and CBS are both present)

lipoic Acid (avoid if MTRR 11 and CBS are both present) The Energy or Citric Acid

The Energy or Citric Acid Cycle made simpler

The Krebs cycle, also called the citric acid cycle or the “Energy Cycle,” is a series of chemical reactions that convert food (sugar, protein, and fat) into energy (ATP). It is referred to as a cycle since it should always end where it began. T his process occurs through three main stages within each cell :

1). Glycolysis, otherwise known as the brea kdown of sugar, yields 2 molecules of ATP, 2 molecules of NADH, and two forms of pyruvate (6 forms of currency in all). This is act ually a step that takes pla ce before the energy cycle’s work begins and is generally included as the foundation . 2). The Citric Acid Cycle (CAC) or Krebs Cycle occur s within the mitochondria . Recall that the m itochondria are the engines or powerhouses of the cell. 3). The Electron Transport Chain (ETC), which is where the bul k of ATP is manufactured. Most importantly, NADH is converted into useable energy, specifically ATP, through this conveyor belt like process within the mitochondria . Incidentally, in recent years scientists have discovered this as the source behind many health issues in those with autism and CFS/ME. This is due to the severe energy deficit required for all cellular activity.

The compound known as pyruvate contains a substantial amount of energy, yet in order to utilize it, the cell must convert this energy into ATP. Initially, sugar (or fat/protein) is broken down to a simpler, compatible form known as Acetyl CoA . This process occurs as pyruvate oxidizes, or is used, and loses one of it s’ light bulbs (carbons) to form Acetyl CoA and NADH. Once this occurs , the molecules enter a conveyor belt like processing center within the Energy Cycle, known as the Electron Transport Chain (ETC) . Acetyl - CoA joins with oxaloacetate to form citrate.

It ’ s important t o note that whenever a block occurs within an enzyme, you will see a rise within the enzyme or compound preceding it. For example, if there is a block leading to high citrate (a t 1 o’clock), you will see elevated levels of other intermediates at 11 o’clock, leading to high oxalates. S ince citric acid can build up from poor iron utilization and/or high bacteria l levels , lactoferrin may be in order so that iron enters the cell where it belongs. Otherwise, it simply provides more fuel for bacteria , leading to a vicious cycle . Of course, diverting such resources away from these pathogens may lead to some milder detoxification symptoms. Conversely, low glutathione levels may also lead to elevated citric acid levels. I n this case, curcumin or quercetin may help shift production toward cysteine and glutathione.

It helps to remember that absolutely nothing within the human body occurs in isolation. Please refer to the below diagram, viewing it as a clock like process.

to the below diagram, viewing it as a clock like process. To Learn More Entertaining rap

To Learn More

Entertaining rap video regarding the Citric Acid Cycle & Oxidation for the younger crowd

http://www.youtube.com/watch?v=YyN0wx2AHfE

“Simpler” Academic version with KhanAcademy

http://www.youtube.com/watch?v=juM2ROSLWfw

For those who wish to understand the biochemistry, the following information is Dr. Yasko’s technical overview of the ACAT . I have included a clock in order to provide a visual compariso n for Dr. Yasko’s analogy: (Enter at your own risk !)

The next portion of the pathway that may be impacted by ACAT is the level of acetyl CoA. Remember that acetyl CoA feeds into the top of the TCA cycle at 12:00. For this reason I am suggesting that you consider benfotiamine, riboflavin, and pantothenic acid, all of which help the reactions between pyruvate and the TCA cycle. In addition, the use of low dose ALA as alpha lipoic acid (not to be confused with alpha linolenic acid) may be helpful as it has been shown to replace acetyl CoA in certain reactions (Wagh et al J. Biosci. Vol 11, 1987). Nevertheless, when MTRR and/or CBS defects are present, ALA should be restricted to very low doses in order to avoid excessive waste excretion. For instance, one c ould use a small sprinkle from an ALA capsule or apply the topical ALA with green tea lotion.

Oxalates: A block within this cycle (at the acetyl CoA point) can also lead to an accumulation of oxalates. In order to keep the cycle flowing properly, it is important for the oxalates at 11:00 to combine with acetyl CoA coming in at 12:00. Optimal support includes vitamin K and lactoferrin .

A block at this point can also lead to increased methylmalonic (MMA) levels. For this reason, I have suggested similar support for the ACAT that I do when I see high MMA levels. This includes adenosyl B12, other forms of B12, low dose vitamin E succinate, lactoferrin, a sprinkle of actifol and nucleotides. MMA may inhibit succinate CoQ reductase. This enzyme is important in electron transport. That is why I have suggested vitamin K (menaquinone) as well as CoQ 10 (ubiquinone) to help to serve as electron acceptors when we have high MMA or with ACAT issues .

From a biochemical standpoint, we see higher levels of methionine with ACAT mutations. For this reason I am looking to support the conversion from methionine to SAMe. Supports such as Cholacol, GSH and CoQ10 are all in consideration of the MAT enzyme. Herbs such as curcumin and quercetin may help to shift the transulfu ration pathway toward GSH. Generally, it is better to achieve this by working within the system rather than simply adding in more support. Even so, too much GSH may lead to greater feedback, inhibiting GCL. The GCL is the enzyme that shunts toward gluta thione rather than cysteine and taurine. As always, the goal remains moderation and balance .

CBS C699T cystathionine beta synthase “The Hole in the Bucket” Priority # 3

Tip! It is crucial to address any gut issues before you thoroughly address the CBS d efect. Since chronic gut issues lead to higher bacterial loads, thus leading to higher ammonia production as well as leaky gut (reducing nutrient absorption and increased risk for food sensitivity) this area i s paramount. You can begin to address the CBS prior to fully addressing gut issues though they should be done in concert. Since the CBS is one of the most important issues to address, I’ve decided to expand upon the defects while emphasizing the CBS and its impact on the entire pathway. Also recall that a CBS upregulation substantially drains and floods the urea cycle. This enzyme depletes the precious resource known as BH4 while overloading the urea cycle with its’ faster dumping.

It is paramount to balance any chief defects prior to optimizing the methylation cycle. The CBS enzyme, located at the entrance of the transsulfuration pathway, converts homocysteine to cystathionine. Although the following discussion is somewhat controversial within the research community, my colleagues and I have confirmed (in our own clinical practices) many of Dr. Yasko’s discoveries regarding the CBS upregulation. The increased activity often leads to toxic waste build - up and poor glutathione production in addition to challenges processing sulfur/sulfates. While this may be contingent upon other defects, there may be an elevation in taurine, ammonia, sulfites and hydrogen sulfide. Taurine is an amino acid while the latter three substances are toxic.

Therefore, it is often vital to support this enzyme prior to initiating other methylation treatments. Otherwise, any efforts to support the cycle may only result in increased toxic burden. This may explain the reason some patients cannot tolerate efforts to raise glutathione, particularly since they are sulfur- containing substances, while others derive great benefit without debilitating side effects.

As mentioned, even a partial defect often leads to dumping everything out at 10x the normal rate, hence, the “Hole in the bucket.” This tends to drain the entire pathway of nutrients, homocysteine, and toxins. Once the initial body chemistry and nervous system supports are on board, this is one of the most critical defects to regulate. Nevertheless, since gut bacteria release plenty of ammonia & toxins of their own, it isn’t in your best interest to trap this within the system. The bottom line is that in prematurely addressing the CBS, we could be trapping such waste. The goal is to get basic support on board in order to make detoxification much easier to tolerate. Think of the CBS as an open barn door or a leaky bucket (& please refer to the diagrams I have sent you on this area so that you have a better visual). This means that everything that does & doesn’t belong within the whole pathway are just dumping right on out into the liver & kidneys to be filtered out, much like a hole in the bucket.

This means that as fast as you try to fill your leaky bucket, much of it simply dumps right out. This leads to significant deficiencies within P5P, B6, B - 12, minerals, antioxidants, etc. These compounds often drain out, leaving you without critical methylation support to maintain and police the entire system. Moreover, it is often common to see elevated Ta urine levels on the amino acid tests. And, since Taurine & Beta alanine share the same amino acid transporter; this level may also be elevated. Even so, when we start supplementing this pathway, it continues to drain out, oftentimes, leading to even higher level of taurine. Nevertheless, low taurine levels should no t be supported until proper methylation support is on board. Taurine is a sulfur donor and may trigger more issues. Yet if levels remain low despite methylation support, its’ addition may be very beneficial, particularly for those who suffer from seizures, aggression, anxiety, and/or agitation.

Generally, the transsulfuration pathway (liver pathway) leads to either taurine or glutathione production, though not both. While losing so much toward taurine has its benefits— you often prevent seizures due to its calming qualities— you trade * Glutathione in the process, which is a steep bargain. As your most vital & normally abundant antioxidant, glutathione is required for many processes including immune function and detoxification as well as regulating the function of other antioxidants. In fact, this is the main reason that those with chronic illness suffer from recurrent bacterial, viral, parasitic, & fungal infections as well as cancer, toxic metals, etc. Without glutathione, very little is normally filtered and processed within the system.

Additionally, homocysteine is an indispensable amino acid in the production of SAM and acts as a key precursor for this superstar. Having over 400 known biochemical functions in the body, SAM is the methyl donor or work tag. In the event of a CBS breakdown, Homocysteine quickly escapes, along with other amino acids, vitamins, minerals, toxins, and wastes, both depleting and taxing the system. To make matters worse, everything that dumps out through the CBS often converts into toxic ammonia and sulfites. Unfortunately, this even includes the good supplements and nutrients. This also means that every time you use supplements, diet, and/or medications to support nutritional and methylation deficiencies, you may be inadvertently delivering more & more toxins, thereby adding to your overall toxic burden. This will also extensively raise glutamate levels (as will strep & heavy metals), causing excitotoxicity. As mentioned above, those with the CBS up regulation tend to b reakdown homocysteine in order to make cysteine and taurine, rather than glutathione. Moreover, this whole process triggers an enzyme called G6PD, which is instrumental in protecting & cleaning up your red blood cells as well as regulating the blood sugar . This may lead to blood sugar fluctuations throughout the day, from lows to highs, while it further stresses the fight or flight response and glutamate production.

Furthermore, testosterone impacts the CBS defect, actually increasing output. In animal models, they’ve found that a double defect within the CBS C699T can work up to 40x faster, so coupled with higher testosterone levels

in males, this may considerably increase nutrient and toxic dumping. With this in mind, it’s important to keep an eye on hormone levels as well as important minerals that help support this enzyme such as the copper/zinc ratios, molybdenum, and manganese.

*GSH is the active form of glutathione that we all require for managing free radicals and filtering toxins. GSSG is the “used” version of glutathione that is oxidized (rusting). The redox ratio of glutathione, known as GSH/GSSG, signifies the levels of new to used glutathione

It is important to remember that in concert, several other SNPs can substantially drive CBS act ivity up. *** My suspicion is that the combined MTHFR, CBS, and BHMT defects are taxing the flight or fight system by increasing norepinephrine and cortisol levels. Normally, something would trigger this stress response such as illness, crisis, a busier s chedule, supplements, foods, etc., since these further tax the CBS/NOS. Nevertheless, if you have a Sympathetic Dominant nervous system, you will have almost constant activation of the stress response, particularly if not on the appropriate diet and nutritional supports.

Using the simpler terms as discussed in “Your methylation Community,” this passage to the liver is instrumental in detoxifying much of what accumulates from the entire cycle, from the power plant and the rural farming regions to the Communications Facility and SAM’s own manufacturing plant. The shared passageway between the companies (MTR/MTRR) allows the farmers and chain gang (HCY) more direct access to this freeway. Yet it can also be a potential escape route for the prisoners and such getaways could lead to trouble within the system. Even so, if this route is down for roadwork, travel is still possible via the shortcut (BHMT). In fact, due to of all these ties, SAM and the Farmers have a very close working relationship. After all , it’s the supervisor (AHCY) at SAM’s that decides which guys (HCY) in the Chain Gang are ready for release or not.

Despite the good working relationships, there are many issues that could arise and contribute to complications. For instance, a sudden increase in work production on the freeway (CBS) exiting SAM’s could deplete essential supplies for those down the line. Conversely, a bottleneck or roadblock at a key junction of this freeway (SUOX) has potential for even more poisonous waste overwhelming the system. Everything in this pathway is interdependent and has the potential for a domino effect. And, just as a small town relies on the biggest industry for maintaining the economy, the methylation community depends on SAM’s Corp for most of the jobs (methyl groups) necessary for survival. Nonetheless, it’s also crucial that the major thoroughfares and chief junctions run smoothly in order to avoid draining the community or causing rush hour traffic jams and toxic waste spills.

or causing rush hour traffic jams and toxic waste spills. AMMONIA PROVOKER S : (Limit to

AMMONIA PROVOKER S : (Limit to essentials for CBS +)

protein

B6/P5P

glutathione

taurine

NAC

LIPID DONORS: (limit for CBS+, NOS+)

Any transdermal creams

Lipoceutical EDTA and Lipoceutical glutathione

Higher do ses of essential fatty acids (EFAs)

CoQ10

Alpha Lipoic A cid (ALA)

Idebenone

Ammonia is simply a combination of nitrogen + hydrogen. It is important to note that nitrogen is formed from the breakdown of protein .

Lipid Donors:(limit for CBS+ & NOS+)

Any transdermal creams

Lipoceutical EDTA and Lipoceutica l glutathione

Higher doses of Essential fatty acids (EFAs)

CoQ10

Alpha lipoic acid (ALA)

Idebenone

Immune Factors (due to the ALA in the ingredients)

Per Dr. Yasko, aside from having the NOS defect, an EFA mix of omega 3/6/9 is ideal. She recommends two of the DHA (Neuromins) to one of the Omega 3/6/9 mix for a 5:2:1 ratio of omegas. Additionally, she adds one capsule of cod liver oil per day. Recall that fatty acids slow the NOS enzyme down so if there is a defect, these should be utilized in lower doses.

SULFUR DONORS: (Limit if CBS+ yet avoid much more for SUOX +)

Taurine

Broccoli

Garlic

Onion

Coconut milk or oil

Glutathione

N- Acetylcysteine (NAC)

SAMe

Magnesium sulfate cream

Milk thistle (in MTHFR A1298C caps)

Glucosamine sulfate

Chondro itin sulfate

MSM

Alpha lipoic acid (ALA)

Milk thistle

DMPS

DMSA

Heparin

Epsom salts

We do need some sulfur in the system. Sulfur that is complexed in an herb is usually okay. Hence, I would not eliminate horsetail grass, spirulina, dandelion leaf , or parsley. Consider that methionine, which we need in the form of plain methionine or SAMe, does in fact contain sulfur and is a sulfur amino acid, as is taurine and cysteine. While many require Methionine supplementation, it is often best to avoid ta urine & cysteine. One should only consider

taurine if it remains low once methylation has been fully supported. Moreover, while foods/herbs like eggs, garlic, onion, & broccoli are going to be higher in sulfur, using smaller amounts of these give you many positives. ” Amy Yasko, PhD.

Labs/Tests:

1). Urine Amino Acid ( UAA): Monitor Taurine & Ammonia levels & address— they should be to the left of the report at 50% or less. However, you do need some taurine so the goal is not to eliminate this amino acid. Also, t aurine levels may also be low until methylation support is on board.

***Please recall that you will not always see high taurine levels with CBS defects. In many cases, once you initiate methylation support, these levels will rise.

2). Urine Essential Elements (UEE) : Monitor Manganese & Molybdenum due to heavy use for ammonia detox

Treatment recommendations for the CBS : This is simply an FYI, please do not start the following supports until you have reviewed this with your practitioner!

1. Yucca sprinkled on protein to reduce ammonia levels (can also take capsules with meals)

2. Avoid high protein diets such as The South Beach Diet, Atkins, Specific Carbohydrate Diet (SCD), etc., as well as high sulfur (please see sulfur list) supplements & foods (g lutathione, NAC, SAMe, DMPS, glucosamine, broccoli, etc). This is not to imply that you cannot have any of these foods or supplements in lower doses/portions, it’s simply a caution.

3. CBS/NOS Caps: Start with 1/8 to 1/4 of a capsule once a day and work up t o twice daily. The goal is ½ to 1 cap twice daily for CBS and urea cycle support. Please increase slowly as detox will ensue. This combo supports the CBS, kidneys, NOS, and waste (ammonia) elimination & balance.

4. Spirulina is alkalinizing and assists with ammonia elimination.

5. Molybdenum & Manganese to keep the copper/zinc levels within range & reduce sulfites (monitor electrolytes and essential elements).

6. Curcumin , a methyl donor, may help shunt toward glutathione production.

AND/OR the CBS RNA listed below . Not everyone requires aggressive CBS or ammonia support.

1. CBS RNA, This needs to be diluted since the detox potential is quite high. You will be slowing the CBS down which means you’ll actually be keeping the supplements with in the system, as well as any existing work tags (methyl groups). This means they will be doing their jobs throughout the pathway and that generally leads to heavy metal, aluminum & other toxin filtering as well as viral, bacteria, & other bug clean up.

2. Ammonia RNA, only if leve ls are persistently high.

3. Charcoal flush , followed by mag citrate 1- 2 x weekly to soak up excess ammonia. (This is not necessary for most ).

4. L- carnitine, helps lower ammonia levels

***For those with the CBS defect, avoid magnesium sulfate (Epsom salts), MS M, and Chrondroitin whenever possible. Some sulfur is necessary and even beneficial when taken in at low doses, though generally, may be harmful in higher doses. On the other hand, a bit of garlic, milk thistle, & horsetail are advantageous in smaller doses. It is prudent to choose wisely.

Signs & Symptoms of high ammonia • Flapping or hand tremors • Dark circles under

Signs & Symptoms of high ammonia

Flapping or hand tremors

Dark circles under eyes

Disorientation, and brain fog

Hyperactive reflexes

NMDA receptor activation, leading to glutamate excitotoxicity

Tremor of the hands

Paranoia, panic attacks

Memory loss

Headaches

Irritability

Hyperventilation (often associated with decreased Carbon dioxide/CO2)

Central nervous system toxicity

Dementia Seizures