A Critical Gene For Your Health

Are you sick and tired of feeling sick and tired?

Have you been to 60 doctors and still have no answers?

Are you feeling hopeless about regaining your health?

If you don’t know about your MTHFR C677T gene status, you can be stumbling around in the dark as you try to resolve symptoms. You can be using the wrong supplementation for your genetic type. Knowledge about your MTHFR C677T gene can clarify the mistakes, sort out the confusion, and move you in the right direction.You need to supplement very carefully for this mutation, taking into account not only this gene, but also a number of other genes that impact the pathway in which MTHFR functions.

A mutation at MTHFR C677T reduces the number of methyl groups you can make. A methyl group is a small but mighty molecule. Other important small molecules are O2 (oxygen), H20 (water), and NO (Nitric Oxide), that is important for blood vessel diameter. These small molecules are critical to life.

Below is a depiction of a methyl group:

Methyl groups are central to the regulation of gene activity. They silence genes. At any point 80% of your genes should not be expressing. If you do not have adequate methyl groups, you will have aberrant gene expression and the problems that come with it.

Without enough methyl groups, you don’t form molecules that make DNA and RNA. Without these, making new cells is impaired. You age more rapidly. Wound healing is slow. You do not learn new tasks readily or have the ability to adapt to the changes in your environment easily. Your energy may sink to new lows. You may develop high homocysteine and the vascular inflammation and heart disease that come with this condition.

Beyond that, your methyl group producing pathways are intimately connected to your detox pathway.  An MTHFR C677T mutation will reduce your ability to detox. There are other important biochemical pathways that connect to your methyl group producing ones, like pathways for neurotransmitter production, urinary excretion and folate metabolism. So you really need to address the MTHFR mutation if you have one.

If you are using a mainstream doctor, odds are they won’t know about MTHFR at all. New ideas can take a while to get into the mainstream. If you are using a Functional Medicine practitioner, they may know about it, but they won’t know the intricacies of the biochemistry needed to get the important interconnected pathways to function smoothly. They will give you methyl folate and/or methyl B12 that may help, or it may make you feel awful.

I am one of very few methylation genetics experts in the US. I work with more people who have MTHFR C677T mutations than any other doctor. It is my area of specialization. I work with Dr. Amy Yasko who ‘wrote the book’ on this. Her protocol looks at the intimate biochemistry in the connected group of pathways surrounding the MTHFR C677T mutation that impact on its function.

If you are having a medical problem that you cannot shake, and you know that you have an MTHFR C677T mutation, contact me at NancyMullanMD@aol.com. I will help you optimize the function in these pathways and get your body functioning well again.

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So excellent!  I literally learn something with every single post and I get clarification on things that have been lingering on my mind…
VB

You are giving people a huge gift by empowering them…It’s about helping the patient become their own healer by taking them to a higher level of consciousness…
AL

Thank you so much Dr. Mullan.  Thank you so, so much for everything you do.
MS

Wow!  I have to tell you, it’s so nice to hear good news especially about a child.  Anxiety, OCD and a host of other mental/psychiatric symptoms have been a huge hurdle for me.  So to hear this story of all those awful symptoms totally going away is such a bright light for me!!!!
TR

Nancy Mullan MD

Author, lecturer, clinician
Dr. Nancy Mullan is best known for her natural treatment of chronic illness, MTHFR+, Autism Spectrum Disorders, Psychiatric Disorders and Lyme.

NancyMullanMD@aol.com
www.NancyMullanMD.com
www.NancyMullanMD.com/blog

1122 W. Burbank Boulevard
Burbank, CA 91506

Phone: (818) 954-9267

Posted in Autism, Chronic Disease, depression, MTHFR+ | Tagged , , , , | Leave a comment

Getting the Most Out of Neurotransmitter Testing

Neurotransmitters function in your brain and body in ways that define your personality and your physical abilities. They are the chemicals that move your muscles and generate the feelings that you have, among many other functions. Their importance cannot be overestimated.

Low serotonin has been implicated in many disorders, including OCD, perseverative behavior, depression, anxiety, and GI dysfunction. Dopamine is critical for executive function, attention, focus, goal-motivated behavior, and mood. Higher norepinephrine levels relative to epinephrine appears to be a factor in ADD/ADHD.

Neurotransmitter

Several tests are needed to get a complete sense of neurotransmitter (NT) function, formation, balance, and breakdown. The level of starting materials for serotonin and dopamine is found on a Urine Amino Acid test (UAA). Tryptophan converts into serotonin. Phenylalanine converts into tyrosine and subsequently dopamine. Dopamine then goes on to become norepinephrine and epinephrine. So the UAA test gives you the levels of the starting materials for these as well as other neurotransmitters.

Neurotransmitter testing gives you the level of the particular NT found in your body. So with the UAA and the neurotransmitter test results, you have the level of the starting material and the amount of neurotransmitter made from the starting material.

Finally, you can look at the level of the breakdown product(s) from the particular NT, whether it is serotonin, dopamine, epinephrine, or norepinephrine. This gives you the rate of turnover of the particular NT. The rate of NT breakdown is a major factor in the final level of NT present in your body. Breakdown information is on the Metabolic Analysis Profile test (MAP).

So, in order to assess NT status and performance in your body, first look at a UAA to see what the level of the starting material is for the particular NT. Then, look at a NT test to see the reported NT level. Finally, look at a MAP test to give you a measurement of NT breakdown product(s).

You can see the utility of this way of working. If your NT levels are low, you may need to slow the level of breakdown as opposed to adding the amino acid that forms that neurotransmitter. You may need to do both. You will get a very clear direction from the levels given to you by these three tests. With NT testing alone, you will be guessing about what caused the particular level and what to do.

If you would like to get my input on your health issue, you can get an Exploratory Conversation. It does not involve filling out lengthy history forms or becoming my patient. I will answer your questions, look at whatever data you want to send, and discuss whatever you like for 30 minutes. The fee for this service is $119. This fee can be applied to the cost of a new patient appointment if the appointment occurs within 30 days of the conversation. You will not be invoiced, sent a super bill, or sent written information on whatever it is I may tell you to do.

Exploratory Conversations are meant for folks who are not my patients who would like to talk to me to get my input about their condition or treatment. They are phone calls. They are not office visits. The idea is to streamline the communication of information so that effective work can happen in one half hour.

Email me at NancyMullanMD@aol.com. Let me know that you want an Exploratory Conversation and I will send you the information about how to schedule one.

Check out my YouTube video:
Fine-Tuning Your Treatment of Chronic Illness with MTHFR Genetics

Visit my website:
http://nancymullanmd.com/

Posted in Uncategorized | Leave a comment

MTHFR A1298C, Neurotransmitter Production, and Depression

How does a mutation in the MTHFR A1298C gene impact your body? It is different from the way that MTHFR C677T and MTHFR 03 do. Most people are thinking of MTHFR C677T when they refer to MTHFR, because it is a common MTHFR mutation and it has a major impact. But there are actually three MTHFR mutations that make a significant difference in the way your body functions.

First, a little background… Genes encode for enzymes. The gene and the enzyme for which it encodes have the same name. These enzymes have an impact on your body’s biochemical reactions. They can make the reaction go more quickly, they can make it go more slowly, or they can have no impact.

Not all mutations are characterized yet. We do not know what all of them do, but we are certain that some of them do nothing.

Methylation_Pathway1
MTHFR C677T and MTHFR 03 work in the same way. Mutations in either of these genes slow down MTHFR enzyme activity. MTHFR 03 generates the more profound slowdown of the two. As a result of either of these mutations, less 5-methylfolate is produced, and fewer homocysteine molecules are converted into methionine to ultimately produce methyl groups.

I have a downloadable, no-cost ebook on my website www.NancyMullanMD.com that explains this process in Chapter 3.

MTHFR A1298C works in an entirely different way from MTHFR C677T or MTHFR 03. It performs a regulatory function. It regulates the amount of SAMe, S-adenosyl methionine that is produced. SAMe is your body’s main methyl group supplier. It is necessary to have not too many and not too few methyl groups. Their production is strictly regulated.

When the cycles are going in a forward direction, SAMe is produced. If the level of SAMe gets too high, it stimulates a regulatory sensor at the MTHFR A1298C position. Triggering this mechanism makes the biochemical reaction go in a different direction, halting the production of SAMe and hence methyl groups. When you have a mutation at A1298C, the sensor is less sensitive to the amount of SAMe in the fluid surrounding the cells, and this regulation does not work as well. You may get an overload of methyl groups and an underproduction of neurotransmitters.

The cycles in this representation of biochemical activity work together like gears. When cycle 4, the methionine cycle, is working in a clockwise direction, cycle 3, the folate cycle, is working in a counterclockwise direction. This makes methionine, SAMe and methyl groups.

When the cycles reverse, cycle 3, the folate cycle, and cycle 2, a representation of neurotransmitter production, interact in important ways to produce neurotransmitters. Dihydrobiopterin (BH2) is made into tetrahydrobiopterin (BH4). BH4 is necessary for the production of both dopamine and serotonin.

So, an MTHFR A1298C mutation can cut down on the production of neurotransmitters by cutting down the production of BH4. Fortunately, BH4 is available as a supplement through Holistic Health International and Emerson Ecologics. It is called Pteredin-4.

The DHPR enzyme is necessary for the conversion of BH2 to BH4. The DHPR enzyme is inhibited by aluminum. So aluminum can cut down significantly on neurotransmitter production. This is one of the many ways that aluminum is damaging to neurological activity.

If you would like to get my input on your health issue, you can get an Exploratory Conversation. It does not involve filling out lengthy history forms or becoming my patient. I will answer your questions, look at whatever data you want to send, and discuss whatever you like for 30 minutes. The fee for this service is $119. This fee can be applied to the cost of a new patient appointment if the appointment occurs within 30 days of the conversation. You will not be invoiced, sent a super bill, or sent written information on whatever it is I may tell you to do.

Exploratory Conversations are meant for folks who are not my patients who would like to talk to me to get my input about their condition or treatment. They are phone calls. They are not office visits. The idea is to streamline the communication of information so that effective work can happen in one half hour.

Email me at NancyMullanMD@aol.com. Let me know that you want an Exploratory Conversation and I will send you the information about how to schedule one.

Check out my YouTube video:
Fine-Tuning Your Treatment of Chronic Illness with MTHFR Genetics

Visit my website:
http://nancymullanmd.com/

Posted in depression, Methylation, MTHFR A1298C, MTHFR+, neurotransmitters | Tagged , , , , , , , | Leave a comment

MTHFR Mutations, Depression, and Other Chronic Illness

What would happen if all the traffic lights in your county started to malfunction at the same time? Say they all came on and stayed on. Or they all went dark. Even lesser degrees of malfunction, delays in lights’ changing for example, or one light out here or there at important intersections, would cause major SNAFU’s in traffic flow. The orderly, clockwork traffic performance that we all expect would be interrupted. You wouldn’t be able to get anywhere without major delays.

Methyl groups are like the traffic lights of your biochemical pathways. They turn on certain reactions and turn off others. They are involved in both the formation and deactivation of neurotransmitters. They are necessary for the fluidity of your cell membranes that need to pass substances into and out of the cell. The receptor sites embedded in the cell membrane also do not work well unless the membrane is methylated.

methylgroup-300x170

Methyl groups are primary epigenetic regulators, a regulation of genetic function that comes from outside of the gene, ‘epi-‘ meaning around. The methyl groups in the cellular fluid surrounding a chromosome impact the function of the gene. When a methyl group attaches to a gene, it silences the expression of that gene. It turns the gene off. This is important for genes that cause inflammation or immune activation. You don’t want those genes expressing when they should not be active, thereby causing an inflammatory disorder or autoimmunity.

Your MTHFR gene encodes for the MTHFR enzyme. The MTHFR enzyme catalyzes the production of methylfolate, a B vitamin that is critically necessary to methyl group generation. When there is a mutation in the MTHFR C677T gene or the MTHFR 03 gene, there is a slowdown in methyl group production. Other genes in the methyl group-forming pathway may be mutated also, which further compromises methyl group production.

In order to get free from depression, you need appropriate methyl group formation because methyl groups are pivotal to neurotransmitter function. They play a role in both neurotransmitter production and breakdown. In addition, methyl groups function in the activation of your immune system. If your immune system does not have an appropriate supply of methyl groups, you can’t mount a defense against gastrointestinal infection or yeast infestation. You may be aware of the depression caused by dysbiosis, non-optimal organisms in your GI tract.

Your gastrointestinal lining breaks down on an ongoing basis. Methyl groups are necessary for cellular regeneration. If you do not have sufficient methyl groups to rebuild your gastrointestinal lining, you cannot absorb the nutrition in your food into your body properly. This is a major cause of depression.

There are myriad impacts from the production of too few methyl groups. MTHFR C677T and MTHFR 03 are major actors in the production of methyl groups. Supplementing to bypass mutations in these genes is essential to health, and to a feeling of well-being and being free from depression.

If you would like to get my input on your health issue, I would like to offer you an Exploratory Conversation. It does not involve filling out lengthy history forms or becoming my patient. I will answer your questions, look at whatever data you want to send, and discuss whatever you like for 30 minutes. The fee for this service is $119. This fee can be applied to the cost of a new patient appointment if the appointment occurs within 30 days of the conversation. You will not be invoiced, sent a superbill, or sent written information on whatever it is I may tell you to do. 

Exploratory Conversations are meant for folks who are not my patients who would like to talk to me to get my input about their condition or treatment. They are phone calls. They are not office visits. The idea is to streamline the communication of information so that effective work can happen in one half hour.

Email me at NancyMullanMD@aol.com. Let me know that you want an Exploratory Conversation, and I will send you the information about how to schedule one.

Visit my website:
http://nancymullanmd.com/

Posted in Chronic Disease, depression, MTHFR+ | Tagged , , , , , , | Leave a comment

An Exploratory Conversation with Dr. Mullan. What’s in It for You?

I have been working to find a way to balance the current economy against the very effective but relatively complicated and costly protocol that I do.  Despite Dr. Amy Yasko’s and my knocking ourselves out to make it simple, it can only be simplified so much. The subject matter of finding solutions for chronic illness, psychiatric disorder or autism is inherently complex.

Testing to discover underlying problems, and then supplementing to bypass the genetic blocks that may be present, helps to balance your biochemistry. Doing this addresses the medical conditions outlined in the illustration below. Repetitive testing is expensive and supplementation is also. The complexity of chronic illness and the layers of improvement that you may need to go through mean that testing and supplementation go on over time.

If you would like to get my input on your situation, I can offer you an Exploratory Conversation. It does not involve filling out lengthy history forms or becoming my patient. I will answer your questions, look at whatever data you want to send, and discuss whatever you like in the time frame that we have. Exploratory Conversations are scheduled for 30 minutes. The fee for this service is $119. This fee can be applied to the cost of a new patient appointment if the appointment occurs within 30 days of the conversation. You will not be invoiced, sent a super bill, or sent written information on whatever it is I may tell you.

Exploratory Conversations are meant for folks who are not my patients who would like to talk to me to see if I am the doctor for them, or to get my input about their condition or treatment. They are phone calls. They are not office visits. Even if you live within commuting distance of my office in Burbank, California, this conversation takes place over the phone. It is not even a Skype call. The idea is to streamline the communication of information so that effective work can happen in one half hour.

Email us at NancyMullanMD@aol.com. Let us know that you want an Exploratory Conversation and we will send you the information about how to schedule one…

I am looking forward to helping you get well!
Dr. Mullan

Visit my website:
http://nancymullanmd.com/

Posted in Autism, Chronic Disease, Dopamine and Dopamine Signaling, Epigenetics, Excitotoxicity, Monsanto GMO Chemicals, MTHFR+, Treating Chronic Illness Series | Tagged , , | Leave a comment

Folate – What’s in It for You?

Folic acid deficiency results in the inability to degrade formiminoglutamic acid (FIGLU). As a result, FIGLU accumulates in your urine. High FIGLU on an organic acid test is a marker for low folate.

It is important to use both folic acid and folate supplementation for several reasons. The pathway that involves MTHFS, an enzyme in the methylation pathway, functions in the folate cycle. There it catalyzes a reaction that turns formyl tetrahydrofolate, or folinic acid, into tetrahydrofolate (THF). THF is what you ordinarily think of as folic acid.

Big shot scientists
MTHFS also impacts the formation of two purines that are necessary for DNA and RNA formation. DNA and RNA are important for the formation of fast turnover cells like blood cells, GI tract lining, or wound healing. If you have a mutation that reduces MTHFS activity, folinic acid can build up to high levels. When that happens, your synthesis of these purines is reduced, and your tetrahydrofolate level is also decreased.

I work with Dr. Amy Yasko. Her program uses only low dose folinic acid so that this build up does not occur. The two purines are supplemented to support DNA and RNA production, and low dose folic acid along with probiotics are added as a secondary way to make THF. In this way, the impact of any possible MTHFS mutation is bypassed, even if you not have data regarding this gene.

Dr. Amy covers all her bases when adding nutritional support. She includes low dose 5 methyl THF in her supplementation because that is the only way to bypass an MTHFR C677T mutation. No amount of folinic acid, folate, or folic acid will do it. Using high dose 5 methyl THF at the beginning of a treatment for MTHFR + can trigger more detox than is optimal, especially for an adult. Your body may need nutritional groundwork to ease into 5 methyl THF administration.

Folate is basically a chain of glutamates. The difference between folic acid and folate is the stability of the  molecule and the length of their glutamate chains. So, if you are MTHFR C677T++ and you take high dose folate, you potentially have a chain of unused glutamate molecules left in your body. You cannot process it efficiently to 5 methyl THF because of your mutation. There is the risk of folate’s breaking down to release glutamate. Most of the folate that is used for Dr. Amy’s program is 5 methyl THF, with some low dose folinic acid.

Dr. Amy has specific reasons for the choices she makes in terms of supplements and the forms that she uses. The RDA for folate/folic acid is 300 micrograms for a child that is 1 year old, and up to 1,000 micrograms daily for an individual 19 years of age or older. Thus, the 15 to 40 micrograms used for her program is not an issue, especially since the body does need some folate and folic acid aside from the need for 5 methyl THF and folinic. To put this in an easily understandable perspective, a bowl of cheerios has 400 micrograms of folic acid, as compared to the 15 to 40 micrograms used in her program.

If you are MTHFR C677T or have other methylation genetic issues, you may not be satisfied with the treatments you have tried. You may still be tired, hurting, brain-fogged, depressed, or having gut or autoimmune issues. You need a medical professional who know this area and who can help. Contact Dr. Mullan at NancyMullanMD@aol.com for information or to set up an office visit or remote appointment.

Check out Dr. Mullan’s YouTube video
Posted in Epigenetics, MTHFR+ | Tagged | Leave a comment

Of Mice and Men…Inheriting Epigenetic Changes

The intracellular environment surrounding your DNA can either help repair problems in your DNA structure, or make those problems worse. This happens because of ‘epigenetic’ changes, changes in the expression of the gene because of what is ‘epi’ or around the gene.

It is only common sense that different substances in the environment surrounding the gene itself would make the gene function differently. This is where heredity and environment interface.

Methyl groups are one of the most important substances that can impact genes this way. Methyl groups are primary epigenetic modifiers of DNA. Methyl groups are made of one carbon and three hydrogen molecules. They attach to and regulate the function of the DNA.mice

These epigenetic changes are inheritable. The two mice above are genetically identical. Their mothers were fed differently, hence their differences. The obese white mouse on the left had a mother who was fed regular mouse rations.

The smaller brown mouse on the right is normal. His mother was fed a diet with added B12, folic acid and methyl donors. B12 and folic acid enhance methyl group formation.

None of this is news to you. What is news is that researchers have uncovered that a human mother’s diet before conception can permanently affect how her child’s genes function. According to a study published in Nature Communications, this is the first evidence of the effect in humans.

The study utilized a unique ‘experiment of nature’ in rural Gambia, where the population’s dependence on grown foods and a markedly seasonal climate impose a large difference in people’s dietary patterns between rainy and dry seasons.

child

While a child’s genes are inherited directly from their parents, how these genes are expressed is controlled through ‘epigenetic’ modifications to the DNA. One such modification involves tagging gene regions with methyl groups that results in silencing the genes.  The addition of methyl groups requires key nutrients including folate, vitamins B2, B6 and B12, choline and methionine.

Senior author Dr. Branwen Hennig, Senior Investigator Scientist at the MRC Gambia Unit and the London School of Hygiene & Tropical Medicine, said:

“Our results represent the first demonstration in humans that a mother’s nutritional well-being at the time of conception can change how her child’s genes will be interpreted, with a life-long impact.”

The researchers found that infants from rainy season conceptions had consistently higher rates of methyl groups present in all six genes they studied, and that these were linked to nutrient levels in the mother’s blood.

Strong associations were found with two compounds in particular, homocysteine and cysteine, and the mothers’ body mass index (BMI) had an additional influence.

Andrew Prentice, Professor of International Nutrition at the London School of Hygiene & Tropical Medicine, said:

“Our ongoing research is yielding strong indications that the methylation machinery can be disrupted by nutrient deficiencies and that this can lead to disease. Our ultimate goal is to define an optimal diet for mothers-to-be that would prevent defects in the methylation process. Pre-conceptional folic acid is already used to prevent defects in embryos. Now our research is pointing towards the need for a cocktail of nutrients, which could come from the diet or from supplements.”

There is an e-book on www.NancyMullanMD.com called “The Methyl Group: What It Can Do for You, Plus Three Mistakes Not to Make with MTHFR.” It goes into these issues more and includes a description of which genes specifically impact methyl group production. This is important information if your body is not functioning properly.

Posted in Epigenetics, Folate, folic acid, Methylation | Leave a comment

“I’d rather try to change someone’s religion than his diet.” Sidney Baker, MD

Every time I tell the average person that it is necessary to eat organic, I cringe a little. I know that it automatically puts me in the same category as a wacked-out nut. They think about all the restaurants that are immediately wiped off of their lists, and about how expensive organic food is. I lose credibility with that one thing.


Pretty much everyone in the functional health community knows about the dangers of glyphosate, the active ingredient in Round-Up, Monsanto’s infamous weed killer. Its use on crops has increased dramatically over the last 15 to 20 years. Corn, soy, wheat, canola, sugar beets, and alfalfa are grown in huge amounts in the US and Canada. These crops have been genetically engineered to resist being killed by glyphosate, and they are sprayed with copious amounts of it. So, North Americans are getting more exposure to it in our food than ever before. The US uses 25% of the world’s supply of Round-Up. We eat more glyphosate than any other nation in the world, and we don’t really know that it’s safe.

Monsanto claims that they provided safety studies 30 years ago, but independent investigators looking at the studies claim that the data are not proof of safety. Particularly around the issue of cancer, specifically mammary (breast) cancer, the studies seem to have been manipulated to make the chemical appear safe, when in fact, it is not. The increased use of glyphosate correlates with the increased incidence of diseases like diabetes, autism, ADHD, Alzheimer’s disease, celiac disease, irritable bowel syndrome, kidney disease/cancer, and liver disease. The curves match remarkably well, according to Massachusetts Institute of Technology Computer Sciences professor Stephanie Seneff (people.csail.mit.edu/seneff).

Glyphosate interferes with your body’s function in the following ways:

  • Energy production in the mitochondria is disturbed.
  • The function of important minerals such as sulfur and manganese is being compromised.
  • Gastrointestinal bacteria are being killed and replaced with non-optimal organisms.
  • Bile acid metabolism is negatively impacted.
  • Folic acid metabolism is disturbed.
  • Estrogen metabolism is disrupted.

Glyphosate was introduced in 1975. GMO Round-Up ready crops were introduced in 1996. Since 1996, an explosion of Round-Up that increases every year has been sprayed on food crops. Predictably, weeds have become resistant to this toxin, so now Monsanto has added another chemical to Round-Up, a component of Agent Orange, that makes Round-Up 1000 times more toxic.

You need to eat organic food. I am sorry to tell you this, but if you want to remain healthy and free of degenerative disease, you need to eat organic.

It is up to YOU to learn about treating your chronic illness successfully.

You need to know about the role of optimizing both methyl group production and your capacity for methylation in order to be healthy.

This is your opportunity.

Check out my YouTube video:
Fine Tuning Your Treatment of Chronic Illness with MTHFR Genetics

 

Posted in Chronic Disease, Epigenetics, Excitotoxicity, Monsanto GMO Chemicals, MTHFR+, Treating Chronic Illness Series | Tagged , , , , | Leave a comment

Lithium’s Pivotal Role in Your Body

Lithium has been known for years to be useful for bipolar disorder. Despite all that is known about lithium and its impact on biochemical pathways, no one has defined the mechanism by which lithium has its impact. It is likely to be an effect on multiple pathways, since there are a number of enzymes in the body that are activated or inhibited by lithium.

Lithium comes together with methylation at COMT, the enzyme catechol-o-methyl-transferase. COMT breaks down dopamine and norepinephrine. Dopamine is a critical neurotransmitter for motivation, focus, and attention, among other functions. Norepinephrine is involved with modulating the impact of stressors. Both are central to nervous system function.

COMT uses methyl groups to accomplish this deactivation. COMT –/– breaks down dopamine at a steady even rate and uses significant numbers of methyl groups. COMT +/+ breaks down these neurotransmitters more slowly and uses fewer methyl groups.

We know that giving a patient more methyl groups than they can use produces symptoms. They get mood swings and start to look bipolar. Children will become hyperactive or “stimmy,” or get other symptoms when they are put on methyl B12 if it is too much for them.

Lithium may inhibit the production of a central enzyme in the sulfur system, thioredoxin reductase. It appears that lithium may be increasing the production of COMT and inhibiting the production of thioredoxin reductase. COMT and thioredoxin reductase have genes that are on opposite strands of chromosome 22. Their promoter regions overlap, which implies some mutual regulation. Having a shared promoter means that at any given time you can make either COMT or you can make thioredoxin, but you cannot make both.

This circumstance is analogous to a roadway being closed down to one lane. The line of traffic can move only in one direction at a time. One lane is stopped while the other one can go. A shared promoter generates the same situation in gene transcription. You can make either COMT or thioredoxin, but not both at the same time.

Dr. Amy emphasizes that this is her hypothesis; it is not scientific fact. But based on this hypothesis, she started looking carefully at lithium levels and opened up a whole new area in her program. Using this hypothesis makes a difference for patients. She noticed that MTR+ is associated with excess lithium excretion. An out-of-balance methylation cycle will also cause increased lithium excretion. The vast, vast majority of patients using this protocol come in with low lithium levels.

Dr. Amy suggests only low dose lithium support because lithium also inhibits ribonucleotide reductase. Ribonucleotide reductase takes ribonucleotides, i.e., RNAs, and breaks them down into building blocks for DNA and other RNAs. So one of the toxic impacts of high dose lithium is this impact on RNA breakdown. You need to support with DNA building blocks, for example using Nucleotide Immune Support. The RNA formulas also supply these building blocks.


Lithium is an essential trace element. You must get it from your diet. The average intake of lithium from the diet should be up to 3100 mcg, or 3.1 mg. Dr. Amy wants to supplement with very low level lithium, around 2.5 mg. She wants to do it consistently and she does not want to get near biologic doses. What it takes to actually increase a patient’s lithium levels can be significantly more, especially with sicker patients.

You have to keep watching the lithium and cobalt levels on a UEE. High lithium levels on a UEE may indicate excess excretion, but when cobalt, the oxidized form of B12, starts to show, you know the lithium level is coming into balance and you can start to push the long route instead of just the short route.

Why is this important?

There is a connection between lithium and COMT, bipolar disorder, and schizophrenia (SZ). It is possible that imbalances in the COMT pathway need regulation by low dose lithium in order to get the kind of levels of COMT that you need for proper dopamine processing. When the levels of COMT in the brains of patients with SZ and bipolar disorder were compared with normal controls, the levels of COMT in those affected were lower than in controls. Lithium seems to increase the activity of COMT.

Lithium induces B12 transport into the cells, thus driving the long route. This can happen with just the standing levels of B12 without additional supplementation. B12 binding capacity as well as white count will go up in the presence of lithium. B12 deficiency is known to lead to degeneration of the central nervous system and psychiatric disturbances such as affective disorders and manic psychosis. Violent criminals as a group have the lowest levels of lithium in hair. There is not only a relationship between lithium, B12, and folate, but also between low lithium and anxiety, aggression, bipolar disorder, and SZ.

In studies with patients known to be low in B12, the following psychiatric manifestations were reported to remit with vitamin B12 therapy: confusion , hallucinations, delusions, disorientation, confabulation, anxiety, restlessness, fatigue, depression, irritability, sleepiness, psychosis, stupor, slowed ability to process thoughts, decreased memory, acute delirium, mania, apathy, lack of energy, weakness, violent behavior, flight of ideas, negativism, and acute paranoid states. These symptoms may occur in the absence of hematological evidence of B12 deficiency.

So certain behavioral problems, depression, and learning disability could be caused or aggravated by low nutritional intake of lithium coupled with marginal deficiencies of B12.

Lithium has a direct effect on norepinephrine pathways. Lithium indirectly inhibits thioredoxin reductase. There is an inverse relationship between thioredoxin reductase and COMT, so it may be that lithium increases COMT leading to decreased norepinephrine.

Other positives of lithium:

  • Lithium stimulates tyrosine hydroxylase, which is a secondary pathway to dopamine production.
  • Lithium has neuroprotective actions against a variety of insults. It increases GABA activity. It helps to protect against glutamate excitotoxicity by inhibiting the NMDA receptor-induced calcium influx.
  • Lithium plays a role with sodium and potassium balance.
  • Lithium may help to repair neurons and reduce some of the trauma after injury.
  • It induces enhancement of mitochondrial oxidative phosphorylation in human brain tissue.
  • It plays a role with respect to myelination by enhancing the expression of brain-derived neurotrophic factor.
  • And finally, lithium has been shown to be protective in Alzheimer’s disease.

Check out my YouTube video:
Fine Tuning Your Treatment of Chronic Illness with MTHFR Genetics

Posted in Chronic Disease, Dopamine and Dopamine Signaling, Epigenetics, MTHFR+, Treating Chronic Illness Series, Uncategorized | Tagged , , , , , , , | Leave a comment

Critical Keys to Getting Over Psychiatric Symptoms

Keep Methylation Central

There are few things that destroy your life as immediately and completely as the cognitive function loss involved with neuropsychiatric syndromes.

I am Dr. Nancy Mullan. I help people who have mental function disability because of psychosis or a mood disorder, who want to feel their heads and lives quit swirling, and make progress toward their most important goals.

This discussion concerns the neurotransmitter dopamine. Dopamine is responsible for attention, motivation, and reward-motivated behavior. It is an important neurotransmitter. It is the predominant neurotransmitter in your pre-frontal cortex (PFC).


Cognitive behavior is processed in your PFC. It is where your executive function resides. It’s the brain power you use to cross the street,  the mental apparatus that you need to make decisions. It’s the seat of your personality, the home of all the characteristics that make you you.

The levels of dopamine in your PFC determine how well it functions. All of the genes and the biochemical pathways that impact these levels are tremendously important to your cognitive function.

One of these genes is the catechol O-methyltransferase (COMT) gene. The COMT gene is named after the enzyme. The COMT gene encodes the production of the COMT enzyme.

Catechol-O-methyltransferase, the enzyme, deactivates dopamine. So both the gene and the enzyme are very involved with the level of dopamine in the brain, and both are important to cognitive processing.

A SNP in the COMT gene decreases the activity of the COMT enzyme, so less dopamine gets deactivated. As a result, the dopamine levels in the brain may become higher than optimal.

Methyl groups are needed to deactivate dopamine. When the COMT enzyme is less active, fewer methyl groups are used. COMT deactivates less dopamine and uses fewer methyl groups to do so. Your methyl group production and supplementation needs to be less.

Too much methyl group supplementation with a slowed down COMT enzyme can generate depression and mood swings in adults. In children, the symptoms are hyperactivity and stims, among others. Too many methyl groups in your body is a chemical stressor and a tax on your adrenal glands.

Besides having a connection with depression and mood swings, COMT SNPs that slow down enzyme function have been associated with bipolar disorder, schizophrenia, and ADHD. Studies show that COMT enzyme slowdown related to COMT gene SNPs impact executive function, working memory, verbal fluency, and intelligence.

Too much dopamine results in intense, psychotic anxiety. Your thinking processes go off; you are “not right.” Anti-psychotic medications are all dopamine antagonists. Too much dopamine is very intimately associated with psychosis.

Dopamine is also an important catecholamine, a class of amino acid that includes norepinephrine and epinephrine. These are all excitatory neurotransmitters. Too much of any one of these is overstimulating.

It is only common sense that you should know your COMT status so you can adjust your methyl group intake to accommodate it, especially if you are having symptoms or “psychological” problems.

Lithium has been used for psychiatric disorders for more than fifty years. Its mechanism of action is still unknown. Lithium has many functions in the body, and it has a key function in the formation of methyl groups.

B12 and folic acid are essential to methyl group formation, and lithium is critical for the uptake of B12 and folic acid into the cell, which is where the formation of methyl groups happens. Methyl groups are made inside the cells of the liver, kidneys, and brain.

Beyond that, lithium may increase the production of the COMT enzyme. So no matter what the status of your COMT gene is, lithium can help to assure that you have enough COMT enzyme to process dopamine and other catecholamines.

There are things you should be doing for psychiatric problems other than taking pharmaceuticals and hoping for the best.

Psych patients have been demonstrated to have the same issues that are seen in other adults with chronic illness.

You may be dealing with immune impairment, gastrointestinal disorders, persistent bacterial and viral infection, yeast infestation, multiple food sensitivities, and heavy metal toxicity. You cannot afford to sit around, take meds, and attend daycare while your life passes. Your time is too valuable, your life too precious.

Are you ready to discover the role of genetics in your health issue?

Have you had it with your mood?

Do you believe that you have had all the help there is out there?

I know that you have not.

Read the materials I have put out on optimizing diet, supplementation, and methylation capacity. They can be accessed at www.NancyMullanMD.com and https://chronicdiseaserecovery.wordpress.com/. Get familiar with all of the conditions that optimizing these factors can correct.

You need to know the status of all of the genes encoding for the enzymes in your methyl group-producing pathways, so you can bypass any problem genetics and be sure you have the methyl groups you need to perform all of the important functions that involve methyl groups, including keeping your dopamine at optimal levels.

It is up to YOU to learn about treating psychiatric illness successfully, and the role of optimizing both methyl group production and your capacity for methylation.

Check out my new YouTube video:
Fine Tuning Your Treatment of Chronic Illness with MTHFR Genetics

 

Posted in Autism, Chronic Disease, Dopamine and Dopamine Signaling, Epigenetics, Excitotoxicity, MTHFR+, Treating Chronic Illness Series | Tagged , , , , , , | Leave a comment