What is the official name of the MTHFR gene?
The official name of this gene is “methylenetetrahydrofolate reductase (NAD(P)H).”
MTHFR is the gene's official symbol. The MTHFR gene is also known by other names, listed below.
Read more about gene names and symbols on the About page.
What is the normal function of the MTHFR gene?
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the B-vitamin folate (also called folic acid or vitamin B9). Specifically, this enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.
How are changes in the MTHFR gene related to health conditions?
homocystinuria - caused by mutations in the MTHFR gene
At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria. Most of these mutations change single amino acids in methylenetetrahydrofolate reductase. These changes impair the function of the enzyme, and some cause the enzyme to be turned off (inactivated). Other mutations lead to the production of an abnormally small, nonfunctional version of the enzyme. Without functional methylenetetrahydrofolate reductase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.
Anencephaly - associated with the MTHFR gene
Several variations (polymorphisms) in the MTHFR gene have been associated with an increased risk of neural tube defects (NTDs), a group of birth defects that occur during the development of the brain and spinal cord. Anencephaly is one of the most common types of neural tube defect. Affected individuals are missing large parts of the brain and have missing or incompletely formed skull bones.
The most well-studied polymorphism related to the risk of neural tube defects changes a single DNA building block (nucleotide) in the MTHFR gene. Specifically, it replaces the nucleotide cytosine with the nucleotide thymine at position 677 (written as 677C>T). This variant, which is relatively common in many populations worldwide, produces a form of methylenetetrahydrofolate reductase that has reduced activity at higher temperatures (thermolabile). People with the thermolabile form of the enzyme have increased levels of homocysteine in their blood.
It is unclear how variations in the MTHFR gene increase the likelihood of neural tube defects. However, the increased risk may be related to differences in the ability of methylenetetrahydrofolate reductase to process folate. A shortage of this vitamin is an established risk factor for neural tube defects.
Spina bifida - associated with the MTHFR gene
Polymorphisms in the MTHFR gene are also associated with an increased risk of spina bifida, another common type of neural tube defect. In people with this condition, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. As a result, part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage.
As described above, variations in the MTHFR gene may increase the risk of neural tube defects by changing the ability of methylenetetrahydrofolate reductase to process folate.
Other disorders - increased risk from variations of the MTHFR gene
Polymorphisms in the MTHFR gene have also been studied as possible risk factors for a variety of common conditions. These include heart disease, stroke, high blood pressure (hypertension), high blood pressure during pregnancy (preeclampsia), an eye disorder called glaucoma, psychiatric disorders, and certain types of cancer.
The 677C>T polymorphism in the MTHFR gene has also been suggested as a risk factor for cleft lip and palate, a birth defect in which there is a split in the upper lip and an opening in the roof of the mouth. Studies of MTHFR gene variations in people with these disorders have had mixed results, with associations found in some studies but not in others. Therefore, it remains unclear what role changes in the MTHFR gene play in determining the risk of these complex conditions.
Methylation: Critical for Biochemical Function
Research reveals that environmental factors, such as diet and toxicity have an enormous influence on how methylation pathways function. For example, deficiencies in certain key nutrient substrates such as L-methionine, folate, B-6 and B-12 will greatly impact activity in methylation pathways. Genetic defects in methylation pathways are also a factor that can block the expression of certain genes, or cause the expression of others.
Methylation is a critical series of pathways in biological systems. How important is methylation?
Consider that methylation results in:
Neurotransmitter synthesis, chiefly dopamine, norepinephrine and serotonin, which influence mood, sleep, behavior, cognition and memory
regulation of gene expression & protein function
synthesis of cellular antioxidants such as glutathione
modification of toxic, heavy metals
immune activation and regulation
regulation and expression of homocysteine
the expression or suppression of a disease, and the suppression of genes that should not be expressed
repair and regeneration of cells, tissues and DNA
hormone activity and expression
Consider that blocks or defects in methylation pathways can have very serious consequences. For example, improper re-methylation of homocysteine can cause a high level of homocysteine in blood, and become a primary factor in the development of cardiovascular disease and cancer. Or, due to a congenital defect in a methylation gene, such as MTHFR, homocysteine levels may be elevated significantly and be the missing link in the development of cardiovascular disease, leukemia, colon cancer, vascular disease and others.
If mutations or defects in certain methylation genes exist, the complex methylation sequence will be negatively affected, and consequently, the synthesis of certain biochemical substrates may be produced in reduced quantities. In recent years, an enormous amount of research has surfaced regarding one gene/enzyme in particular, MTHFR (methylenetetrahydrofolate reductase). There are actually more than 50 genes that make up MTHFR. This gene mutation is implicated as a causative factor in a very long list of diseases, including mental illness, neurological diseases such as Parkinson’s, Alzheimer’s, autism, as well as fibromyalgia, multiple sclerosis, spina bifida and many more.
If an MTHFR gene mutation exists, a person may not convert enough of the folate substrates into the correct forms needed, and consequently there will be immense blocks in how the methylation pathways function. This will effect other parts of the methylation pathways, and can result in serious mental illnesses, disease progression and various toxicities. Nutritional biochemical science has responded by formulating the missing nutrient if an MTHFR mutation exists. The nutrient is called L-5 MTHF.
Identification of Other Gene Mutations
There are many, many genes involved in the methylation cycle. Genetic methylation tests can now identify many of the core genes that may be damaged, or mutated.
Other gene defects such as MTRR indicates a person may not properly methylate B-12. As a result, homocysteine toxicity will take place, as well as poor conversion of L-methionine into SAMe. An MTRR mutation can result in birth defects, high levels of homocysteine, down syndrome and cancer, and like other gene mutations, will alter other aspects of how the methylation pathways function. If an MTRR gene mutation exists, supplementing with the correct form of B-12 may be imperative in order to bypass the mutation, or to stimulate the biochemical reaction needed.
Another example of a methylation gene mutation is CBS mutation. In this mutation, it has been observed there can be a major up-regulation of sulfur bi-products, such as sulfite and sulfate. As a result, there may be a high amount of ammonia produced and glutathione levels become depleted.
The above are 2 examples of gene mutations in the methylation pathways. Obviously, things can get complicated when there is more than one genetic mutation present. Fortunately there is brilliant research that is emerging with rapid fervency.
Methyl Cycle Abnormality that predisposed you to ill health.
What is a Methyl Cycle Abnormality?
Methyl Cycle Abnormalities are not disease specific or smoking gun genetic defects. Yes, there are specific genetic abnormalities that code for Sickle Cell Anemia, Huntington’s Chorea, or Phenylketonuria, and if you are born with these genotypes (referring to one’s genetic code), then we can be 100% certain that you will develop these disease states (the phenotype, or expression of the genetic code). There is a great deal or dread and anxiety regarding testing for these genes. After all, if you can’t do anything to prevent the phenotype, why even look for the genotype?
Methyl Cycle Defects are different. None code for a specific disease state, but all play a role in predisposing you to disease in general. The more Methyl Cycle Defects present in your genotype, the greater is your susceptibility to toxicity and infection, and the greater will be your risk for these (usually) age-related degenerative disease states that plaque our society today. These disease states are usually age-related (but are occurring in you earlier than in others) because it takes time for toxicity to build up within you, to overcome the still intact defense systems that are trying to defend your physiology. On the other hand, a little bit of toxicity during a vulnerable time period can do a lot of damage to an individual with impaired Methyl Cycle defenses. The frequency of Methyl Cycle Defects in autistic kids will likely be 100% - a little bit of Mercury in a genetically defenseless kid will damage a developing brain. Their parents and grandparents harbored these genes (likely in lower concentration) but when they were born our uterine and early life environment was toxin free. Their brains had the chance to develop normally. Exposing them to toxicity now isn’t good for them, but their brains did have the chance to develop normally, so they do not develop “adult onset autism”. But individuals harboring Methyl Cycle Defects are going to get sick, before their time, likely with conditions that make little sense such as Fibromyalgia, Chronic Fatigue, Multiple Chemical Sensitivity, or they will present early in life with what used to be diseases seen only in “old people”: - coronary disease, cardiomyopathy, Parkinson’s disease, and dementia.
I’ve looked at disease as a combination of lifestyle, environment, and heredity. Yes, if you smoke, you will eventually experience lung disease. If you are exposed to lead then it will eventually build up in your body and cause hypertension and kidney disease. But some people smoke and get lung disease at an early age, some only at old age, and some seem to be able to puff away into their 80s. We are all exposed to multiple toxins, we all live in the same general environment, but only some of us get heart disease and cancer – why? If toxicity is so bad, then why don’t all of us have toxicity associated cancer? Well, we’re on our way, but some of us can live within this toxic environment unscathed. How can one boy be autistic while his fraternal twin is normal - same uterine environment, same maternal diet, same vaccinations – but different genotypes. It is our genotype, specifically the status of the genes making up our Methyl Cycle that render us more or less susceptible to environmental influences (toxins and microbes).
The term “methyl group” refers to CH3, one carbon atom attached to three hydrogens. The enzymes of the Methyl Cycle add or subtract a methyl group from another molecule to open or close biochemical pathways, to open our DNA when it should be read, or to close it when it would not be in our best interest to decode a specific gene. We need methyl groups to silence viral RNA, to defend against other microbes, and to defend against environmental toxins. Optimal methylation is thus more important today than it was in years past, when the environment was less toxic. Individuals with Methyl Cycle Defects are the canaries of our society. Toxins will hurt all of us eventually but those of us with Methyl Cycle Defects will be the first to go down.
I am now looking at disease as a combination of lifestyle, environment, and Methyl Cycle Genomic Defects.
Your packet contains your genotype. It is up to you to adjust your diet, and it is up to me to change your treatment program, in order to optimize your phenotype (your health status – the expression of your genotype). We can’t change your genotype, but we can optimize its expression. We can eliminate from your diet and treatment program substances that you cannot handle, and we can supplement you with substances that you cannot make on your own. We can bridge gaps in your metabolic software and shore up your weak links – now that we know what your weak links are. This will be a lot of work and involve a not insignificant out-of-pocket expense, and likely a major change in your diet. This may irritate you. You may initially be frustrated and mad. If you want to be mad, you can be mad at me – but don’t go after me on a busy day – I am COMT -/- and VDR Taq +/+; thus if you stress me out too much I will be susceptible to a fall off in dopamine, serotonin, and norepinephrine, so I won’t think so well (a little Methyl Cycle humor). Please do not take out your frustration on my staff. If you are really angry you can complain to your parents, Charles Darwin, or God – a better idea will be to accept and understand this challenge and get to work addressing it. Along with your genotype report, your packet will contain Dr. Yasko’s general recommendations (which focuses on kids with Autism), my analysis of your genotype with specific recommendations for diet change, nutritional supplementation, and follow-up testing. Information regarding sulfur avoidance (critical for CBS and SUOX genotypes) and food excitotoxin avoidance (useful for all of us) will be enclosed, along with a supplement check list and information regarding how to obtain these supplements on line or at the office.
90% of you will have an abnormality in the trans-sulfuration pathway (CBS and/or SUOX). Sulfites and Chronic Disease, by Rick Williams (available at the office or you can go to www.readingtarget.com/nosul
... 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.
When both parents are homozygous (+/+) all of their kids will be homozygous (+/+)
When both parents are homozygous (-/-) all of their kids will be homozygous (-/-)
When both parents are heterozygous,
1/4 of their kids will be homozygous (-/-),
½ will be heterozygous (+/-), and
1/4 will be homozygous (+/+)
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.
CBS: Cystathionine Beta Synthase
CBS initiates the trans-sulfuration pathway, converting homocysteine in to cystathionine and its downstream metabolites. This is the most important Methyl Cycle defect and is present in 90% of the patients who we have tested. The CBS defect is an up regulation. CBS is operating at up to ten times its normal rate. Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. The C699T and (to a somewhat lesser extent) A360A defects are associated with CBS up regulation. Homozygotes (+/+) will be more severely affected than will be individuals heterozygous (+/-) for a CBS abnormality. We treat CBS ( +) individuals with dietary animal protein and sulfate restriction and supplements designed to neutralize ammonia and speed up clearance of sulfite/sulfate. Laboratory findings consist of an elevated urine sulfate level, a low or low normal blood homocysteine level, an elevated or high normal blood ammonia level, and positive findings of ammonia, sulfite, or sulfite upon Asyra testing. My initial observation is that individuals with high heavy metal burdens upon provocative challenge testing are likely to be CBS positive. CBS (+) individuals will be intolerant to sulfur containing drugs, nutritionals, and foodstuffs (I am +/- for CBS A360A and cannot tolerate DMPS or glucosamine sulfate. A cold beer tastes great but I do not like wine, which is high in sulfite).
Biochemistry – The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate, which stimulate the stress/cortisol “fight or flight” response), excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia), hydrogen sulfide (producing “brain fog”), and alpha-keto glutarate (leading to “excitotoxicity”). The G6PDH enzyme system may be affected, leading to abnormalities in sugar control. Methylation intermediates will “fall through this drain”, so the entire system suffers; our defenses against viral invasion and toxicity suffer. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy.
Ammonia is produced during the metabolism of dietary protein. The CBS up regulation drains methyl cycle intermediates in to ammonia, more ammonia than your system can handle. Ammonia detoxification is metabolically expense, using up two molecules of BH4 per molecule of ammonia. BH4 is necessary to generate neurotransmitters (dopamine, serotonin, and norepinephrine) and nitric oxide, our key vasoprotective molecule. Thus it is easy to see how a CBS up regulation, by generating ammonia and depleting BH4, can set you up for neurological, psychological, and cardiovascular disease states. We cannot change your DNA. We cannot stop CBS from generating excess ammonia, but if we restrict animal protein in your diet, we can decrease your ammonia burden, preserving BH4, such that you can start making neurotransmitters and nitric oxide again – in other words, we can compensate for your genetic challenge. The herb Yucca, Dr. Yasko’s Ammonia support RNA product, and supplementation with charcoal and carnitine will bind up or neutralize ammonia, and add to your dietary efforts.
Sulfite is neurotoxic. Sulfite will be over produced by the CBS up regulation, and then requires conversion in to the less toxic sulfate molecule by the enzyme Sulfite Oxidase (SUOX). SUOX can easily be overwhelmed. Molybdenum is required for SUOX function, and is typically depleted in CBS (+/+) or (+/-) individuals. Molybdenum supplementation (3 drops or 75 mcg of e-lyte Molybdenum twice a day), Boron 3 mg/day, Vitamin E succinate 400 IU/day, and hydroxy-B12 2000 mcg/day are also utilized to speed up SUOX activity.
While sulfate is less toxic than is sulfite, it will stimulate the adrenergic (fight or flight) limb of the autonomic nervous system and stimulate a cortisol stress response, revving you up into an unrelenting biochemical overdrive. If you have a CBS defect, we need to restrict your sulfur intake, at least until your urine sulfate (and your body sulfate burden) has decreased. The amino acids methionine, taurine, and cysteine all contain sulfur; they are concentrated in animal protein (thus the restriction on animal protein intake). Many nutritional supplements (MSM, N-acetyl cysteine, glutathione) that are good for most people are a problem for you. While certain aspects of your health will benefit from these agents, they will add to your sulfate/sulfite overload problem, adversely affecting the Methyl Cycle Defect that is the common denominator to all of your health problems. Many drugs are loaded with sulfur (sulfates, sulfites, metabolically active sulfur), so if you are CBS positive and I treat your hypertension with the diuretic hydrochlorothiazide, your diabetes with the sulfonylurea drug glipizide, and your urinary tract infection with a sulfa containing antibiotic, I will be lowering your blood pressure, lowering your blood sugar, and clearing bacteria from your bladder, but I will also be adding to your sulfate burden, compromising your biochemistry, and contributing to an ongoing decline in your health. I will be treating the manifestations of an underlying problem and at the same time adding to the underlying problem. If I treat your Mercury overload with DMSA or DMPS, I will remove a toxin from your body, but if you are CBS (+), I will be adding to your sulfate/sulfite pool, and sulfate/sulfite overload due to the CBS up regulation is likely playing a key role in your sensitivity to heavy metals and/or your inability to clear them. We can avoid this. We can hold sulfur containing agents until your sulfate burden has come under control. Learn all you can about the sulfur content of foodstuffs, supplements, and prescription drugs. Sulfites and Chronic Disease by Rick Williams (available at the office or at www.readingtarget.com/nosul
... is an invaluable resource. Do not expect us to know the sulfur content of foodstuffs. Some tips on low sulfur eating are included at the end of this document, but do not expect us to tell you what to eat. We can’t do this. We do not have this knowledge. Please attend our monthly Methyl Cycle support groups meetings, and you may sign up for individual (or group) dietary change counseling. It is your responsibility to become expert in this area. I will work with you to phase out high-sulfur drugs and nutritionals from your program, but don’t expect me to get in right every time – please study your food, drug, and supplement labels.
Excitotoxicity – The CBS up regulation leads to excess production of alpha-ketoglutarate, which is converted in to glutamate, a stimulatory neurotransmitter. Under normal circumstances, glutamate will be converted in to GABA, a calming neurotransmitter, but the enzyme systems that convert glutamate in to GABA are compromised by lead and mercury, the clearance of which seems to be compromised in individuals with methyl cycle defects (here is a situation where dysfunction of a genetically abnormal enzyme leads to acquired dysfunction of a genetically normal enzyme system). The result is “excitotoxicity”, stimulatory behavior in autistic kids (“stims”) and anxiety and sleeplessness in adults. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on Excitotoxicity to follow; diet tips in appendix) and by supplementing you with GABA, aiming to restore GABA:Glutamate balance. GABA is initiated at 500 mg once or twice a day, advancing the dose as you see fit by your response.