Methylation Nutrigenomics --HeartFixer

Return to Autism PagePage 1 of 50 Return to Heartfixer Home Page Return to CHC Home Page Return to Treatments Available Return to Diagnostic Studies Return to Autism Page Return to AMRI - Preparation and Outcome Enhancement 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 (Ÿ5-Methyl-Folate) SHMT: Serine Hydroxymethyltransferase http://www.heartfixer.com/AMRI-Nutrigenomics.htm 4/18/2015 Return to Autism Page Page 2 of 50 MTR: Methionine Synthase 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 (ŸBH4) NOS: Nitric Oxide Synthase ACE: Angiotensin Converting Enzyme Glutamate – GABA Imbalance Ÿ 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 http://www.heartfixer.com/AMRI-Nutrigenomics.htm 4/18/2015 Return to Autism Page Page 3 of 50 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. http://www.heartfixer.com/AMRI-Nutrigenomics.htm 4/18/2015 Return to Autism Page Page 4 of 50 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/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 didn’t 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, 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 (+/+) 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 (+/-) + - http://www.heartfixer.com/AMRI-Nutrigenomics.htm Parents (+/+) and (+/-) + Mother (+/-) - 4/18/2015 Return to Autism Page Page 5 of 50 Father (+/-) + +/+ +/+/-/When both parents are heterozygous, 1/ of their kids will be homozygous (-/-), 4 ½ will be heterozygous (+/-), and 1/ will be homozygous (+/+) 4 Father (+/+) + +/+ +/+ +/+ +/With (+/+) and (+/-) parents, ½ of their kids will be homozygous +/+), and ½ 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 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 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 http://www.heartfixer.com/AMRI-Nutrigenomics.htm 4/18/2015 This is the most important Methyl Cycle defect and is present in 90% of the patients who we have tested. Laboratory findings consist of an elevated urine sulfate level. Vitamin E succinate 400 IU/day. adversely affecting the Methyl Cycle Defect that is the common denominator to all of your health problems. Many drugs are loaded with sulfur (sulfates. we need to restrict your sulfur intake. Sulfite will be over produced by the CBS up regulation. 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. a low or low normal blood homocysteine level. sulfites. our key vasoprotective molecule.Return to Autism Page Page 6 of 50 tabs. but I will also be adding to your sulfate burden. so if you are CBS positive and I treat your hypertension with the diuretic hydrochlorothiazide. We can avoid this. We can hold sulfur containing agents until your sulfate burden has come under control. Boron 3 mg/day. serotonin. sulfite. Sulfites and http://www. hydrogen sulfide (producing “brain fog”). N-acetyl cysteine. Methyl Cycle Slides Part One Methyl Cycle Slides Part Two CBS: Cystathionine Beta Synthase CBS initiates the trans-sulfuration pathway. and contributing to an ongoing decline in your health. If you have a CBS defect. but if you are CBS (+). I will remove a toxin from your body. A cold beer tastes great but I do not like wine.htm 4/18/2015 . Methylation intermediates will “fall through this drain”. The C699T and (to a somewhat lesser extent) A360A defects are associated with CBS up regulation. and norepinephrine) and nitric oxide. The G6PDH enzyme system may be affected. Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. The amino acids methionine. and alpha-keto glutarate (leading to “excitotoxicity”). and hydroxy-B12 2000 mcg/day are also utilized to speed up SUOX activity. so the entire system suffers. which stimulate the stress/cortisol “fight or flight” response). and supplementation with charcoal and carnitine will bind up or neutralize ammonia. converting homocysteine in to cystathionine and its downstream metabolites. Sulfite is neurotoxic. and prescription drugs. robbing you of energy. While certain aspects of your health will benefit from these agents. leading to abnormalities in sugar control. and clearing bacteria from your bladder. Co-Q10 and Carnitine generation will fall off due to impaired methylation. excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia). can set you up for neurological. metabolically active sulfur). glutathione) that are good for most people are a problem for you. Biochemistry – The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate.com/AMRI-Nutrigenomics. CBS is operating at up to ten times its normal rate. I will be adding to your sulfate/sulfite pool. they are concentrated in animal protein (thus the restriction on animal protein intake).heartfixer. Homozygotes (+/+) will be more severely affected than will be individuals heterozygous (+/-) for a CBS abnormality. they will add to your sulfate/sulfite overload problem. but if we restrict animal protein in your diet. Molybdenum supplementation (3 drops or 75 mcg of e-lyte Molybdenum twice a day). supplements. and cysteine all contain sulfur. Thus it is easy to see how a CBS up regulation. nutritionals. CBS (+) individuals will be intolerant to sulfur containing drugs. by generating ammonia and depleting BH4. and then requires conversion in to the less toxic sulfate molecule by the enzyme Sulfite Oxidase (SUOX). Molybdenum is required for SUOX function. I will be treating the manifestations of an underlying problem and at the same time adding to the underlying problem. Yasko’s Ammonia support RNA product. and add to your dietary efforts. and positive findings of ammonia. and your urinary tract infection with a sulfa containing antibiotic. We cannot change your DNA. Learn all you can about the sulfur content of foodstuffs. If I treat your Mercury overload with DMSA or DMPS. revving you up into an unrelenting biochemical overdrive. our defenses against viral invasion and toxicity suffer. it will stimulate the adrenergic (fight or flight) limb of the autonomic nervous system and stimulate a cortisol stress response. While sulfate is less toxic than is sulfite. using up two molecules of BH4 per molecule of ammonia. Ammonia detoxification is metabolically expense. your diabetes with the sulfonylurea drug glipizide. an elevated or high normal blood ammonia level. and cardiovascular disease states. preserving BH4. psychological. We cannot stop CBS from generating excess ammonia. and ATP levels fall. Dr. such that you can start making neurotransmitters and nitric oxide again – in other words. The herb Yucca. Ammonia is produced during the metabolism of dietary protein. more ammonia than your system can handle. I will be lowering your blood pressure. The CBS defect is an up regulation. My initial observation is that individuals with high heavy metal burdens upon provocative challenge testing are likely to be CBS positive. We treat CBS ( +) individuals with dietary animal protein and sulfate restriction and supplements designed to neutralize ammonia and speed up clearance of sulfite/sulfate. compromising your biochemistry. which is high in sulfite). taurine. and foodstuffs (I am +/.for CBS A360A and cannot tolerate DMPS or glucosamine sulfate. Many nutritional supplements (MSM. BH4 is necessary to generate neurotransmitters (dopamine. at least until your urine sulfate (and your body sulfate burden) has decreased. The CBS up regulation drains methyl cycle intermediates in to ammonia. or sulfite upon Asyra testing. lowering your blood sugar. and is typically depleted in CBS (+/+) or (+/-) individuals. SUOX can easily be overwhelmed. we can compensate for your genetic challenge. we can decrease your ammonia burden. your BH4 status should begin to return towards normal. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on Excitotoxicity to follow. I am homozygous (+/+) for MTHFR C677T so 100% of my MTHFR enzymes are defective. Abnormalities in BHMT (Betaine-Homocysteine Methyltransferase) aggravate and frequently co-exist with CBS defects. Carnitine. By neutralizing the consequence of your CBS up regulation and/or BHMT down regulations. SUOX (Sulfite Oxidase) converts sulfite in to sulfate. the key ultimate consequence of CBS/BHMT abnormalities will be BH4 deficiency. A defect in BHMT. is also used up by the enzyme xanthine oxidase. If long-closed detox pathways are suddenly opened up. 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 you are taking an anti-depressant drug or nutritional that preserves neurotransmitter levels. We will be more liberal with their use in individuals who are COMT (-/-). you could experience a detox reaction. For reasons that make no sense to me. and then “crash”. advancing the dose as you see fit by your response. Some tips on low sulfur eating are included at the end of this document. which is converted in to glutamate. and not in to its one beneficial metabolic product. who need methyl donors. meaning that I am overproducing sulfite and having trouble converting sulfite in to less toxic sulfate. I am (+/-) for SUOX and (+/-) for CBS. when energy is in short supply. drawing homocysteine away from the trans-sulfuration pathway that is up regulated in CBS (+) individuals. and supplement labels. We can’t do this. far lower nutritional doses (2. glutathione.htm 4/18/2015 . BHMT mediates the “backdoor” pathway of homocysteine metabolism. It is your responsibility to become expert in this area. drug. I will thus need to be particularly vigilant with respect to supporting SUOX function. GABA is initiated at 500 mg once or twice a day. and alpha-ketoglutarate. in short supply in CBS + individuals. Thus we need to be patient. a defect in a Methyl Cycle enzyme is typically described with a (+). In a sense. Excitotoxicity – The CBS up regulation leads to excess production of alpha-ketoglutarate. 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). To make matters worse.heartfixer. It is strongly recommended that BH4 supplementation be held until all other Methyl Cycle pathways have been optimized. but the latter three agents also can serve as methyl donors. 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). but don’t expect me to get in right every time – please study your food. will thus mimic or add to a CBS defect. but the enzyme systems that convert glutamate in to GABA are compromised by lead and mercury. and one or more of these agents will be included in our treatment program for CBS (+) and/or BHMT (+) individuals. with the long goal in mind. someone decided that the normal designation for the SUOX gene should be http://www. Energy Production will falter. stimulatory behavior in autistic kids (“stims”) and anxiety and sleeplessness in adults. (I am getting ahead of myself. and we need to be prepared. a calming neurotransmitter. but do not expect us to tell you what to eat. BHMT can be stimulated with Phosphatidylserine. Under normal circumstances. especially if they have cardiovascular disease.5 mg four times a day) are typically employed. which tend to be in short supply in individuals with Methyl Cycle defects. and its non-oxidizeable 1st cousin Idebenone will all help with ATP energy production. Molybdenum. and can be taken as well. Ribose increases ATP regeneration in individuals with cardiovascular disease or other conditions associated with energy deficiency. The result is “excitotoxicity”. as we attempt to spin other metabolic wheels forward that are still stuck in the “off position”. and their use makes sense in patients with CBS up regulations. Xanthine oxidase is present in pasteurized milk. NADH. A note regarding nomenclature. Co-enzyme Q10. Please attend our monthly Methyl Cycle support groups meetings. I will work with you to phase out high-sulfur drugs and nutritionals from your program. so we need to get the rest of your systems up and running before we open these closed gates.readingtarget. so skip this entry if you wish. take things step by step. To generate ATP energy. with fatigue and malaise.com/nosulfites) is an invaluable resource. diet tips in appendix) and by supplementing you with GABA. a stimulatory neurotransmitter. Phosphatidylcholine (which is combined with the metal chelator EDTA in Lipophos EDTA). but to manufacture these co-factors you need methyl groups. If we give you BH4 before you are ready. hydrogen sulfide. you need Co-enzyme Q10 and Carnitine. and the methyl donor TMG (Trimethylglycine). and in dealing with Methyl Cycle defects. We do not have this knowledge. homocysteine is shunted in to ammonia. We also can supplement you with BH4. If neurotransmitter generation suddenly comes back on line.com/AMRI-Nutrigenomics. you could experience a neurotransmitter surge if we have not cut back on the drug dose. Do not expect us to know the sulfur content of foodstuffs. which is best avoided or minimized in CBS (+) individuals. and you may sign up for individual (or group) dietary change counseling. and more conservative in their dose in individuals who are COMT (+/+). glutamate will be converted in to GABA.Return to Autism Page Page 7 of 50 Chronic Disease by Rick Williams (available at the office or at www. but here a little bit of BH4 can go a long way. you will feel great for a day or two. aiming to restore GABA:Glutamate balance. who will be more sensitive to methyl group supplementation). metabolic flow down the CBS pathway is designed to generate the important anti-oxidant and detoxifying molecules glutathione. ½ capsule twice a day (sprinkled on food containing protein). Carnitine.(half of your CBS enzymes abnormal) for one of the two CBS up regulations and you may also be +/+ or +/. Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration pathway. with a second study for toxic and nutritional minerals. Additional information is available on our heartfixer.com/chc). The CBS C677T and A360A genes code for enzyme function that is pathologically up regulated.or +/+ CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. If I refer to an individual as CBS (+). Boron 3 mg/day. hydrogen sulfide (to produce brain fog). 7. Carry out 24 hour urine studies for ammonia and amino acids. Your urine sulfate score will thus be our primary measuring stick.com/AMRI-Nutrigenomics. CBS: Alternate Explanation and Generic Plan of Action Gene by Gene Approach – CBS +/. Repeat some of the lab work. nutritionals that will now require more intensive supplementation. and possible a SpectraCell intracellular nutritional assessment. predisposing you to hypertension and cardiovascular and inflammatory disease states.htm 4/18/2015 . Of the two. 10. In my shorthand. 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).take two tablets three times a day).or +/+ with/without BHMT +/. sulfate/sulfite/-SH excess blocks cellular up take of the key detoxifiers glutathione and cysteine. Additional measures designed to speed up the “back door” BHMT reaction will be discussed later. Check and record your urine sulfate level every 7 days. Ammonia Support RNA ½ dropper with meals. two to three times a day. Vitamin E succinate 400 IU/day (contained in the NHF multi). and then to keep it there for two months (at which time you will feel better). Yasko’s book. a calming neurotransmitter). Supplement with GABA 500 mg once or twice a day to blunt excitotoxicity. leading to insufficient dopamine and serotonin production). specifically looking for nutrients that have been drawn in to your now open pathways. 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 (+). Consider wearing the Life Wave Glutathione patch 4-6 hours each day. we need to check your baseline blood homocysteine. 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.for one of the BHMT down regulations (which act like CBS up regulations). taurine and cysteine (all involved in detoxification and endothelial health). To stimulate SUOX begin Molybdenum 3 drops twice a day. along with kidney and liver chemistries (if not done recently). Co-Enzyme Q10. removing the patch if you feel poorly (this would reflect a detoxification reaction . especially in individuals not troubled with CV disease) supplement with NADH 5 mg. magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). ammonia. too much alpha-ketoglutarate (which leads to glutaminergic excitotoxicity). Favorable results will also allow us to back off on the dose of now less necessary supplements. In 8-10 weeks we will likely wish to: a.heartfixer. and Ribose 5 grams in water. Genetic Bypass. and a charcoal supplement at bedtime (away from other supplements. Co-Enzyme Q10 100 mg or Idebenone 100 mg. You are +/+ (all CBS enzymes abnormal) or +/. in this process generating excessive sulfur break down products (sulfite and sulfate. any measure that increases your sulfate burden is either inappropriate or is being added to your program prematurely. While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification. and alpha-ketoglutarate (which can be converted into GABA. You thus suffer from “too much of a good thing and way too much of several bad things”. I am referring to an individual with a CBS abnormality. Switch to a multi that does not contain B6 (B6 stimulate CBS. the idea here being to use up free sulfur groups to generate Glutathione. 3. 4. and Vitamin D levels. thus if you are (-/-) for SUOX you are homozygous abnormal. Yasko’s NHF multi is low in B6 . producing enzyme activity that is 10 fold greater than normal. if you feel that GABA is helping you can increase the dose. We will use the results to modify our nutritional measures.Return to Autism Page Page 8 of 50 (+/+). My general treatment program for CBS (+) individuals and for BMHT (+) individuals who are overproducing ammonia and sulfite/sulfite will consist of: 1. and hydroxy-B12 2000 mcg/day.com website. During normal physiology. This deficiency in BH4 allows NOS (nitric oxide synthase) to convert arginine in to free radicals (superoxide and peroxynitrite) as opposed to nitric oxide. the C677T allele is the most important. To increase energy production (this step is less critical and can be omitted for cost containment. the P-5-P form of B6 is less of a problem – Dr.see our info sheet and lifewave. Endogenous detoxification is thus blunted (nearly all kids with Autism Spectrum Disorders bear http://www. 2. 11. and are thus of additional value to COMT (-) and/or VDR Taq (+) individuals. 9. Additional mineral support will be needed and here we start with Trace Minerals Complex at 4 drops/day. 8. either (+/+) or (+/-). Measures that decrease your sulfate burden are beneficial. b. Carnitine 500-1000 mg daily. which stimulate the stress/cortisol “fight or flight” response). Conversely. 6. Restrict animal protein (anything with eyes) from your diet and limit your exposure to sulfur group containing drugs and nutritionals. This is the only gene where (-/-) is abnormal and (+/+) is normal. and too much ammonia (which depletes BH4. To squelch ammonia. I will refer to any defect in any Methyl Cycle gene as a (+). supplement with Yucca. 5. If not done already. and Idebenone all provide Methyl groups. when alpha-ketoglutarate is in excess. Plan of action for CBS +/. individuals + for CBS will likely be energy depleted. Thus if you bear CBS or BHMT abnormalities. creating toxic intermediates that cannot be metabolized further due to the block in glutathione utilization – and you will feel horrible. To neutralize ammonia (generated from animal protein). Lee Cowden. Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR (compromising methyl-B12) abnormalities. we cannot convert arginine in to nitric oxide. and to do so BH4 (tetrahydrobiopterin) must be “spent”. and GABA. you can use Ammonia Support RNA ½ dropper with meals and with methyl cycle supplements (relatively expensive). and thus you will need and benefit from corresponding supplementation (with these molecules that they are having trouble making).ec). twice a day. in moderation. as does phosphatidylcholine (which we use to treat atherosclerosis). http://www. You will feel great for 1-2 days. and can be utilized if you are not overly sensitive to methyl group supplementation (based upon you COMT/VDR status). glutamine. creating a quite useful supplement. your detox pathways open up (and why. Vitamin E succinate. which is thus depleted in CBS + individuals. persistent high sulfate spills indicates that your diet/treatment program needs further modification. Glutamate is involved in alertness and learning. sulfur containing supplements. is not a problem. and sulfur containing drugs (see attached sulfur avoidance instruction sheets and read Sulfites and Chronic Disease by Rick Williams.Return to Autism Page Page 9 of 50 CBS up regulations – why they are compromised by environmental toxins and the kid next door is just fine). Without BH4. or BH4. VDR.com/nosulfites/. Sparga was developed by fellow Cardiologist Dr. and here supplementation (in relation to your COMT/VDR status) with CoEnzyme Q10. and personal health status) To address this constellation of alleles I will recommend: 1. Yucca. 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. You’ve lived your entire life with a gene set that is maladaptive to the toxic environment of modern man. available at the office or at www. Conversely. MTR. specifically to address the CBS abnormality (see www. or after adding a new treatment or changing your diet). 2. DMG (dimethylglycine) and TMG (trimethylglycine) stimulate BHMT. However. Phosphatidylserine stimulates BHMT (and we also use it to moderate elevated cortisol levels). 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. and are best avoided or minimized. serving as a “back door” pathway to “pull” homocysteine away from the CBS “sulfate drain”. Conversely. away from other supplements (magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). These supplements can be tapered down as ammonia levels fall. The excess ammonia generated must be detoxified. COMT. you will experience detox phenomena). BHMT (Betaine Homocysteine Methyl Transferase) directly methylates homocysteine back in to methionine. 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”. beginning at ½ capsule.com/AMRI-Nutrigenomics. as beneficial neurotransmitters are generated.heartfixer. Sparga Detox. Methyl-folate and methyl-B12 detox pathways will then open up. which is then metabolized by SUOX (Sulfite Oxidase) to the less neurotoxic (but still problematic at high levels) sulfate. after we decrease your sulfate/sulfite pool. 10 drops in water (wait at least one minute before consuming). As Methyl Cycle function is needed in the biosynthesis of Co-Enzyme Q10 and Carnitine. which uses up molybdenum. and B12 are felt to stimulate SUOX activity. 3. We should be able to interconvert alpha-ketoglutarate into glutamate. instead vascular wall toxic free radicals such as superoxide and peroxynitrite are created. Alpha-ketoglutarate. if we move too fast. along with a charcoal supplement at bedtime every other evening. (or sprinkled on food containing protein). 3. it makes sense to support BHMT function. twice a day makes sense. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables. but excess glutamate leads to irritability and over-excitement. Monitor urine sulfate levels every 3-7 days (or when you feel particularly good or poorly.readingtarget. methyl-B12. Homogenized dairy products contain xanthine oxidase. then we suffer a buildup of the excitatory neurotransmitter glutamate. leading to hypertension and cardiovascular disease.or +/+ (BHMT discussed further in other sections) (made out of context of your MTHFR. 4. and NADH may be helpful. boron. 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). Carnitine. 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). MTRR. It will take us some time to change your internal environment to “bypass” these genomic challenges. may help with ammonia detoxification. or if toxic metals compromise the interconversion enzymes. if we treat you with methyl-folate. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until CBS/BHMT are under control. Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a liberalization of your diet. However.htm 4/18/2015 .nutramedix. SUOX activity requires molybdenum. Phosphatidylcholine can be admixed with EDTA (detoxifies metals). while our Complete Mineral Complex. a methyl donor) twice a day. They may be taken individually as Molybdenum 3 drops in water twice a day and Boron 3 mg once a day.com/AMRI-Nutrigenomics. and cysteine. This will take some time. makes sense. If they are helpful you can double the dose. and we are looking for low levels of ammonia. OUR FIRST GOAL WILL BE TO REDUCE YOUR SULFATE STORES AND DECREASE AMMONIA AND GLUTAMATE GENERATION MTHFR C677T: 5. and as the environment is not going to become less toxic. Charcoal. 8. with concomitant utilization of free sulfate/sulfhydryl groups – a double win for you.htm 4/18/2015 . A low protein diet could become a high carbohydrate. 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). The active form of B6. if we could convince your biochemistry to up regulate biosynthesis of glutathione. 3 daily will cover the mineral base. unexplained illness or significant toxicity would do well to follow the “nothing with eyes” diet until urine sulfate and ammonia levels have fallen. Sparga. the more protein you will be able to take in without compromising your biochemistry. then we need to back off on your treatments. 9. is less of a problem here and serves as a B6 substitute. You may need to accept some transient fatigue. as your genes are not going to change.com for additional information.10-Methylenetetrahydrofolate Reductase (Ÿ Ÿ5-Methyl-Folate) Ÿ http://www. B. Rectifying your genomic predispositions and detoxifying your system is not a sprint – it is a marathon. Toxicity testing (discussed in more detail in other presentations and on heartfixer. please use sublingual hydroxy-B12 2000 mcg/day. or if deficiencies are identified on your NutrEval study. Magnesium supplementation may help with GABA physiology and often helps with sleep. 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). Be self-observant and keep records. If energy is low. and achiness to allow toxic molecules to be cleared. 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. Ammonia Support RNA) treatments in your program. methyl-B12. We need to keep in mind that Methyl Cycle Genomics is not the sole determinant of your health. weight gain diet in an overweight individual with adult onset diabetes. and better overall health). take GABA 500 mg or Zen (GABA 550 mg with Theanine 200 mg. Avoid B6 (unless you need it for other functions). along with Molybdenum and Boron. then your anti-oxidant and detox capacity will increase. To stimulate SUOX activity. malaise. Which foods. while keeping an eye on these biochemical markers. This could take the form of: A. Toxicity testing** may also be carried out. 6.heartfixer. if detox symptoms are debilitating or compromise your ability to work or care for your family. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. taurine. And. D. ** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Your homocysteine level will give us important information as to the functional expression of your CBS/BHMT genomic abnormalities. In addition. Formal nutritional testing will be carried out in 8-12 weeks.auraexplorationpatches. nor do we wish to create an essential amino acid deficiency. For nutritional support. supplements. The US BioTek study gives us information on seven major organic pollutants ($126).com) thus makes sense.Return to Autism Page Page 10 of 50 5. and should be drawn before any diet change/nutritional intervention is carried out. 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. A formal provocative challenge gives us our best assessment of tissue metal burden. 11. Yasko’s All in One. This is all about balancing diet against treatment response. 7. then we will begin supplementation with methyl-folate. If you feel anxious or “wired up” (glutamate overload). * 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. This could involve separate 24 hour urine studies for nutritional minerals and for ammonia/amino acids. a low-sulfate multi such as Dr. NADH does not provide methyl groups and should be well tolerate by all. lower urine sulfate and ammonia levels. while individuals who are methyl group sensitive (COMT+) will likely do better with GABA. However. and BH4. Individuals with chronic. I can’t prove this approach with an allopathic lab test but it has been quite helpful in solving complex medical problems in my personal patients. 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. P-5-P. could simply cut back on animal protein. We need to make sure your mineral/nutritional stores are replete. Conversely. to demonstrate that flow down the CBS pathway has been decreased to a physiologic level. This can be achieved with the use of the Life Wave (needleless acupuncture) Glutathione patch. based upon your clinical and genomic status). 10. you will need to be mindful of these principles for the rest of your (long and healthy) life. later on we will liberalize your diet. the greater representation of ammonia reducing (Yucca. GABA does not work rapidly. to which you may be sensitive. or we might use the Genova Labs NutrEval. glutamate. After sulfate levels have fallen (to a level that you and I feel is optimal for you. fully covered under non-HMO Medicare). Individuals in whom the CBS up regulation is less important (A360A as opposed to C677T. This maneuver isn’t fun and will require personal strength. Dr. keeping in mind that these substances provide methyl groups. which stimulates CBS. two twice a day. Right now this “good thing” could actually set you back. but it also may turn your health around. Balance needs to be achieved. Individuals who need methyl groups (normal COMT and/or abnormal VDR Taq alleles) will do better with Zen. Hunts CD is available for your review and you can go to www. we can supplement you with Co-Enzyme Q and Carnitine. C. utilizing various cocktails of folic acid.6 mg. not THF itself. are those with the lowest homocysteine levels. excess folic acid can be converted in to alpha-ketoglutarate. which is used as a building block for DNA. low dose 5-methyl folate supplementation will bypass this defect with 100% efficacy. catalyzed by SHMT.10-methylene THF is converted in to 5-formyl folate (also known as folinic acid). B6. or a placebo agent in large groups of individuals. we must also point out that the sickest patients. Metanx (5-methyl folate 2. Dietary folic acid. known as tetrahydrofolate. which usually is not in short supply. we can block absorption of the sparse 5-methyl folate present in your diet. Sources of 5-methyl folate include Folapro (800 mcg 5-methyl folate). Actually. abnormal clotting. but the consequence of the MTHFR abnormality in kids appears to be profound. I used to think of homocysteine as an individual bad actor. but your health insurance typically will not cover their cost as they “are just vitamins”. It is actually 5. and Cerafolin NAC (5-methyl folate 5. An elevated homocysteine level increases your risk for cardiovascular and neurological disease. they will respond with a reduction in homocysteine and a reduction in disease risk or event rate. If we give folic acid to individuals with an elevated homocysteine level and normal MTHFR function.10-methylene THF generated from THF by SHMT will take another metabolic pathway. NAC 500 mg. Elevated homocysteine leads to free radical stress. and one study of folic acid supplementation in the elderly showed an increased rate of dementia. if we flood you with folic acid that you cannot use. I could go on and try to link homocysteine levels with the story of the three bears. with or without known disease states. Now I look at an elevated homocysteine not as a bad actor.Return to Autism Page Page 11 of 50 The MTHFR C677T defect is easy to understand and even easier to treat. that is converted in to 5-methyl folate by MTHFR. SHMT converts THF in to 5. Of interest. is readily converted in to one of the active forms of folic acid. Metanx and Cerafolin are available as prescription agents.10-methylene THF. an intermediate step is involved. aggravating a co-existent CBS abnormality.10-methylene THF (upper left in the diagram). vascular plaque formation. P5P 25 mg. and methyl-B12 2 mg). and 5-methyl folate (as without 5. in the process regenerating THF.8 mg. Folapro is available over-the-counter. but some studies show no effect. more commonly referred to as 5-methyl folate. we need to provide you with 5-methyl folate. but because they harbor the CBS up regulation. homocysteine is a known bad actor. MTR (methionine synthase) then combines 5-methyl folate with homocysteine to form methionine. SHMT C1420T: Serine Hydroxymethyltransferase Our diagrams indicate that the MTHFR "forward reaction" converts THF (obtained from dietary folic acid) in to 5-methyl folate. folinic acid. a cause of cardiovascular and neurological disease. as we cannot efficiently convert dietary folic acid into its 5-methyl folate form. Individuals who are (+/+) for MTHFR C677T (10% of the population. which is then used by MTR to convert homocysteine in to methionine. but instead we will cover the SHMT abnormality in THF (dietary folate) processing.com/AMRI-Nutrigenomics. whereby 5. Also. but as a marker of a real bad actor. and then move on to MTR/MTRR. If you have a MTHFR C677T defect.heartfixer. then not much happens. including me) have a great deal of trouble using dietary folic acid to detoxify homocysteine. Thus we can understand how supplementation inappropriate for one’s genotype can have an undesired negative consequence. because their homocysteine levels are low not due to a good diet. but not all subjects will respond with a reduction in homocysteine.10-methylene THF the MTHFR enzyme has nothing to work with). However. at the office or on line. In reality. Clinical event rates typically fall in response to supplementation. MTHFR converts THF in to 5-methyl THF. Some of the 5. being acted upon by SHMT a second time. so your homocysteine level might even rise.htm 4/18/2015 . supplementation with folic acid is not the answer – it can’t help you. Many studies have been carried out. and an increased risk for cardiovascular and neurologic disease – yikes! If you are (+/+) or (+/-) for MTHFR (another 20% of the population). MTR: Methionine Synthase http://www. that being a Methyl Cycle abnormality. and methyl-B12 2 mg). We can address a SHMT down regulation by supplementing you with its products. such that the parents of Autistic kids add a few more vowels to MTHFR in naming it. and B12. but if we give folic acid to an individual who is MTHFR (+/+) or (+/-). To further confuse and befuddle research attempting to link homocysteine with disease states. or the still healthy but at greatest risk individuals in our society. Average homocysteine levels will fall. or THF. Why did this occur? You’ve already figured it out. and there goes your health. Needed downstream methyl donors such as SAMe will not be generated. MTRR: Methionine Synthase Reductase MTRR generates the methyl-B12 needed by MTR and many other methyl-B12 requiring enzymes. normal B12 physiology cannot be carried out. Without methyl-B12. MTRR (Methionine Synthase Reductase) serves the needs of MTR. The consequence is deficient methyl-B12. so does your biochemistry. 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. In the process 5-methyl folate is converted back to THF. B12 blood levels may be normal.Return to Autism Page Page 12 of 50 MTR combines 5-methyl folate and homocysteine to form methionine and tetrahydrofolate (THF). but if MTRR is (+/+) or (+/-). The MTR A2756G defect is an up regulation. MTR cannot convert homocysteine in to methionine. which converts homocysteine directly in to methionine (more on this approach later). but as levels of methyl-B12 will be low. d. MTR Up Regulation (+) and MTRR Down Regulation (+) http://www. methylation in general will be compromised.heartfixer. then tacks it on to homocysteine to form methionine. MTR is always on. and your physiology will be compromised. one molecule of methyl-B12 is degraded. and with each spin of the MTR enzyme. processing them to methionine and THF. Methyl-B12 is required for normal function of MTR. Supplementing you with methyl-B12. homocysteine levels will be elevated. b. We can treat the MTR up regulation by: a. grabbing every homocysteine and 5-methyl folate molecule that it can get its hands on. methyl-B12 formation will be compromised. Methylation fails. which is otherwise formed from the methionine generated by the MTR/MTRR reaction. We can also bypass the dysfunctional MTR step by stimulating the “backdoor” BHMT reaction. MTR removes a methyl group from 5-methyl folate. Blood B-12 levels may be normal. our most important methyl donor. Measures designed to increase formation of methyl-B12. The enzyme is always on.htm 4/18/2015 . using up methyl-B12 faster than MTRR can regenerate it. When the MTR A2756G defect is present. SAMe generation and methylation in general will be compromised. More specifically. regenerating methyl-B12 from available methyl donors and B12.com/AMRI-Nutrigenomics. Homocysteine levels will typically be elevated. c. in the process using up methyl groups. I will give you specific recommendations.htm 4/18/2015 . we can bypass these blockages by stimulating BHMT to convert homocysteine directly in to methionine (I know this is difficult. You can’t make much because MTRR is not functioning well. We will give you hydroxy-B12. will be affected by your COMT (basic need for and tolerance to methyl group donors) status. administered IV as Lipostabile/Plaquex. and heavy metal detoxification. and it gets worse when we consider the individual who is (+/-) for COMT. conflicting. BHMT: Betaine-Homocysteine Methyltransferase BHMT converts homocysteine directly in to methionine. providing us with BHMT stimulation. B12 is reasonably well absorbed orally or via the sublingual route. and as such have a lot of methyl groups floating around. The basic approach is as follows: 1. to stimulate the BHMT reaction. so please read on). This combination produces a double whammy on methyl-B12. We will talk about COMT a little later. and we can also administer it by injection. We are giving you the methyl-B12 that you need. Individuals who are COMT (-/-) have normal COMT function. For example. who thus need methyl groups. and you are also COMT (-/-). reverse cholesterol transport. 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. So if you are (+) for the MTR up regulation and/or (+) for the MTRR down regulation. or in oral liposomal format as Lipophos Forte. http://www. COMT (-/-) individuals need and tolerate methyl donors quite well. But remember.heartfixer. COMT degrades dopamine. we know that you have an excess of methyl groups floating around. Now let’s move on to the previously alluded to “backdoor” reaction. Here the need to supplement with B12 is greatest. hydroxyB12. This is all very confusing. but bypassing blocked enzymes sure beats surgery to bypass blocked arteries. and any B12 that you do make gets sucked up by the overactive MTR. or both in combination. 2.com/AMRI-Nutrigenomics. all we need to do is to give you methyl-B12. one daily. and therapeutically confusing physiologic system in the body. or if an MTR up regulation or MTRR down regulation leaves us short in the methylB12 department. and any extra methyl groups left over can be put to good use. Our approach to BHMT. Conversely. and this leads to mood swings related to fluctuations in neurotransmitter levels. or as a less expensive alternative. too much of a good thing. a triple benefit. Stimulating a genetically normal BHMT system will partially ameliorate the adverse affects of Methyl Cycle defects elsewhere. this is the Methyl Cycle that we are talking about. In individuals who are COMT (-/-). You can’t make it well because MTRR is not functioning well. whether you need methyl-B12. provides a powerful anti-atherosclerotic benefit (discussed on the website and in a DVD). in my analysis of your Methyl Cycle genotype. who will be sensitive to free methyl groups). if we cannot convert homocysteine in to methionine because a MTHFR defect renders us deficient in methyl-folate. or when we want to stimulate BHMT to help bypass MTR/MTRR defects.Return to Autism Page Page 13 of 50 This combination leads to a double whammy on methyl-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). if it is defective. Specifically it removes a methyl group from TMG (trimethylglycine) and tacks it on to homocysteine to form methionine and DMG (dimethylglycine). Phosphatidylcholine. if you are COMT (+/+). depending upon your individual needs and preferences. or when we want to pull homocysteine away from a CBS up regulation. they break down dopamine rapidly. and any B12 that you do make gets sucked up by the overactive MTR. using up methyl groups in the process. Phosphatidylserine 100 mg daily. the most convoluted. and when we factor in how one’s VDR gene status interacts with their COMT status. Here the need to supplement with methyl-B12 (or to help you make it on your own) is greatest. The former. Phosphatidylserine can be used in combination with the methyl donor DMAE as Pedi-Activ. Individuals who are COMT (+/+) degrade dopamine slowly. You’d think that the treatment would be straight forward – give the patient methyl-B12. Oral Lipophos EDTA contains Phosphatidylcholine admixed with EDTA. TMG can be used to stimulate BHMT (but not in COMT (+/+) individuals. http://www. and will need and tolerate dopamine precursor substances and methyl donors. an issue because 90% of my patients have low or low normal Vitamin D levels. which influences dopamine production in relation to Vitamin D. We need dopamine to defend against microbes and heavy metals. leaving more BH4 available for other critical functions. BH4 deficiency is the consequence of CBS.htm 4/18/2015 . Panic attacks and bi-polar mood disorder are seen with greater frequency in COMT (+) individuals. we do not need to “spend” BH4 to make dopamine. With respect to methyl group need and tolerance. as you are not using them up breaking down dopamine. Individuals with a normal Vitamin D receptor. 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. we also utilize methyl donors to generate dopamine. BHMT. Pertinent to this discussion. The downside of being COMT (+) is that you will have a lot of free methyl groups floating around. a good reason to keep your Vitamin D level up. impacting on your tolerance and need for dopamine precursors and methyl groups. and to a somewhat lesser extent other neurotransmitter substances. Thus if we need to give you other Methyl Cycle intermediates (such as methyl-B12 if you have MTR/MTRR issues). this makes sense. from our perspective it is not necessarily a bad thing.com/AMRI-Nutrigenomics. We need BH4 to carry out multiple physiologic steps. and the “backward” MTHFR A1298C defects. Individuals (+/+) or (+/-) for VDR Taq defect have lower Vitamin D levels. here being (+) for COMT is actually in our favor. They tend not to need or to tolerate methyl groups or dopamine precursor substances. including the generation of dopamine. Now. norepinephrine. Individuals (+) for COMT 61 breakdown dopamine quite rapidly and are at greatest need for methyl donors. Too many methyl groups can lead to mood swings. they behave like COMT (+) individuals. on the other hand. The V158M and H62H alleles of COMT are down mutations. we risk ODing you with methyl groups. 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 (-/-). as we need dopamine to defend against microbes and metals. VDR Taq (+) individuals behave like COMT (-) individuals. those who are VDR Taq (-/-). COMT (-) individuals. Vitamin D stimulate the enzymes that generate dopamine. If our COMT (+) status keeps us from breaking down dopamine. Individuals (+/+) or (+/-) for these genes will degrade dopamine only slowly. I acknowledge that this is all very difficult to understand.heartfixer. With respect to methyl donor tolerance. VDR Taq: Vitamin D Receptor Taq Abnormality Vitamin D has many functions. by tacking on to them a free methyl group that COMT obtains from SAMe. make plenty of dopamine. All sorts of permutations are possible here. While we utilize SAMe (and indirectly other methyl group donors) to degrade dopamine. and less frequently encountered COMT abnormality. is a down regulation defect. COMT 61. make less dopamine. need and tolerate methyl groups. Hopefully the chart below will help. A third.Return to Autism Page Page 14 of 50 COMT: Catechol–O–Methyl Transferase COMT degrades dopamine. and to keep our mood up. while COMT (+) status is not the norm. 10-MethyleneTetraHydroFolate Reductase (Ÿ ŸBH4) Ÿ The MTHFR C677T defect effects the “forward reaction”. we would use Zen. we would utilize the methylated forms of Methyl Cycle intermediates. We would not advise a diet high in tyrosine. We treat MTHFR A1298C with 5-methyl folate supplementation (aiming to push the reaction backwards) and. which contains Phosphatidylserine and DMAE. It is poisoned by mercury. and especially aluminum. MTHFR A1298C: 5. Dopamine precursors such as quercetin. Rather than using GABA to deal with excitotoxicity. the molecule that resists plaque formation. TMG. after your other Methyl Cycle challenges have been addressed. so their combination with MTHFR A1298C leads to a BH4 deficiency double whammy. expecting that with enough hydroxy-B12 and free methyl groups floating around you will form up some methyl-B12. We will also endeavor to decrease your need for BH4. even if MTRR activity is compromised by a defect. in this individual we would start with hydroxy-B12. the amino acid precursor of dopamine. as would a diet high in tyrosine. COMT (+/-) and VDR (-/-) behaves like COMT (+/+) COMT (+/-) and VDR (+/+) behaves like COMT (-/-) Multiple (+/-) combinations of COMT and VDR Taq are possible. along with MSM and SAMe (the latter two only for CBS (-/-) individuals) would make sense. and conversion of arginine not in to nitric oxide but instead in to free radicals such as superoxide and peroxynitrite. with nutritional doses of BH4. NOS: Nitric Oxide Synthase In a BH4 dependent reaction. Individuals with abnormalities in CBS and BHMT will be low in BH4. which combines GABA with the methyl donor threanine. a methyl donor. the amino acid precursor to dopamine. vasospasm. The result is a progressive drain on BH4. If you have cardiovascular disease and if we can successfully reboot your Nitric Oxide system. a progressive impairment in neurotransmitter production. as it is being used up detoxifying ammonia that these defects have generated. whereby 5-methyl folate is converted back in to THF. lead. but it does compromise the “backward” reaction. such that you will need to use less BH4 to generate more. 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. and individuals with Methyl Cycle abnormalities have particular trouble dealing with them. and abnormal clotting. If you are COMT (-/-). If you are MAO A (-/-). and the herb macuna puriens might be helpful. in the process generating one molecule of BH4. the conversion of THF in to 5-methyl folate. We will address these “intermediate” genotypes with intermediate levels of methyl group supplementation.com/AMRI-Nutrigenomics. DHPR is the enzyme that regenerates BH4 from BH2. including methyl-B12 if n TR/MTRR defect is present.Return to Autism Page Page 15 of 50 intermediates. and we will have to watch for this and supplement accordingly.heartfixer. COMT (+/+) VDR Taq (-/-) individuals will be susceptible to iodine and lithium depletion as they detoxify. To support BHMT. Nitric Oxide Synthase (NOS) converts Arginine in to Nitric Oxide. If you can make and maintain Nitric Oxide then you will not develop cardiovascular disease.htm 4/18/2015 . than we can stabilize your http://www. Other methyl donors. turmeric. These toxins are wide spread in our environment. I will be more specific on your individual report. we would use Pedi-Activ. theanine. MTHFR A1298C has no adverse affect on 5-methyl folate production. Metal detoxification will help here and with every other biochemical function in your body. we can provide nutritional support to help maintain dopamine levels. and will be part of your overall program. we can do the same thing with serotonin precursors such as high tryptophan foodstuffs. to avoid ODing you with methyl groups. We would not give your dopamine precursors such as quercetin or the herb macuna puriens. instead of Phosphatidylserine. including melatonin. ginkgo biloba. If an MTR/MTRR defect increases your need for methyl-B12. The basic philosophy is to stimulate the action of still open pathways to take the stress off your impaired pathways. a job that distracts it from its Nitric Oxide generating duties and which uses up BH4. demonstrated a reduction in cardiovascular event and death rate over the ensuing five years. elevated lipoprotein (a). If you are NOS (+) we will pay particular attention to maneuvers designed to lower your ammonia burden. ACEI (angiotensin converting enzyme inhibitors) target this enzyme. which we have on cassette tape (we will likely have a DVD presentation available late next fall). or over active Angiotensin Converting Enzyme. 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). The rest likely relates to inherited abnormalities in NOS. aggressive antioxidant supplementation makes sense here (while a broad spectrum program of antioxidant supplementation is always wise. for our purposes a nasty angiochemical that mediates hypertension. and OraAdrenal in kids with ACE problems. As the products of a compromised or genetically abnormal NOS system are the free radicals superoxide and peroxynitrite. plaque deposition. and for restenosis following balloon angioplasty.Return to Autism Page Page 16 of 50 disease. we specifically use Vitamin C to neutralize superoxide and 5-methyl folate to neutralize peroxynitrite). The NOS D298E abnormality codes for a dysfunctional NOS enzyme. The potassium and magnesium sparing diuretic Spironolactone blocks the deleterious effects of Aldosterone. Every risk factor (or causative factor for cardiovascular disease) compromises Nitric Oxide generation or maintenance. another mediator that is up regulated by Angiotensin II (of interest to those of you with CBS/BHMT problems. OraKidney. Every maneuver in drug and non-drug cardiovascular medicine that improves patient symptomatic status and outcome works on this system. we will have a low threshold for intervening pharmacologically with ACEI and Spironolactone.heartfixer. ACE (+) individuals . Spironolactone is low in Sulfur). Of interest. a weak vasoconstrictor.htm 4/18/2015 . here she recommends use of the Stress and Anxiety Support RNA product. The ACE Del16 involves the insertion and deletion of genetic material at a specific location (intron16) of the ACE gene. and to address risk factors that compromise Nitric Oxide. which like Quinapril enters the vascular wall and preserves endothelial function) was administered to individuals with diabetes and one other risk factor. and abnormal clotting. BH4 supplementation has been demonstrated to improve Nitric Oxide generation and endothelial function in individuals with risk factors such as hyperlipidemia. coding for an up regulated. NOS is also involved in ammonia detoxification. and the other Methyl Cycle genes. ACE: Angiotensin Converting Enzyme Angiotensin Converting Enzyme (ACE) converts Angiotensin I. seeking to block generation of Angiotensin II. and iron over absorption. for experiencing adverse events. ACE may be associated with increased anxiety. magnesium and potassium wasting. If you are ACE (+) and have problems with BP or fluid control. into Angiotensin II. but rather in to undesirable free radical species such as superoxide or peroxynitrite.are at increased risk for hypertension and cardiovascular disease.I am ACE (+/+). Yasko recommends the use of Kidney Support RNA. a large study (HOPE) where a tissue specific ACEI (Ramipril. Glutamate – GABA Imbalance Ÿ Excitotoxicity http://www. A component of “a positive family history of cardiovascular disease” is related to genes coding for high cholesterol. yikes! . It has trouble breaking down ammonia and it has trouble generating Nitric Oxide. and we presume that it will do the same in individuals with Methyl Cycle abnormalities. Without adequate levels of BH4 Nitric Oxide Synthase will not convert Arginine in to beneficial Nitric Oxide. I give two separate two hour presentations on Endothelial Dysfunction. salt and water retention. ACE. NOS (+) individuals are at greater risk for developing all forms of cardiovascular disease. Dr.com/AMRI-Nutrigenomics. com/AMRI-Nutrigenomics. so supplement with magnesium to keep calcium in check. Supplementing with GABA 4. insufficient GABA. 5.htm 4/18/2015 . Many other physiologic processes require a balance between glutamate and GABA. Excessive alpha-ketoglutarate generated due to the CBS up regulation can be converted into glutamate. nystagmus. Glutamate excess does the same and also wastes glutathione and increases levels of TNF-alpha. peas. GABA damps the propagation of sounds so that a distinction can be made between the onset of sound and a background noise. poor eye contact. leading to excess glutamate. Genomic defects. Remove heavy metals with a chelating agent. 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). glutamine. 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. 2. blocking GABA production (this is felt to occur in the pancreas in kids with juvenile onset diabetes). the glutamate so created cannot be converted into GABA. Glutamate Aspartate Whey protein Malted barley Gelatin Vegetable gum Sources of Excitotoxins – Short List* Glutamic acid. and GABA can be interconverted via the enzymes depicted above. agitated behavior. 6. aggressive behavior. Addressing CBS up regulation/BHMT down regulations to decrease alpha-ketoglutarate production. which has methyl groups. and eventual neuron loss. mercury and glutamate synergize to damage nerve cells. Calcium is involved in glutamate toxicity. anxiety. Low GABA leads to impaired speech. an inflammatory mediator that can produce heart cell dysfunction and gut inflammation. and heavy metals will compromise this balance. alpha-ketoglutarate. The result is glutamate-GABA imbalance. Of interest. but in the presence of lead and aluminum. viral illness. GABA. Copper inhibits conversion of glutamate to GABA by glutamate decarboxylase so avoid copper excess. or back to alpha-ketoglutarate. tomatoes. poor socialization. or better stated. Decreasing intake of food precursors of glutamate (see list below).heartfixer. glutamine. 3.Return to Autism Page Page 17 of 50 Glutamate is the main excitatory neurotransmitter in the body. and constipation. an imbalance between copper and zinc. glutamine. Glutamate is also the precursor to our primary inhibitory or calming neurotransmitter. Aluminum poisons this enzyme as well. It is essential for learning and short and long-term memory. excitotoxicity. We can restore glutamate-GABA balance by: 1. toxicity due to mercury is aggravated by glutamate excess. and eventually nerve loss. which is usually easy to achieve as glutamate. parmesan cheese Aspartame. avoid if COMT (+) http://www. MSG. the key methyl donor generated from methionine. This information will alter the way I treat you. hopefully normalizing serotonin production.htm 4/18/2015 .com and in our presentations (DVDs and information sheets are available to you). VDR Fok The VDR (Vitamin D Receptor) Fok defect affects blood sugar control and pancreatic function. While we can’t change your DNA. individuals with the R297R defect should avoid large doses of high tryptophan foods (see appendix). is metabolized in to S-Adenosyl Methionine. every toxic molecule from your body – to return your biochemistry to the pristine state that Evolution and/or Our Creator intended. Fat. These concepts are outlined below and are discussed in greater detail on heartfixer. 2. BH4 levels should stabilize. and toxin burden. which then rise and fall in response to treatment. Individuals (+) for both AHCY and CBS often have low baseline urine sulfate levels. ACAT dysfunction may lead to B12 deficiency. Methyl Cycle Nutrigenomics: The Methyl Cycle is the backbone of your biochemistry. could lead to mood swings as serotonin levels fluctuate. an understanding of your inherited weak links will alter (and improve) our approach. if we know your weaknesses. etc. Once the cycle starts to spin. Yasko recommends Vitamin K and generalized support of pancreatic function and sugar regulation (low carbohydrate diet. Chronic. and then remove. John’s Wort. pesticides. How best to address the MAO A R297R abnormality is not clear to me. supplementation with chromium.Return to Autism Page Page 18 of 50 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. and then move Heaven and Earth to identify. Approaches to Detoxification Overview – Environmental toxicity (organic pollutants and heavy metals) is a grave threat to health – your health and that of your descendents. Dr. Organic Pollutants: These are non-metallic. ACAT 102: Acetyl Co-Enzyme A Acetyltransferase ACAT is involved in cholesterol and energy metabolism. viral and bacterial invaders.heartfixer. Defects in AHCY are addressed by measures designed to improve overall Methyl Cycle function. a neurotransmitter that is generated from the dietary amino acid tryptophan. Detoxification Genomics: We vary in our ability to activate (Phase I) a toxin.com). 5HTP (a tryptophan metabolite). and the Mood S RNA formula if serotonin support is needed. and petroleum products are a few of the 100s of organic pollutants to which we (and our Mothers) have been exposed to (yes. Upon request. Later. including the SSRIs (Serotonin Selective Reuptake Inhibitors) work by blocking the breakdown of serotonin. bisphenol A. If I know your detox weak links then I can support them with specific supplements/dietary interventions. neurodegenerative conditions involving the young and premature “age related” conditions likely reflect an interaction between environmental toxins and Methyl Cycle predispositions. I can create a detailed analysis/treatment plan.) when the VDR Fok abnormality is an issue. based upon your DNA findings. liver. Agent Orange.com and | $100 through 23andme. Defects in serotonin metabolism have been associated with mood and neurological disorders. fat-soluble molecules that bioaccumulate and compromise our physiology (and that of our offspring). helping to mediate the conversion of foodstuffs into biological energy. Yasko recommends frequent dosing in small amounts of St. Dr. personal health and nutritional status. Right now. Detox Genomic testing is available through Genova Diagnostics (| $500) or through 23andme. in response to a low animal protein/low sulfur diet. often taken to address depression. homocysteine is made available to CBS. as the “bottle neck” abnormal AHCY enzyme has been “limiting the supply” of homocysteine. phyllates. 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). this stuff readily crosses the placenta). improving your ability to detoxify and defend. John’s Wort. Methyl Cycle defects prevent you from coping with environmental toxins.com/AMRI-Nutrigenomics. Diagnosis – Which toxins do you bear and why did you retain them? 1. and then to combine it with a chaperone molecule (Phase II) that escorts it out through the kidneys or GI tract. and compromise proper reading of your genetic code. We can estimate your tissue pollutant burden with: http://www. and neurologic disease. we can create nutritional “work arounds”. and then on to homocysteine by AHCY. The most important thing that we can do (after getting you through an acute health care crisis) is to optimize your intracellular nutritional status. Genomic Analysis: While we can and will detoxify you without knowledge of your genomic status. If serotonin production is impaired on the basis of BH4 deficiency secondary to a Methyl Cycle abnormality. AHCY S-Adenosylhomocysteine Hydrolase S-Adenosyl Methionine (SAMe). A goal of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. particularly with respect to weight gain. urine sulfate levels will fall. such as Methyl support RNA 1/8th dropper per day. Early on the levels rise. It does not affect dopamine metabolism. and urine sulfate will rise. Methyl Cycle testing is available (| $550 via holisticheal. High doses of St. in a BH4 requiring reaction. As serotonin metabolism is adversely affected. difficult to explain disease states. as the abnormality itself is addressed. diabetes. Many anti-depressant drugs. and nerve biopsies would give us the most complete measure of organic pollutant burden but obviously are not practical. I do not understand ACAT well and am not sure how important this is.com (included in the $100 for your Methyl Cycle data). Toxicity testing and detoxification thus makes sense. B. 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). 2. malaise. Red cell metal levels tell us what your physiology has been exposed to over the preceding three months. Lead. industrial exposure in adults. hair. Tissue levels rise with age. Cost is $ 350. and the IV and oral chelating agents utilized. EDTA does not remove Mercury from your cells! We remove mercury with “di-thiol” chelators: DMSA and DMPS. 10 drops in 2 oz. Metametrics provides more extensive organic pollutant testing. I have been treating my patients with Mg-EDTA for 20 years. Battle Plan is typically run over 2-3 months and consist of: A. or could be obtained for $ 136 from Drs. and http://www. was developed by my mentor and good friend Dr.if at all (the half-life of mercury in the nervous system is 10-20 years).Return to Autism Page Page 19 of 50 A. Algas. 10 nights on. This protocol is typically well tolerated by individuals with CBS up regulations. When Lead and Cadmium are the problem. 1. Robert Battle. Metal exposure may vary. the lab fee. but it will also bind. Your cost ($250) includes our fee. particularly Mercury. DMPS: 25 years ago. The magnesium content is also helpful in BP management. inorganic in nature. 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). with metal quantitative in a subsequent six hour urine collection. 3.htm 4/18/2015 . Blood levels reflect recent exposure. The NutrEval is covered by Medicare (not with Aetna/Humana secondary). 9. and leave only slowly . Lipophos EDTA serves as a slow and steady approach to metal detoxification. DMSA: Available over-the-counter or by standard or compounded prescription. over 3 consecutive days. but as innate detox is so slow. We need to estimate your body burden and then remove these elements that can do nothing but harm. C. blood metal levels bear little relation to body burden. Data. Mg-EDTA was used in the NIH sponsored Trial to Assess Chelation Therapy (TACT. Metallothione’s job in health is to store Zinc and Copper. and EDTA was all we needed. toxic metals such as Lead. Cadmium. Metalloclear promotes nuclear translocation of Nrf2 and MTE (Metal Transcription Factor).medfive. Nrf2. So how best to estimate the level of metal accumulation within your internal organs? A. and are not of value in adult detoxification medicine. metals bioaccumulate. B. our only toxin was Lead. both IV approaches are likely equally effective. 4. Dr. 8. of water (let it sit 1 minute before drinking) twice a day – odd days. This $125 test is easily done at home (a dipstick is dipped in a morning urine sample and then sent to the lab). DMSA is typically taken as 500 mg. Red cell metals (and minerals) is included in the NutrEval. when translocated to the nucleus. then the doses of Algas and NDF may be decreased. Battle often uses this protocol to help clear Mercury before beginning Lead and Cadmium detoxification with EDTA. QuickSilver provides a blood. once a month. Treatment – How do we get this stuff out of you? Methyl Cycle and Detoxification Genomic Abnormalities: Nutritional supplementation and dietary avoidance measures are recommended. B. all days. C. at a cost between $ 250 and $ 600. Compared to EDTA. Metalloclear: This Metagenics product promotes metal and organic pollutant detoxification. 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. I helped design Med Five and am a co-holder of its patent. 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.heartfixer. of particular value to patients with vascular insufficiency (please see our DVD presentation). 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). in relation to where you live and work. This is the best test available but perhaps not the best use of your resources. EDTA is the most effective chelator. However. Here we administer oral and IV metal binding agents. This is the best single test in Metabolic Medicine. bind to proteins. and then transport to the liver for elimination. 5 nights off. Today we are being bombarded with “new and improved” toxins. DMSA will bind to and remove Mercury. which addresses heavy metal overload with specific focus on Mercury. and in epidemiology studies. muscle aching) develop. but DMSA is not as powerful as EDTA or DMPS. Mg-EDTA: A series (20-30) of 3-hour IV infusions containing Mg-EDTA. B-Complex and Vitamin C. 6. codes for the production of antioxidant and detoxification enzymes. NDF. Ca-EDTA: Calcium-EDTA alone is infused over 10 minutes.com). we were first amongst cardiology practices and third overall with respect to patient participation in TACT). Its downside is that it weighted more towards recent exposure then to chronic body burden. 3 times a day. 5. 8 drops sublingual twice a day . 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. with commercial insurance the out-of-pocket co-pay is $170.even days (start at 1 drop and increase as tolerated). along with a great deal of ancillary information regarding nutritional and detox function. We can address Mercury toxicity with IV DMPS. Provocative Challenge is the accepted best estimate of body burden. 3. Heavy Metals: Metals enter our tissues. Liposomal Phosphatidylcholine-EDTA (DetoxMax Plus): Liposomes of Phosphatidylcholine serve as drug delivery vehicles for EDTA. and are of value in monitoring lead exposure in kids. D. Battle Plan for Mercury: This protocol.com/AMRI-Nutrigenomics. or within a program of DMSA 500 mg near bedtime. & C. Chlorella 5 twice a day. 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). but here you do not receive IV nutritional support. Dr. 7. and urine mercury assessment. dramatically enhancing its absorption following oral administration. and Cadmium. 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). but the application of liposomal DMPS complexed with Glutathione to your skin is easier for you and is more cost-effective. which codes for the generation of our endogenous metal binder Metallothionine. My personal patients can obtain Med Five at a discount (you receive a password). DMPS binds less avidly to Lead and is not an efficient Cadmium chelator. and estimates the percentage of your mercury burden that is organic vs. but if detox symptoms (fatigue. and IV therapy is the most efficient approach. specific to your individual inherited weak links. With respect to metal removal. The Genova Labs NutrEval gives us markers of Styrene and Petroleum product exposure. but rather electrostatically neutralized (allowing us to remove them in a deliberate fashion). I am not interested in verbally sparing with other physicians who don’t know anything more about nutritional biochemistry and detoxification than I do about delivering babies or removing gall bladders. 15. but I think that you are worth it. into a homeopathic carrier liquid – you take sublingual drops twice a day. but basically the patches emit frequencies that permeate your meridian system and neutralize toxins that you bear. Provolone. Far Infrared Sauna (FIS): Sweat carries out with it toxic substances.we can’t have people prancing around the office in their bathing suits). While TENS therapy seeks to obliterate pain signals. That toxins are being removed has been verified by third party chemical evaluations (see Asyra. and I also realize that being sick ultimately will cost me more than staying healthy. with FSM we seek to communicate with or entrain our physiology to carry out a desired activity. Colby. FSM can be applied to many health challenges (see our information sheet or www. detox. and appears to break ionic bonds between toxins and your normal molecules.htm 4/18/2015 . Red plums. Italian broad beans Salami. Again. Boursalt. Emmental. Selenium. 16.frequencyspecific. Monotherapy with MetalloClear involves three tablets twice a day (with food) over 10 days. The toxins will not be removed.com).com. Platinum Footbath: Your feet or hands are immersed in salt water. My personal patients receive a discount when they purchase a negative field only sleep pad at magneticosleep.heartfixer. along with Broccoli extract. If you do not wish. 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. 14. Figs. I’m not sure whether metals can be removed by the footbath. Glutaclear: This Metagenics product provides N-Acetyl Cysteine. nontransdermal skin patch (see lifewave.and we will help you .com/AMRI-Nutrigenomics. Marmite. to undergo detoxification. and lots of running shoes). Regular sauna will sweat out toxins.Return to Autism Page Page 20 of 50 Mercury. and Vitamin C. to increase Glutathione production. insurance companies. we cannot prove this approach with an allopathic lab study. our Asyra device imprints treatment frequencies. 11. Aged game Canned meats. Romano. 13. This is the basis for MME and magnetic sleep pad assisted chelation – a huge step forward! MME combined with chelation is providing outcomes that aren’t supposed to occur – please review the website to see what we are accomplishing. This methodology can also be used to estimate your body burden of toxins and screen for other health challenges. Frequency Specific Microcurrent (FSM): FSM applies frequencies (via skin electrodes or a moistened towel) at 1/5000th the amplitude of the TENS unit. Why not prevent this? I personally spend a lot of time and money on my personal health (supplements. Asyra Homeopathic Detoxification: Utilizing a physics similar to that of the Aura Patches. Liver Commercial gravies and Soy sauce Salted dried fish (Herring. Costs – Your insurer will not cover the costs of any form of detoxification therapy. home FSM. but our observation is that our patients receive benefit from this approach. Aura (Digital Homeopathy) Organ Detox Patches: Digital homeopathy is an in-depth discussion (so we have DVDs. Please consider what you spend on a new car.com/chc). Appendix I: Foods High in Tyrosine or Tryptophan Foods High In Dopamine (or Amino Acid Precursor Tyrosine) Bananas.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. 17. then we can still help you . Parmisan. and it seems to be particularly well suited to patients with gout. Brie. Asyra is repeated and new drops are generated every 2-3 months over 1-2 years. Brick. The water is ionized. in to which specific frequencies are applied. or on a vacation. soup cubes Aged Cheese (Blue.com). but we don’t offer this treatment . and it is not inexpensive. the field enters your body. Raisins Eggplant. Gouda. CDs. FIS is therapeutic in several cardiovascular conditions (FIS is covered under Medicare. and then ask yourself what your health is worth. but the extreme heat will not be tolerated by many of you. and handouts). FIS utilizes lower heat levels coupled with low level radiant energy derived from ceramic plates to generate active sweating. 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. and Stilton) http://www. Do not expect me to compromise on science to meet the expectations of other doctors. and it is relatively inexpensive ($35 for a one month supply – typically worn over 2-3 months). The toxins are drawn out in to the water in a sort of “reverse electroplating” or “forced sweating” effect. Sausage. or government agencies that just don’t 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. Roquefort. We typically recommend one tab twice a day. I like the idea of vibrant health and a vibrant mind. They will describe it as “medically unnecessary” or “experimental”. specific to you. but I think it does. Cheddar. but we often use it as an adjunctive or maintenance therapy at one tab twice a day. Glutathione Patch – Your body’s own production of Glutathione increases (and blood levels rise) while you wear this drug free. or cannot afford. Mozarella. Aged game Homemade yeast breads Some alcoholic beverages (not all) Yeast concentrates. Green Bean pods. We sweat less as we age (aluminum containing anti-perspirants harm us here). We can’t prove that this method works. 10. but hydrocarbon toxins are. Footbath therapy lends itself well to in-home use. 12. Detoxification is a comprehensive and often long-term process. I will not write letters to request “pre-authorization” – this is simply a waste of time and risks labeling you as a “troublemaker”. Camembert. Cod) Canned meats. to promote Nrf2 translocation. Recognize that methionine and SAMe do contain sulfur. Organic foods are preferable here. often this is not on the label.heartfixer. Yoghurt.beer is less of an issue. Cottage cheese Spirulina (seaweed). Peanuts. Eliminate them only if having trouble turning your strips pink. “What Can I Eat?” Low Sulfur Foods: i Quinoa hot & cold in salads or with fruit i Brown rice. Aged game Homemade yeast breads DMSA and DMPS (Metal Chelators) Milk thistle. and SUOX mutations – here one needs to avoid foods and supplements high in sulfur (sulfites and sulfates). spirulina. while watching your strips to be sure they stay pink.htm 4/18/2015 . but sulfur deficiency is rarely an issue. Do not begin taking horsetail grass.Return to Autism Page Page 21 of 50 Foods High In Serotonin (or Amino Acid Precursor Tryptophan) Turkey. Chicken Liver. Excess sulfur can be a problem for those with CBS. as most foods contain sulfur or sulfur containing compounds. many of which contain sulfur. especially German beer) Soft Drinks Animal Products Dairy Eggs Brazil Nuts Peanuts Soy All packaged and commercially prepared foods contain food additives. not vodka . After strict sulfur elimination for 3 to 4 months you will have eliminated the deep stores of sulfur in your body.com/nosulfites) Dietary Sulfur Issues Sulfur is necessary for many metabolic functions.com/AMRI-Nutrigenomics. you can begin adding very small amounts of sulfur and ammonia producing products back into your diet. Supplements High In Sulfur Taurine Cysteine Methionine Glutathione Glucosamine Sulfate Chondroitin Sulfate and MSM Epsom Salts Magnesium Sulfate Cream Canned meats. Tofu Almonds. If they are already part of your protocol. Brewer’s yeast Watermelon Seeds Appendix II: Foods High in Sulfur (but please review Sulfites and Chronic Disease. BHMT.readingtarget. Soy Nuts Milk. you may continue taking them. and Heparin Foods High In Sulfur Vegetables: Garlic. or parsley. Thereafter. 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. 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. as they contain low levels of sulfur. as do the sulfur containing amino acids taurine and cysteine. non-gluten grains i Fruit (except those on the high sulfur list) i Vegetables (except those on the high sulfur list) http://www. Beyond C. by Rick Williams (available at the office or you can go to www. dandelion leaf. Chicken. Return to Autism Page Page 22 of 50 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. stuffed with apple.heartfixer. i Salads without high sulfur veggies and dressing. or spicy sauce i Sauté 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. fiber such as flax and blend with rice or nut milk until smooth http://www.com/AMRI-Nutrigenomics. Simmer one hour. green beans. 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. i Apple or berry sauce mixed with flax seed i Nut-Milk Shake: Take frozen fruit chunks. stevia. zucchini squash.htm 4/18/2015 . Lay flat on baking sheet and bake until crispy. 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. and celery to alkaline water. berry. flavor with salt as needed. chopped vegetables. or ginger. i White bean or lentil soups with rice crackers. and MSG. and bake until crispy. tomatoes. fish. butternut. Smoke Bouillon. Broth. Season as desired.com/AMRI-Nutrigenomics. High levels are found in foods such as peas. Beef.Return to Autism Page Page 23 of 50 i Cut vegetables. quinoa. Flavorings Malt Flavoring Or Concentrate Glutamate Food From Fast-Food Chains Other Sources of MSG OTC Medications http://www. Cut into thin slices and bake flat until crispy. Whey Protein Isolate. Cut up brown rice tortillas (found at Trader Joe’s) place on baking sheet. and form into patties. i Mashed Squash: Take acorn. 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. glutamine. or other hard squash and cut in half. Appendix III: Foods High in Excitotoxins Sources of Excitotoxins Glutamic acid. rice). mix with olive oil and seasonings and bake i Brown rice tortillas chips: Coat pan with olive oil.htm Chicken Pox Vaccine 4/18/2015 . Brown in olive oil. butternut. i Cold quinoa with cut vegetables and Italian dressing. Add enough non gluten flour (chickpea. parmesan cheese. salt or other seasonings. Mash with xylitol and cinnamon. Malt Extract. or other hard squash and steam. i Boil vegetables like potatoes and dress with olive oil and seasoning. and many vegetables Aspartate Aspartame. mushrooms. milk. Whey Protein. i Squash Fries: Take acorn.heartfixer. Or Stock Barley Malt. i Vegan burger: Combine cooked sweet potato or yams. nutmeg. Pork. generating excessive sulfite/sulfate). Powdered Dry Food Mixes Soy Sauce Dough Conditioners Some Spices Chocolates / Candy Bars Frostings And Fillings Mustards Canned And Smoked Tuna. 1%.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.heartfixer. Frozen. 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. Is an elevated urine sulfate diagnostic of a Methyl Cycle defect? B. or http://www. medication adjustment. 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. So what exactly does this mean? What should you do know? Is the study 100% diagnostic? Right now. 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 Boar’s Head Cold Cuts/Hot Dogs Planter’s 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. Are there false positives (high sulfate with normal genes) and false negatives (low sulfate and abnormal genes)? C. we are on to something very important here and it likely affects you. 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. but on the other hand it doesn’t 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. these individuals have “upstream” abnormalities that limited Homocysteine production. 2%.150. Methyl Cycle testing is expensive: $1. 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. There are clinical “tip offs” to a Trans-Sulfuration pathway defect.150 for the testing. nor does anyone else.Return to Autism Page 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.htm 4/18/2015 .com/AMRI-Nutrigenomics. all tailored to the individual’s genotype. Clams Flavored Teas. analysis. However. 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 . The questions that we have regarding the link between urine sulfate and the presence/absence of a specific genomic defect are: A. Is there a quantitative relationship between the sulfate level and the severity of the genomic impairment? D. while the urine sulfate test costs $10 . we do not have absolute answers to these questions. looking for the underlying “common denominator” causes of the otherwise difficult to explain and address disease states with which many of our patients present. As you are by now aware.so we carried out the urine sulfate test in you and it returned above 1. giving CBS/BHMT less homocysteine to force down the Trans-Sulfuration pathway. My initial impression is that individuals with markedly elevated urine sulfate levels all have CBS and/or BHMT abnormalities.600 mg/liter. Obviously it doesn’t make sense to test every patient who we see. can lead to a major change in the health of these individuals. Dietary change. and recommendations. We have seen a few false negatives (CBS/BHMT abnormality present but urine sulfate only in the 400 mg/liter range). and specific nutritional support. Non-Fat. Methyl Cycle Genomic testing costs $1. Oysters. we are actively involved in Methyl Cycle Genomic testing. com/nosulfites/. this approach is medically reasonable. Boron. our diagnostic and treatment methods will evolve and improve – it‘s always been this way. If money is an issue but you wish to take some positive steps. Molybdenum to help SUOX break down sulfite into less toxic sulfate. Still. use Ammonia Support RNA. 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. and alphaketoglutarate. which depletes BH4 (leading to insufficient dopamine and serotonin production. Others may wish to take action while waiting the two months for the lab results to return. Carnitine. The “tip offs” to a Trans-Sulfuration Methyl Cycle defect are sulfite sensitivity (and to a lesser extent asthma and easy bruising). supplementation will be helpful but probably not critical. and a lack of nitric oxide). We could also. while ours is on adults with chronic or unexplained illnesses. such that sulfate could not be generated from sulfite (the entity actually generated by CBS). You could also wait. These supplements can be tapered down as ammonia levels fall. but this is too important a concept to just “sit on”. and when patients with known CBS/BHMT abnormalities switch to a low sulfur. As there is nothing inherently dangerous about our approach to CBS/BHMT dysregulation.readingtarget. Yasko’s website holistichealth. Homocysteine (as well as its methyl cycle precursors) is being drawn down the transulfuration pathway. too much alpha-ketoglutarate (which leads to excitotoxin activation).SUOX co-factors become depleted. 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. magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). 2. and our invitation to you to learn more. this letter. designed to fit the genotype of the patient. their urine sulfate levels do fall. adjust your drugs and nutritionals while watching your urine sulfate level.$5 admission) and by studying the information discussed above in this section of the website. 8. Many drugs and nutritional supplements are loaded with sulfite/sulfate (typically not a problem for individuals who do not harbor Trans-Sulfuration defects). P-5-P will be less of an issue. a low or low normal homocysteine level.com. and/or they were already on a Vegan type diet. keeping in mind that her focus is on Autism. No animal protein diet (anything with eyes) and avoid sulfur rich vegetables. 5. To address CBS up regulation/BHMT down regulation we typically recommend: 1. 3.or +/+ for one of the CBS up regulations and +/+ or +/. and Yucca. a charcoal supplement at bedtime (away from other supplements. and are best avoided or minimized.for BHMT 1-8. which stimulates CBS. Dietary change and nutritional supplementation. and this is a better diet than the one most of us are currently following. 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. thus the need for supplementation). Plan of action for CBS/BHMT http://www. 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. and too much ammonia. Co-Q.150. which act like CBS up regulations. So far we have not identified any false positive patients. sulfur containing supplements. Vitamin E succinate.heartfixer.htm 4/18/2015 . Homogenized dairy products contain xanthine oxidase. 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). sulfate. is turning around the lives of some previously quite ill people. and NADH will help increase energy production. You can learn more at our monthly Methyl Cycle support group meetings (third Monday of every month at the Secor Clarion . there could be causes for a false positive study. As we gain more experience in this area. You can also review Dr. Some individuals may choose to omit Methyl Cycle testing and proceed directly to treatment. you could change your diet “as if” you have a CBS/BHMT abnormality.$1. 6. After your sulfur and ammonia pools have been depleted down towards normal we can be more liberal with other methyl cycle supplements. available at the office or at www. low animal protein diet. and sulfur containing drugs (see CBS and Appendix II: Foods High in Sulfur and/or read Sulfites and Chronic Disease by Rick Williams. then undergo Methyl Cycle testing. Avoid excitotoxins (see list on heartfixer. as if they have this genomic defect. Minimize B6. in this process generating too much sulfite and sulfate (which stimulate the stress/cortisol “fight or flight” response). thus the urine sulfate screening. Monitor urine sulfate every 4-7 days. To neutralize ammonia.com/AMRI-Nutrigenomics. 4. It is not inconceivable that if you take these drugs or supplements that your urine sulfate will be elevated regardless of your genomic status. Again. Please review the attached instruction sheet.com) and supplement with GABA twice a day. So what should you do with this information? If money is not a concern. The supplements we use in CBS/BHMT individuals are all benign. and B12 are felt to stimulate SUOX activity (SUOX is “overworked” by the sulfite load presented to it by CBS/BHMT .Return to Autism Page Page 25 of 50 a “downstream” defect in SUOX (Sulfite Oxidase). and/or add in BH4. we will have more definitive information in the future. Idebenone. 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 . in a step-by-step fashion. 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. Overview We assume that you are +/. which uses up molybdenum. 7. 9. Olive Oil 3 Stalks Organic Celery (sliced ¼”) 6-8 oz small Organic Carrots 3 T. two twice a day along with Trace Minerals Complex at 4 drops/day. use Ammonia Support RNA ½ dropper with meals and with methyl cycle supplements. thus drawing homocysteine away from the CBS “drain”. 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). These are the key nutritional interventions. beginning at ½ capsule. homocysteine. and we will try to phase out anything high is sulfur. if you feel that GABA is helping a lot then you can increase the dose. 3. along with a charcoal supplement at bedtime (away from other supplements.htm 4/18/2015 . your current multi likely contains B6. A better program involves the Yasko NHF multi. Fresh Basil 2 T..Return to Autism Page Page 26 of 50 1. Oregano 1 T. twice a day. baseline Vitamin D. Lipophos Forte 900 mg/day will stimulate BHMT. watch for peel to come off then add to ice bath or 1 can 14. and NADH one per day are ideal but not critical. 8. and hydroxy-B12 2000 mcg daily to stimulate SUOX (the enzyme that converts sulfite in to less toxic sulfate). and use the results to refine your supplementation program. magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation). Carnitine 500 mg twice a day. 7. Alkaline Water (about 2 quarts) then add 2 Fresh Tomatoes (peeled and chopped) to peel/score add to boiling water 15-30 sec. Co-Enzyme Q10 100 mg/day. 6. Begin Molybdenum 3 drops twice a day. may help with ammonia detoxification.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 Organic—Enjoy! Created by Cheryl Church Orange Spaghetti Sauce 2 T.Fresh Ground Pepper Sauté about 15 min Add 2 L. ½ bottle twice a week. Celtic Sea Salt http://www. Add GABA 500 mg once a day to blunt excitotoxicity. Check the sulfur (sulfite) content of your medications and supplements. if it is not doing anything for you then it can be discontinued. Boron 3 mg/day. Celtic Sea Salt 1 T .com/AMRI-Nutrigenomics. the clearance of which appears to be reduced in individuals with Methyl Cycle abnormalities. will also remove heavy metals. Fresh Oregano 2 small Zucchini (green and yellow) sliced ¼” 1 T. Appendix VI: Methyl Cycle Recipes Veggie Organic Soup 2 T. Olive Oil 3 Stalks Celery/diced 1 Orange Bell Pepper/diced 1 Med Carrot/diced Sauté until tender. 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. Regarding nutritional support. To neutralize ammonia. Lipophos EDTA. and then add 1 T. Yucca. If not already done. 5.heartfixer. 10. 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. 4. 2. (or sprinkled on food containing protein). and ammonia levels will be helpful (and will be considered at your next office visit). Begin the diet discussed above and the supplements described below. Return to Autism Page Page 27 of 50 1 T. Fluff with a fork and set aside to cool. Bake at 350 degree oven for 20-25 minutes Season to taste. Serve chilled.14. In a large frying pan on medium heat.zucchini. 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. Simmer for 15 minutes or until cooked.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 sauté 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. cover and reduce heat to medium low. Bring to a boil. peaches etc) 1-2 tea. Fresh lemon juice 1 T. peppers whatever veggie you like. lemon juice. yams. Celtic Sea Salt Blend in food processor until smooth Sprinkle with chopped fresh parsley Serve with Rice Chips or Sweet potato and Beet Chips http://www. stir together the quinoa and water. Black Pepper 3. cinnamon 1-2 tea real maple syrup # 2 Brown Rice Crisps Fruit (blueberries) Rice Milk #3 Roasted Potatoes with beets . olive oil 1 medium red bell pepper/chopped 1 tsp cumin ¼ cup fresh cilantro/chopped 2 T. Mix well and cool in refrigerator. Real Maple Syrup In a medium saucepan.htm 4/18/2015 .heartfixer. cilantro. In a large bowl.com/AMRI-Nutrigenomics. Drizzle with Olive Oil. vinegar and maple syrup. Set aside until cool. Add the peppers and cumin and sauté for an additional 2 minutes. combine the quinoa. sauté the yams until they are tender but firm to the bite. 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. Brown Rice Vinegar 1 T. Return to Autism Page Page 28 of 50 #4Avocado Dip 1 medium size avocado/mashed with potato masher 1 chopped medium tomato 1 fresh squeezed lemon 1 T. Fresh cracked pepper. Add 4 cups chopped red skin potatoes. 1 T.holisticheal. In separate pot boil 4 cups chopped red skins potatoes to mash and add to soup for creamy texture. 1 T. olive oil Sauté 4 above items until a little brown then add 3 cups alkaline water or filtered water. fresh cracked pepper. ¼ tsp cumin. Sprinkle with fresh basil and small amount of Parmesan Reggiano.heartfixer.com www. 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. 1/8 tsp red pepper (cayenne) and a dash of nutmeg. Celtic Sea Salt.com ww. To add protein serve over cooked quinoa. 1 tsp. Makes about 6-7 cups To add protein serve over quinoa pasta. if you like pepper this soup tastes great with lots of black pepper. 1 T.emersonecologics. Cover with alkaline water or filtered water.lef. ¼ tsp thyme. Bring to boil and simmer until potatoes are tender about 15-20 minutes. 1 bay leaf. Created by Cheryl Church Corn and Potato Chowder 2-3 T. Created by Cheryl Church Nurtigenomic Supplements and Supplies Nurtigenomic Supplements and Supplies (* are available at office) Holistic Health (Dr. Add all to blender and mix until smooth. 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 2 ½ cups chopped organic celery 4 cups organic corn (from can or cut from cob) Sauté until celery is a little tender. Celery Blend a product made by Celtic Sea Salt Selina Naturally. 1 tsp Celtic sea salt.htm 4/18/2015 .com/AMRI-Nutrigenomics. ¼ tsp cinnamon. 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.org Comments $55 for a package of 100 sulfate test strips $55 for a package of 100 sulfite test strips Ammonia support (neutralizes ammonia)* http://www. Simmer for 15 minutes. $28.60 Quercetin 500 mg with Bioflavonoids – 50 for $14.19 12.05 200 mg SAMe – 50 for $33.5 mg – 90 for $27 2 oz.20 750 mg TMG – 100 caps for $15. 25 mg P5P.holisticheal. 2 mg methyl B12. 60 for $17.100 for $6.99 100 caps for $11.95 75 mcg/3 drops – 2 oz. & 2 mg methylB12 5 mg methyl folate.10 Dr.46 100 260 mg capsules for $9. bottle providing 265 doses for $12. 100 for $21 5 mg tabs.90 50 mg phosphatidyl serine with 50 mg DMAE – 120 for $28.htm 4/18/2015 . and 500 mg NAC Stabilized Super Oxide dismutase – 90 for $28 15 for $90 (each should last for 7 days) .90 Ubiquinol 100 mg – 60 for $55 100 mg – 60 for $40.99 for 180 Perque 2000 mcg hydroxy-B12.8 mg methyl folate.lifewave. for $12.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.$24 500 mg Montiff GABA.99 2.com/AMRI-Nutrigenomics. 30 for $33.75 5-methyl folate 800 mcg.49 800 mcg/tablet . Yasko’s 6-a-day multi for neuro health – $29.heartfixer.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.com x Click on Advance search x Scroll down to box that states “Search for product” x Click on Advance search option x You will see: search category: sku: price: x Enter sku # from list for the product you are looking for x Click on search x Under Quantity enter how many you want to order x Click on add all items to cart http://www.99 275 mg GABA and 100 mg Threanine – 60 for $21 Carnitine 500 mg – 60 for $39.60 for $11 Metanx: 2.20 3 mg .5 month supply for $10.Return to Autism Page Page 29 of 50 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 $17.50 400 IU . No .org x On right side of screen enter product code in Search Catalog Number x Then click add to cart Methyl Cycle Genomic Testing and Treatment .we got involved in Methyl Cycle testing for the usual reason.What you Can and Cannot Expect from Us We got involved in Methyl Cycle testing not because we had to. to http://www.com x On left side of screen click on “Product search” x Enter code from list in box “By Product Code” x Do not use any spaces with letters or numbers x Check selection box x Click add to shopping cart x Then click add more product x Follow same protocol for other items x When all items are selected proceed to check out x Follow directions to “Register Now” x Click “I am a patient” x Click continue x Enter all info requested x Click continue and follow directions for payment Ordering from Life Extension Foundation x Log onto www.heartfixer. and not because we don’t have anything else to do.emersonecologics.lef.com/AMRI-Nutrigenomics.htm 4/18/2015 .Return to Autism Page x Screen will show items in cart x Click on Advance search and follow same protocol until all items are in cart x Then click “check out” x Review order and select delivery option x If everything is ok then where you see update click “GO” x Enter your delivery information and submit x Follow directions for payment Page 30 of 50 Ordering from Emerson Ecologics x Log onto www. on an individual basis. It also doesn’t follow that we should work for free or lose money.heartfixer. 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).125 fee covers the cost of the laboratory Methyl Cycle testing. it doesn’t follow that we caused the problem. 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. If we are to continue to provide new and innovative services like Methyl Cycle testing.com/AMRI-Nutrigenomics. New treatments. Roberts to call me”. always generate a lot of questions. and it’s not our fault that your genes are what they are. and that dietary change is difficult. 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.Return to Autism Page Page 31 of 50 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. and then transmit my answer back to you. We do put a lot of information regarding diet in to our Methyl Cycle reports. Your $1. brings the issue to my attention. 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. Dr. just because we are the first practice in the area to provide Methyl Cycle testing and you have a lot of questions. which integrates the Methyl Cycle findings into your past and current medical status. just as they can’t explain the biophysics that allow the Glutathione patch to work or the bioengineering that allows the MME machine to regenerate damaged cells. We do this because our current best methods are not good enough. Remember. Also. when a staff member takes your message. We have added to our program various means by which you can learn more. Take advantage of these resources. We’d like to answer all of your questions. we are not dietitians nor are we nutritional counselors (but Krista McCarthy Mignin is). We can’t do this. ranging from our monthly Methyl Cycle support group meetings to individual sessions with Krista McCarthy Mignin MS.htm 4/18/2015 . and Dr. This is why we brought MME to town 4 years ago. but please remember. Please remember. or “is a certain food OK”? We do not have ready answers to these questions. Roberts’ analysis and recommendations. but in reality we can’t. Roberts MD FACC 8/24/08 Sample Report One Nutrigenomic Report . We do give you resources where you can learn more. James C. the answer to which 75% of the time will be in my written 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 http://www. especially new treatments not available elsewhere in the area. We provide a lot of innovative services that generate a lot of questions. Roberts can answer these questions (well. Dr. that you feel lousy. We realize this and we need you to realize this as well. If you cannot accept this then please undergo Methyl Cycle Genomic testing elsewhere. All of you know how hard I work. and why we continue to bring innovative and low risk diagnostic and therapeutic modalities to NW Ohio. please put it off until your office visit or until the next Methyl Cycle support group meeting. well. Yasko’s report. Staff members cannot answer questions regarding the biochemical genetics of specific Methyl Cycle pathways. a lot of staff time is taken up – and I am paying for it. and do so in a timely fashion. Call us when you need to (and there will be times when you need to) but if a question can wait. please avoid expressing anger at staff members. 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. It takes Dr. Please do not call with questions like “what can I eat”. on an individual basis. we are going to need your cooperation. but it’s not our fault that you’re sick. but he cannot answer them for you. 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). most of them). pulls your chart. and the staff overhead generated can easily get out of hand. outside of your office visits – it’s just not logistically possible. We realize that you are sick. just because we found an important problem that may be difficult to address. SHMT (serine hydroxyl methyl transferase – you are +/.for at least one of the three BHMT alleles (which act like CBS up regulations .heartfixer. After the problems in the trans-sulfuration pathway (CBS and BHMT) have come under control. your sulfate levels are 800-1200). The antioxidant/detoxification molecules cysteine. which is then converted to 5-methyl folate by MTHFR. Your DHFR (+/-) status may also compromise BH4 recycling. in this process generating excessive sulfur break down products (sulfite and sulfate. 5. which is http://www. you are having some trouble breaking down folinic acid. the oxidized dietary folate molecules that we take in must first be reduced to Tetrahydrofolate (THF) by dihydrofolate reductase (DHFR). in lipid metabolism. BH4. BH4 or additional methyl-folate as a BH4 precursor/mimic can be added to your program. you are having trouble with these steps and in recycling folate derivatives back in to THF. However. and then to initiate a slow but steady detox program that you can tolerate. too much excitotoxic glutamate (which you may have trouble converting in to GABA due to your GAD1 +/+ status. PEMT (which is stimulated by estradiol) uses three SAMe molecules to generate phosphatidylcholine. Being +/+ for MTHFD1. and too much ammonia (which depletes BH4. Aggressive methyl group supplementation can lead to fluctuations in dopamine. and thus you are having trouble generating phosphatidylcholine. optimize your nutritional status.for both of the CBS up regulations and +/. and supplement you based upon the results. a point in your favor as dopamine helps defend against toxic metals. Yasko feels that MTHFR A1298C (+/+) status compromises recycling of BH4 from “spent” BH2. as was methionine. along with a high SAMe:SAH ratio. SAMe. Thus we will be ginger with respect to methylB12 supplementation (also. As you are COMT +/+. B.to generate the building blocks for DNA and RNA generation. need to generate neurotransmitters and nitric oxide. you will break down dopamine only slowly.10-MethyleneTHF can also be acted upon by MTHFD1. methylmalonic acid.here). however your glutamate level was not elevated on your 9/12 NutrEval).htm 4/18/2015 . To become useful. the universal methyl donor.for one of the MTRR alleles.no call means that for technical reasons 23and me could not determine the status of a particular allele). necessary for biological methylation. Being +/. you are getting hit at both ends – reduced production and increased utilization. MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine. You are ++ for a loss of function PEMT allele. or we could use a combination of low dose folinic acid and methyl-folate. producing mood swings. which stimulate the stress/cortisol “fight or flight” response. such that conversion of dietary folates in to useful THF may be compromised.for MTHFS. using up methyl groups in the process. You are +/.com/AMRI-Nutrigenomics. You are (+/-) for a DHFR reduced function allele.10-MethyleneTHF. taurine. We can measure folate metabolites. and in the generation of the neurotransmitter acetylcholine. Phosphatidylcholine supplementation makes sense here. as you are +/+ for COMT. This deficiency in BH4 allows NOS (nitric oxide synthase) to convert Arginine in to free radicals as opposed to nitric oxide. which in turn is converted in to S-AdenosylMethionine (SAMe). and glutathione. leading to insufficient dopamine and serotonin production). so with respect to the precious molecule BH4. which will be a little difficult to address with supplementation. hopefully improve your energy level and sense of well being. COMT breaks down dopamine. a pyridoxal-5-phosphate (active form of B6) dependent enzyme. an index of B12 need. C. Dr. Being +/+ for FOLR2 (folate receptor) your cells may have trouble taking up folic acid (more so then with methyl-folate). My hypothesis is that these genomic predispositions have set you up for organic pollutant and metal toxicity and stressed your nutritional status. We use phosphatidylcholine in the remethylation of homocysteine into methionine by BHMT (also pulling homocysteine away from the “CBS drain”). being COMT +/+ renders you sensitive to methyl groups. was normal on your NutrEval study. tacks on a methyl group derived from the amino acid serine to generate 5. Folate molecules serve to transfer methyl groups within our physiology (think of folates as “methyl group taxis”). You are +/. Overall my thought would be to address your genomic predispositions. Your Methyl Cycle and Detox Genomic findings are significant. Homocysteine (and its Methyl Cycle precursors) is thus being drawn down the trans-sulfuration pathway. predisposing you to hypertension and cardiovascular disease. and thus you may benefit from greater than usual levels of methyl-folate.Return to Autism Page Page 32 of 50 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. sulfate. meaning that you are having some trouble converting B12 in to methyl-B12. likely as your glutathione reserves are being used up dealing with mercury).Return to Autism Page Page 33 of 50 generated from homocysteine in a B12 dependent fashion. In thinking about your Methyl Cycle status. which stimulate the stress/cortisol “fight or flight” response). Yasko feels can be converted into GABA. and too much ammonia (which depletes BH4. Being +/. quite slowly.com/AMRI-Nutrigenomics. noting however that your glutamate level was not elevated in 9/14). Genetic Bypass. you are getting hit at both ends – reduced production and increased utilization. Your COMT +/+ status is limiting conversion of 2-OH estrogen molecules in to the protective 2-methyoxyestrogens. A deficiency in BH4 allows NOS (nitric oxide synthase) to convert arginine in to free radicals as opposed to nitric oxide. Dr. predisposing you to hypertension and cardiovascular disease. Your Methyl Cycle abnormalities likely predispose you to impaired detoxification. You are +/. which acts like VDR Taq). while being +/+ for CYP1B1 you are predisposed towards 4-hydroxylation. and the ratio of SAMe to SAH could fall. Your ammonia level was not elevated in 9/14. May placed you on iodine to promote metabolism of 16-hydroxy estradiol to estriol. so it is best that you minimize caffeine (especially coffee) intake. Approaches that make the most sense to me receive a (—). a toxic derivative of homocysteine). taurine (why your taurine level is elevated) cysteine (elevated). 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). The Gene by Gene sections provide generic information while specific recommendations for you are described in the Plan of Action sections. your 2/16 ratio is OK at 2. May has you on I3-C. hydrogen sulfide (to produce brain fog). Those that are less critical (or more costly) are designated (+/-).for DHFR. You are +/. Dr. so you will break down serotonin relatively slowly. Being +/+ for CYP1A2 you are having trouble breaking down caffeine.(half of your CBS enzymes are abnormal) for one of the CBS up regulations and +/. During normal physiology. in this process generating excessive sulfur break down products (sulfite and sulfate. I will be doing a little bit of brainstorming as we discuss your Methyl Cycle status. and thus methylation of B12 is likely not seriously compromised). Being +/+ for MTHFR A1298C and +/.for VDR Taq (and VDR Bsm. CYP1A2 compromises your ability to 2-hydroxylate estrogen molecules. PON1 +/. we need to keep in mind that recommendations based upon Dr. and Dr.htm 4/18/2015 . and can be addressed with pomegranate intake. given your well characterized food sensitivities.8. a calming http://www. and your evaluation has demonstrated problems with mercury and tin (the primary source of both is likely your prior mercury fillings). and being +/+ for COMT you are having trouble breaking down catecholamine molecules (dopamine and norepinephrine – “adrenalins”). but +/+ COMT.for at least one of the BHMT down regulations (which act like CBS up regulations). such that SAH levels may build up. which lead to oxidative stress and inflammation. and improving your overall antioxidant status should help here as well (we use antioxidants to reduce 16-OH estradiol to estriol). Your work up to date has been incredibly comprehensive. so with respect to the precious molecule BH4. I can see how the CBS “nothing with eyes” diet would be problematic for you. and thus you probably do not have a great need for serotonin precursor therapy. and your +/.status for GPX and GSTP compromise your ability to neutralize hydrogen peroxide with glutathione. Gene by Gene Approach – CBS +/.status compromises interconversion of glutamate and GABA. meaning that you are not making enough dopamine in response to Vitamin D (somewhat mitigating your methyl group sensitivity). likely as you are not taking in excessive animal protein. meaning that you are breaking down dopamine. particularly with respect to diet. now that we understand their origin and biological significance. which stimulates 2-hydroxylation. AHCY converts S-Adenosyl Homocysteine (SAH). Compounding this predisposition towards increased production of superoxide. Instead your genomic status predisposes nitric oxide synthase to generate the free radicals superoxide and peroxynitrite. compromising your ability to utilize SAMe as a methyl-donor. and +/. However. Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration pathway. You are +/+ for MAO A. Thus we need to keep everything in proper perspective. your +/+ status for SOD compromises your ability to neutralize superoxide. Yasko’s work with autistic kids may be problematic in adults with other genomic or acquired health challenges.and BHMT +/- CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. too much glutamate (which leads to glutaminergic excitotoxicity – a double problem for you as your GAD +/. you are having trouble regenerating BH4.for MAO B.for AHCY this reaction may be sluggish. I realize that this sounds awful but these are all issues that we can deal with. leading to insufficient serotonin and dopamine production. Smith to consider. and have some ideas for you and Dr. Yasko’s book. metabolic flow down the CBS pathway is designed to generate the important anti-oxidant and detoxifying molecules glutathione (your level is not high. and alpha-ketobutyrate (which Dr. MAO A breaks down serotonin.compromises the antioxidant function of HDL (and our ability to detoxify homocysteine thiolactone. Smith knows a lot of things that I don’t ands he has a great understanding of your health status. generated whenever a SAMe is “spent” in to homocysteine. thus you will not need nor will you likely tolerate dopamine precursor therapy or high dose methyl group supplementation.heartfixer. and using up methyl groups in this process. Thus your ability to generate neurotransmitters and nitric oxide will be compromised. Yasko’s position. 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. we cannot convert arginine in to nitric oxide. when homocysteine is drawn down the CBS pathway. MSG.heartfixer. or if toxic metals compromise the interconversion enzymes. Actually. who is a gastroenterology fellow). However. an excitotoxin. has been shown to be a safe and effective approach to ammonia reduction in liver failure. and if one experiences agitation/anxiety than aspartate can be dropped in favor of more ornithine. Yasko’s diagrams indicate that CBS generates alpha-ketoglutarate. which can be converted into glutamate. then we suffer a buildup of the excitatory neurotransmitter glutamate. CBS generates sulfite and sulfate)? While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification. we can achieve the same end nutritionally with vitamin C and magnesium. Gastroenterologists utilize the cathartic lactulose to accelerate GI tract motility. and thus individuals with advanced liver disease experience hyperammoniaemia. as SAMe stimulates CBS. or glutamate. others dispute this position but we typically see elevated glutamate in individuals with CBS/BHMT + alleles). Systemic ammonia detoxification takes place in the liver. Glutamate is involved in alertness and learning. and to do so BH4 (tetrahydrobiopterin) must be “spent”. Charcoal seems to absorb ammonia generated within the GI tract. These and other amino acids are best absorbed on an empty stomach or with a carbohydrate. a dietary source of glutamate. 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. Gastroenterologists use antibiotic therapy (Rifaxamin. as moving your bowels 2-3 times a day is important in detoxification and ammonia neutralization. Intestinal microbes generate ammonia. concomitant protein intake will blunt their absorption. impaired coordination). individuals with CBS + alleles nearly always display elevated glutamate. leading to hypertension and cardiovascular disease. 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. blocking ammonia absorption. to generate the above listed antioxidants needed to allow the body to respond to an oxidative challenge – a good thing. instead vascular wall toxic free radicals such as superoxide and peroxynitrite are created. increasing to one teaspoon as needed. and we can utilize this low cost approach to deal with ammonia excess in Methyl Cycle patients. We should be able to interconvert alpha-ketoglutarate into glutamate. starting with 1000 mg (1/3rd teaspoon) three times a day. 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. SAMe has been used to treat lead overload (and presumably will work against mercury). and GABA. you will experience detox phenomena).com/AMRI-Nutrigenomics. after we decrease your sulfate/sulfite pool. However. thus these SNIPs which direct homocysteine towards glutathione and away from SAMe regeneration). CBS generates alpha-ketobutyrate. a poorly absorbed antibiotic that does not enter the circulation) to sterilize the gut. if glutamate is in excess. I can’t back this up from my review of the scientific literature but her position seems to work in practice). an enzyme pathway that utilizes several amino acids (ornithine. your detox pathways will open up (and why. aspartate. Aspartic acid has a glutamate-like stimulating effect. 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. In this fashion oxidative stress (something we wish to avoid) leads to reduced SAMe. Oxidative stress (the accumulation of free radicals) increases flow down the CBS pathway. confusion. Ornithine/Aspartate supplementation (LoLa). Without BH4. Ornithine monotherapy has been used to increase exercise capacity in healthy people. a huge negative here. Charcoal can also cause constipation. 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. Dr. Nonetheless. as ammonia production is a metabolic consequence of energy utilization. Ammonia is metabolized within the urea cycle. thus blunting ammonia production. The excess ammonia generated must be detoxified. glutamine. if we move too fast. administered IV or orally. and thus taking charcoal at bedtime seems to lower one’s ammonia burden.htm 4/18/2015 .Return to Autism Page Page 34 of 50 neurotransmitter. arginine. can precipitate atrial fib)? We address high glutamate/excitotoxicity by avoiding high http://www. which inevitably converts homocysteine into glutathione. but excess glutamate leads to irritability and over-excitement. SAMe itself stimulates flow down the CBS pathway (if you have plenty of SAMe you do not need to worry about recycling it). 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). and indirectly alpha-ketoglutarate) to break down ammonia. it is “lost forever” such that it cannot be remethylated and used to regenerate SAMe. While we may recommend antimicrobial therapy to address bacterial overgrowth demonstrated on a CDSA (Comprehensive Digestive Stool Analysis). with attendant neurological dysfunction (tremor. sulfate/sulfite/-SH excess seems to block cellular up take of the key detoxifiers glutathione and cysteine (this is Dr. You thus suffer from “too much of a good thing and way too much of several bad things”. leading to loose stools and diarrhea). 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. and thus the same physiology holds. 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). so the less ammonia formed the better. (or sprinkled on food containing protein). BH4 is used up in ammonia metabolism. twice a day makes sense (already on board). and boron. Methyl-folate and methyl-B12 detox pathways will then open up. as beneficial neurotransmitters are generated. Phosphatidylcholine can be admixed with EDTA (detoxifies metals). Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR (compromising methyl-B12) abnormalities. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables. 5. then your anti-oxidant and detox capacity will increase. Ribose. twice a day. all have health benefits but all add to your sulfite/sulfate burden. creating a quite useful supplement.as charcoal may lead to constipation). specifically to address the CBS abnormality (see www. which is thus depleted in CBS + individuals. Conversely. promoting ammonia degradation. which is then metabolized by SUOX (Sulfite Oxidase) to the less neurotoxic (but still problematic at high levels) sulfate. or BH4. 3. as does phosphatidylcholine (which we use to treat atherosclerosis). 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). and here supplementation (in relation to your COMT/VDR status) with Co-Enzyme Q10. if we treat you with methyl-folate. Yucca. While your ammonia level was not elevated. However. serving as a “back door” pathway to “pull” homocysteine away from the CBS “sulfate drain”. It will take us some time to change your internal environment to “bypass” these genomic challenges. Sparga was developed by fellow Cardiologist Dr. 6. you can use Ammonia Support RNA ½ dropper with meals and with methyl cycle supplements (relatively expensive). Homogenized dairy products contain xanthine oxidase. Smith have the bases covered based upon your NutrEval study. Lee Cowden. TMG (trimethylglycine) stimulate BHMT. As Methyl Cycle function is needed in the biosynthesis of Co-Enzyme Q10 and Carnitine. individuals + for CBS will likely be energy depleted. if we could convince your biochemistry to up regulate biosynthesis of glutathione. Sparga Detox. persistent high sulfate spills indicates that your diet/treatment program needs further modification. Basically. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. To neutralize ammonia (generated from animal protein). 10 drops in water (wait at least one minute before consuming).com/nosulfites/. This can be achieved with the use of the Life Wave (needleless acupuncture) Glutathione patch. Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a liberalization of your diet. Ornithine/Aspartate 1000-3000 mg three times a day (taken away from other sources of protein) will stimulate the urea cycle. Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until CBS/BHMT are under control. Plan of action for CBS +/. please add molybdenum 500 mcg daily to complement the boron. be very conservative early on. creating toxic intermediates that cannot be metabolized further due to the block in glutathione utilization – and you will feel horrible. http://www.optimally twice a day . away from other supplements (magnesium citrate and Vitamin C may be used as needed to keep the GI tract moving .htm 4/18/2015 . and B12 are felt to stimulate SUOX activity.nutramedix.(BHMT discussed further in other sections) To address this constellation of alleles I will recommend: 1. which uses up molybdenum. SUOX activity requires molybdenum. 2. which are already present in your program. Thus if you bear CBS or BHMT abnormalities. With respect to overall nutritional support. We may or may not wish to stop these agents. Vitamin E succinate. and NADH or NAD+ may be helpful.readingtarget. Some of your current supplements may contain sulfhydryl groups. with concomitant utilization of free sulfate/sulfhydryl groups – a double win for you.ec).Return to Autism Page Page 35 of 50 glutamate/MSG in foods (please see appendix) and by taking GABA to neutralize the excitatory affects of high glutamate. 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. methy-B12. sulfur containing supplements. from the Methyl Cycle perspective.heartfixer. Phosphatidylserine stimulates BHMT (and we also use it to moderate elevated cortisol levels). and are best avoided or minimized. This approach may be added in the future. 4. 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). beginning at ½ capsule. 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. To stimulate SUOX. You’ve lived your entire life with a gene set that is maladaptive to the toxic environment of modern man. CBS up regulations lead to an initial buildup of potentially neurotoxic sulfite. Carnitine. after your CBS/BHMT situation has been addressed. hydroxy-B12. Right now this “good thing” could actually set you back. and thus you will need and benefit from corresponding supplementation (with these molecules that you are having trouble making). along with a charcoal supplement at bedtime every other evening. BHMT (Betaine Homocysteine Methyl Transferase. boron. you and Dr. Please see separate information sheet on Life Wave patch use. may help with ammonia detoxification. and results of urine sulfate testing will help with decision making here. The Life Wave people have demonstrated an increase in Glutathione levels in relation to patch use. and can be utilized if you are not overly sensitive to methyl group supplementation (but you likely are due to your COMT +/+ status). returning to a vegetarian diet makes sense for you. 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”. and should increase your energy level.com/AMRI-Nutrigenomics. 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. 3. it makes sense to support BHMT function. a zinc-dependent enzyme) directly methylates homocysteine back in to methionine. You will feel great for 1-2 days. However. in your long-term favor with respect to dealing with heavy metals and microbes. This is all about balancing diet against treatment response. NADH 5 mg/day (NAD+ might be even more effective) sometimes helps.com/AMRI-Nutrigenomics. 11. The Health Diagnostics and Research Institute (www. malaise. 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. 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. This also means that you will be sensitive to methyl groups. We need to keep in mind that Methyl Cycle Genomics is not the sole determinant of your health. C.for VDR Taq means that Vitamin D will not increase dopamine levels in the normal fashion. Regarding energy production. D.heartfixer. B. an oral DMPS challenge could be carried out. Alternatively. Balance needs to be achieved. but the extra methyl groups could cause a rise in dopamine. but I feel that mercury will be out first detox priority.$350) can give us levels of SAMe. Alternately. and in the process using up free methyl groups. later on we will liberalize your diet. after your sulfate levels have fallen. ** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. Later.com for additional information. a positive response indicates that you are having trouble generating ATP energy.and MTRR +/This constellation of alleles is discussed on pages 193-196 of Dr. as your genes are not going to change. Magnesium supplementation may help with GABA physiology and often helps with sleep and is already on board. Individuals with chronic. 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. while keeping an eye on these biochemical markers. and DHFR alleles). if detox symptoms are debilitating or compromise your ability to work or care for your family. Which foods. If you are already on methyl-folate. then we may increase methyl-folate and/or add BH4 to your program. You have already undergone toxicity testing. 13.auraexplorationpatches. After sulfate levels have fallen (to a level that you and I feel is optimal for you. Toxicity testing (discussed in more detail in our Approaches to Detoxification brochure and on heartfixer. we will begin to remove the toxins themselves.hdri-usa. 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). the more protein you will be able to take in without compromising your biochemistry. Charcoal. And. AMMONIA. take GABA 500 mg.com) thus makes sense. This approach is low in cost and likely has value for all of us. A formal provocative challenge ($250) gives us our best assessment of tissue metal burden. but I do not feel this is necessary as your red cell mercury level serves as a target for intervention. which we can address in the future. somewhat mitigating this sensitivity to methyl groups. and achiness to allow toxic molecules to be cleared. If you feel anxious or “wired up” (glutamate overload). unexplained illness or significant toxicity would do well to follow the “nothing with eyes” diet until urine sulfate and ammonia levels have fallen. Sparga. While on the subject of energy medicine. MTHFS. Rectifying your genomic predispositions and detoxifying your system is not a sprint – it is a marathon. The idea here is not to remove the toxins (hard to do) but to homeopathically neutralize them). Yasko’s book. leading to mood swings. Individuals in whom the CBS up regulation is less important (A360A as opposed to C677T. GABA does not work rapidly. Being COMT +/+ means that you are breaking down dopamine. the greater representation of ammonia reducing (Yucca. Dr. Conversely.com . Ammonia Support RNA) treatments in your program. and as the environment is not going to become less toxic. I can’t prove this approach with an allopathic lab test but it has been quite helpful in solving complex medical problems in my personal patients. I do not think they need to be stopped unless urine sulfate levels remain high and/or you do not improve clinically. * 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. supplements. 9. then we need to back off on your treatments. and better overall health). Doctors Data gives us a less extensive but still useful Methylation Panel for $155. This dietary maneuver isn’t fun but may also turn one’s your health around. we need to check homocysteine now along with a repeat Vitamin D level. I can’t back this up with a clinical study. you will need to be mindful of these principles for the rest of your (long and healthy) life. and folic acid derivatives (which will help us understand the affects of your MTHFD. While normally I do not start methyl-folate and methyl-B12 until sulfate levels have fallen. 12. SAH. In addition. With respect to lab testing. 8.Return to Autism Page Page 36 of 50 7. but the use of Aura Organ Detox patches for two months make sense. lower urine sulfate and ammonia levels. The NutrEval tells us that you bear an organic pollutant burden. Hunts CD is available for your review and you can go to www. based upon your clinical and genomic status). My colleague Dr. weight gaining diet in an overweight individual with type two diabetes. A low protein diet can become a high carbohydrate. Lithium and iodine may be lost (swept out) in the process of heavy metal detoxification. could simply cut back on animal protein. You may need methyl-B12 due to your MTRR status. The US BioTek study gives us information on seven major organic pollutants ($126). Co-Enzyme Q 50 mg odd days and carnitine 500 mg even days (we start slow here as these agents are methyl donors). learn about the grounding/earthing concept. only slowly. After you have been on your program for 4-6 weeks. and GLUTAMATE BURDENS Gene by Gene Approach – COMT +/+ with VDR Taq +/. You may need to accept some transient fatigue.htm 4/18/2015 . we can measure SAMe and SAH. Be self-observant and keep records. These minerals are felt http://www. Sinatra wrote a book on this subject (heartmdinstitute. If this is helpful you can double the dose. twice a day. OUR MOST IMPORTANT INITIAL GOAL WILL BE TO REDUCE YOUR SULFATE. Genetic Bypass. Being +/. A trial of ribose 5 gm in water two to three times a day makes sense. creating a “treatment conflict”.com). Additional toxicity testing could consist of: A. This is not an issue in COMT -/. as there is plenty of COMT function to go around. Your COMT +/+ status also explains why your 2-methoxyestradiol levels are relatively low (you are having trouble tacking on the methyl group). and GABA. this is neutralized by VDR +/+ or +/. it will not work normally within your biochemistry. SAH builds up behind it. but theanine provides methyl groups. and thus excess methyl group supplementation may lead to irritability in COMT +/+ individuals. leading to vascular and neurological disease. Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes. so for you GABA alone is a better choice. or “as needed”. and with less dopamine floating around. alphaketoglutarate. GABA does not work quickly. to which you are sensitive. GABA counterbalances glutamate.status. which itself stimulates the adrenal gland to release catecholamines. If agitation or anxiety is an issue (perhaps on the basis of excessive glutamate production due to a CBS up regulation). Endogenous and caffeine induced catecholamines. and one will be less sensitive to methyl group donors. we can address this with GABA 500 mg. CYP1A2 +/+ (down regulation) status means that your ability to 2-hydroxylate estrogen molecules will be compromised. increasing risk of breast and prostate malignancy. anti-vascular disease 2-methoxy estrogens and inactivation of the stronger. which converts glutamate in to GABA).com/AMRI-Nutrigenomics. as your methionine and methylmalonic acid levels are OK. and catecholamines “compete” for the attention of COMT. with secondary inability to metabolize catecholamines and estrogen molecules. estrogen molecules. Dr.status renders one sensitive to methyl group supplementation. Stated otherwise. Dr. This is certainly difficult biochemistry. which in turn must be broken down by COMT. quercetin. or dependency (as valium class drugs may). Other approaches to dealing with an imbalance between glutamate and GABA include avoiding glutamate http://www. Zen contains GABA and theanine. and this maneuver will also draw methyl cycle intermediates away from sulfate/sulfite production. This explains how stress and caffeine increases risk of cardiovascular disease and reproductive organ malignancy to different degrees in different people (genomic-environment interaction). We need glutamate for learning and alertness. potentially genotoxic 4-hydroxy and 16hydroxy estrogen molecules. Individuals who harbor VDR Taq or VDR Bsm alleles will make less dopamine. watching for mood swings. TMG (trimethylglycine) will stimulate BHMT but will also provide methyl groups. to which you are likely sensitive. COMT metabolic dysfunction.8. S-Adenosyl Homocysteine (SAH) serves as a “non-competitive” COMT inhibitor. please see the Estrogen Metabolism section of the website for more information on Estrogen Metabolism and how we can affect it). including GAD. May has you on I3C to stimulate 2-hydroxylation and your 2/16 ratio is thus OK at 2.means that ½ 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. S-Adenosyl Methionine (SAMe) donates the methyl group that COMT uses to O-methylate its substrate. but excessive glutamate leads to “excitotoxicity”. competition becomes more of an issue. A build up of SAH will thus turn down COMT activity. Thus we will start not with methyl-B12. By stimulating BHMT. Phosphatidylserine and phosphatidylcholine stimulate BHMT and makes sense. COMT +/+ status is also associated with increased sensitivity to pain. Caffeine and stress increase catecholamine production. 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. While elevated Homocysteine is always deleterious to overall health.individuals. 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). COMT is also involved in estrogen metabolism. norepinephrine. and epinephrine).Return to Autism Page Page 37 of 50 to help balance or mitigate mood swings that might occur as a result of fluctuations in dopamine levels. From the perspective of mood and childhood neurodevelopmental conditions. the function of which in you (+/+ for the reduced function alleles) is compromised.you will be sensitive to methyl groups. lethargy. CYP1A2 +/+ (down regulation) status also compromises your ability to degrade caffeine. MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine.(up regulation) status promotes conversion of estrogens down the 4-hydroxylation pathway. COMT +/+ individuals cannot utilize methyl groups efficiently.individuals). As you are COMT +/+ and VDR +/. and caffeine induced insomnia will be more of an issue in those with COMT +/+. but with high doses of hydroxy-B12. and quercetin “compete” for COMT mediated methylation. another GABA agonist. but the enzymes systems involved in this process are sensitive to heavy metals. we can bypass any block that MTRR places on homocysteine detoxification. is a key mechanism through which elevated homocysteine damages our health. high coffee intake increases cardiovascular risk in COMT +/+ individuals but not in those with normal COMT status. likely a problem in you. while your serum B12 level may be “within normal limits”. whether they are genetically normal or abnormal. Yasko feels that VDR status effects dopamine generation. 1-2 twice a day. while COMT +/+ or +/. Individuals with genomic or acquired COMT dysfunction are thus more sensitive to their effects. manifested clinically as agitation and anxiety and pathologically as neural damage. producing an O-methylated substrate and SAH. Unmetabolized catecholamines and estrogen molecules generate oxidative stress. B12 methylation does not appear to be a problem for you.htm 4/18/2015 . When Homocysteine builds up. Stated otherwise. While estrogens. but when COMT function is limited (COMT +/+ individuals have only 25% the O-methylating capacity of COMT -/. We should be able to interconvert glutamate. 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). so low dose supplementation makes sense in COMT +/+ individuals. and is thus best avoided. Thus in your situation caffeine avoidance will be important. we could add in methyl-B12 cautiously. mediating generation of the anti-cancer. COMT (Catechol-O-Methyl Transferase) inactivates catecholamines (dopamine. providing a calming effect (all drugs of the valium class stimulate the GABA receptor). The MTRR abnormality (+/. aiming for the hydroxy-B12 to bind with the methyl groups available to form methyl-B12.heartfixer. while your CYP1B1 +/. Unmetabolized estrogen molecules damage DNA. impaired dopamine inactivation due to one’s COMT +/+ or +/status becomes less of an issue. If we do not feel that this approach is getting the job done. Conversely. which affect the reading of your DNA in a fashion beneficial for specific genomic challenges. Methylation support RNA ¼ dropper per day would be ideal here (and expensive and thus not critical). we can back off on your program. so low dose supplementation makes sense in COMT +/+ individuals. 4. Iodine supplementation may improve thyroid function. Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes. 2. Plan of action for COMT +/+ with VDR Taq +/. the effects of excessive methyl groups (despite our biochemical precautions). Unless we are taking in iodized table salt. with plans to obtain a 24 hour urine mineral assessment and serum iodine level in 8 weeks. Lithium and iodine may be lost (swept out) in the process of heavy metal detoxification. 5. 6. BHMT (Betaine-Homocysteine Methyltransferase) mediates the “backdoor” pathway of homocysteine metabolism. This is not a negative – we want you to detoxify. compromising or metabolism and possibly thyroid function. They are expensive. However.heartfixer. Lithium Orotate 5 mg alternating with Iodoral three days a week (Sundays off) makes sense. COMT (Catechol-O-Methyl Transferase) breaks down dopamine and norepinephrine and to a somewhat lesser extent other neurotransmitter substances. in some individuals. Yasko’s RNA products. and proof of efficacy has not been provided (and we do not hold this against Dr. Dr. MTR (Methionine Synthase) transfers a methyl group from Methyl-folate to Homocysteine to form Methionine. this could represent allergy/intolerance to one of your therapies. EDTA efficiently removes lead and cadmium. most of us in non-coastal regions will be iodine deficient. 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). excessive iodine may compromise thyroid function or induce thyroiditis (I’ve seen this). EDTA is typically well tolerated in individuals with a CBS up regulation. are “silencing” or “interference” RNAs. but more likely this will represent a detox reaction. with dosing guided by blood levels. Their inclusion in your program is ideal but adds significantly to your costs. whether they are genetically normal or abnormal. Before switching to methyl-B12 (which you probably do not need) I would like to measure your SAMe level with the Doctor’s Date methylation panel (in 8 weeks).. and has activity against aluminum.com/AMRI-Nutrigenomics. phosphatidyl choline (PhosChol) 900 mg/day makes sense. by tacking on to them a free methyl group that COMT obtains from SAMe. and arsenic. These minerals are felt to help balance or mitigate mood swings that might occur as a result of fluctuations in dopamine levels. If you feel poorly. May feel you are physiologically strong enough for metal detoxification. as dammed up toxins start leaving your body. and MSM. while paradoxically.htm 4/18/2015 .. When you and Dr. To stimulate BHMT and spare BH4. Soy bean lecithin 1-2 tablespoons/day would serve as a lower cost alternative to PhosChol. to my knowledge. nickel. theanine. 3. if a detox reaction is compromising your functional status. such as melatonin. and then resume at a lower dose when you are feeling better.Return to Autism Page Page 38 of 50 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). Thus it makes sense to check thyroid chemistries several months after beginning iodine supplementation. which converts glutamate in to GABA). particularly if you are receiving thyroid hormone supplementation. EDTA is not an efficient mercury chelator. http://www. Yasko as proving anything in biological medicine costs millions of dollars). as we need to “make room” for methylB12. we could utilize a program of Lipophos EDTA (stimulates BHMT and pulls out metals) ¼ bottle twice a week in juice (we may later increase to ½ bottle twice a week). directly methylating homocysteine back to SAMe. turmeric. Limit supplements that provide methyl groups. MTRR (Methionine Synthase Reductase) adds the Methyl group to otherwise inactive B-12. and thus you may need to endure some short-term discomfort to achieve your long-term goal (a return of good health). including GAD. 7. You are entering this process because your health has been compromised and allopathic (drugs and surgery) medicine has not helped you. We need to check you vitamin D level. with Phosphatidylcholine 900-1800 mg the remaining five days of the week. so from my perspective their use can be deferred (or added later if our initial approaches are not getting the job done). Sublingual Hydroxy-B12 is already on board to stimulate SUOX and seems to be covering your MTRR +/. and MTRR +/- 1.status. but a pathway does exist (mediated by DHFR) such that poor methyl-folate status will compromise BH4 recycling. a problem in that BH4 is being used up detoxifying ammonia (which you are making in excess due to your CBS up regulations). also known as folinic acid. Methyl folate supplementation may stimulate the backward reaction and will help regenerate BH4.and not +/+ for SHMT please add 5-formyl THF. Yasko describes MTHFR A1298C as an abnormality in the SAMe binding site of MTHFR that compromises the “backward reaction” that generates BH4. Gene by Gene Approach and Plan of Action – FOLR2 +/+ To some degree.htm 4/18/2015 .10-methylene THF. Gene by Gene Approach – SHMT +/SHMT combines the amino acid serine with folic acid to form 5. Our approach here is general support of the Methyl Cycle and the inclusion of methyl folate in your program. This “backward reaction” is not supported by other authors. Our approach here involves methyl-folate and folinic acid supplementation. 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). and in recycling “spent” BH2 back in to useful BH4. and methyl-folate can “stand in” for BH4 when the latter is depleted.heartfixer. 400 mcg daily (or 800 mcg every other day) to your program. patients may feel great for one day and then experience an incomplete detox reaction. This is probably less of an issue with methyl-folate.Return to Autism Page 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. After your urine sulfate levels have fallen we may advance methyl-folate or add in BH4 supplementation. Gene by Gene Approach and Plan of Action – DHFR +/Here you are having some trouble reducing oxidized dietary folates into useful Tetrahydrofolate. Gene by Gene Approach and Plan of Action – MTHFD1 G1958A +/+ http://www. You may need more methyl-folate than others. Plan of Action – SHMT +/As you are +/. your cellular folate receptors are having trouble incorporating folic acid.com/AMRI-Nutrigenomics. We can bypass this block with 5-formyl THF. If we supplement aggressively in the presence of high urine sulfate. Sauna increases BH4 production and promotes detoxification and could be utilized. as discussed above. which is used to generate the building blocks for DNA and RNA generation. also known as Folinic acid. we suffers from a buildup of free radicals. As you are +/+ for COMT and have a high urine dopamine. Oxidative stress: When the generation of free radicals (superoxide. we should also consider means to reduce SAMe expenditure (Mother Nature balances supply and demand – the government should pay heed)! Stated otherwise. which leads to disease states such as atherosclerosis. more will be available to meet critical demands (e. SAH is rapidly converted to Homocysteine and Adenosine. it is the buildup of SAH. if nutritional supplementation decreases demand for SAMe. cancer. Homocysteine will build up. Our approach here involves general support of the Methyl Cycle and the inclusion of methyl-folate and folinic acid in to your program. MTHFD. due either to SNIPS. and DHFR alleles). intermediates. 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. and physiologic (not excessive) supplies of: A. 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. Homocysteine will then be back converted to SAH. So what processes “steal” SAMe? In considering this issue. and C. BH4.10-methylenyltetrahydrofolate cyclohydrolase/ 10formyltetrahydrofolate synthetase (MTHFD1) is responsible for the conversion of 5. CBS flow will decrease. Homocysteine itself is not the problem. 5. sulfate. The Health Diagnostics and Research Institute (www. Progesterone may stimulate MAO A activity. we create a SAH (S-Adenosylhomocysteine). B. and useful methylation grinds to a halt. Tryptophan in food is converted into serotonin and tyrosine in food in to dopamine. Adenosine is efficiently removed.Return to Autism Page Page 40 of 50 The trifuncitonal enzyme. This disorder is associated with an increased tendency to mood swings and panic disorders. Oxidative stress damages our physiology and kills cells.htm 4/18/2015 . glutathione. MTHFR. and hydrogen peroxide) outpaces our ability to neutralize them with endogenous (e. and mood disorders. not for the sake of generating high levels of these Methyl Cycle intermediates (yes. Gene by Gene Approach – MAO A +/+ MAO breaks down serotonin and to a lesser extent dopamine and norepinephrine. toxins. replenishable.10-methylene THF (generated from THF by SHMT) to the corresponding 10-formyl. compromising methylation potential. that drives forward useful methylation reactions).g.$350) can give us levels of SAMe.hdri-usa. but if the Methyl Cycle is sluggish. 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. 5. and taurine) are in adequate supply. and folic acid derivatives (which will help us understand the affects of your SHMT. SAH.10-methenyl and 5. A. You are generating (or taking) methyl folate and methyl B12. BH4 (needed to generate neurotransmitters and nitric oxide). Fortunately. A declining SAMe:SAH inhibits methylation reactions. taurine. hydroxyl. which in turn inhibits methylation. This all makes sense. SAMe. along with and an appropriate SAMe to SAH ratio (it is the ratio. the SAMe:SAH ratio falls. so our key dietary recommendation is to avoid animal protein). it does us no good to increase SAMe if at the same time we buildup SAH. remember that each time we “spend” a SAMe (S-Adenosylmethionine) to carry out a specific methylation reaction. Key antioxidant and detoxification molecules (glutathione. and cysteine. it makes sense to divert Methyl Cycle resources towards antioxidant generation.heartfixer. When faced with oxidative death.com . but rather to help ensure that the Methyl Cycle work products (SAMe. not just the SAMe level. related to fluctuations in serotonin levels.10-methylene derivatives.10-methylenetetrahydrofolate dehydrogenase/ 5. To address this immediate threat to health. not finished products). taurine. superoxide dismutase) or exogenous (supplemental antioxidants). and cysteine). you do not need to emphasize with tyrosine or tryptophan rich foods in your diet (and our initial goal is to lower sulfate. Serotonin formation may pick up as BH4 levels are restored with other maneuvers to address methyl cycle abnormalities. or nutritional deficiency. cysteine.com/AMRI-Nutrigenomics. DNA methylation to silence inflammatory and proto-oncogenes). Homocysteine metabolism down the CBS pathway (irrespective of SNIP status) will increase. Homocysteine http://www. 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. While our focus has been on improving SAMe supply. 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. After oxidative stress has been neutralized.g. leaky gut. Athletes take 5 grams of creatine. which we can address with GliSODin supplementation. Only SAMe can shut down the transcription (reading into protein formation) of viral. We use serum creatinine to gauge kidney function. and more will be available for useful methylation reactions. In addition. regenerating ATP such that cellular work can continue. Only SAMe can methylate DNA. four times a day (saturation dose) for one week.Return to Autism Page Page 41 of 50 will start flowing back towards SAMe. PC containing two unsaturated linoleic acid molecules (polyenylphosphatidylcholine) is used IV and orally to treat cardiovascular. Should we suddenly run out of ATP energy (sprinting. We http://www. MTR. more free radicals build up. in this fashion blocking useful remethylation of Homocysteine back into methionine for conversion into SAMe). Mercury compromises MTR. than you cannot silence inflammatory genes. 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). Homocysteine will thus be shunted down the CBS pathway. etc. around 30% of our total supply. such as TNF-alpha. and Il-1E also increase flow down the CBS pathway. and while the literature is not 100% consistent. inflammatory. and supplementing with SAMe “sparers” as described below. Thus PC supplementation will lower an elevated Homocysteine and increase SAMe supply along with the SAMe:SAH ratio. and BHMT). Both are useful in fighting infection. We actually store 10 heart beats of energy as Phosphocreatine. creatine supplementation will decrease expenditure of SAMe and increase the SAMe:SAH ratio. This does not mean that kidney function is decreasing. but both processes are persistently elevated as our immune system misinterprets as infection the chronic “pseudoinfections” of visceral obesity. forming Phosphocreatine. Creatine formation: Around 50% of our SAMe is “spent” in the generation of creatine. PC/lecithin is essentially a triglyceride like molecule with two fatty acids and one phosphocholine group attached to a three carbon glycerol backbone. Other than a mild depression in glutathione your oxidative stress/inflammatory markers were within the reference range. If you cannot methylate your DNA. However. and then takes steps to resolve any challenges present. C. We can thus use nutritional medicine to help you generate SAME and to prevent oxidative stress from “stealing” Homocysteine away from SAMe regeneration. When energy is plentiful. What processes deplete our SAMe stores? Are some less critical than others? Can we decrease SAMe demand with nutritional supplementation? A.g. and proto-oncogenes (promote cancerous transformation) while maintaining the transcription of tumor suppressing and anti-inflammatory genes. Your SOD2 +/+ status compromises superoxide dismutase and thus your ability to degrade the free radical superoxide. This will involve removing from your body phenomena that generate free radicals (e. DNA methylation: This is sacrosanct. 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. Of interest. more Homocysteine is diverted away from SAMe regeneration. and catecholamines will be compromised. which is filtered out by the kidneys. Il-6. PC is also a critical component of the cell membrane.). or when we feel that chronic oxidative/inflammatory stress is depleting SAMe regeneration. and neurological disease (see our DVD presentation).for a loss of function PON allele). If you cannot methylate catecholamines. 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. organic pollutants) while concomitantly shoring up your antioxidant defenses with nutrients that we find to be in short supply (selenium. Phosphocreatine can download a high energy phosphate bond back to ADP.com/AMRI-Nutrigenomics.htm 4/18/2015 . then oxidative stress will develop within your blood vessels. B. you can simply add 5 grams of creatine/day to your program. unless you have an athletic competition coming up. weight lifting. creatine has been shown to lower cholesterol. but by resolving oxidative/inflammatory stress. Creatine is not unsafe. If we supplement you with PC. rather this is an artifact due to creatine supplementation. smoking. estrogen molecules.g. As residual heavy metals are removed. toxic metals. Paraoxonase is involved in organic pollutant metabolism. creatine supplementation has been shown to be helpful in anaerobic athletic performance as well as in heart failure. PC can be converted into choline. and you are now chronically ill.for GSTP1 and GPX1 you are having some trouble utilizing glutathione. As a side note. Inflammation leads to oxidative stress and oxidative stress leads to inflammation. Creatine lowers homocysteine in individuals with MTHFR abnormalities. a molecule critical to energy maintenance. Inflammation: Inflammatory TH1/TH17 cytokines. 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). we can maintain adequate SAMe (with a high SAMe:SAH ratio) to ensure optimal DNA methylation. liver. Furthermore. You thus make more inflammatory molecules. and useful methylation reactions will resume. CBS. B. there will be less strain on your glutathione stores. it also provides the antioxidant activity of HDL and is involved in the metabolism of homocysteine thiolactone. the less SAMe spent. We do work by splitting a high energy bond within ATP (Adenosine Triphosphate) to produce ADP and phosphate. As you would expect. such that useful methylation of DNA. are used to methylate phosphoethanolamine into phosphatidylcholine. toxic metals not only “steal” SAMe. Vitamin C. they also compromise its formation (e. Creatine is converted in to Creatinine. The common name for PC is lecithin. ATP will transfer a phosphorus group to creatine.heartfixer. Phosphatidylcholine: Three SAMe molecules. or if oxygen supply:demand is compromised by a blocked artery or failing heart). Pomegranate juice intake makes sense to stimulate paraoxonase (you are +/. less SAMe will be spent generating PC. draining Homocysteine away from useful remethylation back in to SAMe. We can’t scrimp on DNA methylation. Creatine supplementation at 5 grams/day makes sense for individuals with Methyl Cycle SNIPS that might compromise SAMe generation or maintenance (MTHFR. Being +/. The solution is to undergo an assessment of oxidative stress. A trivial rise in serum creatine may occur when you supplement with creatine. and environmental toxicity. Vitamin E. followed by 5 grams/day (maintenance dose). Phosphatidylcholine (PC) is involved in lipoprotein formation and reverse cholesterol transport. We burn carbon and use this energy to rephosphorylate ATP. the less SAH and Homocysteine will be formed. The biochemical utility of PC relates to the composition of its two fatty acids. When caffeine intolerance develops anew. Smith (who will receive a copy of this report. D. we look for new problems that might be compromising SAMe supply or COMT functionality. Being +/. Phosphatidylcholine supplementation will bypass your PEMT status and spare SAMe. When you and Dr. drugs (e.Return to Autism Page Page 42 of 50 use PhosChol (unsaturated phosphatidylcholine rich in linoleic acid) 900 to 2700 mg/day in the treatment of cardiovascular and liver disease. The Hunt aura patch approach is typically well tolerated and a good place to start. While bioflavonoids such as Quercetin have many beneficial properties. Creatine 5 gm/day makes sense. Matching detox therapies to the individual patient is sort of an art of medicine concept. the SAMe:SAH ratio falls. Pomegranate juice 1 oz/day (Pom Wonderful was used in the cardiovascular research. Smith feel you are ready. when insufficient dopamine is the problem. We address this alleles with general support of the Methyl Cycle and measures to ensure that Homocysteine levels are not elevated Additional Thoughts 1. cadmium. Conversely. Please forward to me a current treatment list. Being +/+ for PEMT. Caffeine increases catecholamine production. 2. Regarding the recurrent viral outbreaks the Aura OLE patch might work.SAH ratio. GliSODin 250 mg/day would be ideal. PhosChol at 900 mg/day. MTR. PEMT is stimulated by estradiol and this may explain why homocysteine levels rise when ovarian hormone levels decline. and COMT and all other methyl-transferase enzymes are inhibited. Caffeine intolerant individuals are typically COMT +. Foot bath/sauna therapy is also typically well tolerated. while EDTA based preparations (good for lead. Chi’s approach to metal overload and his brochure is enclosed 2. and BHMT SNIPs or if our ability to methylate estrogen molecules is impaired) then decreasing intake of Quercetin and related bioflavonoids would be prudent.com/AMRI-Nutrigenomics. 3.for AHCY. 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). Each time this occurs. 3. The digital picture analysis will tell us if the corresponding frequency is present.). and aluminum) would likely be reasonably well tolerated (and later we could return for mercury using a non-sulfhydryl based therapy). catecholamines (dopamine and norepinephrine).heartfixer. Please look through our Detoxification Options brochure. Plan of action for Methyl Thieves and SAMe Stealers ) 1. COMT (Catechol-O-Methyl transferase) metabolizes estrogen molecules. 4. Please run all of this by Dr. then further metal detoxification makes sense. we might use Quercetin to blunt dopamine degradation by “clogging up” COMT. with positive effects). A negative field only sleep pad is of value to all but quite expensive. and you have given me permission to consult with her regarding your care). and thus decrease SAMe utilization by COMT. L-Dopa used in the treatment of Parkinson’s disease) and bioflavonoids (particularly Quercetin) by transferring a methyl group from SAMe to an oxygen molecule on the compound being methylated. Lowering stress will lower norepinephrine. SAH is generated. a double win for you. If we are interested in sparing SAMe and maintaining a high SAMe. MTRR. Grounding is inexpensive and reasonable. which is converted in to homocysteine by AHCY. Our standard mercury chelators (DMSA and DMPS) are sulfite-rich and would likely not be tolerated. you are having trouble generating phosphatidylcholine. 4. 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 http://www. James C. with doses in mg or mcg units. if SAMe preservation is critical (high Homocysteine in the presence of MTHFR. I just came across Dr. advancing to 900 mg twice a day if the initial dose of 900 mg daily agrees with you. you may be having trouble with SAH degradation. Gene by Gene Approach and Plan of Action – AHCY +/SAMe is converted in to S-adenosylhomocysteine.htm 4/18/2015 . COMT utilization. it would be prudent to reduce the need for COMT-driven methylation. My hypothesis is that your Methyl Cycle abnormalities have rendered you more susceptible to metal toxicity. and we can certainly discuss all of the above during a phone conference.g. Our dose in Methyl Cycle patients will relate to your SNIP status and baseline Homocysteine level. molybdenum. You are +/. and too much ammonia. and Vitamin E succinate can be considered. the precursor for serotonin. one year out from stent placement. Conversely. meaning that you have some difficulty converting folic acid in to 5-methyl folate. boron.for MTHFR C677T. My knowledge of Detoxification Genomics is far less extensive than that of the Methyl Cycle.htm 4/18/2015 . an individual with intact 2C19 status (likely not an issue now. Thus you may not be experiencing the same anti-platelet effect vs. but if another stent is required one of the newer agents that does not require 2C19 activation would be preferred). Hydrocarbon pollutants are activated by 1B1.for both of the CBS up regulations. which must be processed to sulfate. We can bypass this block with 5. This deficiency in BH4 predisposes NOS (nitric oxide synthase) to convert Arginine in to free radicals as opposed to nitric oxide. Early on. predisposing you to hypertension and cardiovascular disease. You are already on BH4 and methyl-folate. favoring 4-hydroxyglation of estradiol/estrone. using up methyl groups in doing so. which is then converted in to SAMe. You are also +/.heartfixer. oxidative tissue damage may follow. but my understanding is that the CYP1B1 alleles present are an up regulation. a block that is (biochemically) easy to overcome with 5-methyl folate supplementation (already in place). and if they cannot be neutralized by phase II enzyme systems. however. the universal methyl donor.com/AMRI-Nutrigenomics.Return to Autism Page Page 43 of 50 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 +/. meaning that you can breakdown dopamine rapidly. and thus you will have an increased susceptibility to toxic metals and viral infection.for COMT. the precursor to dopamine. too much alpha-ketoglutarate (which may lead to glutaminergic excitotoxin activation). an overall restriction of dietary animal protein will be suggested. and -/. Even thought your urine sulfite level is normal. an issue that we can address by favoring foods rich in tyrosine. which is used to generate the building blocks for DNA and RNA generation. 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). you are having trouble breaking down serotonin. over foods rich in tryptophan. thus increasing one’s risk of breast/prostate malignancy. by SUOX (sulfite oxidase). CYP2C19 metabolizes a number of commonly utilized pharmaceuticals. which you need. support for this enzyme with hydroxy-B12. MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine. Methylation http://www. leading to insufficient dopamine and serotonin production. which depletes BH4. also known as Folinic acid. SHMT combines the amino acid serine with folic acid to form 5. the BH4 and methyl-folate doses could be increased. CBS actually generates sulfite. Homocysteine (and its Methyl Cycle precursors) is thus being drawn down the transsulfuration pathway. a problem that you have already addressed with methyl-B12 supplementation. meaning that you are having some trouble converting B12 in to methyl-B12. You are +/+ for VDR Taq. to decrease the ammonia burden imposed on you by your CBS up regulation status.10-methylene THF.for one of the MTRR alleles. 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”).10-methylene THF. and is also responsible for activating Plavix. Being +/+ for MAO A. such that Vitamin D will be less efficient in generating dopamine. and after the up regulated trans-sulfuration pathway (CBS) has come under control. but you harbor alleles compromising acetylation and SOD (superoxide dismutase) generation (thus neutralization of superoxide will be compromised. which uses up molybdenum. and GABA. 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. producing enzyme activity that is 10 fold greater than normal. Crestor. boron. The CBS C677T and A360A genes code for enzyme function that is pathologically up regulated. Gene by Gene Approach – CBS +/- CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr.Return to Autism Page Page 44 of 50 based (COMT) phase II detoxification is intact. You are +/. Fortunately you are -/. taurine and cysteine (all involved in detoxification and endothelial health). 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. hydrogen sulfide (to produce brain fog).(normal function or “wild type”) for the BHMT down regulations (which act like CBS up regulations). Glutamate is involved in alertness and learning. we cannot convert arginine in to nitric oxide. cardiovascular and inflammatory disease states. I have a number of additional diagnostic and therapeutic ideas (please see below). Those that are less critical (or more costly) are designated (+/-). after we decrease your sulfate/sulfite pool. and too much ammonia (which depletes BH4. or if toxic metals compromise the interconversion enzymes. You thus suffer from “too much of a good thing and way too much of several bad things”. Without BH4. instead vascular wall toxic free radicals such as superoxide and peroxynitrite are created. a calming neurotransmitter). which is thus depleted in CBS + individuals. Vitamin E succinate. you will experience detox phenomena). http://www. which is then metabolized by SUOX (Sulfite Oxidase) to the less neurotoxic (but still problematic at high levels) sulfate. while the Plan of Action sections contain specific recommendations. Based upon review of your medical history. in this process generating excessive sulfur break down products (sulfite and sulfate.htm 4/18/2015 . and B12 are felt to stimulate SUOX activity. but on board you have SOD up regulators in the form of Losartan.(half of your CBS enzymes abnormal) for both of the two CBS up regulations. 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). and alpha-ketoglutarate (which can be converted into GABA. The Gene by Gene Approach sections provide general information about the alleles you possess. The excess ammonia generated must be detoxified. and are best avoided or minimized. the C677T allele is the most important. Homocysteine (and its Methyl Cycle precursors) is being drawn down the trans-sulfuration pathway. SUOX activity requires molybdenum. Given your CBS up regulations. then we suffer a buildup of the excitatory neurotransmitter glutamate. However. metabolic flow down the CBS pathway is designed to generate the important anti-oxidant and detoxifying molecules glutathione. and to do so BH4 (tetrahydrobiopterin) must be “spent”. Alpha-ketoglutarate.com website. leading to hypertension and cardiovascular disease. We should be able to interconvert alpha-ketoglutarate into glutamate. but excess glutamate leads to irritability and over-excitement. Genetic Bypass.com/AMRI-Nutrigenomics. glutamine. Additional information is available on our heartfixer.heartfixer. While sulfate and sulfhydryl (-SH) bearing molecules are important in detoxification. which stimulate the stress/cortisol “fight or flight” response). and Berberine). too much alphaketoglutarate (which leads to glutaminergic excitotoxicity). Of the two. Approaches that make the most sense to me receive a (—). 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). is not a problem. when alpha-ketoglutarate is in excess. Conversely. if we move too fast. leading to insufficient dopamine and serotonin production). During normal physiology. Yasko’s book. Homogenized dairy products contain xanthine oxidase. sulfate/sulfite/-SH excess blocks cellular up take of the key detoxifiers glutathione and cysteine. in moderation. your detox pathways open up (and why. twice a day. and thus you will need and benefit from corresponding supplementation (with these molecules that they are having trouble making). However. along with a charcoal supplement at bedtime every other evening. Low levels will allow an increase in methyl cycle supplementation and later the addition of BH4 and/or a liberalization of your diet. 6. we can supplement you with Co-Enzyme Q and Carnitine. available at the office or at www. Phosphatidylcholine can be admixed with EDTA (detoxifies metals). creating toxic intermediates that cannot be metabolized further due to the block in glutathione utilization – and you will feel horrible. while our Complete Mineral Complex. a methyl donor) twice a day. Magnesium supplementation may help with GABA physiology and often helps with sleep. a low-sulfate multi such as Dr. Sparga was developed by fellow Cardiologist Dr. or after adding a new treatment or changing your diet). or BH4.com/AMRI-Nutrigenomics. is less of a problem here and serves as a B6 substitute. as beneficial neurotransmitters are generated. with a http://www. Glutathione supplementation runs the risk off adding to your sulfite/sulfate burden. They may be taken individually as Molybdenum 3 drops in water twice a day and Boron 3 mg once a day. with concomitant utilization of free sulfate/sulfhydryl groups – a double win for you. sulfur containing supplements. you are already on methyl-folate. or if deficiencies are identified on your NutrEval study. methy-B12. you can use Ammonia Support RNA ½ dropper with meals and with methyl cycle supplements (relatively expensive). 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. For nutritional support. Avoid B6 (unless you need it for other functions). and NADH may be helpful. Statin therapy predictably depletes Co-Enzyme Q. away from other supplements (magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation).nutramedix.htm 4/18/2015 . Plan of action for CBS +/To address this constellation of alleles I will recommend: 1. DMG (dimethylglycine) and TMG (trimethylglycine) stimulate BHMT. as does phosphatidylcholine (which we use to treat atherosclerosis). twice a day makes sense. persistent high sulfate spills indicates that your diet/treatment program needs further modification. The active form of B6. If you feel anxious or “wired up” (glutamate overload). and BH4 and I do not think that you need to stop them simply on the basis of this “new Methyl Cycle patient” principle.Return to Autism Page Page 45 of 50 As methyl cycle function is needed in the biosynthesis of Co-Enzyme Q10 and Carnitine. NADH does not provide methyl groups and should be well tolerate by all. it makes sense to support BHMT function.com/nosulfites/. 2. then your anti-oxidant and detox capacity will increase. However. Phosphatidylserine stimulates BHMT (and we also use it to moderate elevated cortisol levels).readingtarget. If they are helpful you can double the dose. 3. Monitor urine sulfate levels every 3-7 days (or when you feel particularly good or poorly. along with Molybdenum and Boron. Yasko’s Neurological Health Formula. serving as a “back door” pathway to “pull” homocysteine away from the CBS “sulfate drain”. These supplements can be tapered down as ammonia levels fall. 7. take GABA 500 mg or Zen (GABA 550 mg with Theanine 200 mg. Moderate* animal protein intake (anything with eyes) and avoid sulfur rich vegetables. individuals + for CBS will likely be energy depleted. You will feel great for 1-2 days.heartfixer. Yucca. 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. Many of you with CBS and BHMT abnormalities will also bear MTHFR (compromising methyl-folate generation) and MTRR (compromising methyl-B12) abnormalities. (or sprinkled on food containing protein). Thus we need to resist the temptation to treat your MTHFR/MTRR abnormalities until CBS/BHMT are under control. please use sublingual hydroxy-B12 2000 mcg/day. Right now this “good thing” could actually set you back. Methyl-folate and methyl-B12 detox pathways will then open up. beginning at ½ capsule. if we could convince your biochemistry to up regulate biosynthesis of glutathione. and here supplementation (in relation to your COMT/VDR status) with Co-Enzyme Q10. Thus if you bear CBS or BHMT abnormalities. and can be utilized if you are not overly sensitive to methyl group supplementation (based upon you COMT/VDR status). What is your homocysteine level? A low level suggests that your CBS up regulation is of great functional significance. 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”. which stimulates CBS. However. This can be achieved with the use of the Life Wave (needleless acupuncture) Glutathione patch. may help with ammonia detoxification. creating a quite useful supplement. BHMT (Betaine Homocysteine Methyl Transferase) directly methylates homocysteine back in to methionine. 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). 5. Conversely. 8.ec). If energy is low. makes sense (or we may have you on another preparation in relation to your other health concerns). if we treat you with methyl-folate. 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). 10 drops in water (wait at least one minute before consuming). 9. and sulfur containing drugs (see attached sulfur avoidance instruction sheets and read Sulfites and Chronic Disease by Rick Williams. GABA/Zen do not work rapidly. 3 daily will cover the mineral base. To neutralize ammonia (generated from animal protein). while individuals who are methyl group sensitive (COMT+) will likely do better with GABA. Lee Cowden. To stimulate SUOX activity. Sparga Detox. P-5-P. 4. Carnitine. Individuals who need methyl groups (normal COMT and/or abnormal VDR Taq alleles – your situation) will do better with Zen. 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. specifically to address the CBS abnormality (see www. 3-6/day. 3. methyl-B12. you will need to be mindful of these principles for the rest of your (long and healthy) life. 11. watching for detox reactions). to demonstrate that flow down the CBS pathway has been decreased to a physiologic level. Individuals with chronic. You need and should tolerate dopamine precursors and methyl donors. This dietary maneuver isn’t fun but may also turn one’s your health around. or we could use the Genova Labs NutrEval. and could be utilized (low exposure at first. if detox symptoms are debilitating or compromise your ability to work or care for your family. by moving the cycle of homocysteine metabolism forward. and as the environment is not going to become less toxic.com website. MTR uses 5-methyl folate and methyl-B12 to convert homocysteine in to methionine. Sauna therapy increases BH4 production and promotes detoxification. Being +/+ for VDR Taq means that dopamine production is compromised. and better overall health). Further nutritional testing can be carried out in 8-12 weeks. Genetic Bypass. and I am now liberal with its use. ** The point of Methyl Cycle analysis/treatment is to help you become a more efficient detoxifier. weight gaining diet in an overweight individual with type two diabetes. Dr. This is all about balancing diet against treatment response. As you are COMT -/.or COMT +/+ individuals to bear a metal burden). After sulfate levels have fallen (to a level that you and I feel is optimal for you.or +/+ This constellation of alleles is discussed on pages 112-115 of Dr. Hunt’s CD is available for your review and you can go to www. Sparga. could lead to increased ammonia and http://www. supplements. I can’t back this up with a clinical study. this is less extensive than the Metametrix study that you have already carried out and will not add any new information. as your genes are not going to change.or +/+. malaise. Conversely. Testing options for new patients include: A. Why wait for sulfate to fall? Methyl-B12 supplementation. we can take further aim at the toxins themselves. Dr. 11. C. And. Later. Rectifying your genomic predispositions and detoxifying your system is not a sprint – it is a marathon. You have already undergone toxicity testing (and I would like to review with you the results). We need to make sure your mineral/nutritional stores are replete. B. If not previously measured we should check it now. based upon your clinical and genomic status).com for additional information. In addition.com) thus makes sense. This approach has been helpful when I have been stumped despite a full allopathic laboratory work up. A key goal of Methyl Cycle analysis is to improve your ability to detoxify. 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). after your sulfate levels have fallen. This could involve separate 24 hour urine studies for nutritional minerals and for ammonia/amino acids.heartfixer.means that you are breaking down dopamine rapidly and in doing so using up available methyl groups. the greater representation of ammonia reducing (Yucca. A formal provocative challenge ($250) gives us our best assessment of tissue metal burden. and BH4 (nutritional testing will help with decision making here). 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. I can’t prove this approach with an allopathic lab test but it has been quite helpful in solving complex medical problems in my personal patients. Being COMT -/. 12.with VDR Taq +/+ and MTRR +/. Balance needs to be achieved. Ammonia Support RNA) treatments in your program. Additional information is available on our heartfixer. D. * 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. and we are looking for low levels of ammonia. then we need to back off on your treatments. Toxicity testing (discussed in more detail in other presentations and on heartfixer. 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. This approach does not remove toxins but is felt to homeopathically neutralize them). Be self-observant and keep records. methyl-B12. The US BioTek study gives us information on seven major organic pollutants ($126). and achiness to allow toxic molecules to be cleared. You may need to accept some transient fatigue. Footbath therapy is another means of removing toxins without adding foreign molecules to your body. We need to keep in mind that Methyl Cycle Genomics is not the sole determinant of your health. Yasko’s book. VDR Taq influences dopamine production. taurine. unexplained illness or significant toxicity would do well to follow the “nothing with eyes” diet until urine sulfate and ammonia levels have fallen.auraexplorationpatches. could simply cut back on animal protein.htm 4/18/2015 . Which foods.Return to Autism Page Page 46 of 50 homocysteine “drain” overcoming the MTHFR and MTRR abnormalities (which otherwise would be associated with an elevated homocysteine level). and thus toxicity testing** (which you have already undergone) and treatment make sense. but the use of Aura Organ Detox patches for two months may help you. you are having trouble converting B12 into methyl-B12. a problem that is biochemically easy to overcome with methyl-B12 supplementation. lower urine sulfate and ammonia levels. fully covered under non-HMO Medicare). Hunts CD is available for your review and you can go to www. we could advance supplementation with methyl-folate. later on we will liberalize your diet. the more protein you will be able to take in without compromising your biochemistry.and VDR +/+ you should tolerate methyl group supplementation reasonable well. 10. Being MTRR +/. OUR MOST IMPORTANT INITIAL GOAL WILL BE TO REDUCE YOUR SULFATE STORES Gene by Gene Approach – COMT -/.auraexplorationpatches. glutamate. and cysteine. compromising your ability to deal with toxins and microbes (thus you are more likely than COMT +/. 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. Individuals in whom the CBS up regulation is less important (A360A as opposed to C677T. Charcoal. A low protein diet can become a high carbohydrate.com/AMRI-Nutrigenomics. while keeping an eye on these biochemical markers.com for additional information. EDTA efficiently removes lead and cadmium. we can address this with GABA or Zen (GABA + Theanine). antioxidant. curcumin. MTRR abnormalities compromise the generation of methyl-12. a methyl donor. Pedi-Activ contains phosphatidyl serine. Lipophos EDTA ½ . Zen (GABA and the methyl donor theanine) twice a day if anxiety or agitation is an issue for you. exogenous SAMe will provide methylation support and with your COMT -/. both of which support dopamine production. Thus you need and should tolerate methyl donors such as Methyl-B12.½ bottles twice a week can be matched with Lipophos Forte five days a week. While we would prefer that you generate SAMe endogenously. or Procite-D. 2. whether they are genetically normal or abnormal. Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes.and VDT+R Taq +/+ status you should tolerate it well. you should tolerate and benefit from the methyl groups provided by theanine. At some point in the future.000 mcg daily after urine sulfate levels have fallen to 800 (or if subsequent testing indicates an increased need for B12 nutriture). which converts glutamate in to GABA) and cadmium (which contributes to hypertension and cancer risk). As you are COMT -/. which converts glutamate in to GABA). or MSM (hold off on MSM if urine sulfate levels are high). As you are COMT -/. or SAMe). and MTRR +/- 1. Unless agitation (suggesting too many free methyl groups) occurs.heartfixer. we can bypass any block that MTRR places on homocysteine detoxification. Alternatively. which stimulates BHMT. If you are troubled by agitation or anxiety (perhaps on the basis of excessive glutamate production due to a CBS up regulation). then sulfate generation is not an issue.and VDR +/+. and this maneuver will also draw methyl cycle intermediates away from sulfate/sulfite production. 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. You might benefit from quercetin and macuna puriens. MTR cannot use methyl-folate to recycle homocysteine into methionine. and dopamine support makes sense. 3. try adding SAMe 200 mg/day to your program. melatonin. MTR (Methionine Synthase) transfers a methyl group from Methyl-folate to Homocysteine to form Methionine. please advance to 5. Lipophos EDTA provides phosphatidyl choline to stimulate BHMT and EDTA to remove lead (which compromises function of multiple enzymes. EDTA is typically well tolerated in individuals with a CBS up regulation. MTRR (Methionine Synthase Reductase) adds the Methyl group to otherwise inactive B-12. 3.Return to Autism Page Page 47 of 50 sulfite/sulfate generation. so normally we do not push with methyl-B12 until urine sulfate levels have decreased. which does the same By stimulating BHMT. Without methyl-B12. curcumin. if agitation occurs. http://www. after urine sulfate levels have declined.and VDR Taq +/+. including GAD. SAMe. you may supplement freely with methyl donors such as melatonin. and its use makes sense. 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. Lipophos Forte provides phosphatidyl choline which stimulates BHMT. and Procite-D serve as alternative approaches to augment dopamine status. Methyl-B12 is already present at 1. if metal detoxification is appropriate.htm 4/18/2015 . macuna puriens. However. including GAD. 5.000 mcg daily. 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). you are making less dopamine in response to Vitamin D and you are breaking dopamine down rapidly. TMG. whether they are genetically normal or abnormal. 6. 4.with VDR Taq +/+. and DMAE. and arsenic. Quercetin + daily to provide methyl group. Supplement to keep Vitamin D | 50. Plan of action for COMT -/. 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). TMG. which does not contain methyl groups (both GABA and theanine stimulate the GABA receptor. nickel. and thus provide a “Valium” like effect without concern for drowsiness or dependency). If you possessed normal CBS alleles. we can utilize GABA. and has activity against aluminum. suggesting methyl group excess.com/AMRI-Nutrigenomics. ginkgo biloba. EDTA is not an efficient mercury chelator. this should not produce any tolerance issues. When NOS (nitric oxide synthase) is not functioning normally (i. Tryptophan in food is converted into serotonin and tyrosine in food in to dopamine.6 mg. P5P 25 mg.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. and methyl-B12 2 mg).(impaired) status compromises the production of dopamine. Sources of 5-methyl folate include Folapro (800 mcg 5-methyl folate).(normal function) allows rapid breakdown of the dopamine you can generate. when BH4 is deficient). and Cerafolin NAC (5-methyl folate 5. thus sparing BH4. Superoxide (neutralized by Vitamin C) can further degrade nitric oxide. http://www. Serotonin formation may pick up as BH4 levels are restored with other maneuvers to address methyl cycle abnormalities. NAC 500 mg.com/AMRI-Nutrigenomics. also known as Folinic acid. but rather into the damaging free radicals superoxide and peroxynitrite. then emphasizing foods higher in tyrosine (see Appendix I) than in tryptophan makes sense (however.10-methylene THF. keeping it available such that NOS can generate nitric oxide. VDR Taq+/+ with COMT -/. We can bypass this block with 5. Gene by Gene Approach – SHMT +/SHMT combines the amino acid serine with folic acid to form 5.heartfixer. Without 5-mehtyl folate MTR cannot detoxify homocysteine in to methionine.000 mcg per day. the vasoprotective molecule that we need . We can easily bypass the MTHFR C677T block with 5-methyl folate supplementation. 5-methyl folate can neutralize peroxynitrite. Metanx (5-methyl folate 2. so the recommendation to avoid animal protein overrides the recommendation to take in foods high in tyrosine).Return to Autism Page Page 48 of 50 VDR Taq +/+ or +/. Plan of Action – MTHFR C677T +/Please continue with methyl-folate at 1. while peroxynitrite degrades BH4 (stimulating a vicious cycle). 5-methyl folate has another role here .e. our initial goal is to lower sulfate.htm 4/18/2015 . Plan of Action – SHMT +/Begin Folinic Acid 800 mcg/day. 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. If one is abnormal for MAO and normal for COMT.thus the need to maintain healthy production/levels of 5methyl folate. related to fluctuations in serotonin levels. This disorder is associated with an increased tendency to mood swings and panic disorders.10-methylene THF. Gene by Gene Approach – MAO A +/+ MAO breaks down serotonin and to a lesser extent dopamine and norepinephrine.it can neutralize peroxynitrite. after urine sulfate levels fall we will advance the dose (and possibly advance BH4). arginine is converted not into the vasoprotective molecule nitric oxide. and methyl-B12 2 mg). which is used to generate the building blocks for DNA and RNA generation. COMT -/.8 mg. it selectively emanates frequencies into the Meridian communication system. utilizing the Metagenics Clear Change program (other nutraceutical companies have similar programs). 3. as a function of where on the system the patch is placed. in TACT we demonstrated that old-fashioned. e. rather they absorb frequencies emanating from your body and then selectively return some of them. the following detox modalities are available: a. Lp(a). The science and clinical studies underlying this concept can be reviewed at lifewave. and/or carry out the diagnostic studies listed above. three days in a row. Genova has a urine estrone/estradiol hydroxylation/methylation study. most likely they all are effective. one size fits all EDTA chelation therapy improves outcome when added to standard post-infarction management. aiming for a ferritin | 100. 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).heartfixer. You could repeat the Metametrix pollutant panel in the future. Attached are DVDs. We could carry out a phone consultation regarding the above if you wish.com/AMRI-Nutrigenomics. Here we typically use oral DMSA or IV or topical DMPS. The best approach is supplementation with agents that up regulate phase I and to a greater extent phase II. b. three times a day. the Genova NutrEval gives similar but less extensive information regarding organic pollutant burden (and if covered under Medicare). 2. However. Free testosterone and estradiol. Ferritin (predominately under genomic control). With respect to atherosclerosis management.htm 4/18/2015 . but if you have not I have the following thoughts A. and then. James C. given your CBS + status. Here you could try DMSA. and if no prostate contraindications supplement to obtain high normal free testosterone and low normal estradiol levels. they are technically described as “non-transdermal”. please check: a. an effective approach would be to carry out a 10 day organic pollutant detox. metals seem to be playing an important role in the oxidative stress and immune dysregulation that characterize atherosclerosis. 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. and might not be well tolerated. C.Return to Autism Page Page 49 of 50 Additional Thoughts 1. or not carrying out efficiently. and if elevated undergo periodic phlebotomy/give blood to the Red Cross. but if tolerance is not an issue. This approach can be used at home as well. immune modulation could be added to your program (particular is CRP or other inflammatory markers are elevated). and papers pertaining to the topics discussed above. Energy flow within the Meridian system is increased.4000 mg two to three times a day) or add in Citrulline (likely boosts intracellular arginine). Regarding metals. but both are sulfhydryl group rich. Proven approaches include Pentoxifylline (please see DVD) and Colchicine (best article attached). Regarding CYP1B1 and the risk of malignancy. This creates a treatment dilemma – these agents you need are the ones you tolerate the least. frequencies leaving your body cause the molecules within the patch to self-assemble in to a crystal structure. once a month. which we encourage you to study. The crystal structure serves as an antenna. Testosterone works within this framework as well. If 1B1 is functionally significant. With respect to atherosclerosis. Far Infrared Sauna – detox at home while watching the playoffs. IV EDTA is the most powerful approach to lead and cadmium removal. another approach involves the use of QuickSilver resin or Pectasol (modified citrus pectin – please see econeugenics. and additional Vitamin C. The http://www. The Life Wave patches are not homeopathic (as are the Aura patches that we also use). your ration of 4-OH to 2-OH will be high. c. while Lipophos EDTA will up regulate your BHMT pathway and unsaturated phosphatidylcholine (please see DVD) has an anti-atherosclerotic effect. beginning at 100 mg and working up to 500 mg. C. EDTA is a poor mercury chelator. B. I am happy to help in any capacity. With respect to organic pollutant detoxification. proline. d. and if at all elevated begin Lp(a) neutralizing therapy with lysine. three times a year. In your case. Stated otherwise. E. We have switched to the Platinum Footbath device which seems to be more effective and user friendly. b. When you place a patch on or near your body. EndoPAT endothelial function testing. information sheets. D. In DMSA/DMPS intolerant individuals. Footbath therapy – the Ion Cleanse people demonstrated that organic materials are removed with their device. No physical molecules leave the patch (in contrast to a Nitropatch or an Estrogen patch).com/chc. Fibrinogen – if high you can use turmeric or nattokinase to lower the level and thus blood viscosity. and if subpar you could advance Arginine further (most clinical trials used 2-. directing your body to carry out actions that it currently is not carrying out. As the principle involved is common to all of the devices available. depending on the function of the patch. Roberts MD FACC FAARFM 1/4/14 Life Wave Patch Instructions The Life Wave patches utilize a needless acupuncture concept to favorably influence physiology. capturing frequencies leaving your body (kind of like a FM receiver). All contain sulfhydryl donors (sometimes a problem is CBS + individuals).com). You have likely undergone an extensive nutritional/risk factor/toxicity work up. 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). The Life Wave patches do not spontaneously emit energies. heartfixer. Glutathione is the key antioxidant/detoxification molecule in your body. Life Wave recommends that you wear the glutathione patch for 2 months before beginning the weight loss program. The patch is activated when it is placed on or near your body (so do not carry them around in your pocket). the idea being that your body (in its wisdom) packs fat-soluble toxins like pesticides and herbicides in to body fat. glutathione one day and carnosine the next. one for total body pain and another to address a focal source of pain. I alternate between the two. but if you are ill. as these toxins are released. A note of caution . Another issue. and if you are loaded with toxins – then you will begin to detoxify. each patch appears to be able to work for 48 hours of contact time. or you could wear it for 6 hours/day over 8 days (adhesive tape may be needed). In any event. or liver failure in Tylenol overdose situations). and then the white patch 4-6 inches away. We do not yet have any experience with the weight loss or sleep patches. then a goal has been achieved. a molecule that you can put to good use and a molecule that you likely need. The Carnosine patch directs your body to produce carnosine. and when we use these agents we sometimes have to back off on your Nitrate dose. Drink plenty of water to facilitate this process. you will likely be able to wear the patch for 6-8 hours on your first day. a powerful antioxidant. glutathione depletion occurs in response to chronic oxidative stress and toxicity (as in the average American). The patch does not provide you with Sulfurcontaining molecules. you might want to try only 2-4 hours on your first day. If they fall off. Conversely. then the patches might actually speed up healing (by drawing energy into the region of pain. just as standard needle Acupuncture does). over one of the specific glutathione control points. than it makes sense to wear the glutathione patch. James C. 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). The instructions tell you to discard a patch after it has been removed. and/or less anti-inflammatory drug therapy. but if the patch system allows you to use less pain medication. If you are vigorous and healthy. If this maneuver lowers pain even more. to augment pain relief. When you attempt to lose weight. You can then place a glutathione patch in the palm of your right hand. Vitamin C and N-Acetyl Cysteine both resolve Nitrate tolerance (loss of clinical effect due to Nitrate-induced glutathione depletion). We can increase the cost-effectiveness of this system. Place the tan patch over the point of greatest pain. 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 wear the patch glutathione production will increase. you may feel poorly.com/AMRI-Nutrigenomics.htm 4/18/2015 . So if a patch works over 48 hours. A reduction of pain is typically noted within 10 seconds. then tape them back on. you do not have to remove the backing of a patch to activate it.a “good problem”. Feel free to experiment with patch positioning. In my mind I think of the white patch as “draining pain away” from the tan patch (this isn’t actually what is happening. to protect more important regions (like your nervous system). Each type of patch comes with step by step instructions. The pain patch system is a little different. Oral glutathione is not absorbed. It inactivates when it is removed. IV administration of glutathione increases excretion of toxic substances. It is energy (frequencies) emanating from your body that activate the patch. The most important patch is the Y-Age Glutathione patch. Remember. however. then replace the patches on this schedule). Regarding the weight patch. and then gradually increase your “patch on” time on a day-byday basis. you could wear it 48 hours straight. The same may occur with the patch . Wear the pain patches for 48 hours or as you see fit (if the effect attenuates at 24-36 hours. A deep injury is obviously not going to heal with energy flow alone. tolerance to long-acting nitrates. using raw materials already present and your body’s own enzyme systems. This patch directs your body to manufacture more glutathione. Positioning of the white patch can be altered to obtain the best result. but the concept helps when considering patch placement). rather it directs you to assemble these molecules into glutathione. instead we give your its precursor substance NAcetyl Cysteine (used in Medicine to prevent kidney failure during angiographic procedures. Roberts MD FACC 5/27/08 http://www. more glutathione cannot be anything but good you.Return to Autism Page Page 50 of 50 Life Wave patch is like a program that we insert into your computer to make certain programs run more efficiently. There are also patch placement positions to deal with total body pain. You can wear two sets. Those of you with the Methyl Cycle Cystathionine Beta Synthase (CBS) up regulation will not tolerate NAcetyl Cysteine (due to its Sulfur content). If an injury is minor. but you should have no trouble with the patch.