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Methyl Cycle NutriGenomics

The Methyl Cycle is the backbone of our physiology. It's functional status determines our resistance or susceptibility to environmental toxins
and microbes. This is a confusing array of biochemistry, but suffice it to say, a defect at any one point in these interlocking cycles will
inevitably affect the remaining pathways, and your overall health will then suffer. Methyl Cycle abnormalities explain why you are sick
from environmental toxins while the guy next door is just fine, why you are autistic while your fraternal twin brother is not. While we cannot
change your DNA, if we know your weak links we can create "nutritional workarounds" - we can supplement alternative pathways or
withhold from your diet molecules that you cannot handle. If we do not address the Methyl Cycle abnormalities that underlie unexplained or
chronic illness - well then the illnesses will remain chronic and unexplained, because it is the Methyl Cycle Abnormalities that predisposed
you to ill health.

Methyl Cycle Genomic Analysis and Supplementation Overview


Methyl Cycle Presentation Power Point Slides
CBS: Cystathione Beta Synthase
CBS: Alternate Explanation and Generic Plan of Action

MTHFR C677T: 5,10-Methylenetetrahydrofolate Reductase (5-Methyl-Folate)


SHMT: Serine Hydroxymethyltransferase

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MTR: Methionine Synthase


MTRR: Methionine Synthase Reductase
BHMT: Betaine-Homocysteine Methyltransferase
COMT: CatecholOMethyl Transferase

VDR Taq: Vitamin D Receptor Taq Abnormality


MTHFR A1298C: 5,10-Methylene TetraHydroFolate Reductase (BH4)
NOS: Nitric Oxide Synthase
ACE: Angiotensin Converting Enzyme

Glutamate GABA Imbalance Excitotoxicity


Approaches to Detoxification
MAO A, ACAT, AHCY, and VDR Fok
Appendix I: Foods High in Tyrosine or Tryptophan
Appendix II: Foods High in Sulfur
Appendix III: Foods High in Excitotoxins
Appendix IV: Elevated Urine Sulfate - What Do You Do Next?
Appendix V: General Recommendations Based Upon the Sulfate Value
Appendix VI: Methyl Cycle Recipes
Nurtigenomic Supplements and Supplies
Ordering Supplements from Websites
What You Can and Cannot Expect From Us
Sample Report One
Sample Report Two

Life Wave Patch Instructions

Methyl Cycle Genomic Analysis and Supplementation

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Understanding how to incorporate the science of Methyl Cycle Genomics in to your treatment program, and how best to monitor your
individual response, will be a challenge to both of us. If we accept this challenge, and spend time, energy, and resources in dealing with your
Methyl Cycle Abnormalities, then you can take strides forward in improving your health. If we do not well, most of you are undergoing
Methyl Cycle testing because you have a health problem that makes little sense; you have seen multiple doctors and you are not getting better
if we do not address your Methyl Cycle abnormalities then we cannot expect that you will get better because it is the
Methyl Cycle Abnormality that predisposed you to ill health.
What is a Methyl Cycle Abnormality? The chart above describes mutations, scientifically a correct descriptor, but not a good common
language description of your condition. You do not have a mutation, a one-time genetic accident that occurred during your embryonic
development. Methyl Cycle Abnormalities are not disease specific or smoking gun genetic defects. Yes, there are specific genetic
abnormalities that code for Sickle Cell Anemia, Huntingtons Chorea, or Phenylketonuria, and if you are born with these genotypes (referring
to ones genetic code), then we can be 100% certain that you will develop these disease states (the phenotype, or expression of the genetic
code). There is a great deal or dread and anxiety regarding testing for these genes. After all, if you cant do anything to prevent the
phenotype, why even look for the genotype?
Methyl Cycle Defects are different. None code for a specific disease state, but all play a role in predisposing you to disease in general. The
more Methyl Cycle Defects present in your genotype, the greater is your susceptibility to toxicity and infection, and the greater will be your
risk for these (usually) age-related degenerative disease states that plaque our society today. These disease states are usually age-related (but
are occurring in you earlier than in others) because it takes time for toxicity to build up within you, to overcome the still intact defense
systems that are trying to defend your physiology. On the other hand, a little bit of toxicity during a vulnerable time period can do a lot of
damage to an individual with impaired Methyl Cycle defenses. The frequency of Methyl Cycle Defects in autistic kids will likely be 100% a little bit of Mercury in a genetically defenseless kid will damage a developing brain. Their parents and grandparents harbored these genes
(likely in lower concentration) but when they were born our uterine and early life environment was toxin free. Their brains had the chance to
develop normally. Exposing them to toxicity now isnt good for them, but their brains did have the chance to develop normally, so they do
not develop adult onset autism. But individuals harboring Methyl Cycle Defects are going to get sick, before their time, likely with
conditions that make little sense such as Fibromyalgia, Chronic Fatigue, Multiple Chemical Sensitivity, or they will present early in life with
what used to be diseases seen only in old people: - coronary disease, cardiomyopathy, Parkinsons disease, and dementia.
Ive looked at disease as a combination of lifestyle, environment, and heredity. Yes, if you smoke, you will eventually experience lung
disease. If you are exposed to lead then it will eventually build up in your body and cause hypertension and kidney disease. But some people
smoke and get lung disease at an early age, some only at old age, and some seem to be able to puff away into their 80s. We are all exposed to
multiple toxins, we all live in the same general environment, but only some of us get heart disease and cancer why? If toxicity is so bad,
then why dont all of us have toxicity associated cancer? Well, were on our way, but some of us can live within this toxic environment
unscathed. How can one boy be autistic while his fraternal twin is normal - same uterine environment, same maternal diet, same vaccinations
but different genotypes. It is our genotype, specifically the status of the genes making up our Methyl Cycle that render us more or less
susceptible to environmental influences (toxins and microbes).
The term methyl group refers to CH3, one carbon atom attached to three hydrogens. The enzymes of the Methyl Cycle add or subtract a
methyl group from another molecule to open or close biochemical pathways, to open our DNA when it should be read, or to close it when it
would not be in our best interest to decode a specific gene. We need methyl groups to silence viral RNA, to defend against other microbes,
and to defend against environmental toxins. Optimal methylation is thus more important today than it was in years past, when the
environment was less toxic. Individuals with Methyl Cycle Defects are the canaries of our society. Toxins will hurt all of us eventually but
those of us with Methyl Cycle Defects will be the first to go down.
I am now looking at disease as a combination of lifestyle, environment, and Methyl Cycle Genomic Defects.

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Your packet contains your genotype. It is up to you to adjust your diet, and it is up to me to change your treatment program, in order to
optimize your phenotype (your health status the expression of your genotype). We cant change your genotype, but we can optimize its
expression. We can eliminate from your diet and treatment program substances that you cannot handle, and we can supplement you with
substances that you cannot make on your own. We can bridge gaps in your metabolic software and shore up your weak links now that we
know what your weak links are. This will be a lot of work and involve a not insignificant out-of-pocket expense, and likely a major change
in your diet. This may irritate you. You may initially be frustrated and mad. If you want to be mad, you can be mad at me but dont go
after me on a busy day I am COMT -/- and VDR Taq +/+; thus if you stress me out too much I will be susceptible to a fall off in dopamine,
serotonin, and norepinephrine, so I wont think so well (a little Methyl Cycle humor). Please do not take out your frustration on my staff. If
you are really angry you can complain to your parents, Charles Darwin, or God a better idea will be to accept and understand this challenge
and get to work addressing it. Along with your genotype report, your packet will contain Dr. Yaskos general recommendations (which
focuses on kids with Autism), my analysis of your genotype with specific recommendations for diet change, nutritional supplementation, and
follow-up testing. Information regarding sulfur avoidance (critical for CBS and SUOX genotypes) and food excitotoxin avoidance (useful
for all of us) will be enclosed, along with a supplement check list and information regarding how to obtain these supplements on line or at the
office.
90% of you will have an abnormality in the trans-sulfuration pathway (CBS and/or SUOX). Sulfites and Chronic Disease, by Rick Williams
(available at the office or you can go to www.readingtarget.com/nosulfites) contains a great deal of information regarding the sulfite/sulfate
content of common foods and pharmaceuticals. Read and research on your own, particularly with respect to diet, and report back to us on
what worked and what didnt work with respect to lowering your sulfate/sulfite levels with feedback from you we can improve our general
recommendations.
Regarding our terminology: homozygous, heterozygous, (+/+), (+/-), and alleles, lets start with a review of genetics and gene distribution we can use me as an example. I am homozygous (+/+) for MTHFR C677T. C (cytosine) has been replaced by T (thymidine) in the 677th
nucleotide position in my genes for the MTHFR enzyme. C codes for the amino acid alanine and T for the amino acid valine. Thus I have a
valine where I should have an alanine within the amino acid structure of 100% of my MTHFR enzymes. This enzyme will not work well. It
will not efficiently convert folic acid in to one of its active forms, 5-methyl folate. I can take all the folic acid I want, but I cannot use it.
With respect to this biochemical step, folic acid will actually be toxic to me, as it will crowd out the sparse methyl-folate present in my diet.
If my diet is confined only to folic acid, I am going to have trouble metabolizing homocysteine, and I am going to have trouble carrying out
many other critical biochemical steps. I will be at risk for premature cardiovascular and neurological disease. If on the other hand I
supplement with 5-methyl folic acid, I will have bypassed this genetic block, my biochemistry will revert to normal, and my increased
individual risk associated with the C677T abnormality will be 100% resolved. I also realize that 100% of my kids will be at least
heterozygous (+/-) for the C677T allele (if they are not then we will have to look closely at the mailman), and if my wife is heterozygous (+/) or homozygous (+/+) for the C677T allele, then they too may be homozygous (+/+). Allele refers to a variant, or a slightly different
copy, of a gene. You get one allele for each of your genes from your Mother, and one allele from your Father. If you know the genotype of
both parents, you can predict genotype likelihoods of their offspring (allowing nutritional planning before and during pregnancy hows that
for intelligent early intervention). I am heterozygous for MTRR A66G. A (adenine) has been replaced by G (guanidine) at the 66th position
in 50% of my genes form MTRR. Thus 50% of my MTRR enzymes will be defective. I may have received the A66G allele from my
Mother or from my Father. I am going to have trouble converting B12 in to methyl-B12, and this will compromise my health, but as 50% of
my MTRR enzymes will function normally, my relative need for methyl-B12 is less than my relative need for methyl-folate, as 100% of my
MTHFR enzymes are functioning abnormally. There are also Methyl Cycle Defects involving deletions or insertion of nucleotides
(components of the genetic code) within a gene, and they are referred to by number. I am (+/+) for ACE Del16. This means that nucleotides
that should be present at position16 of the ACE gene are not present. This heightens my risk for CV disease. Other Methyl Cycle Defects
are named after the scientist who first described them, such as in VDR Taq or VDR Fok.
Punnett Square analysis allows us to predict the genotype of our offspring as a function of the genotype of both parents. Several examples
are presented below. Ive used myself as an example, so youve seen that I share with you several genetic liabilities and I am not sick. Just
because you have genetic predispositions it doesnt follow that you have to be sick. I havent missed a day of work in 15 years and once a
year I run a 26 mile Marathon but I do try to take care of myself, I do take a lot of nutritional supplements, and I have applied the principles
of heavy metal and hydrocarbon detoxification to myself. Now that I understand my Methyl Cycle predispositions, I will be in a better
position to promote my own good health. We want to help you to do the same thing. Of interest, based upon my current understanding of
the link between the Methyl Cycle and disease susceptibility, and what we are seeing in the Methyl Cycle findings of our own patients, I
think that if I was born today I would likely suffer from Autism. But in 1955 there was little if any toxicity in the environment. The fish did
not contain mercury, my Mom did not have Mercury amalgam fillings, and we were not then using Mercury containing vaccines, so my brain
was allowed to develop normally. I will still be susceptible to Mercury and other toxins, but it is a lot easier to defend a fully developed and
otherwise healthy physiology from Mercury, microbes, and other toxins, than it is to defend an immature or developing physiology from the
same noxious influences.

Both Parents (+/+)


Mother (+/+)
100% of kids (+/+)
+
+
Father
+
+/+
+/+
(+/+)
+
+/+
+/+
When both parents are homozygous (+/+) all of
their kids will be homozygous (+/+)
Both Parents (+/-)
Kids will be

Both Parents (-/-)


Mother (-/-)
100% of kids (-/-)
Father (-/-)
-/-/-/-/When both parents are homozygous (-/-) all of
their kids will be homozygous (-/-)

Mother (+/-)
+
-

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Parents
(+/+) and (+/-)

Mother (+/-)
-

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Father (+/-)

+
+/+
+/+/-/When both parents are heterozygous,
1/ of their kids will be homozygous (-/-),
4
will be heterozygous (+/-), and
1/ will be homozygous (+/+)
4

Father
(+/+)

+
+/+
+/+
+/+
+/With (+/+) and (+/-) parents,
of their kids will be homozygous +/+),
and
of their kids will be heterozygous
(+/-)

Cost issues - this will not be insignificant, nor can we expect much help from your health insurance. American Medicine focuses on doing
procedures or prescribing drugs to deal with advanced pathology. This is what we get paid to do, so this is the medicine you get. The
concept of using nutritional supplements and dietary change, specific to your genotype, to prevent or stabilize disease states such that you
will require less drug therapy and invasive treatment, will not be well received or encouraged. Your insurer will consider such concepts to be
experimental or not evidence based. There is no point in arguing with these people. The dont get it. Treatment cost (basically the cost
of your supplements) will be your responsibility. Early on this may run up to $200 per month, but as your sulfate and ammonia burdens fall,
so will your requirement for supplementation. If your genetic challenge lies within the trans-sulfuration pathway (90% or you) our most
important approach will be dietary change, and these foodstuffs are less expensive than the foods that you have been eating that have been
making you sick. Also, please put all this in proper perspective. What did you pay for your car? Isnt your health worth a fraction of what
you paid for your car? What is a year of your life worth, to you and to your family? Do you wish to be vital and/or vocationally active in
your 70s, or confined to a nursing home due to a health problem related to a Methyl Cycle predisposition? Now, if you are on board with me
intellectually but are limited with respect to funds, we can try to stream line your program, and again, the harder you work on diet the less
you will need to spend on supplements, but please do your best to follow the supplement program.
Lab testing will be important, and to some extent will be covered by your insurer. Vitamin D, homocysteine, and blood ammonia levels will
likely change in response to our treatments and we will wish to follow these parameters; the cost of these blood levels will likely be covered.
Urine sulfate and/or sulfite testing is critical; here you purchase the urine dipsticks and test yourself and record the results. We will need to
follow your mineral status, as specific nutrients will be drawn in to pathways that were previously closed (we often see deficiencies in
Molybdenum, Boron, and Copper). The best approach is a 24 hour urine study for nutritional minerals (with a concomitant measurement of
toxic metals, which should start coming out on their own as your detox pathways open up). If a 24 hour urine is not possible we could use a
first AM void spot urine or a red blood cell mineral assessment (go to doctorsdata.com for more information on these tests). Dr. Cowden
has reconfigured the Asyra software to help us screen for Methyl Cycle abnormalities. If ammonia shows up, and you do not work with
fertilizer or cleaning solutions, you likely have a problem in trans-sulfuration (CBS and or BHMT) or within the ammonia detoxification
pathway (here the NOS enzyme). If sulfate and/or sulfite show up, then the problem likely lies in CBS/BHMT, while if we see sulfite but no
sulfate, then SUOX (converts sulfite to sulfate) is likely the culprit. Asyra can never be as accurate as actual genomic testing, and at this
point we have seen false positive and false negative Asyra Methyl cycle findings, but Asyra is low in cost and easy to carry out and lab
testing is often high in cost and logistically difficult to carry out, so we will attempt to get the most information that we can out of the Asyra
methodology. Regarding the urine sulfate determination, to our knowledge a high level of urine sulfate, especially coupled with a low blood
homocysteine level, is indicative of a trans-sulfuration (CBS and/or BHMT) defect, but there could be conditions associated with a false
positive urine sulfate. Also, if an upstream defect limits generation of homocysteine (AHCY +/+ or +/- does this), or if for any other
reason you have been limiting animal protein in your diet, you could harbor a CBS defect and have a low urine sulfate (we do see this). Thus
none of these screening tests can be perfect. We will need to interpret your test results in the context of what we know of your health and
your genotype. Incidentally, you do not need to repeat your Methyl Cycle Genomics test these findings will never change.
Individualized medicine, based upon analysis of ones unique genetic code, is the future of medicine. We will do our best to provide you
with this approach in 2008. Right now, our understanding of the Methyl Cycle allows us to translate your unique genomic pattern in to
beneficial clinical recommendations. Over time, more science will become available, as will our expertise in treating abnormalities in your
genotype. Your feedback can only make us better.
The brain behind Methyl Cycle is Amy Yasko PhD. Dr. Yaskos area of clinical expertise is in the treatment of Autism. You can learn much
more form her website holistichealth.com. We use Dr. Yaskos lab for Methyl Cycle testing, and many of the supplements discussed below
can be obtained from her holisticheal.com website. As Dr. Yasko points out, Methyl Cycle abnormalities are not just the predisposing cause
of Autism; they are the predisposing cause of disease in general, the link between environmental toxicity and the degenerative disease states
that now plaque our society. Doctors like me are attempting to utilize Dr. Yaskos teachings in the care of individuals of all ages (and to
optimize their own health).
Now lets discuss the individual genes, and our approach to the abnormal patterns that we see in our patients. 90% of the patients who we
have tested returned with abnormalities in the trans-sulfuration pathway, specifically in the CBS gene, so we will start with the CBS up
regulation.

Methyl Cycle Presentation Power Point Slides


This presentation was given at a Metagenics Midwest meeting in the fall of 2014. An expanded version will be given in 2/15, within Module
1D of the American Academy of Anti-Aging and Regenerative Medicine training program. To view the slides please click the corresponding

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tabs.
Methyl Cycle Slides Part One

Methyl Cycle Slides Part Two

CBS: Cystathionine Beta Synthase


CBS initiates the trans-sulfuration pathway, converting homocysteine in to cystathionine and
its downstream metabolites. This is the most important Methyl Cycle defect and is present
in 90% of the patients who we have tested. The CBS defect is an up regulation. CBS is
operating at up to ten times its normal rate. Homocysteine and all of the upstream methyl
cycle precursors will be pulled down the CBS drain to produce toxic levels of
cystathionine metabolites. The C699T and (to a somewhat lesser extent) A360A defects are
associated with CBS up regulation. Homozygotes (+/+) will be more severely affected than
will be individuals heterozygous (+/-) for a CBS abnormality. We treat CBS ( +) individuals
with dietary animal protein and sulfate restriction and supplements designed to neutralize
ammonia and speed up clearance of sulfite/sulfate. Laboratory findings consist of an
elevated urine sulfate level, a low or low normal blood homocysteine level, an elevated or
high normal blood ammonia level, and positive findings of ammonia, sulfite, or sulfite upon
Asyra testing. My initial observation is that individuals with high heavy metal burdens upon
provocative challenge testing are likely to be CBS positive. CBS (+) individuals will be
intolerant to sulfur containing drugs, nutritionals, and foodstuffs (I am +/- for CBS A360A
and cannot tolerate DMPS or glucosamine sulfate. A cold beer tastes great but I do not like
wine, which is high in sulfite).

Biochemistry The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate, which stimulate the stress/cortisol
fight or flight response), excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia), hydrogen sulfide
(producing brain fog), and alpha-keto glutarate (leading to excitotoxicity). The G6PDH enzyme system may be affected, leading to
abnormalities in sugar control. Methylation intermediates will fall through this drain, so the entire system suffers; our defenses against
viral invasion and toxicity suffer. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing
you of energy.
Ammonia is produced during the metabolism of dietary protein. The CBS up regulation drains methyl cycle intermediates in to ammonia,
more ammonia than your system can handle. Ammonia detoxification is metabolically expense, using up two molecules of BH4 per
molecule of ammonia. BH4 is necessary to generate neurotransmitters (dopamine, serotonin, and norepinephrine) and nitric oxide, our key
vasoprotective molecule. Thus it is easy to see how a CBS up regulation, by generating ammonia and depleting BH4, can set you up for
neurological, psychological, and cardiovascular disease states. We cannot change your DNA. We cannot stop CBS from generating excess
ammonia, but if we restrict animal protein in your diet, we can decrease your ammonia burden, preserving BH4, such that you can start
making neurotransmitters and nitric oxide again in other words, we can compensate for your genetic challenge. The herb Yucca, Dr.
Yaskos Ammonia support RNA product, and supplementation with charcoal and carnitine will bind up or neutralize ammonia, and add to
your dietary efforts.
Sulfite is neurotoxic. Sulfite will be over produced by the CBS up regulation, and then requires conversion in to the less toxic sulfate
molecule by the enzyme Sulfite Oxidase (SUOX). SUOX can easily be overwhelmed. Molybdenum is required for SUOX function, and is
typically depleted in CBS (+/+) or (+/-) individuals. Molybdenum supplementation (3 drops or 75 mcg of e-lyte Molybdenum twice a day),
Boron 3 mg/day, Vitamin E succinate 400 IU/day, and hydroxy-B12 2000 mcg/day are also utilized to speed up SUOX activity.
While sulfate is less toxic than is sulfite, it will stimulate the adrenergic (fight or flight) limb of the autonomic nervous system and stimulate
a cortisol stress response, revving you up into an unrelenting biochemical overdrive. If you have a CBS defect, we need to restrict your
sulfur intake, at least until your urine sulfate (and your body sulfate burden) has decreased. The amino acids methionine, taurine, and
cysteine all contain sulfur; they are concentrated in animal protein (thus the restriction on animal protein intake). Many nutritional
supplements (MSM, N-acetyl cysteine, glutathione) that are good for most people are a problem for you. While certain aspects of your
health will benefit from these agents, they will add to your sulfate/sulfite overload problem, adversely affecting the Methyl Cycle Defect that
is the common denominator to all of your health problems. Many drugs are loaded with sulfur (sulfates, sulfites, metabolically active sulfur),
so if you are CBS positive and I treat your hypertension with the diuretic hydrochlorothiazide, your diabetes with the sulfonylurea drug
glipizide, and your urinary tract infection with a sulfa containing antibiotic, I will be lowering your blood pressure, lowering your blood
sugar, and clearing bacteria from your bladder, but I will also be adding to your sulfate burden, compromising your biochemistry, and
contributing to an ongoing decline in your health. I will be treating the manifestations of an underlying problem and at the same time adding
to the underlying problem. If I treat your Mercury overload with DMSA or DMPS, I will remove a toxin from your body, but if you are CBS
(+), I will be adding to your sulfate/sulfite pool, and sulfate/sulfite overload due to the CBS up regulation is likely playing a key role in your
sensitivity to heavy metals and/or your inability to clear them. We can avoid this. We can hold sulfur containing agents until your sulfate
burden has come under control. Learn all you can about the sulfur content of foodstuffs, supplements, and prescription drugs. Sulfites and

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Chronic Disease by Rick Williams (available at the office or at www.readingtarget.com/nosulfites) is an invaluable resource. Do not expect
us to know the sulfur content of foodstuffs. Some tips on low sulfur eating are included at the end of this document, but do not expect us to
tell you what to eat. We cant do this. We do not have this knowledge. Please attend our monthly Methyl Cycle support groups meetings,
and you may sign up for individual (or group) dietary change counseling. It is your responsibility to become expert in this area. I will work
with you to phase out high-sulfur drugs and nutritionals from your program, but dont expect me to get in right every time please study
your food, drug, and supplement labels.
Excitotoxicity The CBS up regulation leads to excess production of alpha-ketoglutarate, which is converted in to glutamate, a stimulatory
neurotransmitter. Under normal circumstances, glutamate will be converted in to GABA, a calming neurotransmitter, but the enzyme
systems that convert glutamate in to GABA are compromised by lead and mercury, the clearance of which seems to be compromised in
individuals with methyl cycle defects (here is a situation where dysfunction of a genetically abnormal enzyme leads to acquired dysfunction
of a genetically normal enzyme system). The result is excitotoxicity, stimulatory behavior in autistic kids (stims) and anxiety and
sleeplessness in adults. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on
Excitotoxicity to follow; diet tips in appendix) and by supplementing you with GABA, aiming to restore GABA:Glutamate balance. GABA
is initiated at 500 mg once or twice a day, advancing the dose as you see fit by your response.

Abnormalities in BHMT (Betaine-Homocysteine Methyltransferase) aggravate and


frequently co-exist with CBS defects. BHMT mediates the backdoor pathway of
homocysteine metabolism, drawing homocysteine away from the trans-sulfuration
pathway that is up regulated in CBS (+) individuals. A defect in BHMT, will thus
mimic or add to a CBS defect. BHMT can be stimulated with Phosphatidylserine,
Phosphatidylcholine (which is combined with the metal chelator EDTA in Lipophos
EDTA), and the methyl donor TMG (Trimethylglycine), and one or more of these
agents will be included in our treatment program for CBS (+) and/or BHMT (+)
individuals.

In a sense, the key ultimate consequence of CBS/BHMT abnormalities will be BH4 deficiency. By
neutralizing the consequence of your CBS up regulation and/or BHMT down regulations, your BH4
status should begin to return towards normal. We also can supplement you with BH4. It is strongly
recommended that BH4 supplementation be held until all other Methyl Cycle pathways have been
optimized. Pharmacological doses (200 mg/day) of BH4 has been shown to be safe and effective
when used to treat endothelial dysfunction in hyperlipidemic individuals, and in dealing with Methyl
Cycle defects, far lower nutritional doses (2.5 mg four times a day) are typically employed, but here
a little bit of BH4 can go a long way, and we need to be prepared. If long-closed detox pathways are
suddenly opened up, you could experience a detox reaction, so we need to get the rest of your
systems up and running before we open these closed gates. If neurotransmitter generation suddenly
comes back on line, and you are taking an anti-depressant drug or nutritional that preserves
neurotransmitter levels, you could experience a neurotransmitter surge if we have not cut back on the
drug dose. If we give you BH4 before you are ready, you will feel great for a day or two, and then
crash, with fatigue and malaise, as we attempt to spin other metabolic wheels forward that are still stuck in the off position. Thus we
need to be patient, take things step by step, with the long goal in mind.
Energy Production will falter. To generate ATP energy, you need Co-enzyme Q10 and Carnitine, but to manufacture these co-factors you
need methyl groups, which tend to be in short supply in individuals with Methyl Cycle defects. To make matters worse, when energy is in
short supply, homocysteine is shunted in to ammonia, hydrogen sulfide, and alpha-ketoglutarate, and not in to its one beneficial metabolic
product, glutathione. NADH, Carnitine, Co-enzyme Q10, and its non-oxidizeable 1st cousin Idebenone will all help with ATP energy
production, and their use makes sense in patients with CBS up regulations, especially if they have cardiovascular disease. (I am getting
ahead of myself, so skip this entry if you wish, but the latter three agents also can serve as methyl donors. We will be more liberal with their
use in individuals who are COMT (-/-), who need methyl donors, and more conservative in their dose in individuals who are COMT (+/+),
who will be more sensitive to methyl group supplementation). Ribose increases ATP regeneration in individuals with cardiovascular disease
or other conditions associated with energy deficiency, and can be taken as well.
SUOX (Sulfite Oxidase) converts sulfite in to sulfate. I am (+/-) for SUOX and (+/-) for CBS, meaning that I am overproducing sulfite and
having trouble converting sulfite in to less toxic sulfate. I will thus need to be particularly vigilant with respect to supporting SUOX
function. Molybdenum, in short supply in CBS + individuals, is also used up by the enzyme xanthine oxidase, a free radical generating
enzyme system that plays a role in gout (it produces uric acid which precipitates in your joints to cause the pain and inflammation of gout).
Xanthine oxidase is present in pasteurized milk, which is best avoided or minimized in CBS (+) individuals. A note regarding nomenclature;
a defect in a Methyl Cycle enzyme is typically described with a (+). I am homozygous (+/+) for MTHFR C677T so 100% of my MTHFR
enzymes are defective. For reasons that make no sense to me, someone decided that the normal designation for the SUOX gene should be

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(+/+); thus if you are (-/-) for SUOX you are homozygous abnormal. This is the only gene where (-/-) is abnormal and (+/+) is normal. In
my shorthand, I will refer to any defect in any Methyl Cycle gene as a (+). If I refer to an individual as CBS (+), I am referring to an
individual with a CBS abnormality, either (+/+) or (+/-). To keep things as clear as possible (and believe me I am trying) I will also can refer
to individuals who are abnormal for SUOX as SUOX (+).
My general treatment program for CBS (+) individuals and for BMHT (+) individuals who are overproducing ammonia and sulfite/sulfite
will consist of:
1. Restrict animal protein (anything with eyes) from your diet and limit your exposure to sulfur group containing drugs and nutritionals.
2. To squelch ammonia, supplement with Yucca, capsule twice a day (sprinkled on food containing protein), Ammonia Support RNA
dropper with meals, and a charcoal supplement at bedtime (away from other supplements; magnesium citrate may be used as needed to keep
the GI tract moving as charcoal may lead to constipation).
3. Switch to a multi that does not contain B6 (B6 stimulate CBS; the P-5-P form of B6 is less of a problem Dr. Yaskos NHF multi is low
in B6 - take two tablets three times a day). Additional mineral support will be needed and here we start with Trace Minerals Complex at 4
drops/day.
4. To stimulate SUOX begin Molybdenum 3 drops twice a day, Boron 3 mg/day, Vitamin E succinate 400 IU/day (contained in the NHF
multi), and hydroxy-B12 2000 mcg/day.
5. Supplement with GABA 500 mg once or twice a day to blunt excitotoxicity; if you feel that GABA is helping you can increase the dose.
6. To increase energy production (this step is less critical and can be omitted for cost containment, especially in individuals not troubled with
CV disease) supplement with NADH 5 mg, Co-Enzyme Q10 100 mg or Idebenone 100 mg, Carnitine 500-1000 mg daily, and Ribose 5
grams in water, two to three times a day. Co-Enzyme Q10, Carnitine, and Idebenone all provide Methyl groups, and are thus of additional
value to COMT (-) and/or VDR Taq (+) individuals.
7. Additional measures designed to speed up the back door BHMT reaction will be discussed later.
8. Check and record your urine sulfate level every 7 days. Our goal is to reduce your reading to 400 mg/L (one yellow and three pink
squares) or at least to 800 mg/L (two yellow and one pink), and then to keep it there for two months (at which time you will feel better).
Measures that decrease your sulfate burden are beneficial. Conversely, any measure that increases your sulfate burden is either inappropriate
or is being added to your program prematurely. A persistent reduction in your urine sulfate level will open the door to SAMe and/or BH4
supplementation and an eventual liberalization in your diet. Your urine sulfate score will thus be our primary measuring stick.
9. If not done already, we need to check your baseline blood homocysteine, ammonia, and Vitamin D levels, along with kidney and liver
chemistries (if not done recently).
10. Consider wearing the Life Wave Glutathione patch 4-6 hours each day, removing the patch if you feel poorly (this would reflect a
detoxification reaction - see our info sheet and lifewave.com/chc), the idea here being to use up free sulfur groups to generate Glutathione.
11. In 8-10 weeks we will likely wish to:
a. Repeat some of the lab work.
b. Carry out 24 hour urine studies for ammonia and amino acids, with a second study for toxic and nutritional minerals, and possible a
SpectraCell intracellular nutritional assessment. We will use the results to modify our nutritional measures, specifically looking for nutrients
that have been drawn in to your now open pathways, nutritionals that will now require more intensive supplementation. Favorable results
will also allow us to back off on the dose of now less necessary supplements.

CBS: Alternate Explanation and Generic Plan of Action


Gene by Gene Approach CBS +/- or +/+ with/without BHMT +/- or +/+

CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. Yaskos book, Genetic Bypass. Additional information is available
on our heartfixer.com website. You are +/+ (all CBS enzymes abnormal) or +/- (half of your CBS enzymes abnormal) for one of the two
CBS up regulations and you may also be +/+ or +/- for one of the BHMT down regulations (which act like CBS up regulations).
Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration
pathway, in this process generating excessive sulfur break down products (sulfite and sulfate, which
stimulate the stress/cortisol fight or flight response), too much alpha-ketoglutarate (which leads to
glutaminergic excitotoxicity), hydrogen sulfide (to produce brain fog), and too much ammonia
(which depletes BH4, leading to insufficient dopamine and serotonin production). This deficiency
in BH4 allows NOS (nitric oxide synthase) to convert arginine in to free radicals (superoxide and
peroxynitrite) as opposed to nitric oxide, predisposing you to hypertension and cardiovascular and
inflammatory disease states.
During normal physiology, metabolic flow down the CBS pathway is designed to generate the
important anti-oxidant and detoxifying molecules glutathione, taurine and cysteine (all involved in
detoxification and endothelial health), and alpha-ketoglutarate (which can be converted into GABA,
a calming neurotransmitter). The CBS C677T and A360A genes code for enzyme function that is
pathologically up regulated. Of the two, the C677T allele is the most important, producing enzyme
activity that is 10 fold greater than normal. You thus suffer from too much of a good thing and
way too much of several bad things.
While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification, sulfate/sulfite/-SH excess blocks cellular up take of the
key detoxifiers glutathione and cysteine. Endogenous detoxification is thus blunted (nearly all kids with Autism Spectrum Disorders bear

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CBS up regulations why they are compromised by environmental toxins and the kid next door is just fine). Conversely, after we decrease
your sulfate/sulfite pool, your detox pathways open up (and why, if we move too fast, you will experience detox phenomena).
The excess ammonia generated must be detoxified, and to do so BH4 (tetrahydrobiopterin) must be spent. This is a problem in that we
need BH4 to generate neurotransmitters (serotonin to maintain calm/prevent depression and dopamine to maintain motivation and drive).
Without BH4, we cannot convert arginine in to nitric oxide; instead vascular wall toxic free radicals such as superoxide and peroxynitrite are
created, leading to hypertension and cardiovascular disease.
Alpha-ketoglutarate, in moderation, is not a problem. We should be able to interconvert alpha-ketoglutarate into glutamate, glutamine, and
GABA. However, when alpha-ketoglutarate is in excess, or if toxic metals compromise the interconversion enzymes, then we suffer a
buildup of the excitatory neurotransmitter glutamate. Glutamate is involved in alertness and learning, but excess glutamate leads to
irritability and over-excitement; toxic levels may play a role in seizure activity and
cardiac arrhythmia (could this be why we are seeing so much atrial fibrillation
now then we were ten years ago)?
CBS up regulations lead to an initial buildup of potentially neurotoxic sulfite,
which is then metabolized by SUOX (Sulfite Oxidase) to the less neurotoxic (but
still problematic at high levels) sulfate. SUOX activity requires molybdenum,
which is thus depleted in CBS + individuals. Homogenized dairy products contain
xanthine oxidase, which uses up molybdenum, and are best avoided or minimized.
Vitamin E succinate, boron, and B12 are felt to stimulate SUOX activity.
As Methyl Cycle function is needed in the biosynthesis of Co-Enzyme Q10 and
Carnitine, individuals + for CBS will likely be energy depleted, and here supplementation (in relation to your COMT/VDR status) with CoEnzyme Q10, Carnitine, and NADH may be helpful.

BHMT (Betaine Homocysteine Methyl Transferase) directly methylates homocysteine back in to methionine, serving as a back door
pathway to pull homocysteine away from the CBS sulfate drain. Thus if you bear CBS or BHMT abnormalities, it makes sense to
support BHMT function. DMG (dimethylglycine) and TMG (trimethylglycine) stimulate BHMT, and can be utilized if you are not overly
sensitive to methyl group supplementation (based upon you COMT/VDR status). Phosphatidylserine stimulates BHMT (and we also use it
to moderate elevated cortisol levels), as does phosphatidylcholine (which we use to treat atherosclerosis). Phosphatidylcholine can be
admixed with EDTA (detoxifies metals), creating a quite useful supplement.
Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR
(compromising methyl-B12) abnormalities, and thus you will need and benefit from corresponding supplementation (with these molecules
that they are having trouble making). However, if we treat you with methyl-folate, methyl-B12, or BH4, before we have the CBS problem
under control (sulfite/sulfate levels decreased enough to allow for appropriate glutathione and cysteine assimilation) then we will be
subjecting you to incomplete detoxification. You will feel great for 1-2 days, as beneficial neurotransmitters are generated. Methyl-folate
and methyl-B12 detox pathways will then open up, creating toxic intermediates that cannot be metabolized further due to the block in
glutathione utilization and you will feel horrible. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until
CBS/BHMT are under control. Youve lived your entire life with a gene set that is maladaptive to the toxic environment of modern man. It
will take us some time to change your internal environment to bypass these genomic challenges.

Plan of action for CBS +/- or +/+ (BHMT discussed further in other sections)
(made out of context of your MTHFR, MTR, MTRR, COMT, VDR, and personal health status)
To address this constellation of alleles I will recommend:
1. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables, sulfur containing supplements, and sulfur
containing drugs (see attached sulfur avoidance instruction sheets and read Sulfites and Chronic Disease by Rick Williams, available at the
office or at www.readingtarget.com/nosulfites/.
2. Check the sulfate/sulfite content of your supplements and prescription agents (many listed in the Williams book) and whenever possible
switch to agents with lower sulfate/sulfite content.
3. Monitor urine sulfate levels every 3-7 days (or when you feel particularly good or poorly, or after adding a new treatment or changing your
diet). Please chart the levels this will be our primary measuring stick our goal is a urine sulfate of 400 (one yellow and three pink) to
800 (two yellow and two pink). Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a
liberalization of your diet. Conversely, persistent high sulfate spills indicates that your diet/treatment program needs further modification.
3. To neutralize ammonia (generated from animal protein), you can use Ammonia Support RNA dropper with meals and with methyl cycle
supplements (relatively expensive), along with a charcoal supplement at bedtime every other evening, away from other supplements
(magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). Yucca, beginning at capsule,
twice a day, (or sprinkled on food containing protein), may help with ammonia detoxification. These supplements can be tapered down as
ammonia levels fall.
4. Sparga Detox, 10 drops in water (wait at least one minute before consuming), twice a day makes sense. Sparga was developed by fellow
Cardiologist Dr. Lee Cowden, specifically to address the CBS abnormality (see www.nutramedix.ec).

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5. For nutritional support, a low-sulfate multi such as Dr. Yaskos All in One, two twice a day, makes sense. To stimulate SUOX activity,
please use sublingual hydroxy-B12 2000 mcg/day, along with Molybdenum and Boron. They may be taken individually as Molybdenum 3
drops in water twice a day and Boron 3 mg once a day, while our Complete Mineral Complex, 3 daily will cover the mineral base. Avoid B6
(unless you need it for other functions), which stimulates CBS. The active form of B6, P-5-P, is less of a problem here and serves as a B6
substitute.
6. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. Right now this good thing could actually set you
back. However, if we could convince your biochemistry to up regulate biosynthesis of glutathione, then your anti-oxidant and detox capacity
will increase, with concomitant utilization of free sulfate/sulfhydryl groups a double win for you. This can be achieved with the use of the
Life Wave (needleless acupuncture) Glutathione patch. The Life Wave people have demonstrated an increase in Glutathione levels in
relation to patch use (please see separate information sheet on Life Wave patch use). Toxicity testing** may also be carried out.
7. If you feel anxious or wired up (glutamate overload), take GABA 500 mg or Zen (GABA 550 mg with Theanine 200 mg, a methyl
donor) twice a day. Individuals who need methyl groups (normal COMT and/or abnormal VDR Taq alleles) will do better with Zen, while
individuals who are methyl group sensitive (COMT+) will likely do better with GABA. If they are helpful you can double the dose. GABA
does not work rapidly, but if you take it twice a day you will build up a GABA reserve to balance the glutamate overload you are
experiencing due to your CBS up regulation. Magnesium supplementation may help with GABA physiology and often helps with sleep.
8. If energy is low, or if deficiencies are identified on your NutrEval study, we can supplement you with Co-Enzyme Q and Carnitine,
keeping in mind that these substances provide methyl groups, to which you may be sensitive. NADH does not provide methyl groups and
should be well tolerate by all.
9. Your homocysteine level will give us important information as to the functional expression of your CBS/BHMT genomic abnormalities,
and should be drawn before any diet change/nutritional intervention is carried out. Formal nutritional testing will be carried out in 8-12
weeks. This could involve separate 24 hour urine studies for nutritional minerals and for ammonia/amino acids, or we might use the Genova
Labs NutrEval. We need to make sure your mineral/nutritional stores are replete, and we are looking for low levels of ammonia, taurine,
glutamate, and cysteine, to demonstrate that flow down the CBS pathway has been decreased to a physiologic level.
10. After sulfate levels have fallen (to a level that you and I feel is optimal for you, based upon your clinical and genomic status), then we
will begin supplementation with methyl-folate, methyl-B12, and BH4. This will take some time.
11. Be self-observant and keep records. Which foods, supplements, or other maneuvers increase or decrease your sulfate spill? Which make
you feel better or worse? Always keep in mind that detoxification is not a fun experience. You may need to accept some transient fatigue,
malaise, and achiness to allow toxic molecules to be cleared. Conversely, if detox symptoms are debilitating or compromise your ability to
work or care for your family, then we need to back off on your treatments. Balance needs to be achieved. Rectifying your genomic
predispositions and detoxifying your system is not a sprint it is a marathon. And, as your genes are not going to change, and as the
environment is not going to become less toxic, you will need to be mindful of these principles for the rest of your (long and healthy) life.
* How tightly should you restrict dietary protein? The degree of protein restriction best suited for you will be in relation to your personal
health characteristics and your clinical and biochemical (urine sulfate and ammonia levels) response to treatment. We need to keep in mind
that Methyl Cycle Genomics is not the sole determinant of your health. A low protein diet could become a high carbohydrate, weight gain
diet in an overweight individual with adult onset diabetes, nor do we wish to create an essential amino acid deficiency. Individuals with
chronic, unexplained illness or significant toxicity would do well to follow the nothing with eyes diet until urine sulfate and ammonia
levels have fallen; later on we will liberalize your diet, while keeping an eye on these biochemical markers. This maneuver isnt fun and will
require personal strength, but it also may turn your health around. Individuals in whom the CBS up regulation is less important (A360A as
opposed to C677T, lower urine sulfate and ammonia levels, and better overall health), could simply cut back on animal protein. In addition,
the greater representation of ammonia reducing (Yucca, Charcoal, Sparga, Ammonia Support RNA) treatments in your program, the more
protein you will be able to take in without compromising your biochemistry. This is all about balancing diet against treatment response.

** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Toxicity testing (discussed in more detail
in other presentations and on heartfixer.com) thus makes sense. This could take the form of:
A. The NutrEval provides us some information regarding organic pollutants and gives us red cell (reflecting what your physiology has been
exposed to over the preceding three months) toxic metals ($170 with commercial insurance; fully covered under non-HMO Medicare).
B. The US BioTek study gives us information on seven major organic pollutants ($126).
C. A formal provocative challenge gives us our best assessment of tissue metal burden.
D. The Hunt Digital picture approach assesses for toxicity (and other health challenges) by analyzing the frequencies emitted by your body
(and tells us which Digital Homeopathic Patches would be most appropriate). I cant prove this approach with an allopathic lab test but it has
been quite helpful in solving complex medical problems in my personal patients. Dr. Hunts CD is available for your review and you can go
to www.auraexplorationpatches.com for additional information.

OUR FIRST GOAL WILL BE TO REDUCE YOUR SULFATE STORES


AND DECREASE AMMONIA AND GLUTAMATE
GENERATION

MTHFR C677T: 5,10-Methylenetetrahydrofolate Reductase (


5-Methyl-Folate)


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The MTHFR C677T defect is easy to understand and even easier to treat, but the consequence of the MTHFR abnormality in kids appears to
be profound, such that the parents of Autistic kids add a few more vowels to MTHFR in naming it. Dietary folic acid, which usually is not in
short supply, is readily converted in to one of the active forms of folic acid, known as tetrahydrofolate, or THF. MTHFR converts THF in to
5-methyl THF, more commonly referred to as 5-methyl folate. MTR (methionine synthase) then combines 5-methyl folate with
homocysteine to form methionine. Individuals who are (+/+) for MTHFR C677T (10% of the population, including me) have a great deal of
trouble using dietary folic acid to detoxify homocysteine, as we cannot efficiently convert dietary folic acid into its 5-methyl folate form.
Elevated homocysteine leads to free radical stress, vascular plaque formation, abnormal clotting, and an increased risk for cardiovascular and
neurologic disease yikes! If you are (+/+) or (+/-) for MTHFR (another 20% of the population), supplementation with folic acid is not the
answer it cant help you. However, low dose 5-methyl folate supplementation will bypass this defect with 100% efficacy. If you have a
MTHFR C677T defect, we need to provide you with 5-methyl folate.
Sources of 5-methyl folate include Folapro (800 mcg 5-methyl folate), Metanx (5-methyl folate 2.8 mg, P5P 25 mg, and methyl-B12 2 mg),
and Cerafolin NAC (5-methyl folate 5.6 mg, NAC 500 mg, and methyl-B12 2 mg). Folapro is available over-the-counter, at the office or on
line. Metanx and Cerafolin are available as prescription agents, but your health insurance typically will not cover their cost as they are just
vitamins.
Of interest, homocysteine is a known bad actor. An elevated homocysteine level increases your risk for cardiovascular and neurological
disease. Many studies have been carried out, utilizing various cocktails of folic acid, B6, and B12, or a placebo agent in large groups of
individuals, with or without known disease states. Average homocysteine levels will fall, but not all subjects will respond with a reduction in
homocysteine. Clinical event rates typically fall in response to supplementation, but some studies show no effect, and one study of folic acid
supplementation in the elderly showed an increased rate of dementia. Why did this occur? Youve already figured it out. If we give folic
acid to individuals with an elevated homocysteine level and normal MTHFR function, they will respond with a reduction in homocysteine
and a reduction in disease risk or event rate, but if we give folic acid to an individual who is MTHFR (+/+) or (+/-), then not much happens.
Actually, if we flood you with folic acid that you cannot use, we can block absorption of the sparse 5-methyl folate present in your diet, so
your homocysteine level might even rise. Also, excess folic acid can be converted in to alpha-ketoglutarate, aggravating a co-existent CBS
abnormality. Thus we can understand how supplementation inappropriate for ones genotype can have an undesired negative consequence. I
used to think of homocysteine as an individual bad actor, a cause of cardiovascular and neurological disease. Now I look at an elevated
homocysteine not as a bad actor, but as a marker of a real bad actor, that being a Methyl Cycle abnormality. To further confuse and befuddle
research attempting to link homocysteine with disease states, we must also point out that the sickest patients, or the still healthy but at
greatest risk individuals in our society, are those with the lowest homocysteine levels, because their homocysteine levels are low not due to a
good diet, but because they harbor the CBS up regulation. I could go on and try to link homocysteine levels with the story of the three bears,
but instead we will cover the SHMT abnormality in THF (dietary folate) processing, and then move on to MTR/MTRR.

SHMT C1420T: Serine Hydroxymethyltransferase


Our diagrams indicate that the MTHFR "forward reaction" converts THF (obtained from dietary folic acid) in to 5-methyl folate, which is
then used by MTR to convert homocysteine in to methionine, in the process regenerating THF. In reality, an intermediate step is involved,
catalyzed by SHMT. SHMT converts THF in to 5,10-methylene THF (upper left in the diagram). It is actually 5,10-methylene THF, not
THF itself, that is converted in to 5-methyl folate by MTHFR. Some of the 5,10-methylene THF generated from THF by SHMT will take
another metabolic pathway, being acted upon by SHMT a second time, whereby 5,10-methylene THF is converted in to 5-formyl folate (also
known as folinic acid), which is used as a building block for DNA. We can address a SHMT down regulation by supplementing you with its
products, folinic acid, and 5-methyl folate (as without 5,10-methylene THF the MTHFR enzyme has nothing to work with).

MTR: Methionine Synthase

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MTR combines 5-methyl folate and homocysteine to form methionine and tetrahydrofolate (THF). More specifically, MTR removes a
methyl group from 5-methyl folate, then tacks it on to homocysteine to form methionine. In the process 5-methyl folate is converted back to
THF.
The MTR A2756G defect is an up regulation. The enzyme is always on, grabbing every homocysteine and 5-methyl folate molecule that it
can get its hands on, processing them to methionine and THF. Methyl-B12 is required for normal function of MTR, and with each spin of
the MTR enzyme, one molecule of methyl-B12 is degraded.
MTRR (Methionine Synthase Reductase) serves the needs of MTR, regenerating methyl-B12 from available methyl donors and B12.
Without methyl-B12, MTR cannot convert homocysteine in to methionine. Needed downstream methyl donors such as SAMe will not be
generated. Methylation fails, so does your biochemistry, and there goes your health.
When the MTR A2756G defect is present, MTR is always on, using up methyl-B12 faster than MTRR can regenerate it. The consequence is
deficient methyl-B12. B12 blood levels may be normal, but as levels of methyl-B12 will be low, normal B12 physiology cannot be carried
out. Homocysteine levels will typically be elevated. SAMe generation and methylation in general will be compromised. We can treat the
MTR up regulation by:
a. Supplementing you with methyl-B12.
b. Measures designed to increase formation of methyl-B12.
c. We can also bypass the dysfunctional MTR step by stimulating the backdoor BHMT reaction, which converts homocysteine directly in
to methionine (more on this approach later).
d. When we do not need to limit sulfur intake (CBS normal or under control with low urine sulfate readings) we can simply supplement you
with SAMe, our most important methyl donor, which is otherwise formed from the methionine generated by the MTR/MTRR reaction.

MTRR: Methionine Synthase Reductase

MTRR generates the methyl-B12 needed by MTR and many other methyl-B12 requiring enzymes. Blood B-12 levels may be normal, but if
MTRR is (+/+) or (+/-), methyl-B12 formation will be compromised, homocysteine levels will be elevated, methylation in general will be
compromised, and your physiology will be compromised.

MTR Up Regulation (+) and MTRR Down Regulation (+)

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This combination leads to a double whammy on methyl-B12. You cant make much because MTRR is not functioning well, and any B12
that you do make gets sucked up by the overactive MTR. Here the need to supplement with methyl-B12 (or to help you make it on your
own) is greatest. Youd think that the treatment would be straight forward give the patient methyl-B12. But remember, this is the Methyl
Cycle that we are talking about, the most convoluted, conflicting, and therapeutically confusing physiologic system in the body.
We will talk about COMT a little later. COMT degrades dopamine, in the process using up methyl groups. Individuals who are COMT
(+/+) degrade dopamine slowly, and as such have a lot of methyl groups floating around. If we supplement a COMT (+/+) individuals with
methyl-B12 (or any other methyl donor for that matter) we can OD them with free methyl groups, too much of a good thing, and this leads
to mood swings related to fluctuations in neurotransmitter levels. Individuals who are COMT (-/-) have normal COMT function; they break
down dopamine rapidly, using up methyl groups in the process. COMT (-/-) individuals need and tolerate methyl donors quite well. So if
you are (+) for the MTR up regulation and/or (+) for the MTRR down regulation, and you are also COMT (-/-), all we need to do is to give
you methyl-B12. We are giving you the methyl-B12 that you need, and any extra methyl groups left over can be put to good use.
Conversely, if you are COMT (+/+), we know that you have an excess of methyl groups floating around. We will give you hydroxy-B12,
expecting it to combine with the methyl groups available to form the methyl-B12 you need (without ODing you with too many free methyl
groups). This is all very confusing, and it gets worse when we consider the individual who is (+/-) for COMT, and when we factor in how
ones VDR gene status interacts with their COMT status. I will give you specific recommendations, whether you need methyl-B12, hydroxyB12, or both in combination, in my analysis of your Methyl Cycle genotype. B12 is reasonably well absorbed orally or via the sublingual
route, and we can also administer it by injection, depending upon your individual needs and preferences. Now lets move on to the
previously alluded to backdoor reaction.
This combination produces a double whammy on methyl-B12. You cant make it well because MTRR is not functioning well, and any B12
that you do make gets sucked up by the overactive MTR. Here the need to supplement with B12 is greatest.

BHMT: Betaine-Homocysteine Methyltransferase


BHMT converts homocysteine directly in to methionine. Specifically it removes
a methyl group from TMG (trimethylglycine) and tacks it on to homocysteine to
form methionine and DMG (dimethylglycine). Stimulating a genetically normal
BHMT system will partially ameliorate the adverse affects of Methyl Cycle
defects elsewhere. For example, if we cannot convert homocysteine in to
methionine because a MTHFR defect renders us deficient in methyl-folate, or if
an MTR up regulation or MTRR down regulation leaves us short in the methylB12 department, we can bypass these blockages by stimulating BHMT to convert
homocysteine directly in to methionine (I know this is difficult, but bypassing
blocked enzymes sure beats surgery to bypass blocked arteries, so please read
on). Our approach to BHMT, if it is defective, or when we want to stimulate
BHMT to help bypass MTR/MTRR defects, or when we want to pull
homocysteine away from a CBS up regulation, will be affected by your COMT
(basic need for and tolerance to methyl group donors) status. The basic approach is as follows:

1. Phosphatidylcholine, or as a less expensive alternative, Phosphatidylserine 100 mg daily, to stimulate the BHMT reaction. The former,
administered IV as Lipostabile/Plaquex, or in oral liposomal format as Lipophos Forte, provides a powerful anti-atherosclerotic benefit
(discussed on the website and in a DVD). Oral Lipophos EDTA contains Phosphatidylcholine admixed with EDTA, providing us with
BHMT stimulation, reverse cholesterol transport, and heavy metal detoxification, a triple benefit. In individuals who are COMT (-/-), who
thus need methyl groups, Phosphatidylserine can be used in combination with the methyl donor DMAE as Pedi-Activ, one daily.
2. TMG can be used to stimulate BHMT (but not in COMT (+/+) individuals, who will be sensitive to free methyl groups).

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COMT: CatecholOMethyl Transferase


COMT degrades dopamine, norepinephrine, and to a somewhat lesser extent other
neurotransmitter substances, by tacking on to them a free methyl group that COMT
obtains from SAMe. The V158M and H62H alleles of COMT are down mutations.
Individuals (+/+) or (+/-) for these genes will degrade dopamine only slowly. Now,
while COMT (+) status is not the norm, from our perspective it is not necessarily a bad
thing. We need dopamine to defend against microbes and heavy metals; here being (+)
for COMT is actually in our favor. BH4 deficiency is the consequence of CBS, BHMT,
and the backward MTHFR A1298C defects. We need BH4 to carry out multiple
physiologic steps, including the generation of dopamine. If our COMT (+) status keeps
us from breaking down dopamine, we do not need to spend BH4 to make dopamine,
leaving more BH4 available for other critical functions. The downside of being COMT
(+) is that you will have a lot of free methyl groups floating around, as you are not using
them up breaking down dopamine. Thus if we need to give you other Methyl Cycle
intermediates (such as methyl-B12 if you have MTR/MTRR issues), we risk ODing you
with methyl groups. Too many methyl groups can lead to mood swings. Panic attacks
and bi-polar mood disorder are seen with greater frequency in COMT (+) individuals;
this makes sense. COMT (-) individuals, on the other hand, need and tolerate methyl
groups. A third, and less frequently encountered COMT abnormality, COMT 61, is a
down regulation defect. Individuals (+) for COMT 61 breakdown dopamine quite
rapidly and are at greatest need for methyl donors. To summarize in chart form:
COMT H62H (+/+)
COMT L136L (+/+)
COMT 61
(-/-)
COMT H62H (-/-)
COMT L136L (-/-)
COMT 61
(+/+)

Highest dopamine levels


Lowest need for and tolerance to methyl group donors
Greatest susceptibility to mood swings
Lowest dopamine levels
Greatest need for and tolerance to methyl group donors
Lower susceptibility to mood swings*

* I am COMT H62H and L136L (-/-), but my wife refuses to believe this!
Dopamine levels as they relate to our COMT status will also be affected by the VDR Taq gene,
which influences dopamine production in relation to Vitamin D.

VDR Taq: Vitamin D Receptor Taq Abnormality


Vitamin D has many functions, an issue because 90% of my patients have low or low normal Vitamin D levels. Pertinent to this discussion,
Vitamin D stimulate the enzymes that generate dopamine, a good reason to keep your Vitamin D level up, as we need dopamine to defend
against microbes and metals, and to keep our mood up. While we utilize SAMe (and indirectly other methyl group donors) to degrade
dopamine, we also utilize methyl donors to generate dopamine. Individuals with a normal Vitamin D receptor, those who are VDR Taq (-/-),
make plenty of dopamine. They tend not to need or to tolerate methyl groups or dopamine precursor substances. With respect to methyl
group need and tolerance, they behave like COMT (+) individuals. Individuals (+/+) or (+/-) for VDR Taq defect have lower Vitamin D
levels, make less dopamine, and will need and tolerate dopamine precursor substances and methyl donors. With respect to methyl donor
tolerance, VDR Taq (+) individuals behave like COMT (-) individuals. All sorts of permutations are possible here, impacting on your
tolerance and need for dopamine precursors and methyl groups. I acknowledge that this is all very difficult to understand. Hopefully the
chart below will help.

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intermediates. If an MTR/MTRR defect increases your need for methyl-B12, in this


individual we would start with hydroxy-B12, to avoid ODing you with methyl groups,
expecting that with enough hydroxy-B12 and free methyl groups floating around you
will form up some methyl-B12, even if MTRR activity is compromised by a defect. We
would not give your dopamine precursors such as quercetin or the herb macuna puriens.
We would not advise a diet high in tyrosine, the amino acid precursor of dopamine.
COMT (+/+) VDR Taq (-/-) individuals will be susceptible to iodine and lithium
depletion as they detoxify, and we will have to watch for this and supplement
accordingly.
Lowest dopamine levels
COMT (-/-)
Poor tolerance to toxins and microbes
Needs and tolerates dopamine precursors and methyl donors
VDR Taq (+/+)
Lowest susceptibility to mood swings
In such an individual, we would utilize the methylated forms of Methyl Cycle
intermediates, including methyl-B12 if n TR/MTRR defect is present. Dopamine
precursors such as quercetin, ginkgo biloba, and the herb macuna puriens might be
helpful, as would a diet high in tyrosine, the amino acid precursor to dopamine. Other
methyl donors, including melatonin, TMG, turmeric, theanine, along with MSM and
SAMe (the latter two only for CBS (-/-) individuals) would make sense. To support
BHMT, instead of Phosphatidylserine, we would use Pedi-Activ, which contains
Phosphatidylserine and DMAE, a methyl donor. Rather than using GABA to deal with
excitotoxicity, we would use Zen, which combines GABA with the methyl donor
threanine.
COMT (+/-) and VDR (-/-) behaves like COMT (+/+)
COMT (+/-) and VDR (+/+) behaves like COMT (-/-)
Multiple (+/-) combinations of COMT and VDR Taq are possible. We will address these
intermediate genotypes with intermediate levels of methyl group supplementation. I
will be more specific on your individual report.

MTHFR A1298C: 5,10-MethyleneTetraHydroFolate Reductase (


BH4)


The MTHFR C677T defect effects the forward reaction, the conversion of THF in to
5-methyl folate. MTHFR A1298C has no adverse affect on 5-methyl folate
production, but it does compromise the backward reaction, whereby 5-methyl folate
is converted back in to THF, in the process generating one molecule of BH4.
Individuals with abnormalities in CBS and BHMT will be low in BH4, as it is being
used up detoxifying ammonia that these defects have generated, so their combination
with MTHFR A1298C leads to a BH4 deficiency double whammy. DHPR is the
enzyme that regenerates BH4 from BH2. It is poisoned by mercury, lead, and
especially aluminum. These toxins are wide spread in our environment, and
individuals with Methyl Cycle abnormalities have particular trouble dealing with
them. The result is a progressive drain on BH4, a progressive impairment in
neurotransmitter production, and conversion of arginine not in to nitric oxide but
instead in to free radicals such as superoxide and peroxynitrite. We treat MTHFR
A1298C with 5-methyl folate supplementation (aiming to push the reaction backwards)
and, after your other Methyl Cycle challenges have been addressed, with nutritional
doses of BH4. Metal detoxification will help here and with every other biochemical
function in your body, and will be part of your overall program. We will also endeavor
to decrease your need for BH4. If you are COMT (-/-), we can provide nutritional
support to help maintain dopamine levels, such that you will need to use less BH4 to
generate more. If you are MAO A (-/-), we can do the same thing with serotonin precursors such as high tryptophan foodstuffs. The basic
philosophy is to stimulate the action of still open pathways to take the stress off your impaired pathways.

NOS: Nitric Oxide Synthase


In a BH4 dependent reaction, Nitric Oxide Synthase (NOS) converts Arginine in to Nitric Oxide, the
molecule that resists plaque formation, vasospasm, and abnormal clotting. If you can make and
maintain Nitric Oxide then you will not develop cardiovascular disease. If you have cardiovascular
disease and if we can successfully reboot your Nitric Oxide system, than we can stabilize your

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disease. Every maneuver in drug and non-drug cardiovascular medicine that improves patient
symptomatic status and outcome works on this system. Every risk factor (or causative factor for
cardiovascular disease) compromises Nitric Oxide generation or maintenance. NOS is also involved
in ammonia detoxification, a job that distracts it from its Nitric Oxide generating duties and which
uses up BH4. Without adequate levels of BH4 Nitric Oxide Synthase will not convert Arginine in to
beneficial Nitric Oxide, but rather in to undesirable free radical species such as superoxide or
peroxynitrite.
The NOS D298E abnormality codes for a dysfunctional NOS enzyme. It has trouble breaking down
ammonia and it has trouble generating Nitric Oxide. NOS (+) individuals are at greater risk for
developing all forms of cardiovascular disease, for experiencing adverse events, and for restenosis
following balloon angioplasty. A component of a positive family history of cardiovascular disease
is related to genes coding for high cholesterol, elevated lipoprotein (a), and iron over absorption.
The rest likely relates to inherited abnormalities in NOS, ACE, and the other Methyl Cycle genes. If
you are NOS (+) we will pay particular attention to maneuvers designed to lower your ammonia
burden, and to address risk factors that compromise Nitric Oxide. As the products of a compromised or genetically abnormal NOS system
are the free radicals superoxide and peroxynitrite, aggressive antioxidant supplementation makes sense here (while a broad spectrum program
of antioxidant supplementation is always wise, we specifically use Vitamin C to neutralize superoxide and 5-methyl folate to neutralize
peroxynitrite). I give two separate two hour presentations on Endothelial Dysfunction, which we have on cassette tape (we will likely have a
DVD presentation available late next fall). BH4 supplementation has been demonstrated to improve Nitric Oxide generation and endothelial
function in individuals with risk factors such as hyperlipidemia, and we presume that it will do the same in individuals with Methyl Cycle
abnormalities.

ACE: Angiotensin Converting Enzyme


Angiotensin Converting Enzyme (ACE) converts Angiotensin I, a weak vasoconstrictor, into Angiotensin II, for our purposes a nasty
angiochemical that mediates hypertension, plaque deposition, salt and water retention, magnesium and potassium wasting, and abnormal
clotting. ACEI (angiotensin converting enzyme inhibitors) target this enzyme, seeking to block generation of Angiotensin II. The potassium
and magnesium sparing diuretic Spironolactone blocks the deleterious effects of
Aldosterone, another mediator that is up regulated by Angiotensin II (of interest to those of
you with CBS/BHMT problems, Spironolactone is low in Sulfur). The ACE Del16
involves the insertion and deletion of genetic material at a specific location (intron16) of the
ACE gene, coding for an up regulated, or over active Angiotensin Converting Enzyme.
ACE (+) individuals - I am ACE (+/+); yikes! - are at increased risk for hypertension and
cardiovascular disease. If you are ACE (+) and have problems with BP or fluid control, we
will have a low threshold for intervening pharmacologically with ACEI and
Spironolactone. Of interest, a large study (HOPE) where a tissue specific ACEI (Ramipril,
which like Quinapril enters the vascular wall and preserves endothelial function) was
administered to individuals with diabetes and one other risk factor, demonstrated a
reduction in cardiovascular event and death rate over the ensuing five years. ACE (+)
individuals respond to statin drugs with larger reductions in cholesterol and plaque burden
than do ACE (-) individuals (who presumably have less need for this form of intervention).
Dr. Yasko recommends the use of Kidney Support RNA, OraKidney, and OraAdrenal in
kids with ACE problems. ACE may be associated with increased anxiety; here she recommends use of the Stress and Anxiety Support RNA
product.

Glutamate GABA Imbalance Excitotoxicity

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Glutamate is the main excitatory neurotransmitter in the body. It is essential for learning and short and long-term memory. Glutamate is also
the precursor to our primary inhibitory or calming neurotransmitter, GABA. GABA damps the propagation of sounds so that a distinction
can be made between the onset of sound and a background noise. Many other physiologic processes require a balance between glutamate
and GABA, which is usually easy to achieve as glutamate, glutamine, alpha-ketoglutarate, and GABA can be interconverted via the enzymes
depicted above.
Genomic defects, viral illness, and heavy metals will compromise this balance, leading to excess glutamate, insufficient GABA,
excitotoxicity, and eventual neuron loss. Viral infection (individuals with Methyl Cycle defects cannot defend well against viral infection)
can lead to antibodies against the vitamin B6 dependent enzyme glutamate decarboxylase (GAD), blocking GABA production (this is felt to
occur in the pancreas in kids with juvenile onset diabetes). Aluminum poisons this enzyme as well. Excessive alpha-ketoglutarate generated
due to the CBS up regulation can be converted into glutamate, but in the presence of lead and aluminum, the glutamate so created cannot be
converted into GABA, glutamine, or back to alpha-ketoglutarate. The result is glutamate-GABA imbalance, agitated behavior, and
eventually nerve loss.
Low GABA leads to impaired speech, anxiety, aggressive behavior, poor socialization, poor eye contact, nystagmus, and constipation.
Glutamate excess does the same and also wastes glutathione and increases levels of TNF-alpha, an inflammatory mediator that can produce
heart cell dysfunction and gut inflammation.
We can restore glutamate-GABA balance by:
1. Addressing CBS up regulation/BHMT down regulations to decrease alpha-ketoglutarate production.
2. Decreasing intake of food precursors of glutamate (see list below).
3. Supplementing with GABA
4. Copper inhibits conversion of glutamate to GABA by glutamate decarboxylase so avoid copper excess, or better stated, an imbalance
between copper and zinc.
5. Calcium is involved in glutamate toxicity, so supplement with magnesium to keep calcium in check.
6. Remove heavy metals with a chelating agent. Of interest, toxicity due to mercury is aggravated by glutamate excess; mercury and
glutamate synergize to damage nerve cells.

Glutamate
Aspartate
Whey protein
Malted barley
Gelatin
Vegetable gum

Sources of Excitotoxins Short List*


Glutamic acid, glutamine, MSG, peas, tomatoes, parmesan cheese
Aspartame, Nutrasweet
Soy protein
Hydrolyzed anything
Cysteine
Malt extract
Natural flavoring(s)
Guar gum
Carrgeenan
Soy sauce
Bouillon
Broth/Stock
Yeast extract
Autolyzed anything
*Long list in the appendix

Treatment Options
Pycnogenol and grape seen extract help balance Glutamate/GABA
Taurine helps in this balance (but contains sulfur so avoid if CBS (+)
Montief GABA
ZEN
Contains threanine, which has methyl groups; avoid if COMT (+)

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The Methyl Cycle abnormalities presented below are not as well understood (at least by myself):

MAO A: Monoamine Oxidase A


Monoamine Oxidase A breaks down serotonin, a neurotransmitter that is generated from the dietary amino acid tryptophan, in a BH4
requiring reaction. Many anti-depressant drugs, including the SSRIs (Serotonin Selective Reuptake Inhibitors) work by blocking the
breakdown of serotonin. Defects in serotonin metabolism have been associated with mood and neurological disorders. How best to address
the MAO A R297R abnormality is not clear to me. As serotonin metabolism is adversely affected, individuals with the R297R defect should
avoid large doses of high tryptophan foods (see appendix). High doses of St. Johns Wort, often taken to address depression, could lead to
mood swings as serotonin levels fluctuate. Dr. Yasko recommends frequent dosing in small amounts of St. Johns Wort, 5HTP (a tryptophan
metabolite), and the Mood S RNA formula if serotonin support is needed. If serotonin production is impaired on the basis of BH4 deficiency
secondary to a Methyl Cycle abnormality, as the abnormality itself is addressed, BH4 levels should stabilize, hopefully normalizing serotonin
production.

ACAT 102: Acetyl Co-Enzyme A Acetyltransferase


ACAT is involved in cholesterol and energy metabolism, helping to mediate the conversion of foodstuffs into biological energy. ACAT
dysfunction may lead to B12 deficiency. Right now, I do not understand ACAT well and am not sure how important this is.

AHCY S-Adenosylhomocysteine Hydrolase


S-Adenosyl Methionine (SAMe), the key methyl donor generated from methionine, is metabolized in to S-Adenosyl Methionine, and then on
to homocysteine by AHCY. Individuals (+) for both AHCY and CBS often have low baseline urine sulfate levels, which then rise and fall in
response to treatment. Early on the levels rise, as the bottle neck abnormal AHCY enzyme has been limiting the supply of
homocysteine. Once the cycle starts to spin, homocysteine is made available to CBS, and urine sulfate will rise. Later, in response to a low
animal protein/low sulfur diet, urine sulfate levels will fall. Defects in AHCY are addressed by measures designed to improve overall Methyl
Cycle function, such as Methyl support RNA 1/8th dropper per day.

VDR Fok
The VDR (Vitamin D Receptor) Fok defect affects blood sugar control and pancreatic function. It does not affect dopamine metabolism. Dr.
Yasko recommends Vitamin K and generalized support of pancreatic function and sugar regulation (low carbohydrate diet, supplementation
with chromium, etc.) when the VDR Fok abnormality is an issue.

Approaches to Detoxification
Overview Environmental toxicity (organic pollutants and heavy metals) is a grave threat to health your health and that of your
descendents. Lifestyle factors (which you can alter) interact with genomic weak links (which we can analyze and help you bypass) to
determine at what age you will become ill (when the toxins will get to you). The most important thing that we can do (after getting you
through an acute health care crisis) is to optimize your intracellular nutritional status, and then move Heaven and Earth to identify, and then
remove, every toxic molecule from your body to return your biochemistry to the pristine state that Evolution and/or Our Creator intended.
A goal of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Toxicity testing and detoxification thus makes
sense. These concepts are outlined below and are discussed in greater detail on heartfixer.com and in our presentations (DVDs and
information sheets are available to you).
Diagnosis Which toxins do you bear and why did you retain them?
1. Genomic Analysis: While we can and will detoxify you without knowledge of your genomic status, an understanding of your inherited
weak links will alter (and improve) our approach.
Methyl Cycle Nutrigenomics: The Methyl Cycle is the backbone of your biochemistry. Methyl Cycle defects prevent you from coping with
environmental toxins, viral and bacterial invaders, and compromise proper reading of your genetic code. Chronic, difficult to explain disease
states, neurodegenerative conditions involving the young and premature age related conditions likely reflect an interaction between
environmental toxins and Methyl Cycle predispositions. While we cant change your DNA, if we know your weaknesses, we can create
nutritional work arounds, improving your ability to detoxify and defend. Methyl Cycle testing is available (| $550 via holisticheal.com
and | $100 through 23andme.com). This information will alter the way I treat you. Upon request, I can create a detailed analysis/treatment
plan, based upon your DNA findings, personal health and nutritional status, and toxin burden.
Detoxification Genomics: We vary in our ability to activate (Phase I) a toxin, and then to combine it with a chaperone molecule (Phase II)
that escorts it out through the kidneys or GI tract. If I know your detox weak links then I can support them with specific supplements/dietary
interventions. Detox Genomic testing is available through Genova Diagnostics (| $500) or through 23andme.com (included in the $100 for
your Methyl Cycle data).
2. Organic Pollutants: These are non-metallic, fat-soluble molecules that bioaccumulate and compromise our physiology (and that of our
offspring), particularly with respect to weight gain, diabetes, and neurologic disease. Agent Orange, phyllates, bisphenol A, pesticides, and
petroleum products are a few of the 100s of organic pollutants to which we (and our Mothers) have been exposed to (yes, this stuff readily
crosses the placenta). Fat, liver, and nerve biopsies would give us the most complete measure of organic pollutant burden but obviously are
not practical. We can estimate your tissue pollutant burden with:

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A. The US BioTek organic pollutant screen looks at seven common organic pollutants and compares your personal levels against that of the
rest of the US population. This $125 test is easily done at home (a dipstick is dipped in a morning urine sample and then sent to the lab).
Its downside is that it weighted more towards recent exposure then to chronic body burden.
B. The Genova Labs NutrEval gives us markers of Styrene and Petroleum product exposure, along with a great deal of ancillary information
regarding nutritional and detox function. The NutrEval is covered by Medicare (not with Aetna/Humana secondary); with commercial
insurance the out-of-pocket co-pay is $170. This is the best single test in Metabolic Medicine.
C. Metametrics provides more extensive organic pollutant testing, at a cost between $ 250 and
$ 600. This is the best test available but perhaps not the best use of your resources.
3. Heavy Metals: Metals enter our tissues, bind to proteins, and leave only slowly - if at all (the half-life of mercury in the nervous system is
10-20 years). Metal exposure may vary, in relation to where you live and work, but as innate detox is so slow, metals bioaccumulate. Tissue
levels rise with age, with a concomitant increase in your risk for metal-induced or metal-aggravated disease states (conditions associated with
inflammation or oxidative stress neurologic and cardiovascular). We need to estimate your body burden and then remove these elements
that can do nothing but harm. So how best to estimate the level of metal accumulation within your internal organs?
A. Blood levels reflect recent exposure, and are of value in monitoring lead exposure in kids, industrial exposure in adults, and in
epidemiology studies. However, blood metal levels bear little relation to body burden, and are not of value in adult detoxification medicine.
B. Red cell metal levels tell us what your physiology has been exposed to over the preceding three months. Red cell metals (and minerals) is
included in the NutrEval, or could be obtained for $ 136 from Drs. Data.
C. Provocative Challenge is the accepted best estimate of body burden. Here we administer oral and IV metal binding agents, with metal
quantitative in a subsequent six hour urine collection. Your cost ($250) includes our fee, the lab fee, and the IV and oral chelating agents
utilized.
D. QuickSilver provides a blood, hair, and urine mercury assessment, and estimates the percentage of your mercury burden that is organic vs.
inorganic in nature. Cost is $ 350.
Treatment How do we get this stuff out of you?
Methyl Cycle and Detoxification Genomic Abnormalities: Nutritional supplementation and dietary avoidance measures are recommended,
specific to your individual inherited weak links.
Chelation Therapy: A generic term referring to the administration of agents that bind to and then remove toxic metals (but not organic
pollutants) from your body.
1. Mg-EDTA: A series (20-30) of 3-hour IV infusions containing Mg-EDTA, B-Complex and Vitamin C. Mg-EDTA was used in the NIH
sponsored Trial to Assess Chelation Therapy (TACT, which demonstrated an 18-38% reduction in 5-year adverse event rate when chelation
therapy was added to standard pharmaceutical/interventional management in individuals with prior heart attack). I have been treating my
patients with Mg-EDTA for 20 years; we were first amongst cardiology practices and third overall with respect to patient participation in
TACT). When Lead and Cadmium are the problem, EDTA is the most effective chelator, and IV therapy is the most efficient approach.
The magnesium content is also helpful in BP management.
2. Ca-EDTA: Calcium-EDTA alone is infused over 10 minutes. With respect to metal removal, both IV approaches are likely equally
effective, but here you do not receive IV nutritional support. We favor Mg-EDTA in individuals with cardiovascular disease/hypertension
and Ca-EDTA in younger patients (or if time constraints preclude you receiving a three hour treatment).
3. Essential Daily Defense (EDD): EDD is a mixed oral chelator that is taken concomitant to any IV chelation (blocks recycling of bound
metals from the GI tract back to the circulation).
4. DMPS: 25 years ago, our only toxin was Lead, and EDTA was all we needed. Today we are being bombarded with new and improved
toxins, particularly Mercury. EDTA does not remove Mercury from your cells! We remove mercury with di-thiol chelators: DMSA and
DMPS. We can address Mercury toxicity with IV DMPS, but the application of liposomal DMPS complexed with Glutathione to your skin
is easier for you and is more cost-effective. Compared to EDTA, DMPS binds less avidly to Lead and is not an efficient Cadmium chelator.
5. DMSA: Available over-the-counter or by standard or compounded prescription, DMSA will bind to and remove Mercury, Lead, and
Cadmium, but DMSA is not as powerful as EDTA or DMPS. DMSA is typically taken as 500 mg, 3 times a day, over 3 consecutive days,
once a month, or within a program of DMSA 500 mg near bedtime, 10 nights on, 5 nights off.
6. Liposomal Phosphatidylcholine-EDTA (DetoxMax Plus): Liposomes of Phosphatidylcholine serve as drug delivery vehicles for EDTA,
dramatically enhancing its absorption following oral administration. Lipophos EDTA serves as a slow and steady approach to metal
detoxification, of particular value to patients with vascular insufficiency (please see our DVD presentation).
7. Med Five: Med Five is a patented enteric coated EDTA/phosphatidylcholine tablet that we feel is better absorbed than standard oral
EDTA preparations (see www.medfive.com). I helped design Med Five and am a co-holder of its patent. My personal patients can obtain
Med Five at a discount (you receive a password). The discount is a plus for you and resolves conflict of interest concerns (otherwise I would
not be able to talk to my own patients about a health promoting approach that I helped create).
8. Battle Plan for Mercury: This protocol, which addresses heavy metal overload with specific focus on Mercury, was developed by my
mentor and good friend Dr. Robert Battle. Dr. Battle Plan is typically run over 2-3 months and consist of:
A. Algas, 10 drops in 2 oz. of water (let it sit 1 minute before drinking) twice a day odd days,
B. NDF, 8 drops sublingual twice a day - even days (start at 1 drop and increase as tolerated), &
C. Chlorella 5 twice a day, all days.
This protocol is typically well tolerated by individuals with CBS up regulations, but if detox symptoms (fatigue, malaise, muscle aching)
develop, then the doses of Algas and NDF may be decreased. Dr. Battle often uses this protocol to help clear Mercury before beginning Lead
and Cadmium detoxification with EDTA.
9. Metalloclear: This Metagenics product promotes metal and organic pollutant detoxification. Nrf2, when translocated to the nucleus, codes
for the production of antioxidant and detoxification enzymes. Metalloclear promotes nuclear translocation of Nrf2 and MTE (Metal
Transcription Factor), which codes for the generation of our endogenous metal binder Metallothionine. Metallothiones job in health is to
store Zinc and Copper, but it will also bind, and then transport to the liver for elimination, toxic metals such as Lead, Cadmium, and

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Mercury. Monotherapy with MetalloClear involves three tablets twice a day (with food) over 10 days, but we often use it as an adjunctive or
maintenance therapy at one tab twice a day.
10. Glutaclear: This Metagenics product provides N-Acetyl Cysteine, Selenium, and Vitamin C, to increase Glutathione production, along
with Broccoli extract, to promote Nrf2 translocation. We typically recommend one tab twice a day.
11. Aura (Digital Homeopathy) Organ Detox Patches: Digital homeopathy is an in-depth discussion (so we have DVDs, CDs, and handouts),
but basically the patches emit frequencies that permeate your meridian system and neutralize toxins that you bear. The toxins will not be
removed, but rather electrostatically neutralized (allowing us to remove them in a deliberate fashion). We cant prove that this method
works, but I think it does, and it is relatively inexpensive ($35 for a one month supply typically worn over 2-3 months). This methodology
can also be used to estimate your body burden of toxins and screen for other health challenges.
12. Static Magnetic Field Chelation: Exposure to a static magnetic field increases intracellular energy potential and increases the efficiency
of any metal chelation program that we might employ. This is the basis for MME and magnetic sleep pad assisted chelation a huge step
forward! MME combined with chelation is providing outcomes that arent supposed to occur please review the website to see what we are
accomplishing. My personal patients receive a discount when they purchase a negative field only sleep pad at magneticosleep.com.
13. Asyra Homeopathic Detoxification: Utilizing a physics similar to that of the Aura Patches, our Asyra device imprints treatment
frequencies, specific to you, into a homeopathic carrier liquid you take sublingual drops twice a day. Asyra is repeated and new drops are
generated every 2-3 months over 1-2 years. Again, we cannot prove this approach with an allopathic lab study, but our observation is that
our patients receive benefit from this approach.
14. Platinum Footbath: Your feet or hands are immersed in salt water, in to which specific frequencies are applied. The water is ionized; the
field enters your body, and appears to break ionic bonds between toxins and your normal molecules. The toxins are drawn out in to the water
in a sort of reverse electroplating or forced sweating effect. That toxins are being removed has been verified by third party chemical
evaluations (see Asyra.com). Im not sure whether metals can be removed by the footbath, but hydrocarbon toxins are, and it seems to be
particularly well suited to patients with gout. Footbath therapy lends itself well to in-home use.
15. Glutathione Patch Your bodys own production of Glutathione increases (and blood levels rise) while you wear this drug free, nontransdermal skin patch (see lifewave.com/chc).
16. Far Infrared Sauna (FIS): Sweat carries out with it toxic substances. We sweat less as we age (aluminum containing anti-perspirants
harm us here). Regular sauna will sweat out toxins, but the extreme heat will not be tolerated by many of you. FIS utilizes lower heat levels
coupled with low level radiant energy derived from ceramic plates to generate active sweating. FIS is therapeutic in several cardiovascular
conditions (FIS is covered under Medicare, but we dont offer this treatment - we cant have people prancing around the office in their
bathing suits).
17. Frequency Specific Microcurrent (FSM): FSM applies frequencies (via skin electrodes or a moistened towel) at 1/5000th the amplitude
of the TENS unit. While TENS therapy seeks to obliterate pain signals, with FSM we seek to communicate with or entrain our physiology to
carry out a desired activity. FSM can be applied to many health challenges (see our information sheet or www.frequencyspecific.com).
Costs Your insurer will not cover the costs of any form of detoxification therapy. They will describe it as medically unnecessary or
experimental. I will not write letters to request pre-authorization this is simply a waste of time and risks labeling you as a
troublemaker. Detoxification is a comprehensive and often long-term process, and it is not inexpensive, but I think that you are worth it.
Please consider what you spend on a new car, or on a vacation, and then ask yourself what your health is worth. If you do not wish, or
cannot afford, to undergo detoxification, then we can still help you - and we will help you - but our focus then (by necessity) will be confined
to nutritional intervention that you can afford and the administration of insurance covered drugs and invasive treatments to deal with the
consequences of long-term toxicity. Why not prevent this? I personally spend a lot of time and money on my personal health (supplements,
detox, home FSM, and lots of running shoes). I like the idea of vibrant health and a vibrant mind, and I also realize that being sick ultimately
will cost me more than staying healthy. I also realize that next day and fully covered surgical approaches to preventable health
conditions may not be available to me in later years (what is the wait time for bypass surgery or a knee replacement in England or Canada)?
Politics Leave this at the door. I am not interested in verbally sparing with other physicians who dont know anything more about
nutritional biochemistry and detoxification than I do about delivering babies or removing gall bladders. Do not expect me to compromise on
science to meet the expectations of other doctors, insurance companies, or government agencies that just dont understand (or wish to
understand) the devastating consequences of organic pollutant and metal accumulation on our health and the health of our children and
grandchildren.

Appendix I: Foods High in Tyrosine or Tryptophan


Foods High In Dopamine (or Amino Acid Precursor Tyrosine)
Bananas, Red plums, Figs, Raisins
Eggplant, Green Bean pods, Italian broad beans
Salami, Sausage, Liver
Commercial gravies and Soy sauce
Salted dried fish (Herring, Cod)
Canned meats, Aged game
Canned meats, Aged game
Homemade yeast breads
Some alcoholic beverages (not all)
Yeast concentrates, Marmite, soup cubes
Aged Cheese (Blue, Boursalt, Brick, Brie, Camembert, Cheddar, Colby, Emmental, Gouda,
Mozarella, Parmisan, Provolone, Romano, Roquefort, and Stilton)

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Foods High In Serotonin (or Amino Acid Precursor Tryptophan)


Turkey, Chicken, Chicken Liver, Tofu
Almonds, Peanuts, Soy Nuts
Milk, Yoghurt, Cottage cheese
Spirulina (seaweed), Brewers yeast
Watermelon Seeds

Appendix II: Foods High in Sulfur


(but please review Sulfites and Chronic Disease, by Rick Williams (available at the office or you can go to
www.readingtarget.com/nosulfites)

Dietary Sulfur Issues


Sulfur is necessary for many metabolic functions, but sulfur deficiency is rarely an issue, as most foods contain sulfur or sulfur containing
compounds. Excess sulfur can be a problem for those with CBS, BHMT, and SUOX mutations here one needs to avoid foods and
supplements high in sulfur (sulfites and sulfates).
Supplements High In Sulfur
Taurine
Cysteine
Methionine
Glutathione
Glucosamine Sulfate
Chondroitin Sulfate and MSM
Epsom Salts
Magnesium Sulfate Cream
Canned meats, Aged game
Homemade yeast breads
DMSA and DMPS (Metal Chelators)
Milk thistle, Beyond C, and Heparin

Foods High In Sulfur


Vegetables:
Garlic, Onion Family Kale
Collards
Pickles
Cabbage
Brussel Sprouts
Kohlrabi
Broccoli
Cauliflower
Bok Choy
Mizuna
Broccoli Rabe
Chinese Cabbage
Napa Cabbage
Turnip / Rutabaga Canola / Rape Seeds; Greens
Mustard Seeds
Tatsoi
Radish
Daikon
Horseradish
Japanese Horseradish Arugula
Watercress
Peas
Spinach
Fruits:
Raspberry
Cranberry
Currents
All Dried Fruit
Others:
Vinegar (especially if prepared from wine)
Alcohol Beverages (especially wine; not vodka - beer is less of an issue, especially German beer)
Soft Drinks
Animal Products
Dairy
Eggs
Brazil Nuts
Peanuts
Soy
All packaged and commercially prepared foods contain food additives, many of which contain sulfur; often this is not on the label. Organic
foods are preferable here. Do not begin taking horsetail grass, spirulina, dandelion leaf, or parsley, as they contain low levels of sulfur. If
they are already part of your protocol, you may continue taking them. Eliminate them only if having trouble turning your strips pink.
Recognize that methionine and SAMe do contain sulfur, as do the sulfur containing amino acids taurine and cysteine. After strict sulfur
elimination for 3 to 4 months you will have eliminated the deep stores of sulfur in your body. Thereafter, you can begin adding very small
amounts of sulfur and ammonia producing products back into your diet, while watching your strips to be sure they stay pink.

What Can I Eat?

Low Sulfur Foods:


i Quinoa hot & cold in salads or with fruit
i Brown rice, non-gluten grains
i Fruit (except those on the high sulfur list)
i Vegetables (except those on the high sulfur list)

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i Small amount of beans


o Lentils
o White Beans
i Small amount of nuts (except those on the high sulfur list)
o Macadamia
o Pine
o Cashew
o Pistachio
o Walnuts
o Almonds
o Pumpkin
o Sunflower seeds
o Chestnuts
i Make milk from nuts: soak almonds overnight.
i Bamboo Shoots
i Corn
i Mung Bean Sprouts
i Boiling removes much of the sulfur from foodstuffs (make sure you discard the water)

Meals:
i Alkaline vegetable soup:
Add cut carrots, green beans, zucchini squash, and celery to alkaline water.
Simmer one hour; flavor with salt as needed.
i Vegetables with olive oil and salt or other flavorings add quinoa to make a meal
i Plain millet and Kamut cereal puffs with nut or rice milk and fruit
i Plain Mochi puffs, stuffed with apple, berry, or spicy sauce
i Saut squash and other vegetables in olive oil and top with non gluten grain
i Healthy Fries:
o Cut up sweet and/or white potatoes in strips and coat with oil and seasoning. Lay flat on baking sheet and bake until crispy.
i Salads without high sulfur veggies and dressing.
i Apple or berry sauce mixed with flax seed
i Nut-Milk Shake:
Take frozen fruit chunks, stevia, fiber such as flax and blend with rice or nut milk until smooth

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i Cut vegetables, mix with olive oil and seasonings and bake
i Brown rice tortillas chips:
Coat pan with olive oil. Cut up brown rice tortillas (found at Trader Joes) place on baking sheet. Season as desired, and bake
until crispy.
i Vegan burger:
Combine cooked sweet potato or yams, quinoa, chopped vegetables, salt or other seasonings. Add enough non gluten flour
(chickpea, rice), and form into patties. Brown in olive oil.
i Mashed Squash:
Take acorn, butternut, or other hard squash and steam. Mash with xylitol and cinnamon, nutmeg, or ginger.
i Squash Fries:
Take acorn, butternut, or other hard squash and cut in half. Cut into thin slices and bake flat until crispy.
i White bean or lentil soups with rice crackers.
i Cold quinoa with cut vegetables and Italian dressing.
i Boil vegetables like potatoes and dress with olive oil and seasoning.

Appendix III: Foods High in Excitotoxins


Sources of Excitotoxins
Glutamic acid, glutamine, and MSG. High levels are found in foods such as peas, tomatoes, parmesan
cheese, milk, mushrooms, fish, and many vegetables
Aspartate
Aspartame, NutraSweet
Other Names for Excitotoxins
Monosodium Glutamate
Glutamate
Natural Flavor(s)
Spice(s)
Maltodextrin
Carrageenan
Gelatin
Seasoning(s)
Seasoned Salt
Dough Conditioner(s) Isolate
Autolyzed Anything
Autolyzed Yeast
Autolyzed Yeast Extract
Broth
Stock
Soup Base
Chicken/Pork/Beef Flavoring
Hydrolyzed Vegetable Protein (HPV)
Hydrolyzed Plant Protein
Hydrolyzed Oat Flour
Hydrolyzed Anything
Yeast Extract
Caseinate
Sodium Caseinate
Calcium Caseinate
Disodium Guanyiate
Hydrolyzed Protein
Disodium Inosinate
Disodium Caseinate
Chicken/Pork/Beef Base
Plant Protein Extract
Bouillon
Vegetable Gum
Smoke Flavoring(s)
Malt Flavoring(s)
Malted Barley Flour
Malt Extract
Malted Barley
Guar Gum
Malted Anything
Textured Protein
Soy Extract
Soy Sauce
Soy Protein
Soy Protein Concentrate
Whey Protein
Whey Protein Concentrate
Whey Protein Isolate
L-Cysteine
Ajinomoto
Kombu Extract
Natural Flavoring(s)
Barley Malt
Foods with MSG (Monosodium Glutamate)
Hydrolyzed Protein
Hydrolyzed Oat Flour
Sodium Caseinate / Calcium Caseinate
Gelatin
Glutamic Acid
Monosodium Glutamate
Autolyzed Yeast or Yeast Extract
Possible Sources of MSG
Textured Protein
Carrageenan Or Vegetable Gum Seasonings Or Spices
Flavorings Or Natural Flavorings
Chicken, Beef, Pork, Smoke
Bouillon, Broth, Or Stock
Barley Malt, Malt Extract,
Whey Protein, Whey Protein Isolate,
Flavorings
Malt Flavoring
Or Concentrate
Glutamate

Food From Fast-Food Chains

Other Sources of MSG


OTC Medications

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NutraSweet
Doritos
Progresso Soups
Sausages / Processed Meats /
Cold Cuts
Restaurant Gravy
Salad Dressings / Croutons
Gelatin
Dry Milk Or Whey Powder
Fresh Produce Sprayed With
Auxigro In The Field
Non-Dairy Creamers
Baked Goods From Bakeries
Chili Sauce
Citric Acid Made From
Processed Corn
Fresh And Frozen Pizza
Tomato Sauce / Stewed
Tomatoes
Tofu And Other Fermented
Soy Products
Anything Fermented
Anything Ultra-Pasteurized
Flowing Agents

Page 24 of 50

Binders and Fillers in Supplements


Foods with Glutamates
Pringles
KFC Fried Chicken
Lipton Soups/Sauces
Gravy Master
Processed Cheese Spread
Molasses
Ramen Noodles
Salty, Powdered Dry Food
Mixes
Soy Sauce
Dough Conditioners
Some Spices
Chocolates / Candy Bars
Frostings And Fillings
Mustards
Canned And Smoked Tuna,
Oysters, Clams
Flavored Teas, Sodas
Egg Substitute
Table Salts
Anything Vitamin Enriched
Carmel Flavoring/Coloring
Xanthan Gum / Other Gums

Bouillon
Flavored Potato Chips
Worcestershire Sauce
Body Builder Protein Mixes
Skim, 1%, 2%, Non-Fat, Or
Dry Milk
Low-Fat / Diet Foods
Catsup
Pickles
Barbeque Sauce
Seasoned Anything
Flour
Anything With Corn Syrup
Added
Anything Protein Fortified
Pectin
L-Cysteine

Prescription Medications
Boars Head Cold Cuts/Hot Dogs
Planters Salted Peanuts
Supermarket Turkey And Chicken
(Injected)
Instant Soup Mixes / Stocks
Restaurants Soups Made From Soup
Base
Kombu Extract
Parmesan Cheese
Whipped Cream Topping Substitutes
Cereals
Mayonnaise
Bottled Spaghetti Sauce
Canned, Frozen, Or Dry Entrees And
Potpies
Some Bagged Salads And Vegetables
Canned Refried Beans
Anything With Milk Solids
Anything Enzyme Modified
Cornstarch

Appendix IV: Elevated Urine Sulfate - What Do You Do Next?


Elevated Urine Sulfate Above 1600 mg/liter
You are receiving this communication because a spot urine sample returned with an elevated sulfate level. As you are by now aware, we are
actively involved in Methyl Cycle Genomic testing, looking for the underlying common denominator causes of the otherwise difficult to
explain and address disease states with which many of our patients present. The vast majority of chronically ill or unexplained ill individuals
who we have tested have demonstrated abnormalities in the Trans-Sulfuration pathway of Homocysteine metabolism. Dietary change,
medication adjustment, and specific nutritional support, all tailored to the individuals genotype, can lead to a major change in the health of
these individuals.
Methyl Cycle testing is expensive: $1,150 for the testing, analysis, and recommendations. Obviously it doesnt make sense to test every
patient who we see, but on the other hand it doesnt make sense to keep doing the same ineffective thing over and over because we really do
not know why a chronically sick person is chronically sick.
There are clinical tip offs to a Trans-Sulfuration pathway defect, the most important of which is an elevated urine sulfate level (the CBS up
regulation and/or BHMT down regulations force Homocysteine down the Trans-Sulfuration pathway, generating excessive sulfite/sulfate).
Methyl Cycle Genomic testing costs $1,150, while the urine sulfate test costs $10 - so we carried out the urine sulfate test in you and it
returned above 1,600 mg/liter.
So what exactly does this mean? What should you do know? Is the study 100% diagnostic? Right now, we do not have absolute answers to
these questions; nor does anyone else. However, we are on to something very important here and it likely affects you.
The questions that we have regarding the link between urine sulfate and the presence/absence of a specific genomic defect are:
A. Is an elevated urine sulfate diagnostic of a Methyl Cycle defect?
B. Are there false positives (high sulfate with normal genes) and false negatives (low sulfate and abnormal genes)?
C. Is there a quantitative relationship between the sulfate level and the severity of the genomic impairment?
D. Will the sulfate level vary day to day and with time of day or meals?
We are comparing the urine sulfate levels against the genomic findings in all patients who are undergoing genomic testing. My initial
impression is that individuals with markedly elevated urine sulfate levels all have CBS and/or BHMT abnormalities. We have seen a few
false negatives (CBS/BHMT abnormality present but urine sulfate only in the 400 mg/liter range); these individuals have upstream
abnormalities that limited Homocysteine production, giving CBS/BHMT less homocysteine to force down the Trans-Sulfuration pathway, or

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a downstream defect in SUOX (Sulfite Oxidase), such that sulfate could not be generated from sulfite (the entity actually generated by
CBS), and/or they were already on a Vegan type diet. So far we have not identified any false positive patients, and when patients with
known CBS/BHMT abnormalities switch to a low sulfur, low animal protein diet, their urine sulfate levels do fall. Still, there could be
causes for a false positive study. Many drugs and nutritional supplements are loaded with sulfite/sulfate (typically not a problem for
individuals who do not harbor Trans-Sulfuration defects). It is not inconceivable that if you take these drugs or supplements that your urine
sulfate will be elevated regardless of your genomic status.
So what should you do with this information? If money is not a concern, then undergo Methyl Cycle testing. Knowledge as to what is
wrong with you (or what could go wrong with you in the future) can only help us optimize your health. If money is an issue but you wish to
take some positive steps, you could change your diet as if you have a CBS/BHMT abnormality, and this is a better diet than the one most
of us are currently following. We could also, in a step-by-step fashion, adjust your drugs and nutritionals while watching your urine sulfate
level. The supplements we use in CBS/BHMT individuals are all benign. Please review the attached instruction sheet. You can learn more
at our monthly Methyl Cycle support group meetings (third Monday of every month at the Secor Clarion - $5 admission) and by studying the
information discussed above in this section of the website. You can also review Dr. Yaskos website holistichealth.com, keeping in mind
that her focus is on Autism, while ours is on adults with chronic or unexplained illnesses. You could also wait. As we gain more experience
in this area, our diagnostic and treatment methods will evolve and improve its always been this way.
Again, we will have more definitive information in the future, but this is too important a concept to just sit on; thus the urine sulfate
screening, this letter, and our invitation to you to learn more.

Appendix V: General Recommendations Based Upon the Sulfate Value


Approach to Patients with Presumed Trans-Sulfuration Pathway Abnormalities
Methyl Cycle Genomic analysis is demonstrating Trans-Sulfuration (CBS up regulation or BHMT down regulation) abnormalities in 90% of
our patients with unexplained disease states who undergo testing. Dietary change and nutritional supplementation, designed to fit the
genotype of the patient, is turning around the lives of some previously quite ill people. The tip offs to a Trans-Sulfuration Methyl Cycle
defect are sulfite sensitivity (and to a lesser extent asthma and easy bruising), a low or low normal homocysteine level, and an elevated urine
sulfate level but so far sick people who are not getting better all seem to have this problem! Methyl Cycle testing is expensive - $1,150.
Some individuals may choose to omit Methyl Cycle testing and proceed directly to treatment, as if they have this genomic defect. Others
may wish to take action while waiting the two months for the lab results to return. As there is nothing inherently dangerous about our
approach to CBS/BHMT dysregulation, this approach is medically reasonable. The following general recommendations make sense for
individuals who may harbor a Trans-Sulfuration pathway abnormality and who do not wish to undergo Methyl Cycle testing or who do not
wish to wait until their lab results return.
Overview
We assume that you are +/- or +/+ for one of the CBS up regulations and +/+ or +/- for BHMT 1-8, which act like CBS up regulations.
Homocysteine (as well as its methyl cycle precursors) is being drawn down the transulfuration pathway, in this process generating too much
sulfite and sulfate (which stimulate the stress/cortisol fight or flight response), too much alpha-ketoglutarate (which leads to excitotoxin
activation), and too much ammonia, which depletes BH4 (leading to insufficient dopamine and serotonin production, and a lack of nitric
oxide).
To address CBS up regulation/BHMT down regulation we typically recommend:
1. No animal protein diet (anything with eyes) and avoid sulfur rich vegetables, sulfur containing supplements, and sulfur containing drugs
(see CBS and Appendix II: Foods High in Sulfur and/or read Sulfites and Chronic Disease by Rick Williams, available at the office or at
www.readingtarget.com/nosulfites/.
2. Monitor urine sulfate every 4-7 days. Low levels (400 or 400-800 mg/liter) will allow an increase in methyl cycle supplementation and
later the addition of BH4 and/or a liberalization of your diet.
3. To neutralize ammonia, use Ammonia Support RNA, a charcoal supplement at bedtime (away from other supplements; magnesium citrate
may be used as needed to keep the GI tract moving as charcoal may lead to constipation), and Yucca. These supplements can be tapered
down as ammonia levels fall.
4. Molybdenum to help SUOX break down sulfite into less toxic sulfate. Homogenized dairy products contain xanthine oxidase, which uses
up molybdenum, and are best avoided or minimized. Vitamin E succinate, Boron, and B12 are felt to stimulate SUOX activity (SUOX is
overworked by the sulfite load presented to it by CBS/BHMT - SUOX co-factors become depleted, thus the need for supplementation).
5. Avoid excitotoxins (see list on heartfixer.com) and supplement with GABA twice a day.
6. Minimize B6, which stimulates CBS; P-5-P will be less of an issue.
7. Co-Q, Carnitine, Idebenone, and NADH will help increase energy production; supplementation will be helpful but probably not critical.
8. After your sulfur and ammonia pools have been depleted down towards normal we can be more liberal with other methyl cycle
supplements, and/or add in BH4. We do not wish to aggressively correct other methyl cycle defects until we have the CBS issue under
control otherwise the intermediates that we do supplement or generate will fall down the CBS drain into ammonia, sulfate, and alphaketoglutarate. Thus the first priority is to decrease blood and urine ammonia levels (easy to achieve with diet and supplementation) and urine
sulfate levels (this will take time likely several months).
Plan of action for CBS/BHMT

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1. Begin the diet discussed above and the supplements described below..
2. Check the sulfur (sulfite) content of your medications and supplements, and we will try to phase out anything high is sulfur.
3. Monitor urine sulfate every 4-7 days (and please chart the levels) this will be our primary measuring stick our goal is 400 mg/liter
(one yellow and three pink).
4. To neutralize ammonia, use Ammonia Support RNA dropper with meals and with methyl cycle supplements, along with a charcoal
supplement at bedtime (away from other supplements; magnesium citrate may be used as needed to keep the GI tract moving as charcoal may
lead to constipation). Yucca, beginning at capsule, twice a day, (or sprinkled on food containing protein), may help with ammonia
detoxification.
5. Regarding nutritional support, your current multi likely contains B6. A better program involves the Yasko NHF multi, two twice a day
along with Trace Minerals Complex at 4 drops/day. Begin Molybdenum 3 drops twice a day, Boron 3 mg/day, and hydroxy-B12 2000 mcg
daily to stimulate SUOX (the enzyme that converts sulfite in to less toxic sulfate). These are the key nutritional interventions.
6. Co-Enzyme Q10 100 mg/day, Carnitine 500 mg twice a day, and NADH one per day are ideal but not critical.
7. Add GABA 500 mg once a day to blunt excitotoxicity; if you feel that GABA is helping a lot then you can increase the dose; if it is not
doing anything for you then it can be discontinued.
8. If not already done, baseline Vitamin D, homocysteine, and ammonia levels will be helpful (and will be considered at your next office
visit).
9. In eight weeks (ideal but obviously not mandatory) we can carry out a 24 hour urine for ammonia and amino acids and a separate 24 hour
urine for nutritional and toxic metals, and use the results to refine your supplementation program. If a 24 hour urine collection is not possible
than we could use a first AM void urine for the ammonia/amino acid levels and a red cell mineral study.
10. Lipophos Forte 900 mg/day will stimulate BHMT, thus drawing homocysteine away from the CBS drain. Lipophos EDTA, bottle
twice a week, will also remove heavy metals, the clearance of which appears to be reduced in individuals with Methyl Cycle abnormalities.

Appendix VI: Methyl Cycle Recipes


Veggie Organic Soup
2 T. Olive Oil
3 Stalks Organic Celery (sliced )
6-8 oz small Organic Carrots
3 T. Fresh Basil
2 T. Fresh Oregano
2 small Zucchini (green and yellow) sliced
1 T. Celtic Sea Salt
1 T .Fresh Ground Pepper
Saut about 15 min
Add 2 L. Alkaline Water (about 2 quarts) then add
2 Fresh Tomatoes (peeled and chopped) to peel/score add to boiling water 15-30 sec.
watch for peel to come off then add to ice bath or 1 can 14.5 oz Organic diced Tomatoes
2 15oz cans white beans rinsed and drained
12 oz fresh long cut Green Beans
Bring to Boil 20 min/ add more sea salt and pepper to taste
The last 6-7 min add 1 cup Quinoa Pasta Veggie Curls
In a separate pot boil 6-8 Gold Potatoes until tender
Add half of potatoes to soup/ the other half mash until creamy (this will give the soup a creamy texture)
Do Your Best to buy All OrganicEnjoy!
Created by Cheryl Church
Orange Spaghetti Sauce
2 T. Olive Oil
3 Stalks Celery/diced
1 Orange Bell Pepper/diced
1 Med Carrot/diced
Saut until tender, and then add
1 T. Oregano
1 T. Celtic Sea Salt

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1 T. Black Pepper
3- 14.5 oz can Dice Tomatoes
Sprinkle small amount of Sugar to cut acid if desired
Bring to boil and simmer about 20-30 minutes
Cook 8 oz box of Quinoa Pasta Spaghetti Noodles
Sprinkle with chopped fresh Basil
Serve with long cut Green Beans or Zucchini chopped and saut in Olive Oil
Makes about 5 cups sauce
Created by Cheryl Church
Quinoa and Yam Salad
1 cup Quinoa
2 cups water
3 cups yams/ chopped
2 T. olive oil
1 medium red bell pepper/chopped
1 tsp cumin
cup fresh cilantro/chopped
2 T. Fresh lemon juice
1 T. Brown Rice Vinegar
1 T. Real Maple Syrup
In a medium saucepan, stir together the quinoa and water. Bring to a boil, cover and reduce heat to medium low. Simmer for 15 minutes or
until cooked. Fluff with a fork and set aside to cool. In a large frying pan on medium heat, saut the yams until they are tender but firm to the
bite. Add the peppers and cumin and saut for an additional 2 minutes. Set aside until cool. In a large bowl, combine the quinoa, yams,
cilantro, lemon juice, vinegar and maple syrup. Mix well and cool in refrigerator.
Serve chilled.
Makes 6 servings
Recipe altered from The Garden of Vegan by Tanya Barnard & Sarah Kramer
Breakfast Ideas
#1 Quinoa Flakes/ Hot Cereal
Any kind of Fruit ( blueberries, peaches etc)
1-2 tea, cinnamon
1-2 tea real maple syrup
# 2 Brown Rice Crisps
Fruit (blueberries)
Rice Milk
#3 Roasted Potatoes with beets ,zucchini, peppers whatever veggie you like. Drizzle with Olive Oil. Bake at 350 degree oven for 20-25
minutes Season to taste.
Snacks
#1 Almond Butter with Rice Cakes and Bananas
#2 Almond Butter with Celery
#3 Bean Dip
1 can 15 oz Great Northern Organic White Beans
1 Fresh Lemon/ juiced
1 tsp. Celtic Sea Salt
Blend in food processor until smooth
Sprinkle with chopped fresh parsley
Serve with Rice Chips or Sweet potato and Beet Chips

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#4Avocado Dip
1 medium size avocado/mashed with potato masher
1 chopped medium tomato
1 fresh squeezed lemon
1 T. coarse ground black pepper
Mix well and serve with Rice Chips
#5 Smoothies
1 large Banana
4-5 large Frozen Strawberries
1 cup Rice Milk
Blend until smooth /Freezes well
Spiced Squash Soup
Bake @ 350 degree oven
1 large Butternut Squash, brush with olive oil and bake until golden brown about 1 hour
3 stalks of celery (chopped)
2 small sweet potatoes (peeled and chopped)
1 large apple (peeled and chopped)
1 T. olive oil
Saut 4 above items until a little brown then add 3 cups alkaline water or filtered water, 1 tsp Celtic sea salt, 1 tsp. fresh cracked pepper, 1
bay leaf, tsp cinnamon, tsp cumin, tsp thyme, 1/8 tsp red pepper (cayenne) and a dash of nutmeg. Simmer for 15 minutes. Add all to
blender and mix until smooth. Sprinkle with fresh basil and small amount of Parmesan Reggiano.
Makes about 6-7 cups
To add protein serve over quinoa pasta.
Created by Cheryl Church
Corn and Potato Chowder
2-3 T. olive oil
2 cups chopped organic celery
4 cups organic corn (from can or cut from cob)
Saut until celery is a little tender.
Add 4 cups chopped red skin potatoes, 1 T. Celtic Sea Salt, 1 T. Fresh cracked pepper, if you like pepper this soup tastes great with lots of
black pepper, 1 T. Celery Blend a product made by Celtic Sea Salt Selina Naturally.
Cover with alkaline water or filtered water. Bring to boil and simmer until potatoes are tender about 15-20 minutes.
In separate pot boil 4 cups chopped red skins potatoes to mash and add to soup for creamy texture.
To add protein serve over cooked quinoa.
Created by Cheryl Church

Nurtigenomic Supplements and Supplies


Nurtigenomic Supplements and Supplies (* are available at office)
Holistic Health (Dr. Yasko)
Emerson Ecologics
Life Extension Foundation
Order Code
Supplement
SKU:30204
Sulfate Test*
SKU:30205
Sulfite Test*
SKU:540
See RNA

Source
HH
HH
HH

www.holisticheal.com
www.emersonecologics.com
ww.lef.org
Comments
$55 for a package of 100 sulfate test strips
$55 for a package of 100 sulfite test strips
Ammonia support (neutralizes ammonia)*

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SKU:560
SKU:
SKU:02041
SKU:01129
TRAC9
SKU:30054
SKU:01092
SKU:01082
BOR04
SKU:30020
GABA 7
SKU:01049
SKU:01023
CAR48
01226
Office
00537
Office
Office
SKU:01043

Products
All $85
Yucca*
Charcoal*
Trace Minerals*
NHF Multi*
Hydroxy-B12*
Molybdenum*
Boron
Vit E Succinate*
Montiff GABA*
NADH*
Zen*
Carnitine*
Co-Q10*
Idebenone*
Methyl-B12*
LipophosEDTA*
Lipophos Forte*
PS*

HH

SKU:01044

Pedi-Activ*

HH

LITH2
Office
IOD14
TMG
SKU:01088
00453
SKU:02017
FOL17

Lithium*
Iodoral*
E-lyte 9
TMG
Quercetin Plus*
SAMe*
Folapro*
Folinic Acid*

EE
EE
EE
HH
LEF
HH
EE

Methyl Folate

Drug

00961
Office

Cerafolin NAC
GliSODin*
Glutathione*

Drug
LEF

HH
HH
EE
HH
HH
HH
HH
HH
EE
HH
HH
EE
LEF
LEF

HH

Methylation support (general methyl cycle support)*


Other RNAs:
600 mg 60 for $17.46
100 260 mg capsules for $9.99
2.5 month supply for $10.10
Dr. Yaskos 6-a-day multi for neuro health $29.99 for 180
Perque 2000 mcg hydroxy-B12, $28.95
75 mcg/3 drops 2 oz. for $12.20
3 mg - 100 for $6.50
400 IU - $24
500 mg Montiff GABA, 100 for $21
5 mg tabs, 30 for $33.99
275 mg GABA and 100 mg Threanine 60 for $21
Carnitine 500 mg 60 for $39.90
Ubiquinol 100 mg 60 for $55
100 mg 60 for $40.00
5 mg chewable tablet - 60 for $32
Phosphatidyl Choline with EDTA 1 bottle for $30
Phosphatidyl Choline
100 mg phosphatidyl serine 60 for $39.90
50 mg phosphatidyl serine with 50 mg DMAE 120 for
$28.99
100 caps for $11.19
12.5 mg 90 for $27
2 oz. bottle providing 265 doses for $12.20
750 mg TMG 100 caps for $15.60
Quercetin 500 mg with Bioflavonoids 50 for $14.05
200 mg SAMe 50 for $33.75
5-methyl folate 800 mcg, 60 for $17.49
800 mcg/tablet - 60 for $11
Metanx: 2.8 mg methyl folate, 25 mg P5P, & 2 mg methylB12
5 mg methyl folate, 2 mg methyl B12, and 500 mg NAC
Stabilized Super Oxide dismutase 90 for $28
15 for $90 (each should last for 7 days) - lifewave.com/chc

Office prices may be different to include shipping and handling

How to Order Supplements from Websites


Ordering from Holistic Health website:
x

Go to www.holisticheal.com

Click on Advance search

Scroll down to box that states Search for product

Click on Advance search option

You will see: search category:


sku:
price:

Enter sku # from list for the product you are looking for

Click on search

Under Quantity enter how many you want to order

Click on add all items to cart

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Screen will show items in cart

Click on Advance search and follow same protocol until all items are in cart

Then click check out

Review order and select delivery option

If everything is ok then where you see update click GO

Enter your delivery information and submit

Follow directions for payment

Page 30 of 50

Ordering from Emerson Ecologics


x

Log onto www.emersonecologics.com

On left side of screen click on Product search

Enter code from list in box By Product Code

Do not use any spaces with letters or numbers

Check selection box

Click add to shopping cart

Then click add more product

Follow same protocol for other items

When all items are selected proceed to check out

Follow directions to Register Now

Click I am a patient

Click continue

Enter all info requested

Click continue and follow directions for payment

Ordering from Life Extension Foundation


x

Log onto www.lef.org

On right side of screen enter product code in Search Catalog Number

Then click add to cart

Methyl Cycle Genomic Testing and Treatment - What you Can and Cannot Expect from Us

We got involved in Methyl Cycle testing not because we had to, and not because we dont have anything else to do. No - we got involved in
Methyl Cycle testing for the usual reason, to

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Help Patients Who We (and Nobody Else in the Area) Could Previously Help
This is why we were the 2nd practice in Ohio to get involved in EECP 12 years ago. This is why we brought MME to town 4 years ago, and
why we continue to bring innovative and low risk diagnostic and therapeutic modalities to NW Ohio. We do this because our current best
methods are not good enough; there are always patients who we cannot help so we are always looking for better methods (and these days the
developers of better methods are bringing them to us).
New treatments, especially new treatments not available elsewhere in the area, always generate a lot of questions. Wed like to answer all of
your questions, on an individual basis, and do so in a timely fashion, but in reality we cant. We realize this and we need you to realize this
as well. Staff members cannot answer questions regarding the biochemical genetics of specific Methyl Cycle pathways, just as they cant
explain the biophysics that allow the Glutathione patch to work or the bioengineering that allows the MME machine to regenerate damaged
cells.
Dr. Roberts can answer these questions (well, most of them), but he cannot answer them for you, on an individual basis, outside of your
office visits its just not logistically possible. If you cannot accept this then please undergo Methyl Cycle Genomic testing elsewhere.
Your $1,125 fee covers the cost of the laboratory Methyl Cycle testing, Dr. Yaskos report, and Dr. Roberts analysis and recommendations,
which integrates the Methyl Cycle findings into your past and current medical status. It takes Dr. Roberts considerable time to write what
will be a 4-5 page report but you are paying for this and you are getting value for your money.
We have added to our program various means by which you can learn more, ranging from our monthly Methyl Cycle support group meetings
to individual sessions with Krista McCarthy Mignin MS. Take advantage of these resources.
Please do not call the office with open ended questions or requests such as I want someone to explain this to me or I want Dr. Roberts to
call me. We cant do this. All of you know how hard I work. I am so busy with our current programs that I had to give up all past hospital
activities except for doing heart catheterizations every other Thursday. I am not going to call you up (and you may not answer your phone at
night or on weekends) to answer non-emergency questions, the answer to which 75% of the time will be in my written report.
Please do not call with questions like what can I eat, or is a certain food OK? We do not have ready answers to these questions. We do
put a lot of information regarding diet in to our Methyl Cycle reports. We do give you resources where you can learn more, but please
remember, we are not dietitians nor are we nutritional counselors (but Krista McCarthy Mignin is). Also, please avoid expressing anger at
staff members. We realize that you are sick, that you feel lousy, and that dietary change is difficult, but its not our fault that youre sick, and
its not our fault that your genes are what they are. If you are upset about your genetic makeup, have a heated discussion with Charles
Darwin or God (but they are not going to give in). Remember, just because we found an important problem that may be difficult to address,
it doesnt follow that we caused the problem.
It also doesnt follow that we should work for free or lose money, just because we are the first practice in the area to provide Methyl Cycle
testing and you have a lot of questions. Please remember, when a staff member takes your message, pulls your chart, brings the issue to my
attention, and then transmit my answer back to you, a lot of staff time is taken up and I am paying for it. We provide a lot of innovative
services that generate a lot of questions, and the staff overhead generated can easily get out of hand.
If we are to continue to provide new and innovative services like Methyl Cycle testing, well, we are going to need your cooperation. Call us
when you need to (and there will be times when you need to) but if a question can wait, please put it off until your office visit or until the
next Methyl Cycle support group meeting.
James C. Roberts MD FACC
8/24/08

Sample Report One


Nutrigenomic Report - 46 y/o Female
Methylation Panel Abnormalities for Genes with Characterized SNIPs
Gene Name
Variation
Finding
COMT
V158M
Homozygous (+/+)
COMT
H62H
Homozygous (+/+)
COMT
P199P
OK
VDR
Bsm
Heterozygous (+/-)
VDR
Taq
Heterozygous (+/-)
MAO A
R297R
Homozygous (+/+)
ACAT
1-02
OK
MTHFR
C677T
OK
MTHFR
3
OK
MTHFR
A1298C
Homozygous (+/+)
MTR
A2756G
OK
MTRR
A66G
Heterozygous (+/-)
MTRR
H595Y
nc

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MTRR
MTRR
MTRR
BHMT
BHMT
BHMT
AHCY
AHCY
AHCY
CBS
CBS
CBS
SHMT

K350A
R415T
A664A
2
4
8
1
2
19
C699T
A360A
N212N
C1420T

OK
nc
Heterozygous (+/-)
OK
nc
Heterozygous (+/-)
Heterozygous (+/-)
nc
Heterozygous (+/-)
Heterozygous (+/-)
Heterozygous (+/-)
nc
nc

Overview
The function of the Methyl Cycle is to maintain (current health status) appropriate levels of:
A. SAMe, along with a high SAMe:SAH ratio, necessary for biological methylation.
B. BH4, need to generate neurotransmitters and nitric oxide.
C. The antioxidant/detoxification molecules cysteine, taurine, sulfate, and glutathione.
Your Methyl Cycle and Detox Genomic findings are significant. My hypothesis is that these genomic predispositions have set you up for
organic pollutant and metal toxicity and stressed your nutritional status. Overall my thought would be to address your genomic
predispositions, optimize your nutritional status, hopefully improve your energy level and sense of well being, and then to initiate a slow but
steady detox program that you can tolerate.
You are +/- for both of the CBS up regulations and +/- for at least one of the three BHMT alleles (which act like CBS up regulations - no call
means that for technical reasons 23and me could not determine the status of a particular allele). Homocysteine (and its Methyl Cycle
precursors) is thus being drawn down the trans-sulfuration pathway, in this process generating excessive sulfur break down products (sulfite
and sulfate, which stimulate the stress/cortisol fight or flight response; your sulfate levels are 800-1200), too much excitotoxic glutamate
(which you may have trouble converting in to GABA due to your GAD1 +/+ status; however your glutamate level was not elevated on your
9/12 NutrEval), and too much ammonia (which depletes BH4, leading to insufficient dopamine and serotonin production). This deficiency in
BH4 allows NOS (nitric oxide synthase) to convert Arginine in to free radicals as opposed to nitric oxide, predisposing you to hypertension
and cardiovascular disease.
Dr. Yasko feels that MTHFR A1298C (+/+) status compromises recycling of BH4 from spent BH2. Your DHFR (+/-) status may also
compromise BH4 recycling, so with respect to the precious molecule BH4, you are getting hit at both ends reduced production and
increased utilization. After the problems in the trans-sulfuration pathway (CBS and BHMT) have come under control, BH4 or additional
methyl-folate as a BH4 precursor/mimic can be added to your program.
Folate molecules serve to transfer methyl groups within our physiology (think of folates as methyl group taxis). To become useful, the
oxidized dietary folate molecules that we take in must first be reduced to Tetrahydrofolate (THF) by dihydrofolate reductase (DHFR). You
are (+/-) for a DHFR reduced function allele, such that conversion of dietary folates in to useful THF may be compromised.
SHMT (serine hydroxyl methyl transferase you are +/- here), a pyridoxal-5-phosphate (active form of B6) dependent enzyme, tacks on a
methyl group derived from the amino acid serine to generate 5,10-MethyleneTHF, which is then converted to 5-methyl folate by MTHFR.
5,10-MethyleneTHF can also be acted upon by MTHFD1,to generate the building blocks for DNA and RNA generation. Being +/+ for
MTHFD1, you are having trouble with these steps and in recycling folate derivatives back in to THF. Being +/- for MTHFS, you are having
some trouble breaking down folinic acid. We can measure folate metabolites, and supplement you based upon the results, or we could use a
combination of low dose folinic acid and methyl-folate.
Being +/+ for FOLR2 (folate receptor) your cells may have trouble taking up folic acid (more so then with methyl-folate), and thus you may
benefit from greater than usual levels of methyl-folate. PEMT (which is stimulated by estradiol) uses three SAMe molecules to generate
phosphatidylcholine. You are ++ for a loss of function PEMT allele, and thus you are having trouble generating phosphatidylcholine. We use
phosphatidylcholine in the remethylation of homocysteine into methionine by BHMT (also pulling homocysteine away from the CBS
drain), in lipid metabolism, and in the generation of the neurotransmitter acetylcholine. Phosphatidylcholine supplementation makes sense
here.

MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine, which in turn is converted in to S-AdenosylMethionine (SAMe), the universal methyl donor. You are +/- for one of the MTRR alleles, meaning that you are having some trouble
converting B12 in to methyl-B12, which will be a little difficult to address with supplementation, as you are +/+ for COMT. COMT breaks
down dopamine, using up methyl groups in the process. As you are COMT +/+, you will break down dopamine only slowly, a point in your
favor as dopamine helps defend against toxic metals. However, being COMT +/+ renders you sensitive to methyl groups. Aggressive
methyl group supplementation can lead to fluctuations in dopamine, producing mood swings. Thus we will be ginger with respect to methylB12 supplementation (also, methylmalonic acid, an index of B12 need, was normal on your NutrEval study, as was methionine, which is

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generated from homocysteine in a B12 dependent fashion, and thus methylation of B12 is likely not seriously compromised).
You are +/- for VDR Taq (and VDR Bsm, which acts like VDR Taq), meaning that you are not making enough dopamine in response to
Vitamin D (somewhat mitigating your methyl group sensitivity), but +/+ COMT, meaning that you are breaking down dopamine, and using
up methyl groups in this process, quite slowly; thus you will not need nor will you likely tolerate dopamine precursor therapy or high dose
methyl group supplementation.
MAO A breaks down serotonin. You are +/+ for MAO A, and +/- for MAO B, so you will break down serotonin relatively slowly, and thus
you probably do not have a great need for serotonin precursor therapy.
AHCY converts S-Adenosyl Homocysteine (SAH), generated whenever a SAMe is spent in to homocysteine. Being +/- for AHCY this
reaction may be sluggish, such that SAH levels may build up, and the ratio of SAMe to SAH could fall, compromising your ability to utilize
SAMe as a methyl-donor. Our approach here will be to make sure downstream homocysteine is cleared efficiently and to decrease the
generation of SAH (likely with creatine and phosphatidylcholine supplementation).
PON1 +/- compromises the antioxidant function of HDL (and our ability to detoxify homocysteine thiolactone, a toxic derivative of
homocysteine), and can be addressed with pomegranate intake. CYP1A2 compromises your ability to 2-hydroxylate estrogen molecules,
while being +/+ for CYP1B1 you are predisposed towards 4-hydroxylation. However, your 2/16 ratio is OK at 2.8, and Dr. May has you on I3-C, which stimulates 2-hydroxylation. Dr. May placed you on iodine to promote metabolism of 16-hydroxy estradiol to estriol, and
improving your overall antioxidant status should help here as well (we use antioxidants to reduce 16-OH estradiol to estriol). Your COMT
+/+ status is limiting conversion of 2-OH estrogen molecules in to the protective 2-methyoxyestrogens. Being +/+ for CYP1A2 you are
having trouble breaking down caffeine, and being +/+ for COMT you are having trouble breaking down catecholamine molecules (dopamine
and norepinephrine adrenalins), so it is best that you minimize caffeine (especially coffee) intake.
The Gene by Gene sections provide generic information while specific recommendations for you are described in the Plan of Action
sections. Approaches that make the most sense to me receive a (). Those that are less critical (or more costly) are designated (+/-). Your
Methyl Cycle abnormalities likely predispose you to impaired detoxification, and your evaluation has demonstrated problems with mercury
and tin (the primary source of both is likely your prior mercury fillings).
In thinking about your Methyl Cycle status, we need to keep in mind that recommendations based upon Dr. Yaskos work with autistic kids
may be problematic in adults with other genomic or acquired health challenges. Thus we need to keep everything in proper perspective,
particularly with respect to diet. I can see how the CBS nothing with eyes diet would be problematic for you, given your well
characterized food sensitivities. Your work up to date has been incredibly comprehensive. Dr. Smith knows a lot of things that I dont ands
he has a great understanding of your health status. I will be doing a little bit of brainstorming as we discuss your Methyl Cycle status, and
have some ideas for you and Dr. Smith to consider.

Gene by Gene Approach CBS +/- and BHMT +/-

CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. Yaskos book, Genetic
Bypass. You are +/- (half of your CBS enzymes are abnormal) for one of the CBS up regulations
and +/- for at least one of the BHMT down regulations (which act like CBS up regulations).
Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration
pathway, in this process generating excessive sulfur break down products (sulfite and sulfate, which
stimulate the stress/cortisol fight or flight response), too much glutamate (which leads to
glutaminergic excitotoxicity a double problem for you as your GAD +/- status compromises
interconversion of glutamate and GABA, noting however that your glutamate level was not elevated
in 9/14), hydrogen sulfide (to produce brain fog), and too much ammonia (which depletes BH4,
leading to insufficient serotonin and dopamine production. Your ammonia level was not elevated in
9/14, likely as you are not taking in excessive animal protein. A deficiency in BH4 allows NOS
(nitric oxide synthase) to convert arginine in to free radicals as opposed to nitric oxide, predisposing
you to hypertension and cardiovascular disease. Being +/+ for MTHFR A1298C and +/- for DHFR,
you are having trouble regenerating BH4, so with respect to the precious molecule BH4, you are
getting hit at both ends reduced production and increased utilization. Thus your ability to generate
neurotransmitters and nitric oxide will be compromised. Instead your genomic status predisposes
nitric oxide synthase to generate the free radicals superoxide and peroxynitrite, which lead to oxidative stress and inflammation.
Compounding this predisposition towards increased production of superoxide, your +/+ status for SOD compromises your ability to
neutralize superoxide, and your +/- status for GPX and GSTP compromise your ability to neutralize hydrogen peroxide with glutathione.
I realize that this sounds awful but these are all issues that we can deal with, now that we understand their origin and biological significance.
During normal physiology, metabolic flow down the CBS pathway is designed to generate the important anti-oxidant and detoxifying
molecules glutathione (your level is not high, likely as your glutathione reserves are being used up dealing with mercury), taurine (why your
taurine level is elevated) cysteine (elevated), and alpha-ketobutyrate (which Dr. Yasko feels can be converted into GABA, a calming

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neurotransmitter, or glutamate, an excitotoxin; others dispute this position but we typically see elevated glutamate in individuals with
CBS/BHMT + alleles). The CBS C677T and A360A genes code for enzyme function that is pathologically up regulated (your ancestors
needed antioxidant support more than they needed methylation support; thus these SNIPs which direct homocysteine towards glutathione and
away from SAMe regeneration). You thus suffer from too much of a good thing and way too much of several bad things.
Oxidative stress (the accumulation of free radicals) increases flow down the CBS pathway, to generate the above listed antioxidants needed
to allow the body to respond to an oxidative challenge a good thing. However, when homocysteine is drawn down the CBS pathway, it is
lost forever such that it cannot be remethylated and used to regenerate SAMe. In this fashion oxidative stress (something we wish to
avoid) leads to reduced SAMe. SAMe itself stimulates flow down the CBS pathway (if you have plenty of SAMe you do not need to worry
about recycling it); this is why we advise you not to begin SAMe (or push with measures designed to up regulate SAMe production) until
your CBS/BHMT alleles have come under metabolic control.
SAMe has been used to treat lead overload (and presumably will work against mercury), as SAMe stimulates CBS, which inevitably converts
homocysteine into glutathione. Could your poor response to SAMe have been a detox reaction + a response to a CBS induction induced
sulfite/sulfate burden (as along with glutathione, CBS generates sulfite and sulfate)?
While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification, sulfate/sulfite/-SH excess seems to block cellular up
take of the key detoxifiers glutathione and cysteine (this is Dr. Yaskos position; I cant back this up from my review of the scientific
literature but her position seems to work in practice). Endogenous detoxification is thus blunted (nearly all kids with Autism Spectrum
Disorders bear CBS up regulations why they are compromised by environmental toxins and the kid next door is just fine could this be
playing a role in your otherwise difficult to explain health conditions)? Conversely, after we decrease your sulfate/sulfite pool, your detox
pathways will open up (and why, if we move too fast, you will experience detox phenomena).
The excess ammonia generated must be detoxified, and to do so BH4 (tetrahydrobiopterin) must be spent. This is a problem in that we
need BH4 to generate neurotransmitters (serotonin to maintain calm/prevent depression and dopamine to maintain motivation and drive).
Without BH4, we cannot convert arginine in to nitric oxide; instead vascular wall toxic free radicals such as superoxide and peroxynitrite are
created, leading to hypertension and cardiovascular disease.
Ammonia is metabolized within the urea cycle, an enzyme pathway that utilizes several amino acids (ornithine, aspartate, arginine, and
indirectly alpha-ketoglutarate) to break down ammonia. Systemic ammonia detoxification takes place in the liver, and thus individuals with
advanced liver disease experience hyperammoniaemia, with attendant neurological dysfunction (tremor, confusion, impaired coordination).
We can thus borrow from the gastroenterology community in our approach to the hyperammoniaemia present in our patients with
CBS/BHMT/MTHFR alleles (also giving me a chance to consult with our daughter, who is a gastroenterology fellow).
Intestinal microbes generate ammonia. Gastroenterologists use antibiotic therapy (Rifaxamin, a poorly absorbed antibiotic that does not enter
the circulation) to sterilize the gut, thus blunting ammonia production. While we may recommend antimicrobial therapy to address bacterial
overgrowth demonstrated on a CDSA (Comprehensive Digestive Stool Analysis), our approach will be to take a probiotic 2-3 times a day to
promote a balanced intestinal flora (not a bad idea for all of us to deal with the effects of antibiotics found in grocery store meats).
Charcoal seems to absorb ammonia generated within the GI tract, and thus taking charcoal at bedtime seems to lower ones ammonia burden.
Charcoal can also cause constipation, a huge negative here, as moving your bowels 2-3 times a day is important in detoxification and
ammonia neutralization. Thus we recommend charcoal three nights a week with magnesium citrate and/or Vitamin C as needed to promote
normal GI tract motility (adjust doses to obtain a balance between ammonia neutralization and proper GI tract function too much
magnesium or vitamin C pulls water into the intestines, leading to loose stools and diarrhea). Gastroenterologists utilize the cathartic
lactulose to accelerate GI tract motility, blocking ammonia absorption; we can achieve the same end nutritionally with vitamin C and
magnesium.
Ornithine/Aspartate supplementation (LoLa), administered IV or orally, has been shown to be a safe and effective approach to ammonia
reduction in liver failure, and we can utilize this low cost approach to deal with ammonia excess in Methyl Cycle patients, starting with 1000
mg (1/3rd teaspoon) three times a day, increasing to one teaspoon as needed. Aspartic acid has a glutamate-like stimulating effect, and if one
experiences agitation/anxiety than aspartate can be dropped in favor of more ornithine. Ornithine monotherapy has been used to increase
exercise capacity in healthy people, as ammonia production is a metabolic consequence of energy utilization. These and other amino acids
are best absorbed on an empty stomach or with a carbohydrate; concomitant protein intake will blunt their absorption.
Dr. Yaskos diagrams indicate that CBS generates alpha-ketoglutarate, which can
be converted into glutamate. Actually, CBS generates alpha-ketobutyrate.
Nonetheless, individuals with CBS + alleles nearly always display elevated
glutamate, and thus the same physiology holds. We should be able to interconvert
alpha-ketoglutarate into glutamate, glutamine, and GABA. However, if glutamate
is in excess, or if toxic metals compromise the interconversion enzymes, then we
suffer a buildup of the excitatory neurotransmitter glutamate. Glutamate is
involved in alertness and learning, but excess glutamate leads to irritability and
over-excitement; toxic levels may play a role in seizure activity and cardiac
arrhythmia (could this be why we are seeing so much more atrial fibrillation now
then we were ten years ago; MSG, a dietary source of glutamate, can precipitate
atrial fib)? We address high glutamate/excitotoxicity by avoiding high

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glutamate/MSG in foods (please see appendix) and by taking GABA to neutralize the excitatory affects of high glutamate.
CBS up regulations lead to an initial buildup of potentially neurotoxic sulfite, which is then metabolized by SUOX (Sulfite Oxidase) to the
less neurotoxic (but still problematic at high levels) sulfate. SUOX activity requires molybdenum, which is thus depleted in CBS +
individuals. Homogenized dairy products contain xanthine oxidase, which uses up molybdenum, and are best avoided or minimized.
Vitamin E succinate, boron, and B12 are felt to stimulate SUOX activity.

As Methyl Cycle function is needed in the biosynthesis of Co-Enzyme Q10 and Carnitine, individuals + for CBS will likely be energy
depleted, and here supplementation (in relation to your COMT/VDR status) with Co-Enzyme Q10, Carnitine, Ribose, and NADH or NAD+
may be helpful.
BHMT (Betaine Homocysteine Methyl Transferase, a zinc-dependent enzyme) directly methylates homocysteine back in to methionine,
serving as a back door pathway to pull homocysteine away from the CBS sulfate drain. Thus if you bear CBS or BHMT
abnormalities, it makes sense to support BHMT function. TMG (trimethylglycine) stimulate BHMT, and can be utilized if you are not overly
sensitive to methyl group supplementation (but you likely are due to your COMT +/+ status). Phosphatidylserine stimulates BHMT (and we
also use it to moderate elevated cortisol levels), as does phosphatidylcholine (which we use to treat atherosclerosis). Phosphatidylcholine can
be admixed with EDTA (detoxifies metals), creating a quite useful supplement.
Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR
(compromising methyl-B12) abnormalities, and thus you will need and benefit from corresponding supplementation (with these molecules
that you are having trouble making). However, if we treat you with methyl-folate, methy-B12, or BH4, before we have the CBS problem
under control (lower your sulfate status such that glutathione and cysteine assimilation improves) then we will be subjecting you to
incomplete detoxification. You will feel great for 1-2 days, as beneficial neurotransmitters are generated. Methyl-folate and methyl-B12
detox pathways will then open up, creating toxic intermediates that cannot be metabolized further due to the block in glutathione utilization
and you will feel horrible. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until CBS/BHMT are under
control. Youve lived your entire life with a gene set that is maladaptive to the toxic environment of modern man. It will take us some time
to change your internal environment to bypass these genomic challenges.

Plan of action for CBS +/- (BHMT discussed further in other sections)

To address this constellation of alleles I will recommend:


1. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables, sulfur containing supplements, and sulfur
containing drugs (see attached sulfur avoidance instruction sheets and read Sulfites and Chronic Disease by Rick Williams, available at the
office or at www.readingtarget.com/nosulfites/. Basically, from the Methyl Cycle perspective, returning to a vegetarian diet makes sense for
you.
2. Check the sulfate/sulfite content of your supplements and prescription agents (many listed in the Williams book) and whenever possible
switch to agents with lower sulfate/sulfite content. Some of your current supplements may contain sulfhydryl groups; all have health benefits
but all add to your sulfite/sulfate burden. We may or may not wish to stop these agents, and results of urine sulfate testing will help with
decision making here.
3. Monitor urine sulfate levels every 3-7 days (or when you feel particularly good or poorly, or after adding a new treatment or changing your
diet). Please chart the levels this will be our primary measuring stick our goal is a urine sulfate of 400 (one yellow and three pink) to
800 (two yellow and two pink). Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a
liberalization of your diet. Conversely, persistent high sulfate spills indicates that your diet/treatment program needs further modification.
3. To neutralize ammonia (generated from animal protein), you can use Ammonia Support RNA dropper with meals and with methyl cycle
supplements (relatively expensive), along with a charcoal supplement at bedtime every other evening, away from other supplements
(magnesium citrate and Vitamin C may be used as needed to keep the GI tract moving - optimally twice a day - as charcoal may lead to
constipation). Yucca, beginning at capsule, twice a day, (or sprinkled on food containing protein), may help with ammonia detoxification.
Ornithine/Aspartate 1000-3000 mg three times a day (taken away from other sources of protein) will stimulate the urea cycle, promoting
ammonia degradation, and should increase your energy level. While your ammonia level was not elevated, BH4 is used up in ammonia
metabolism, so the less ammonia formed the better.
4. Sparga Detox, 10 drops in water (wait at least one minute before consuming), twice a day makes sense (already on board). Sparga was
developed by fellow Cardiologist Dr. Lee Cowden, specifically to address the CBS abnormality (see www.nutramedix.ec).
5. With respect to overall nutritional support, you and Dr. Smith have the bases covered based upon your NutrEval study. Could you please
send me a treatment list with mg/mcg doses? Are you taking in riboflavin? If not please add 50-100 mg/day to your program. To stimulate
SUOX, please add molybdenum 500 mcg daily to complement the boron, hydroxy-B12, and boron, which are already present in your
program.
6. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. Right now this good thing could actually set you
back. However, if we could convince your biochemistry to up regulate biosynthesis of glutathione, then your anti-oxidant and detox capacity
will increase, with concomitant utilization of free sulfate/sulfhydryl groups a double win for you. This can be achieved with the use of the
Life Wave (needleless acupuncture) Glutathione patch. The Life Wave people have demonstrated an increase in Glutathione levels in
relation to patch use. Please see separate information sheet on Life Wave patch use; be very conservative early on. This approach may be
added in the future, after your CBS/BHMT situation has been addressed.

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7. If you feel anxious or wired up (glutamate overload), take GABA 500 mg, twice a day. If this is helpful you can double the dose.
GABA does not work rapidly, but if you take it twice a day you will build up a GABA reserve to balance the glutamate overload you are
experiencing due to your CBS up regulation. Magnesium supplementation may help with GABA physiology and often helps with sleep and
is already on board.
8. Regarding energy production, Co-Enzyme Q 50 mg odd days and carnitine 500 mg even days (we start slow here as these agents are
methyl donors). NADH 5 mg/day (NAD+ might be even more effective) sometimes helps. A trial of ribose 5 gm in water two to three times
a day makes sense; a positive response indicates that you are having trouble generating ATP energy.
9. After sulfate levels have fallen (to a level that you and I feel is optimal for you, based upon your clinical and genomic status), then we may
increase methyl-folate and/or add BH4 to your program. While normally I do not start methyl-folate and methyl-B12 until sulfate levels have
fallen. If you are already on methyl-folate, I do not think they need to be stopped unless urine sulfate levels remain high and/or you do not
improve clinically.
11. I cant back this up with a clinical study, but the use of Aura Organ Detox patches for two months make sense. The idea here is not to
remove the toxins (hard to do) but to homeopathically neutralize them). Later, after your sulfate levels have fallen, we will begin to remove
the toxins themselves.
12. With respect to lab testing, we need to check homocysteine now along with a repeat Vitamin D level. After you have been on your
program for 4-6 weeks, we can measure SAMe and SAH. The Health Diagnostics and Research Institute (www.hdri-usa.com - $350) can
give us levels of SAMe, SAH, and folic acid derivatives (which will help us understand the affects of your MTHFD, MTHFS, and DHFR
alleles). Alternately, Doctors Data gives us a less extensive but still useful Methylation Panel for $155.
13. Be self-observant and keep records. Which foods, supplements, or other maneuvers increase or decrease your sulfate spill? Which make
you feel better or worse? Always keep in mind that detoxification is not a fun experience. You may need to accept some transient fatigue,
malaise, and achiness to allow toxic molecules to be cleared. Conversely, if detox symptoms are debilitating or compromise your ability to
work or care for your family, then we need to back off on your treatments. Balance needs to be achieved. Rectifying your genomic
predispositions and detoxifying your system is not a sprint it is a marathon. And, as your genes are not going to change, and as the
environment is not going to become less toxic, you will need to be mindful of these principles for the rest of your (long and healthy) life.
* How tightly should you restrict dietary protein? The degree of protein restriction best suited for you will be in relation to your personal
health characteristics and your clinical and biochemical (urine sulfate and ammonia levels) response to treatment. We need to keep in mind
that Methyl Cycle Genomics is not the sole determinant of your health. A low protein diet can become a high carbohydrate, weight gaining
diet in an overweight individual with type two diabetes. Individuals with chronic, unexplained illness or significant toxicity would do well to
follow the nothing with eyes diet until urine sulfate and ammonia levels have fallen; later on we will liberalize your diet, while keeping an
eye on these biochemical markers. This dietary maneuver isnt fun but may also turn ones your health around. Individuals in whom the
CBS up regulation is less important (A360A as opposed to C677T, lower urine sulfate and ammonia levels, and better overall health), could
simply cut back on animal protein. In addition, the greater representation of ammonia reducing (Yucca, Charcoal, Sparga, Ammonia Support
RNA) treatments in your program, the more protein you will be able to take in without compromising your biochemistry. This is all about
balancing diet against treatment response.
** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Toxicity testing (discussed in more detail
in our Approaches to Detoxification brochure and on heartfixer.com) thus makes sense. You have already undergone toxicity testing.
Additional toxicity testing could consist of:
A. The US BioTek study gives us information on seven major organic pollutants ($126). The NutrEval tells us that you bear an organic
pollutant burden, which we can address in the future, but I feel that mercury will be out first detox priority.
B. A formal provocative challenge ($250) gives us our best assessment of tissue metal burden. Alternatively, an oral DMPS challenge could
be carried out, but I do not feel this is necessary as your red cell mercury level serves as a target for intervention.
C. The Hunt Digital picture approach ($350) assesses for toxicity (and other health challenges) by analyzing the frequencies emitted by your
body (and tells us which Digital Homeopathic Patches would be most appropriate). I cant prove this approach with an allopathic lab test but
it has been quite helpful in solving complex medical problems in my personal patients. Dr. Hunts CD is available for your review and you
can go to www.auraexplorationpatches.com for additional information.
D. While on the subject of energy medicine, learn about the grounding/earthing concept. This approach is low in cost and likely has value
for all of us. My colleague Dr. Sinatra wrote a book on this subject (heartmdinstitute.com).

OUR MOST IMPORTANT INITIAL GOAL WILL BE TO


REDUCE YOUR SULFATE, AMMONIA, and GLUTAMATE BURDENS

Gene by Gene Approach COMT +/+ with VDR Taq +/- and MTRR +/This constellation of alleles is discussed on pages 193-196 of Dr. Yaskos book, Genetic Bypass. Being COMT +/+ means that you are
breaking down dopamine, and in the process using up free methyl groups, only slowly, in your long-term favor with respect to dealing with
heavy metals and microbes. This also means that you will be sensitive to methyl groups, creating a treatment conflict. You may need
methyl-B12 due to your MTRR status, but the extra methyl groups could cause a rise in dopamine, leading to mood swings. Being +/- for
VDR Taq means that Vitamin D will not increase dopamine levels in the normal fashion, somewhat mitigating this sensitivity to methyl
groups, but we do not need to give you dopamine precursors and we will be on the watch for mood swings as we give you supplements
containing methyl groups. Lithium and iodine may be lost (swept out) in the process of heavy metal detoxification. These minerals are felt

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to help balance or mitigate mood swings that might occur as a result of fluctuations in dopamine levels, so low dose supplementation makes
sense in COMT +/+ individuals.
COMT (Catechol-O-Methyl Transferase) inactivates catecholamines (dopamine, norepinephrine, and epinephrine). Caffeine and stress
increase catecholamine production. Individuals with genomic or acquired COMT dysfunction are thus more sensitive to their effects. Stated
otherwise, high coffee intake increases cardiovascular risk in COMT +/+ individuals but not in those with normal COMT status, and caffeine
induced insomnia will be more of an issue in those with COMT +/+. COMT is also involved in estrogen metabolism, mediating generation
of the anti-cancer, anti-vascular disease 2-methoxy estrogens and inactivation of the stronger, potentially genotoxic 4-hydroxy and 16hydroxy estrogen molecules.
CYP1A2 +/+ (down regulation) status means that your ability to 2-hydroxylate estrogen molecules will be compromised, while your
CYP1B1 +/- (up regulation) status promotes conversion of estrogens down the 4-hydroxylation pathway. Dr. May has you on I3C to
stimulate 2-hydroxylation and your 2/16 ratio is thus OK at 2.8.
CYP1A2 +/+ (down regulation) status also compromises your ability to degrade caffeine, which itself stimulates the adrenal gland to release
catecholamines, which in turn must be broken down by COMT, the function of which in you (+/+ for the reduced function alleles) is
compromised. Thus in your situation caffeine avoidance will be important.
Your COMT +/+ status also explains why your 2-methoxyestradiol levels are relatively low (you are having trouble tacking on the methyl
group). This is certainly difficult biochemistry; please see the Estrogen Metabolism section of the website for more information on Estrogen
Metabolism and how we can affect it).
Endogenous and caffeine induced catecholamines, estrogen molecules, and quercetin compete for COMT mediated methylation. This is
not an issue in COMT -/- individuals, as there is plenty of COMT function to go around, but when COMT function is limited (COMT +/+
individuals have only 25% the O-methylating capacity of COMT -/- individuals), competition becomes more of an issue. This explains how
stress and caffeine increases risk of cardiovascular disease and reproductive organ malignancy to different degrees in different people
(genomic-environment interaction). COMT +/+ status is also associated with increased sensitivity to pain.
While estrogens, quercetin, and catecholamines compete for the attention of COMT,
S-Adenosyl Homocysteine (SAH) serves as a non-competitive COMT inhibitor. S-Adenosyl Methionine (SAMe) donates the methyl
group that COMT uses to O-methylate its substrate, producing an O-methylated substrate and SAH. SAMe and SAH compete for the SAMe
binding site on the COMT molecule (think of the SAMe binding site as the on-off switch for COMT). A build up of SAH will thus turn
down COMT activity. When Homocysteine builds up, SAH builds up behind it. COMT metabolic dysfunction, with secondary inability to
metabolize catecholamines and estrogen molecules, is a key mechanism through which elevated homocysteine damages our health.
Unmetabolized catecholamines and estrogen molecules generate oxidative stress, leading to vascular and neurological disease.
Unmetabolized estrogen molecules damage DNA, increasing risk of breast and prostate malignancy. While elevated Homocysteine is always
deleterious to overall health, high Homocysteine in the presence of COMT dysfunction is a disaster (we will check your homocysteine level
and my prediction is that it will be low).
COMT +/+ individuals cannot utilize methyl groups efficiently, and thus excess methyl group supplementation may lead to irritability in
COMT +/+ individuals. Dr, Yasko feels that VDR status effects dopamine generation. Individuals who harbor VDR Taq or VDR Bsm
alleles will make less dopamine, and with less dopamine floating around, impaired dopamine inactivation due to ones COMT +/+ or +/status becomes less of an issue, and one will be less sensitive to methyl group donors. From the perspective of mood and childhood
neurodevelopmental conditions, while COMT +/+ or +/- status renders one sensitive to methyl group supplementation, this is neutralized by
VDR +/+ or +/- status.
MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine. The MTRR abnormality (+/- means that of your
MTRR enzymes will work poorly while +/+ would signify that all of your MTRR enzymes would be affected) means that you will have
trouble converting B12 in to methyl-B12. Stated otherwise, while your serum B12 level may be within normal limits, it will not work
normally within your biochemistry. As you are COMT +/+ and VDR +/- you will be sensitive to methyl groups. Thus we will start not with
methyl-B12, but with high doses of hydroxy-B12, aiming for the hydroxy-B12 to bind with the methyl groups available to form methyl-B12.
If we do not feel that this approach is getting the job done, we could add in methyl-B12 cautiously, watching for mood swings. B12
methylation does not appear to be a problem for you, as your methionine and methylmalonic acid levels are OK.
By stimulating BHMT, we can bypass any block that MTRR places on homocysteine detoxification, and this maneuver will also draw methyl
cycle intermediates away from sulfate/sulfite production. Phosphatidylserine and phosphatidylcholine stimulate BHMT and makes sense.
Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple
enzymes, whether they are genetically normal or abnormal, including GAD, which converts glutamate in to GABA). TMG
(trimethylglycine) will stimulate BHMT but will also provide methyl groups, to which you are likely sensitive, and is thus best avoided.
If agitation or anxiety is an issue (perhaps on the basis of excessive glutamate production due to a CBS up regulation), we can address this
with GABA 500 mg, 1-2 twice a day. We need glutamate for learning and alertness, but excessive glutamate leads to excitotoxicity,
manifested clinically as agitation and anxiety and pathologically as neural damage. Conversely, GABA counterbalances glutamate,
providing a calming effect (all drugs of the valium class stimulate the GABA receptor). We should be able to interconvert glutamate, alphaketoglutarate, and GABA, but the enzymes systems involved in this process are sensitive to heavy metals, likely a problem in you. GABA
does not work quickly, or as needed, but if taken twice a day your GABA pool will increase such that stress tolerance and your overall
sense of well being should improve. GABA should not produce excessive drowsiness, lethargy, or dependency (as valium class drugs may).
Zen contains GABA and theanine, another GABA agonist, but theanine provides methyl groups, to which you are sensitive, so for you
GABA alone is a better choice. Other approaches to dealing with an imbalance between glutamate and GABA include avoiding glutamate

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rich food products (see list) and supplementation with grape seed extract 100 mg/day (taurine helps here but might aggravate your
CBS/sulfite overload situation). Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which
compromises function of multiple enzymes, whether they are genetically normal or abnormal, including GAD, which converts glutamate in
to GABA). EDTA efficiently removes lead and cadmium, and has activity against aluminum, nickel, and arsenic. EDTA is not an efficient
mercury chelator. EDTA is typically well tolerated in individuals with a CBS up regulation.
Lithium and iodine may be lost (swept out) in the process of heavy metal detoxification. These minerals are felt to help balance or mitigate
mood swings that might occur as a result of fluctuations in dopamine levels, so low dose supplementation makes sense in COMT +/+
individuals, with dosing guided by blood levels. Unless we are taking in iodized table salt, most of us in non-coastal regions will be iodine
deficient, compromising or metabolism and possibly thyroid function. Iodine supplementation may improve thyroid function, while
paradoxically, in some individuals, excessive iodine may compromise thyroid function or induce thyroiditis (Ive seen this). Thus it makes
sense to check thyroid chemistries several months after beginning iodine supplementation, particularly if you are receiving thyroid hormone
supplementation.
Dr. Yaskos RNA products, to my knowledge, are silencing or interference RNAs, which affect the reading of your DNA in a fashion
beneficial for specific genomic challenges. They are expensive, and proof of efficacy has not been provided (and we do not hold this against
Dr. Yasko as proving anything in biological medicine costs millions of dollars). Their inclusion in your program is ideal but adds
significantly to your costs, so from my perspective their use can be deferred (or added later if our initial approaches are not getting the job
done).

Plan of action for COMT +/+ with VDR Taq +/- , and MTRR +/-

1. Sublingual Hydroxy-B12 is already on board to stimulate SUOX and seems to be covering your MTRR +/- status. Before switching to
methyl-B12 (which you probably do not need) I would like to measure your SAMe level with the Doctors Date methylation panel (in 8
weeks).
2. Lithium Orotate 5 mg alternating with Iodoral three days a week (Sundays off) makes sense, with plans to obtain a 24 hour urine mineral
assessment and serum iodine level in 8 weeks..
3. To stimulate BHMT and spare BH4, phosphatidyl choline (PhosChol) 900 mg/day makes sense. If PhosChol agrees with you (most
patients feel better on PhosChol) the dose could be advanced to 900 mg twice a day (more on this in the Methyl Thieves section). Soy bean
lecithin 1-2 tablespoons/day would serve as a lower cost alternative to PhosChol.
4. When you and Dr. May feel you are physiologically strong enough for metal detoxification, we could utilize a program of Lipophos EDTA
(stimulates BHMT and pulls out metals) bottle twice a week in juice (we may later increase to bottle twice a week), with
Phosphatidylcholine 900-1800 mg the remaining five days of the week.
5. Limit supplements that provide methyl groups, such as melatonin, turmeric, theanine, and MSM, as we need to make room for methylB12.
6. We need to check you vitamin D level.
7. Methylation support RNA dropper per day would be ideal here (and expensive and thus not critical).
If you feel poorly, this could represent allergy/intolerance to one of your therapies, the effects of excessive methyl groups (despite our
biochemical precautions), but more likely this will represent a detox reaction, as dammed up toxins start leaving your body. This is not a
negative we want you to detoxify. However, if a detox reaction is compromising your functional status, we can back off on your program,
and then resume at a lower dose when you are feeling better. You are entering this process because your health has been compromised and
allopathic (drugs and surgery) medicine has not helped you, and thus you may need to endure some short-term discomfort to achieve your
long-term goal (a return of good health).

MTR (Methionine Synthase) transfers a methyl group from Methyl-folate to Homocysteine to form Methionine.
MTRR (Methionine Synthase Reductase) adds the Methyl group to otherwise inactive B-12.
BHMT (Betaine-Homocysteine Methyltransferase) mediates the backdoor pathway of
homocysteine metabolism, directly methylating homocysteine back to SAMe.
COMT (Catechol-O-Methyl Transferase) breaks down dopamine and norepinephrine and to a somewhat lesser extent other neurotransmitter
substances, by tacking on to them a free methyl group that COMT obtains from SAMe.

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COMT V158M (+/+)


COMT H62H (+/+)
COMT 61
(-/-)
COMT V158M (-/-)
COMT H62H (-/-)
COMT 61
(+/+)

Page 39 of 50

Highest dopamine levels


Lowest need for and tolerance to methyl group donors
Greatest susceptibility to mood swings
Lowest dopamine levels
Greatest need for and tolerance to methyl group donors
Lower susceptibility to mood swings*

Gene by Gene Approach and Plan of Action MTHFR A1298C +/+


Dr. Yasko describes MTHFR A1298C as an abnormality in the SAMe binding site of MTHFR that compromises the backward reaction
that generates BH4, a problem in that BH4 is being used up detoxifying ammonia (which you are making in excess due to your CBS up
regulations). This backward reaction is not supported by other authors, but a pathway does exist (mediated by DHFR) such that poor
methyl-folate status will compromise BH4 recycling. Methyl folate supplementation may stimulate the backward reaction and will help
regenerate BH4, and methyl-folate can stand in for BH4 when the latter is depleted. After your urine sulfate levels have fallen we may
advance methyl-folate or add in BH4 supplementation. If we supplement aggressively in the presence of high urine sulfate, patients may feel
great for one day and then experience an incomplete detox reaction. As you are already on methyl-folate I do not think you need to stop it
but we will not increase the dose until sulfate levels are under control (< 800). Sauna increases BH4 production and promotes detoxification
and could be utilized.
Gene by Gene Approach SHMT +/SHMT combines the amino acid serine with folic acid to form 5,10-methylene THF, which is used to generate the building blocks for DNA
and RNA generation. We can bypass this block with 5-formyl THF, also known as Folinic acid.
Plan of Action SHMT +/As you are +/- and not +/+ for SHMT please add 5-formyl THF, also known as folinic acid, 400 mcg daily (or 800 mcg every other day) to
your program.

Gene by Gene Approach and Plan of Action DHFR +/Here you are having some trouble reducing oxidized dietary folates into useful Tetrahydrofolate, and in recycling spent BH2 back in to
useful BH4. Our approach here involves methyl-folate and folinic acid supplementation, as discussed above.

Gene by Gene Approach and Plan of Action FOLR2 +/+


To some degree, your cellular folate receptors are having trouble incorporating folic acid. This is probably less of an issue with methyl-folate.
You may need more methyl-folate than others. Our approach here is general support of the Methyl Cycle and the inclusion of methyl folate in
your program.

Gene by Gene Approach and Plan of Action MTHFD1 G1958A +/+

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The trifuncitonal enzyme, 5,10-methylenetetrahydrofolate dehydrogenase/ 5,10-methylenyltetrahydrofolate cyclohydrolase/ 10formyltetrahydrofolate synthetase (MTHFD1) is responsible for the conversion of 5,10-methylene THF (generated from THF by SHMT) to
the corresponding 10-formyl, 5,10-methenyl and 5,10-methylene derivatives. A common mutation at position 1958 within the MTHFD1
gene results in a transition of guanine to adenine (G>A) that may result in a reduction in folate metabolism. Our approach here involves
general support of the Methyl Cycle and the inclusion of methyl-folate and folinic acid in to your program. The Health Diagnostics and
Research Institute (www.hdri-usa.com - $350) can give us levels of SAMe, SAH, and folic acid derivatives (which will help us understand
the affects of your SHMT, MTHFD, MTHFR, and DHFR alleles).

Gene by Gene Approach MAO A +/+


MAO breaks down serotonin and to a lesser extent dopamine and norepinephrine. This disorder is associated with an increased tendency to
mood swings and panic disorders, related to fluctuations in serotonin levels. Serotonin formation may pick up as BH4 levels are restored
with other maneuvers to address methyl cycle abnormalities. Tryptophan in food is converted into serotonin and tyrosine in food in to
dopamine. As you are +/+ for COMT and have a high urine dopamine, you do not need to emphasize with tyrosine or tryptophan rich foods
in your diet (and our initial goal is to lower sulfate, so our key dietary recommendation is to avoid animal protein). Progesterone may
stimulate MAO A activity.

Gene by Gene Approach Methyl Thieves and SAMe Stealers


A key goal of Methyl Cycle physiology (and a focus in our work with you) is to ensure sufficient, replenishable, and physiologic (not
excessive) supplies of:
A. SAMe, along with and an appropriate SAMe to SAH ratio (it is the ratio, not just the SAMe level, that drives forward useful methylation
reactions).
B. BH4 (needed to generate neurotransmitters and nitric oxide), and
C. Key antioxidant and detoxification molecules (glutathione, taurine, sulfate, and cysteine).
You are generating (or taking) methyl folate and methyl B12, not for the sake of generating high levels of these Methyl Cycle intermediates
(yes, intermediates, not finished products), but rather to help ensure that the Methyl Cycle work products (SAMe, BH4, glutathione, cysteine,
and taurine) are in adequate supply.
While our focus has been on improving SAMe supply, we should also consider means to reduce SAMe expenditure (Mother Nature balances
supply and demand the government should pay heed)! Stated otherwise, if nutritional supplementation decreases demand for SAMe, more
will be available to meet critical demands (e.g. DNA methylation to silence inflammatory and proto-oncogenes).
So how are we spending SAMe? What phenomena lead to SAMe wasting or diversion? How do we ameliorate these pathophysiologies to
restore SAMe and appropriate SAMe:SAH balance?
In considering SAMe expenditure, remember that each time we spend a SAMe (S-Adenosylmethionine) to carry out a specific methylation
reaction, we create a SAH
(S-Adenosylhomocysteine), which in turn inhibits methylation. A declining SAMe:SAH inhibits methylation reactions; it does us no good
to increase SAMe if at the same time we buildup SAH.
Fortunately, SAH is rapidly converted to Homocysteine and Adenosine. Adenosine is efficiently removed, but if the Methyl Cycle is
sluggish, due either to SNIPS, toxins, or nutritional deficiency, Homocysteine will build up. Homocysteine will then be back converted to
SAH, the SAMe:SAH ratio falls, and useful methylation grinds to a halt. Homocysteine itself is not the problem; it is the buildup of SAH,
compromising methylation potential, which leads to disease states such as atherosclerosis, cancer, and mood disorders.
So what processes steal SAMe? In considering this issue, we need to be aware that CBS (which irreversible drains Homocysteine down
the trans-sulfuration pathway and away from SAMe reformation) is up regulated (enzymatic activity increases) by oxidative stress and
inflammation.
A. Oxidative stress: When the generation of free radicals (superoxide, hydroxyl, and hydrogen peroxide) outpaces our ability to neutralize
them with endogenous (e.g. superoxide dismutase) or exogenous (supplemental antioxidants), we suffers from a buildup of free radicals. To
address this immediate threat to health, Homocysteine metabolism down the CBS pathway (irrespective of SNIP status) will increase.
Homocysteine (and with it the potential to create new SAMe) will be irreversibly diverted away from remethylation (via MTR and BHMT
back into methionine for conversion to SAMe) and towards the production of glutathione, taurine, and cysteine.
This all makes sense. Oxidative stress damages our physiology and kills cells. When faced with oxidative death, it makes sense to divert
Methyl Cycle resources towards antioxidant generation. After oxidative stress has been neutralized, CBS flow will decrease, Homocysteine

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will start flowing back towards SAMe, and useful methylation reactions will resume. Our problem is that most ill Americans suffer from
unremitting oxidative stress (we can measure your individual level of oxidative stress with the NutrEval study). Homocysteine will thus be
shunted down the CBS pathway, such that useful methylation of DNA, estrogen molecules, and catecholamines will be compromised. If you
cannot methylate catecholamines, then oxidative stress will develop within your blood vessels. If you cannot methylate your DNA, than you
cannot silence inflammatory genes. You thus make more inflammatory molecules, more free radicals build up, more Homocysteine is
diverted away from SAMe regeneration, and you are now chronically ill.
The solution is to undergo an assessment of oxidative stress, and then takes steps to resolve any challenges present. This will involve
removing from your body phenomena that generate free radicals (e.g. smoking, toxic metals, organic pollutants) while concomitantly shoring
up your antioxidant defenses with nutrients that we find to be in short supply (selenium, Vitamin E, Vitamin C, etc.). We can thus use
nutritional medicine to help you generate SAME and to prevent oxidative stress from stealing Homocysteine away from SAMe
regeneration. As a side note, toxic metals not only steal SAMe, they also compromise its formation (e.g. Mercury compromises MTR, in
this fashion blocking useful remethylation of Homocysteine back into methionine for conversion into SAMe). Other than a mild
depression in glutathione your oxidative stress/inflammatory markers were within the reference range. Your SOD2 +/+ status
compromises superoxide dismutase and thus your ability to degrade the free radical superoxide, which we can address with
GliSODin supplementation. Being +/- for GSTP1 and GPX1 you are having some trouble utilizing glutathione. As residual heavy
metals are removed, there will be less strain on your glutathione stores. Paraoxonase is involved in organic pollutant metabolism; it
also provides the antioxidant activity of HDL and is involved in the metabolism of homocysteine thiolactone. Pomegranate juice
intake makes sense to stimulate paraoxonase (you are +/- for a loss of function PON allele).

B. Inflammation: Inflammatory TH1/TH17 cytokines, such as TNF-alpha, Il-6, and Il-1E also increase flow down the CBS pathway,
draining Homocysteine away from useful remethylation back in to SAMe. Inflammation leads to oxidative stress and oxidative stress leads
to inflammation. Both are useful in fighting infection, but both processes are persistently elevated as our immune system misinterprets as
infection the chronic pseudoinfections of visceral obesity, leaky gut, and environmental toxicity. Thus by resolving inflammation (either
with anti-inflammatory nutrition interventions such as turmeric or berberine) or by removing the cause of chronic inflammation (weight loss
or resolving leaky gut) we can resolve the inflammatory drain on SAMe supply and demand.

What processes deplete our SAMe stores? Are some less critical than others? Can we decrease SAMe demand with nutritional
supplementation?

A. DNA methylation: This is sacrosanct. Only SAMe can methylate DNA. Only SAMe can shut down the transcription (reading into
protein formation) of viral, inflammatory, and proto-oncogenes (promote cancerous transformation) while maintaining the transcription of
tumor suppressing and anti-inflammatory genes. We cant scrimp on DNA methylation, but by resolving oxidative/inflammatory stress, and
supplementing with SAMe sparers as described below, we can maintain adequate SAMe (with a high SAMe:SAH ratio) to ensure optimal
DNA methylation.
B. Creatine formation: Around 50% of our SAMe is spent in the generation of creatine, a molecule critical to energy maintenance. We do
work by splitting a high energy bond within ATP (Adenosine Triphosphate) to produce ADP and phosphate. We burn carbon and use this
energy to rephosphorylate ATP. When energy is plentiful, ATP will transfer a phosphorus group to creatine, forming Phosphocreatine.
Should we suddenly run out of ATP energy (sprinting, weight lifting, or if oxygen supply:demand is compromised by a blocked artery or
failing heart), Phosphocreatine can download a high energy phosphate bond back to ADP, regenerating ATP such that cellular work can
continue. We actually store 10 heart beats of energy as Phosphocreatine. As you would expect, creatine supplementation has been shown to
be helpful in anaerobic athletic performance as well as in heart failure. Of interest, creatine has been shown to lower cholesterol, and while
the literature is not 100% consistent, creatine supplementation will decrease expenditure of SAMe and increase the SAMe:SAH ratio.
Creatine lowers homocysteine in individuals with MTHFR abnormalities. Athletes take 5 grams of creatine, four times a day (saturation
dose) for one week, followed by 5 grams/day (maintenance dose). However, unless you have an athletic competition coming up, you can
simply add 5 grams of creatine/day to your program. Creatine is not unsafe, but there have been instances where competitive body builders
dosed up on creatine while decreasing fluid intake (so their muscles will bulge out more) leading to dehydration and kidney compromise.
Creatine is converted in to Creatinine, which is filtered out by the kidneys. We use serum creatinine to gauge kidney function. A trivial rise
in serum creatine may occur when you supplement with creatine. This does not mean that kidney function is decreasing; rather this is an
artifact due to creatine supplementation. Creatine supplementation at 5 grams/day makes sense for individuals with Methyl Cycle SNIPS that
might compromise SAMe generation or maintenance (MTHFR, MTR, CBS, and BHMT), or when we feel that chronic
oxidative/inflammatory stress is depleting SAMe regeneration.
C. Phosphatidylcholine: Three SAMe molecules, around 30% of our total supply, are used to methylate phosphoethanolamine into
phosphatidylcholine. Phosphatidylcholine (PC) is involved in lipoprotein formation and reverse cholesterol transport; PC is also a critical
component of the cell membrane. The common name for PC is lecithin. PC/lecithin is essentially a triglyceride like molecule with two fatty
acids and one phosphocholine group attached to a three carbon glycerol backbone. The biochemical utility of PC relates to the composition
of its two fatty acids. PC containing two unsaturated linoleic acid molecules (polyenylphosphatidylcholine) is used IV and orally to treat
cardiovascular, liver, and neurological disease (see our DVD presentation). If we supplement you with PC, less SAMe will be spent
generating PC, and more will be available for useful methylation reactions. In addition, the less SAMe spent, the less SAH and
Homocysteine will be formed. Furthermore, PC can be converted into choline, which can be converted into Betaine (TMG or
trimethylglycine) which is used by BHMT to directly remethylated homocysteine back in to methionine (which is then converted in to
SAMe). Thus PC supplementation will lower an elevated Homocysteine and increase SAMe supply along with the SAMe:SAH ratio. We

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use PhosChol (unsaturated phosphatidylcholine rich in linoleic acid) 900 to 2700 mg/day in the treatment of cardiovascular and liver disease.
Our dose in Methyl Cycle patients will relate to your SNIP status and baseline Homocysteine level.
Being +/+ for PEMT, you are having trouble generating phosphatidylcholine. PEMT is stimulated by estradiol and this may explain
why homocysteine levels rise when ovarian hormone levels decline. Phosphatidylcholine supplementation will bypass your PEMT
status and spare SAMe, a double win for you.
D. COMT utilization. COMT (Catechol-O-Methyl transferase) metabolizes estrogen molecules, catecholamines (dopamine and
norepinephrine), drugs (e.g. L-Dopa used in the treatment of Parkinsons disease) and bioflavonoids (particularly Quercetin) by transferring a
methyl group from SAMe to an oxygen molecule on the compound being methylated. Each time this occurs, SAH is generated, the
SAMe:SAH ratio falls, and COMT and all other methyl-transferase enzymes are inhibited. If we are interested in sparing SAMe and
maintaining a high SAMe;SAH ratio, it would be prudent to reduce the need for COMT-driven methylation. Lowering stress will lower
norepinephrine, and thus decrease SAMe utilization by COMT. While bioflavonoids such as Quercetin have many beneficial properties, if
SAMe preservation is critical (high Homocysteine in the presence of MTHFR, MTR, MTRR, and BHMT SNIPs or if our ability to methylate
estrogen molecules is impaired) then decreasing intake of Quercetin and related bioflavonoids would be prudent. Conversely, when
insufficient dopamine is the problem, we might use Quercetin to blunt dopamine degradation by clogging up COMT. Caffeine increases
catecholamine production. Caffeine intolerant individuals are typically COMT +. When caffeine intolerance develops anew, we look for
new problems that might be compromising SAMe supply or COMT functionality.

Plan of action for Methyl Thieves and SAMe Stealers )


1. Creatine 5 gm/day makes sense.
2. PhosChol at 900 mg/day, advancing to 900 mg twice a day if the initial dose of 900 mg daily agrees with you.
3. Pomegranate juice 1 oz/day (Pom Wonderful was used in the cardiovascular research, with positive effects).
4. GliSODin 250 mg/day would be ideal.
Gene by Gene Approach and Plan of Action AHCY +/SAMe is converted in to S-adenosylhomocysteine, which is converted in to homocysteine by AHCY. Being +/- for AHCY, you may be
having trouble with SAH degradation. We address this alleles with general support of the Methyl Cycle and measures to ensure that
Homocysteine levels are not elevated

Additional Thoughts
1. My hypothesis is that your Methyl Cycle abnormalities have rendered you more susceptible to metal toxicity, while at the same time
sensitive to side-effects with the use of our SH based mercury detox agents (why you felt poorly with IV DMPS). When you and Dr. Smith
feel you are ready, then further metal detoxification makes sense. Matching detox therapies to the individual patient is sort of an art of
medicine concept. The Hunt aura patch approach is typically well tolerated and a good place to start. A negative field only sleep pad is of
value to all but quite expensive. Grounding is inexpensive and reasonable. Foot bath/sauna therapy is also typically well tolerated. Our
standard mercury chelators (DMSA and DMPS) are sulfite-rich and would likely not be tolerated, while EDTA based preparations (good for
lead, cadmium, and aluminum) would likely be reasonably well tolerated (and later we could return for mercury using a non-sulfhydryl based
therapy). Please look through our Detoxification Options brochure. I just came across Dr. Chis approach to metal overload and his brochure
is enclosed
2. Regarding the recurrent viral outbreaks the Aura OLE patch might work. The digital picture analysis will tell us if the corresponding
frequency is present.
3. Please forward to me a current treatment list, with doses in mg or mcg units.
4. Please run all of this by Dr. Smith (who will receive a copy of this report, and you have given me permission to consult with her regarding
your care), and we can certainly discuss all of the above during a phone conference.).
James C. Roberts MD FACC FAARFM 1/18/15

Sample Report Two


Methyl Cycle Nutrigenomic Report
Methylation Panel Abnormalities for Genes with Characterized SNPs
Gene Name
Variation
Finding
COMT
V158M
OK

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COMT
COMT
VDR
VDR
MAO A
ACAT
MTHFR
MTHFR
MTHFR
MTR
MTRR
MTRR
MTRR
MTRR
MTRR
BHMT
BHMT
BHMT
AHCY
AHCY
AHCY
CBS
CBS
CBS
SHMT

H62H
61
Bsm
Taq
R297R
102
C677T
3
A1298C
A2756G
A66G
H595Y
K350A
R415T
A664A
2
4
8
1
2
19
C699T
A360A
N212N
C1420T

OK
OK
OK
Homozygous (+/+)
Homozygous (+/+)
OK
Heterozygous (+/-)
OK
OK
OK
Heterozygous (+/-)
OK
OK
OK
OK
OK
OK
OK
OK
OK
OK
Heterozygous (+/-)
Heterozygous (+/-)
OK
Heterozygous (+/-)

Overview
You are +/- for both of the CBS up regulations. Homocysteine (and its Methyl Cycle precursors) is thus being drawn down the transsulfuration pathway, in this process generating excessive sulfur breakdown products (sulfite and sulfate and your urine sulfate is 1600 which stimulate the stress/cortisol fight or flight response), too much alpha-ketoglutarate (which may lead to glutaminergic excitotoxin
activation), and too much ammonia, which depletes BH4, leading to insufficient dopamine and serotonin production. This deficiency in BH4
predisposes NOS (nitric oxide synthase) to convert Arginine in to free radicals as opposed to nitric oxide, predisposing you to hypertension
and cardiovascular disease. You are already on BH4 and methyl-folate, and after the up regulated trans-sulfuration pathway (CBS) has come
under control, the BH4 and methyl-folate doses could be increased.
CBS actually generates sulfite, which must be processed to sulfate, by SUOX (sulfite oxidase). Even thought your urine sulfite level is
normal, support for this enzyme with hydroxy-B12, molybdenum, boron, and Vitamin E succinate can be considered.
MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine, which is then converted in to SAMe, the universal
methyl donor. You are +/- for MTHFR C677T, meaning that you have some difficulty converting folic acid in to 5-methyl folate, a block
that is (biochemically) easy to overcome with 5-methyl folate supplementation (already in place).
You are also +/- for one of the MTRR alleles, meaning that you are having some trouble converting B12 in to methyl-B12, a problem that
you have already addressed with methyl-B12 supplementation. You are +/+ for VDR Taq, such that Vitamin D will be less efficient in
generating dopamine, and -/- for COMT, meaning that you can breakdown dopamine rapidly, using up methyl groups in doing so, and thus
you will have an increased susceptibility to toxic metals and viral infection. Conversely, your need and tolerance for methyl groups and
methyl donors will be relatively increased (your problem is not sensitivity to methyl donors but rather sensitivity to
sulfites/ammonia/glutamate that are generated when these agents spin forward the Methyl Cycle and homocysteine is drawn down the up
regulated CBS drain).
SHMT combines the amino acid serine with folic acid to form 5,10-methylene THF, which is used to generate the building blocks for DNA
and RNA generation. We can bypass this block with 5,10-methylene THF, also known as Folinic acid.
Being +/+ for MAO A, you are having trouble breaking down serotonin, an issue that we can address by favoring foods rich in tyrosine, the
precursor to dopamine, which you need, over foods rich in tryptophan, the precursor for serotonin. Early on, however, an overall restriction
of dietary animal protein will be suggested, to decrease the ammonia burden imposed on you by your CBS up regulation status.
My knowledge of Detoxification Genomics is far less extensive than that of the Methyl Cycle, but my understanding is that the CYP1B1
alleles present are an up regulation, favoring 4-hydroxyglation of estradiol/estrone, thus increasing ones risk of breast/prostate malignancy.
Hydrocarbon pollutants are activated by 1B1, and if they cannot be neutralized by phase II enzyme systems, oxidative tissue damage may
follow. CYP2C19 metabolizes a number of commonly utilized pharmaceuticals, and is also responsible for activating Plavix. Thus you may
not be experiencing the same anti-platelet effect vs. an individual with intact 2C19 status (likely not an issue now, one year out from stent
placement, but if another stent is required one of the newer agents that does not require 2C19 activation would be preferred). Methylation

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based (COMT) phase II detoxification is intact, but you harbor alleles compromising acetylation and SOD (superoxide dismutase) generation
(thus neutralization of superoxide will be compromised, but on board you have SOD up regulators in the form of Losartan, Crestor, and
Berberine).
The Gene by Gene Approach sections provide general information about the alleles you possess, while the Plan of Action sections contain
specific recommendations. Approaches that make the most sense to me receive a (). Those that are less critical (or more costly) are
designated (+/-). Based upon review of your medical history, I have a number of additional diagnostic and therapeutic ideas (please see
below).
Gene by Gene Approach CBS +/-

CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. Yaskos book, Genetic Bypass. Additional information is available
on our heartfixer.com website. You are +/- (half of your CBS enzymes abnormal) for both of the two CBS up regulations. Fortunately you
are -/- (normal function or wild type) for the BHMT down regulations (which act like CBS up regulations). Given your CBS up
regulations, Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration pathway, in this process generating
excessive sulfur break down products (sulfite and sulfate, which stimulate the stress/cortisol fight or flight response), too much alphaketoglutarate (which leads to glutaminergic excitotoxicity), hydrogen sulfide (to produce brain fog), and too much ammonia (which depletes
BH4, leading to insufficient dopamine and serotonin production). This deficiency in BH4 allows NOS (nitric oxide synthase) to convert
arginine in to free radicals (superoxide and peroxynitrite) as opposed to nitric oxide, predisposing you to hypertension, cardiovascular and
inflammatory disease states.

During normal physiology, metabolic flow down the CBS pathway is designed to generate
the important anti-oxidant and detoxifying molecules glutathione, taurine and cysteine (all
involved in detoxification and endothelial health), and alpha-ketoglutarate (which can be
converted into GABA, a calming neurotransmitter). The CBS C677T and A360A genes
code for enzyme function that is pathologically up regulated. Of the two, the C677T allele is
the most important, producing enzyme activity that is 10 fold greater than normal. You thus
suffer from too much of a good thing and way too much of several bad things.
While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification,
sulfate/sulfite/-SH excess blocks cellular up take of the key detoxifiers glutathione and
cysteine. Endogenous detoxification is thus blunted (nearly all kids with Autism Spectrum
Disorders bear CBS up regulations why they are compromised by environmental toxins
and the kid next door is just fine). Conversely, after we decrease your sulfate/sulfite pool,
your detox pathways open up (and why, if we move too fast, you will experience detox
phenomena).
The excess ammonia generated must be detoxified, and to do so BH4 (tetrahydrobiopterin)
must be spent. This is a problem in that we need BH4 to generate neurotransmitters
(serotonin to maintain calm/prevent depression and dopamine to maintain motivation and drive). Without BH4, we cannot convert arginine
in to nitric oxide; instead vascular wall toxic free radicals such as superoxide and peroxynitrite are created, leading to hypertension and
cardiovascular disease.

Alpha-ketoglutarate, in moderation, is not a problem. We should be able to


interconvert alpha-ketoglutarate into glutamate, glutamine, and GABA. However,
when alpha-ketoglutarate is in excess, or if toxic metals compromise the
interconversion enzymes, then we suffer a buildup of the excitatory
neurotransmitter glutamate. Glutamate is involved in alertness and learning, but
excess glutamate leads to irritability and over-excitement; toxic levels may play a
role in seizure activity and cardiac arrhythmia (could this be why we are seeing so
much atrial fibrillation)?
CBS up regulations lead to an initial buildup of potentially neurotoxic sulfite,
which is then metabolized by SUOX (Sulfite Oxidase) to the less neurotoxic (but still problematic at high levels) sulfate. SUOX activity
requires molybdenum, which is thus depleted in CBS + individuals. Homogenized dairy products contain xanthine oxidase, which uses up
molybdenum, and are best avoided or minimized. Vitamin E succinate, boron, and B12 are felt to stimulate SUOX activity.

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As methyl cycle function is needed in the biosynthesis of Co-Enzyme Q10 and Carnitine, individuals + for CBS will likely be energy
depleted, and here supplementation (in relation to your COMT/VDR status) with Co-Enzyme Q10, Carnitine, and NADH may be helpful.
Statin therapy predictably depletes Co-Enzyme Q; adding 100-200 mg/day of Co-Enzyme Q makes sense or we could measure your Co-Q
level with a Genova Labs NutrEval study.
BHMT (Betaine Homocysteine Methyl Transferase) directly methylates homocysteine back in to methionine, serving as a back door
pathway to pull homocysteine away from the CBS sulfate drain. Thus if you bear CBS or BHMT abnormalities, it makes sense to
support BHMT function. DMG (dimethylglycine) and TMG (trimethylglycine) stimulate BHMT, and can be utilized if you are not overly
sensitive to methyl group supplementation (based upon you COMT/VDR status). Phosphatidylserine stimulates BHMT (and we also use it
to moderate elevated cortisol levels), as does phosphatidylcholine (which we use to treat atherosclerosis). Phosphatidylcholine can be
admixed with EDTA (detoxifies metals), creating a quite useful supplement.
Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR
(compromising methyl-B12) abnormalities, and thus you will need and benefit from corresponding supplementation (with these molecules
that they are having trouble making). However, if we treat you with methyl-folate, methy-B12, or BH4, before we have the CBS problem
under control (sulfite/sulfate levels decreased enough to allow for appropriate glutathione and cysteine assimilation) then we will be
subjecting you to incomplete detoxification. You will feel great for 1-2 days, as beneficial neurotransmitters are generated. Methyl-folate
and methyl-B12 detox pathways will then open up, creating toxic intermediates that cannot be metabolized further due to the block in
glutathione utilization and you will feel horrible. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until
CBS/BHMT are under control.
However, you are already on methyl-folate, methyl-B12, and BH4 and I do not think that you need to stop them simply on the basis of this
new Methyl Cycle patient principle.

Plan of action for CBS +/To address this constellation of alleles I will recommend:
1. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables, sulfur containing supplements, and sulfur
containing drugs (see attached sulfur avoidance instruction sheets and read Sulfites and Chronic Disease by Rick Williams, available at the
office or at www.readingtarget.com/nosulfites/.
2. Check the sulfate/sulfite content of your supplements and prescription agents (many listed in the Williams book) and whenever possible
switch to agents with lower sulfate/sulfite content.
3. Monitor urine sulfate levels every 3-7 days (or when you feel particularly good or poorly, or after adding a new treatment or changing your
diet). Please chart the levels this will be our primary measuring stick our goal is a urine sulfate of 400 (one yellow and three pink) to
800 (two yellow and two pink). Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a
liberalization of your diet. Conversely, persistent high sulfate spills indicates that your diet/treatment program needs further modification.
3. To neutralize ammonia (generated from animal protein), you can use Ammonia Support RNA dropper with meals and with methyl cycle
supplements (relatively expensive), along with a charcoal supplement at bedtime every other evening, away from other supplements
(magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). Yucca, beginning at capsule,
twice a day, (or sprinkled on food containing protein), may help with ammonia detoxification. These supplements can be tapered down as
ammonia levels fall.
4. Sparga Detox, 10 drops in water (wait at least one minute before consuming), twice a day makes sense. Sparga was developed by fellow
Cardiologist Dr. Lee Cowden, specifically to address the CBS abnormality (see www.nutramedix.ec).
5. For nutritional support, a low-sulfate multi such as Dr. Yaskos Neurological Health Formula, 3-6/day, makes sense (or we may have you
on another preparation in relation to your other health concerns). To stimulate SUOX activity, please use sublingual hydroxy-B12 2000
mcg/day, along with Molybdenum and Boron. They may be taken individually as Molybdenum 3 drops in water twice a day and Boron 3 mg
once a day, while our Complete Mineral Complex, 3 daily will cover the mineral base. Avoid B6 (unless you need it for other functions),
which stimulates CBS. The active form of B6, P-5-P, is less of a problem here and serves as a B6 substitute.
6. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. Right now this good thing could actually set you
back. However, if we could convince your biochemistry to up regulate biosynthesis of glutathione, then your anti-oxidant and detox capacity
will increase, with concomitant utilization of free sulfate/sulfhydryl groups a double win for you. This can be achieved with the use of the
Life Wave (needleless acupuncture) Glutathione patch. The Life Wave people have demonstrated an increase in Glutathione levels in
relation to patch use (please see separate information sheet on Life Wave patch use).
7. If you feel anxious or wired up (glutamate overload), take GABA 500 mg or Zen (GABA 550 mg with Theanine 200 mg, a methyl
donor) twice a day. Individuals who need methyl groups (normal COMT and/or abnormal VDR Taq alleles your situation) will do better
with Zen, while individuals who are methyl group sensitive (COMT+) will likely do better with GABA. If they are helpful you can double
the dose. GABA/Zen do not work rapidly, but if you take these supplements twice a day you will build up a GABA reserve to balance the
glutamate overload you may be experiencing due to your CBS up regulation. Magnesium supplementation may help with GABA physiology
and often helps with sleep.
8. If energy is low, or if deficiencies are identified on your NutrEval study, we can supplement you with Co-Enzyme Q and Carnitine.
NADH does not provide methyl groups and should be well tolerate by all.
9. What is your homocysteine level? A low level suggests that your CBS up regulation is of great functional significance, with a

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homocysteine drain overcoming the MTHFR and MTRR abnormalities (which otherwise would be associated with an elevated
homocysteine level). If not previously measured we should check it now. Further nutritional testing can be carried out in 8-12 weeks. This
could involve separate 24 hour urine studies for nutritional minerals and for ammonia/amino acids, or we could use the Genova Labs
NutrEval. We need to make sure your mineral/nutritional stores are replete, and we are looking for low levels of ammonia, taurine,
glutamate, and cysteine, to demonstrate that flow down the CBS pathway has been decreased to a physiologic level.
10. After sulfate levels have fallen (to a level that you and I feel is optimal for you, based upon your clinical and genomic status), we could
advance supplementation with methyl-folate, methyl-B12, and BH4 (nutritional testing will help with decision making here).
11. A key goal of Methyl Cycle analysis is to improve your ability to detoxify, and thus toxicity testing** (which you have already
undergone) and treatment make sense. I cant back this up with a clinical study, but the use of Aura Organ Detox patches for two months
may help you. This approach does not remove toxins but is felt to homeopathically neutralize them). Later, after your sulfate levels have
fallen, we can take further aim at the toxins themselves. Dr. Hunts CD is available for your review and you can go to
www.auraexplorationpatches.com for additional information. This approach has been helpful when I have been stumped despite a full
allopathic laboratory work up, and I am now liberal with its use.
12. Sauna therapy increases BH4 production and promotes detoxification, and could be utilized (low exposure at first, watching for detox
reactions). Footbath therapy is another means of removing toxins without adding foreign molecules to your body.
11. Be self-observant and keep records. Which foods, supplements, or other maneuvers increase or decrease your sulfate spill? Which make
you feel better or worse? Always keep in mind that detoxification is not a fun experience. You may need to accept some transient fatigue,
malaise, and achiness to allow toxic molecules to be cleared. Conversely, if detox symptoms are debilitating or compromise your ability to
work or care for your family, then we need to back off on your treatments. Balance needs to be achieved. Rectifying your genomic
predispositions and detoxifying your system is not a sprint it is a marathon. And, as your genes are not going to change, and as the
environment is not going to become less toxic, you will need to be mindful of these principles for the rest of your (long and healthy) life.
* How tightly should you restrict dietary protein? The degree of protein restriction best suited for you will be in relation to your personal
health characteristics and your clinical and biochemical (urine sulfate and ammonia levels) response to treatment. We need to keep in mind
that Methyl Cycle Genomics is not the sole determinant of your health. A low protein diet can become a high carbohydrate, weight gaining
diet in an overweight individual with type two diabetes. Individuals with chronic, unexplained illness or significant toxicity would do well to
follow the nothing with eyes diet until urine sulfate and ammonia levels have fallen; later on we will liberalize your diet, while keeping an
eye on these biochemical markers. This dietary maneuver isnt fun but may also turn ones your health around. Individuals in whom the
CBS up regulation is less important (A360A as opposed to C677T, lower urine sulfate and ammonia levels, and better overall health), could
simply cut back on animal protein. In addition, the greater representation of ammonia reducing (Yucca, Charcoal, Sparga, Ammonia Support
RNA) treatments in your program, the more protein you will be able to take in without compromising your biochemistry. This is all about
balancing diet against treatment response.
** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Toxicity testing (discussed in more detail
in other presentations and on heartfixer.com) thus makes sense. You have already undergone toxicity testing (and I would like to review with
you the results). Testing options for new patients include:
A. The NutrEval provides us some information regarding organic pollutants and gives us red cell (reflecting what your physiology has been
exposed to over the preceding three months) toxic metals ($170 with commercial insurance; fully covered under non-HMO Medicare).
B. The US BioTek study gives us information on seven major organic pollutants ($126); this is less extensive than the Metametrix study that
you have already carried out and will not add any new information.
C. A formal provocative challenge ($250) gives us our best assessment of tissue metal burden.
D. The Hunt Digital picture approach ($350) assesses for toxicity (and other health challenges) by analyzing the frequencies emitted by your
body (and tells us which Digital Homeopathic Patches would be most appropriate). I cant prove this approach with an allopathic lab test but
it has been quite helpful in solving complex medical problems in my personal patients. Dr. Hunts CD is available for your review and you
can go to www.auraexplorationpatches.com for additional information.

OUR MOST IMPORTANT INITIAL GOAL WILL BE TO


REDUCE YOUR SULFATE STORES

Gene by Gene Approach COMT -/- with VDR Taq +/+ and MTRR +/- or +/+
This constellation of alleles is discussed on pages 112-115 of Dr. Yaskos book, Genetic Bypass. Additional information is available on our
heartfixer.com website. VDR Taq influences dopamine production. Being +/+ for VDR Taq means that dopamine production is
compromised. Being COMT -/- means that you are breaking down dopamine rapidly and in doing so using up available methyl groups,
compromising your ability to deal with toxins and microbes (thus you are more likely than COMT +/- or COMT +/+ individuals to bear a
metal burden). You need and should tolerate dopamine precursors and methyl donors.
MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine. Being MTRR +/- or +/+, you are having trouble
converting B12 into methyl-B12, a problem that is biochemically easy to overcome with methyl-B12 supplementation.
As you are COMT -/- and VDR +/+ you should tolerate methyl group supplementation reasonable well, so begin supplementation with
methyl-B12 (already on board) with a plan to increase the dose to 5 mg per day after urine sulfate levels have fallen. Why wait for sulfate to
fall? Methyl-B12 supplementation, by moving the cycle of homocysteine metabolism forward, could lead to increased ammonia and

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sulfite/sulfate generation, so normally we do not push with methyl-B12 until urine sulfate levels have decreased. If you possessed normal
CBS alleles, then sulfate generation is not an issue, but you harbor a genomic challenged in this pathway and thus we need to move slowly
with respect to methyl-B12 (and methyl-folate) supplementation.
As you are COMT -/- and VDR +/+, you are making less dopamine in response to
Vitamin D and you are breaking dopamine down rapidly. Thus you need and should tolerate methyl donors such as Methyl-B12, TMG,
melatonin, curcumin, SAMe, or MSM (hold off on MSM if urine sulfate levels are high). You might benefit from quercetin and macuna
puriens, both of which support dopamine production, or Procite-D, which does the same
By stimulating BHMT, we can bypass any block that MTRR places on homocysteine detoxification, and this maneuver will also draw
methyl cycle intermediates away from sulfate/sulfite production. Pedi-Activ contains phosphatidyl serine, which stimulates BHMT, and
DMAE, a methyl donor, and its use makes sense. Lipophos Forte provides phosphatidyl choline which stimulates BHMT. Lipophos EDTA
provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes, whether
they are genetically normal or abnormal, including GAD, which converts glutamate in to GABA) and cadmium (which contributes to
hypertension and cancer risk).
If you are troubled by agitation or anxiety (perhaps on the basis of excessive glutamate production due to a CBS up regulation), we can
address this with GABA or Zen (GABA + Theanine). As you are COMT -/- and VDR Taq +/+, you should tolerate and benefit from the
methyl groups provided by theanine. However, if agitation occurs, suggesting methyl group excess, we can utilize GABA, which does not
contain methyl groups (both GABA and theanine stimulate the GABA receptor, and thus provide a Valium like effect without concern for
drowsiness or dependency). Neither GABA or Zen work quickly (we have other supplements for as needed use) and are best taken twice a
day as a nutritional approach to combat the biochemical consequences of stress (emotional or glutamate-induced stress). Other approaches to
dealing with an imbalance between glutamate and GABA include avoiding glutamate rich food products (see website) and supplementation
with grape seed extract 100 mg/day and/or (if a CBS up regulation is not present) taurine 500 -1000 mg/day. Lipophos EDTA provides
phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes, whether they are
genetically normal or abnormal, including GAD, which converts glutamate in to GABA). EDTA efficiently removes lead and cadmium, and
has activity against aluminum, nickel, and arsenic. EDTA is not an efficient mercury chelator. EDTA is typically well tolerated in
individuals with a CBS up regulation.
Plan of action for COMT -/- with VDR Taq +/+, and MTRR +/-

1. Methyl-B12 is already present at 1,000 mcg daily; please advance to 5,000 mcg daily after urine sulfate levels have fallen to 800 (or if
subsequent testing indicates an increased need for B12 nutriture).
2. Quercetin + daily to provide methyl group, antioxidant, and dopamine support makes sense; ginkgo biloba, macuna puriens, and Procite-D
serve as alternative approaches to augment dopamine status.
3. Unless agitation (suggesting too many free methyl groups) occurs, you may supplement freely with methyl donors such as melatonin,
curcumin, TMG, or SAMe).
3. Lipophos Forte 900 mg (one teaspoon) daily mixed in juice or Phosphatidyl serine can be utilized to stimulate the BHMT pathway
(unsaturated phosphatidylcholine has anti-atherosclerotic activity and of the two is thus preferred). Alternatively, if metal detoxification is
appropriate, Lipophos EDTA - bottles twice a week can be matched with Lipophos Forte five days a week.
4. Zen (GABA and the methyl donor theanine) twice a day if anxiety or agitation is an issue for you.
5. Supplement to keep Vitamin D | 50.
6. At some point in the future, after urine sulfate levels have declined, try adding SAMe 200 mg/day to your program. While we would
prefer that you generate SAMe endogenously, exogenous SAMe will provide methylation support and with your COMT -/- and VDT+R Taq
+/+ status you should tolerate it well.

MTR (Methionine Synthase) transfers a methyl group from Methyl-folate to Homocysteine to form Methionine. MTRR (Methionine
Synthase Reductase) adds the Methyl group to otherwise inactive B-12. MTRR abnormalities compromise the generation of methyl-12.
Without methyl-B12, MTR cannot use methyl-folate to recycle homocysteine into methionine.

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VDR Taq +/+ or +/- (impaired) status compromises the production of dopamine. COMT -/- (normal function) allows rapid breakdown of the
dopamine you can generate. VDR Taq+/+ with COMT -/- individuals will experience low dopamine levels (with consequent increased
sensitivity to metal overload) and will benefit from dopamine precursor therapy and from methyl group donors.
COMT V158M (+/+)
COMT H62H (+/+)
COMT 61
(-/-)
COMT V158M (-/-)
COMT H62H (-/-)
COMT 61
(+/+)

Highest dopamine levels


Lowest need for and tolerance to methyl group donors
Greatest susceptibility to mood swings
Lowest dopamine levels
Greatest need for and tolerance to methyl group donors
Lower susceptibility to mood swings

Gene by Gene Approach MTHFR C677T +/Here the MTHFR enzyme present is having trouble converting folic acid into 5-methyl folate. Without 5-mehtyl folate MTR cannot detoxify
homocysteine in to methionine. 5-methyl folate has another role here - it can neutralize peroxynitrite. When NOS (nitric oxide synthase) is
not functioning normally (i.e. when BH4 is deficient), arginine is converted not into the vasoprotective molecule nitric oxide, but rather into
the damaging free radicals superoxide and peroxynitrite. Superoxide (neutralized by Vitamin C) can further degrade nitric oxide, while
peroxynitrite degrades BH4 (stimulating a vicious cycle). 5-methyl folate can neutralize peroxynitrite, thus sparing BH4, keeping it available
such that NOS can generate nitric oxide, the vasoprotective molecule that we need - thus the need to maintain healthy production/levels of 5methyl folate. We can easily bypass the MTHFR C677T block with 5-methyl folate supplementation. Sources of 5-methyl folate include
Folapro (800 mcg 5-methyl folate), Metanx (5-methyl folate 2.8 mg, P5P 25 mg, and methyl-B12 2 mg), and Cerafolin NAC (5-methyl folate
5.6 mg, NAC 500 mg, and methyl-B12 2 mg).
Plan of Action MTHFR C677T +/Please continue with methyl-folate at 1,000 mcg per day; after urine sulfate levels fall we will advance the dose (and possibly advance BH4).
Gene by Gene Approach SHMT +/SHMT combines the amino acid serine with folic acid to form 5,10-methylene THF, which is used to generate the building blocks for DNA
and RNA generation. We can bypass this block with 5,10-methylene THF, also known as Folinic acid.
Plan of Action SHMT +/Begin Folinic Acid 800 mcg/day; this should not produce any tolerance issues.
Gene by Gene Approach MAO A +/+
MAO breaks down serotonin and to a lesser extent dopamine and norepinephrine. This disorder is associated with an increased tendency to
mood swings and panic disorders, related to fluctuations in serotonin levels. Serotonin formation may pick up as BH4 levels are restored
with other maneuvers to address methyl cycle abnormalities. Tryptophan in food is converted into serotonin and tyrosine in food in to
dopamine. If one is abnormal for MAO and normal for COMT, then emphasizing foods higher in tyrosine (see Appendix I) than in
tryptophan makes sense (however, our initial goal is to lower sulfate, so the recommendation to avoid animal protein overrides the
recommendation to take in foods high in tyrosine).

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Additional Thoughts
1. You have likely undergone an extensive nutritional/risk factor/toxicity work up, but if you have not I have the following thoughts A. With respect to atherosclerosis, please check:
a. Lp(a), and if at all elevated begin Lp(a) neutralizing therapy with lysine, proline, and additional Vitamin C.
b. Free testosterone and estradiol, and if no prostate contraindications supplement to obtain high normal free testosterone and low normal
estradiol levels.
c. Fibrinogen if high you can use turmeric or nattokinase to lower the level and thus blood viscosity.
d. Ferritin (predominately under genomic control), and if elevated undergo periodic phlebotomy/give blood to the Red Cross, aiming for a
ferritin | 100.
e. EndoPAT endothelial function testing, and if subpar you could advance Arginine further (most clinical trials used 2-,4000 mg two to three
times a day) or add in Citrulline (likely boosts intracellular arginine).
B. With respect to atherosclerosis management, immune modulation could be added to your program (particular is CRP or other
inflammatory markers are elevated). Proven approaches include Pentoxifylline (please see DVD) and Colchicine (best article attached).
Testosterone works within this framework as well.
C. With respect to organic pollutant detoxification, the following detox modalities are available:
a. Far Infrared Sauna detox at home while watching the playoffs.
b. Footbath therapy the Ion Cleanse people demonstrated that organic materials are removed with their device. As the principle involved is
common to all of the devices available, most likely they all are effective. We have switched to the Platinum Footbath device which seems to
be more effective and user friendly. This approach can be used at home as well.
C. The best approach is supplementation with agents that up regulate phase I and to a greater extent phase II. All contain sulfhydryl donors
(sometimes a problem is CBS + individuals), but if tolerance is not an issue, an effective approach would be to carry out a 10 day organic
pollutant detox, three times a year, utilizing the Metagenics Clear Change program (other nutraceutical companies have similar programs),
with an agent such as Metagenics Metalloclear or Glutaclear (up regulate detox/antioxidant pathways incidentally Berberine also does this)
when not on the Clear Change program. You could repeat the Metametrix pollutant panel in the future; the Genova NutrEval gives similar
but less extensive information regarding organic pollutant burden (and if covered under Medicare).
D. Regarding metals, in TACT we demonstrated that old-fashioned, one size fits all EDTA chelation therapy improves outcome when added
to standard post-infarction management. Stated otherwise, metals seem to be playing an important role in the oxidative stress and immune
dysregulation that characterize atherosclerosis. In your case, IV EDTA is the most powerful approach to lead and cadmium removal, while
Lipophos EDTA will up regulate your BHMT pathway and unsaturated phosphatidylcholine (please see DVD) has an anti-atherosclerotic
effect. However, EDTA is a poor mercury chelator. Here we typically use oral DMSA or IV or topical DMPS, but both are sulfhydryl group
rich, and might not be well tolerated, given your CBS + status. This creates a treatment dilemma these agents you need are the ones you
tolerate the least. Here you could try DMSA, three times a day, three days in a row, once a month, beginning at 100 mg and working up to
500 mg, and you might tolerate it well. Static magnetic field therapy seems to synergize with biochemical chelation and is a thought (I have
been sleeping on a negative filed sleep pad over the past 10 years). In DMSA/DMPS intolerant individuals, another approach involves the
use of QuickSilver resin or Pectasol (modified citrus pectin please see econeugenics.com).
E. Regarding CYP1B1 and the risk of malignancy, Genova has a urine estrone/estradiol hydroxylation/methylation study. If 1B1 is
functionally significant, your ration of 4-OH to 2-OH will be high. This can be rectified with 1B1 down regulators and 1A1 (promotes 2hydroxylation) up regulators such as DIM or I3C (please see Estrogen Metabolism section on the website).
2. Attached are DVDs, information sheets, and papers pertaining to the topics discussed above.
3. We could carry out a phone consultation regarding the above if you wish, and/or carry out the diagnostic studies listed above. I am happy
to help in any capacity.
James C. Roberts
MD FACC FAARFM 1/4/14

Life Wave Patch Instructions


The Life Wave patches utilize a needless acupuncture concept to favorably influence physiology. The science and clinical studies underlying
this concept can be reviewed at lifewave.com/chc, which we encourage you to study. No physical molecules leave the patch (in contrast to a
Nitropatch or an Estrogen patch); they are technically described as non-transdermal. The Life Wave patches are not homeopathic (as are
the Aura patches that we also use). The Life Wave patches do not spontaneously emit energies; rather they absorb frequencies emanating
from your body and then selectively return some of them. When you place a patch on or near your body, frequencies leaving your body
cause the molecules within the patch to self-assemble in to a crystal structure. The crystal structure serves as an antenna, capturing
frequencies leaving your body (kind of like a FM receiver), and then, depending on the function of the patch, it selectively emanates
frequencies into the Meridian communication system, as a function of where on the system the patch is placed. Energy flow within the
Meridian system is increased, directing your body to carry out actions that it currently is not carrying out, or not carrying out efficiently. The

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Life Wave patch is like a program that we insert into your computer to make certain programs run more efficiently.
Each type of patch comes with step by step instructions. We can increase the cost-effectiveness of this system. The instructions tell you to
discard a patch after it has been removed; however, each patch appears to be able to work for 48 hours of contact time. The patch is activated
when it is placed on or near your body (so do not carry them around in your pocket). It inactivates when it is removed. So if a patch works
over 48 hours, you could wear it 48 hours straight, or you could wear it for 6 hours/day over 8 days (adhesive tape may be needed).
The most important patch is the Y-Age Glutathione patch. This patch directs your body to manufacture more glutathione, using raw
materials already present and your bodys own enzyme systems. Glutathione is the key antioxidant/detoxification molecule in your body.
Conversely, glutathione depletion occurs in response to chronic oxidative stress and toxicity (as in the average American). IV administration
of glutathione increases excretion of toxic substances. Oral glutathione is not absorbed; instead we give your its precursor substance NAcetyl Cysteine (used in Medicine to prevent kidney failure during angiographic procedures, tolerance to long-acting nitrates, or liver failure
in Tylenol overdose situations). Those of you with the Methyl Cycle Cystathionine Beta Synthase (CBS) up regulation will not tolerate NAcetyl Cysteine (due to its Sulfur content), but you should have no trouble with the patch. The patch does not provide you with Sulfurcontaining molecules; rather it directs you to assemble these molecules into glutathione, a molecule that you can put to good use and a
molecule that you likely need.
A note of caution - If you wear the patch glutathione production will increase, and if you are loaded with toxins then you will begin to
detoxify. Drink plenty of water to facilitate this process, and if you feel poorly simply remove the patch then put it back on the next day (it
should give your 48 hours of service). If you are vigorous and healthy, you will likely be able to wear the patch for 6-8 hours on your first
day, but if you are ill, you might want to try only 2-4 hours on your first day, and then gradually increase your patch on time on a day-byday basis. Another issue, Vitamin C and N-Acetyl Cysteine both resolve Nitrate tolerance (loss of clinical effect due to Nitrate-induced
glutathione depletion), and when we use these agents we sometimes have to back off on your Nitrate dose. The same may occur with the
patch - a good problem.
The pain patch system is a little different. Place the tan patch over the point of greatest pain, and then the white patch 4-6 inches away. A
reduction of pain is typically noted within 10 seconds. Positioning of the white patch can be altered to obtain the best result. In my mind I
think of the white patch as draining pain away from the tan patch (this isnt actually what is happening, but the concept helps when
considering patch placement). There are also patch placement positions to deal with total body pain. You can wear two sets, one for total
body pain and another to address a focal source of pain. You can then place a glutathione patch in the palm of your right hand. If this
maneuver lowers pain even more, than it makes sense to wear the glutathione patch, over one of the specific glutathione control points, to
augment pain relief. Feel free to experiment with patch positioning. Remember, you do not have to remove the backing of a patch to
activate it. It is energy (frequencies) emanating from your body that activate the patch. Wear the pain patches for 48 hours or as you see fit
(if the effect attenuates at 24-36 hours, then replace the patches on this schedule). If they fall off, then tape them back on. If an injury is
minor, then the patches might actually speed up healing (by drawing energy into the region of pain, just as standard needle Acupuncture
does). A deep injury is obviously not going to heal with energy flow alone, but if the patch system allows you to use less pain medication,
and/or less anti-inflammatory drug therapy, then a goal has been achieved.
The Carnosine patch directs your body to produce carnosine, a powerful antioxidant. I alternate between the two, glutathione one day and
carnosine the next. We do not yet have any experience with the weight loss or sleep patches. Regarding the weight patch, Life Wave
recommends that you wear the glutathione patch for 2 months before beginning the weight loss program, the idea being that your body (in its
wisdom) packs fat-soluble toxins like pesticides and herbicides in to body fat, to protect more important regions (like your nervous system).
When you attempt to lose weight, you may feel poorly, as these toxins are released. It also may be that your body actively blocks your
attempts at weight loss (by down regulating metabolism) because it wants to protect you from the release of toxicity (this theory may or may
not be true but it makes sense biologically). In any event, more glutathione cannot be anything but good you.
James C.
Roberts MD FACC 5/27/08

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