Methyl Cycle NutriGenomics
Methyl Cycle Genomic Analysis and Supplementation Overview
Getting Started - How to Obtain Your Genomic Profile
Individualized Methyl Cycle, Antioxidant, and Detoxification Genomic Analysis
Methyl Cycle Presentation Power Point Slides
CBS: Cystathionine Beta Synthase - Explanation and Generic Plan of Action
CBS: Cystathione Beta Synthase - Old Explanation
MTHFR C677T and A1298C - Explanation and Generic Plans of Action
MTHFR C677T: 5,10-Methylenetetrahydrofolate Reductase (Þ 5-Methyl-Folate) More In-Depth Explanation
SHMT: Serine Hydroxy Methyl Transferase
MTRR: Methionine Synthase Reductase
BHMT: Betaine-Homocysteine Methyltransferase
COMT: Catechol–O–Methyl Transferase
VDR Taq: Vitamin D Receptor Taq Abnormality
MTHFR A1298C: 5,10-Methylene Tetrahydrofolate Reductase (Þ BH4)
Methyl Thieves and SAMe Stealers
ACE: Angiotensin Converting Enzyme
Glutamate – GABA Imbalance Þ Excitotoxicity
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 - Child with Neurodevelopmental Challenges
Sample Report - Adult with Chemical Sensitivity
Sample Report - Adult with Fatigue and Chemical Sensitivity
Sample Report - Adult with Atherosclerosis
Methyl Cycle Genomic Analysis and Supplementation
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, Huntington's Chorea, or Phenylketonuria, and if you are born with these genotypes (referring to one's 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 can't 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 isn't 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, Parkinson's disease, and dementia.
I've 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 don't all of us have toxicity associated cancer? Well, we're 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.
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 can't 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 don't 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 won't 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. Yasko's 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/
Regarding our terminology: homozygous, heterozygous, (+/+), (+/-), and alleles, let's 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 – how's 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. I've used myself as an example, so you've seen that I share with you several genetic liabilities – and I am not sick. Just because you have genetic predispositions it doesn't follow that you have to be sick. I haven't 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 (+/+) | Both Parents (-/-) | Mother (-/-) | ||||
+ | + | - | - | ||||
Father (+/+) | + | +/+ | +/+ | Father (-/-) | - | -/- | -/- |
+ | +/+ | +/+ | - | -/- | -/- | ||
When both parents are homozygous (+/+) all of their kids will be homozygous (+/+) | When both parents are homozygous (-/-) all of their kids will be homozygous (-/-) | ||||||
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Both Parents (+/-) | Mother (+/-) | Parents | Mother (+/-) | ||||
+ | - | + | - | ||||
Father (+/-) | + | +/+ | +/- | Father (+/+) | + | +/+ | +/- |
- | +/- | -/- | + | +/+ | +/- | ||
When both parents are heterozygous, | With (+/+) and (+/-) parents, | ||||||
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 don't 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? Isn't 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 one's 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. Yasko's area of clinical expertise is in the treatment of Autism. You can learn much more form her website holistichealth.com. We use Dr. Yasko's 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. Yasko's teachings in the care of individuals of all ages (and to optimize their own health).
Now let's 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 in 2/15, within Module 1D of the American Academy of Anti-Aging and Regenerative Medicine physician training program (the FAARFM behind my name indicates that I have completed the course; now I have the privilege of teaching within three of the modules). To view the slides please click the corresponding tabs. Some day I will construct a 3-4 DVD audio-visual presentation (but this takes time and a production cost of $5,000; if any of you want to help here, the money will be placed in escrow and used only to produce a Methyl Cycle DVD presentation).
[dont go into these if not a a hardcore researcher, or student of this new field, as this is just too deep]
Methyl Cycle Slides Part One
Methyl Cycle, Antioxidant, and Detoxification Genomic Analysis - Getting Started
The cost of genomic testing has decreased. Through 23and me (23andme.com), extensive and useful genomic testing can be carried out for $99. Previously, through Dr. Yasko's organization, we could obtain Methyl Cycle genomic testing alone for $550. Dr. Yasko's report includes extensive discussion and a set of generic recommendations. 23and me provides only raw data. Useful information can be derived from this data, but you need to do the electronic footwork.
Generic information regarding Methyl Cycle Genomic Analysis is available on our website, heartfixer.com, and we have constructed fact sheets on many of the key genomic variants. Upon request, an individualized analysis with specific recommendations can be prepared for you (see Methyl Cycle and Detox Genomic Analysis at heartfixer.com).
The first step is to obtain your genomic data. We can provide you with a Yasko kit, or you can go to www.23andme.com. For $99 they will send you a saliva collection kit. You send in the sample and 4-6 weeks later they will contact you (via e-mail) that your results are in.
Your next step is to download your results (file) into www.geneticgenie.org (.org – not .com) and obtain the Methylation Analysis and Detox Profiles (click the tabs and follow their directions). Print out the reports in color and forward them to the office. Mailing is better than faxing (if you fax the report, make sure that the scanning intensity is light to prevent burn out).
23andme will not help you do this, nor will they let us (they need to safeguard your confidentiality). Please do not forward the raw data to us as we can do nothing with it.
23and me will provide you with some statistical data regarding your risk for specific disease states, but this information does not pertain to the work that we will do.
Next go to mthfrsupport.com, download your file, and for $30, you can print out pages and pages of genomic data (more detailed instructions below). Some of these genes I understand well, others I am learning, and others will be of interest to us in the future as we learn more.
Last, you can download your file at Nutrahacker.com. For a small fee, Nutrahacker will provide you with statistical data and a brief explanation of the key genomic variants that you bear (more detailed instructions below).. I find their analysis to be helpful.
If you are my patient and I suggest you undergo genomic testing, then I will use this information as we jointly make decisions as to the best approaches to you health concerns. I may suggest metabolic testing to help us understand how your genomic makeup (your genotype) is expressing itself within your current physiology (your phenotype.).
Testing that helps us integrate your genomic data into your overall care includes:
A. The GenovaLabs NutrEval (covered by Medicare; $170 co-pay with commercial insurance) provides a great deal of information as to your nutritional status and level of oxidative and inflammatory stress and gives us some information regarding your organic pollutant and heavy metal burden.
B. A Drs. Data 24 hour urine mineral assessment covers nutrition mineral adequacy.
C. I frequently will request serum iodine, Vitamin D, and ammonia levels.
D. SAMe and SAH testing is quite valuable. The Health Diagnostics and Research Institute (www.hdri-usa.com - $350) can give us levels of SAMe, SAH, and folic acid derivatives. Alternately, Doctors Data gives us a less extensive but still useful Methylation Panel for $155.
E. A Sanesco study (covered by Medicare; $90 co-pay with commercial insurance) will give us salivary cortisol values and urine neurotransmitter (serotonin, dopamine, etc.) values.
F. For individuals with CBS/BHMT abnormalities, periodic monitoring of urine sulfate is appropriate. The QuantoFix sulfate strips are obtained via amazon.com.
I view disease as an interaction between genomic predisposition, toxin/infection exposure, nutritional status, and diet/lifestyle. Knowledge as to our genomic predispositions, our strengths and weaknesses, helps in determining the best approach to resolving health challenges and in optimizing health.
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