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

Why Your Brain Works Better When You Methylate

40ca05a8-eb1f-4398-98df-5f109391e39c

This article concerns attention, attention-based learning, and D4 dopamine receptors.

The membrane surrounding your cell, the plasma or cell membrane, is represented here by a three-dimensional fluid mosaic. The cell membrane is composed of a bi-lipid layer, a double layer of lipid or fat, which has a head at one end. The lipid is actually phospholipid.

Nerve cells have a phospholipid cell membrane. In this depiction, the head is represented by the red, green, purple and lime green rounded structures. Anyone who has listened to the Tuesday night calls has heard me talk about phospholipids at length. Phosphatidyl serine complex, that important shortcut support everybody starts out on, is a complex of the same phospholipids that make up the nerve cell wall.

Receptor sites are positioned in the cell membrane. They are represented by pink lobed molecules with antenna-like structures projecting out of them. The antenna-like structures grab the appropriate molecule for the type of receptor involved and transport it into the cell.

The cell membrane must be fluid…. It can’t be rigid. If it is too rigid, the molecules in the membrane can’t move or function properly. They need to be able to move in order to signal appropriately.

Some receptors function by totally inverting into the cell. They invert and pull the substance into the cell by doing so. You cannot have a stiff, inflexible cell membrane and do this effectively. That is what is wrong with trans fats: they are too stiff.

The receptor I am focusing on today is the D4 dopamine receptor. Dopamine is the neurotransmitter responsible for attention, motivation, and reward-motivated behavior. It is an extraordinarily important neurotransmitter because it is the predominant neurotransmitter in your pre-frontal cortex.

Cognitive behavior is processed in your pre-frontal cortex. 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 D4 dopamine receptor is responsible for attention and attention-initiated learning. It operates by inverting into the cell. A very fluid cell membrane is necessary to do this.

Methylation of the heads of the phospholipid layers, called phospholipid methylation, or PLM, increases the fluidity of the cell membrane. Dopamine activation of the D4 receptor initiates a cycle of phospholipid methylation.

Depicted above is the bi-lipid layer of the phospholipid cell membrane. The oval structure is a representation of a receptor site which is made of protein.
 
On the left side, there is no phospholipid methylation. There are no methyl groups between the heads of the molecules in the membrane.
 
When there is space made by the methyl groups between the phospholipid heads, there is more room for the receptors to be able to move and function. It is a more fluid membrane. The protein receptor will be able to move around better and will be able to signal and react with other proteins more easily.
 
Inadequate methylation negatively impacts your ability to attend and learn. The dopamine receptor needs to be able to reconfigure itself. It needs to be able to invert itself into the cell and then come back out again. It is not able to do that if the membrane is too solid.
 
Phospholipid methylation, the addition of a methyl group to phospholipids, reduces the packing density of the membrane and enhances the activity of embedded, integral membrane proteins like the D4 receptor.
 
The activity of the D4 receptor mediated phospholipid methylation cycle is affected by the availability of 5 methyl tetrahydrofolate (5 MTHF). When the level of 5 MTHF is decreased, it becomes a limiting factor. The receptors sit waiting for a new methyl group to start the activation. This greatly reduces the impact of any dopamine present. Even very high amounts of dopamine that may be present will not activate the receptor if there is too little 5 MTHF.
 
What determines 5 MTHF availability? The function of the MTHFR C677T mediated enzyme is critical for an adequate supply of 5MTHF. MTHFR 3 is even a more profound down-regulation of enzyme activity than MTHFR C677T.
 
Recent work suggests that supporting with methylfolate may be a help in offsetting depression for those who are resistant to SSRI therapy. However, the methylation cycle needs to be supported in a more general way, rather than simply adding methylfolate.
 
Also, we are talking here about appropriate dosing of 5 MTHF for your personal genetics, not the massive amounts of 5 MTHF that is sometimes recommended.
  
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.

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

Posted in MTHFR+ | Leave a comment

Fine Tuning Your Treatment of Chronic Illness with MTHFR Genetics

40ca05a8-eb1f-4398-98df-5f109391e39c
fine-tuning-your-treatment-of-chronic-illnes

Finally… an organized, simplified explanation
of what Dr. Amy and Dr. Mullan do!

Click on the link below… See what you think!

Fine Tuning Your Treatment of ASD, Psych Disorders and Other Chronic Illness with MTHFR Genetics


What people like you are saying about Dr. Mullan’s work:

So excellent! I literally learn something every single time and I get clarification on things that have been lingering in 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, this was such an uplifting session. 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

Email me today at nancymullanmd@aol.com.

 

Posted in Uncategorized

Not Every Birthday Is So Red Hot…

Especially if you are chronically ill…

dog
Babybear was not a happy camper on his birthday. From there, he descended into being really sick. I will spare you the details. After three days in a hospital, he came out with a diagnosis of liver disease.

Babybear is the runt of a seven puppy litter and, as fate would have it, he has some congenital issues. Plus, he has a small liver on x-ray and abnormal findings on a chemistry panel, so it was an easy conclusion to jump to.

Directly from the hospital, I took him to a naturopathic vet. She changed his diet and he started to improve. Still, he was not great, plus he had frank blood in his stool, so a few days later, I took him to an Internal Medicine vet/liver specialist.

As you may be aware, this has the potential to run up some real vet bills…

His liver markers were now in the normal range… low normal, but normal. The only thing I had changed was diet. Oh, no, the specialist insisted, diet did not do this. I have news: diet is the single most important thing you do for your body ALL DAY LONG. We get so high tech that we blip out on the basics…

This veterinary liver super specialist was very willing to believe a bad test, but not the improved one. In order to plumb the depths of this thing, it was going to be thousands of dollars more…

I decided to do first things first. Parasites. His symptoms were very consistent with a bad parasitic infection. I had been trying to get the standard medical vet to give me worming medicine for six months. He would not do it without a positive test and the tests kept coming back negative.

The specialist vet gave it to me without testing or blinking…

She gave me the parasite med and solemnly warned me about the dangers of oversimplification. She sent her notes to both my standard medical vet and to the holistic vet to let them know that I had refused the diagnostic testing and that I had a very sick puppy. She called and spoke with both of them.

I am totally immune to this kind of pressure, if that is what was intended. It just gets my back up. If the standard medical vet had given me the parasite meds I asked for last January, none of this would have happened. If I had looked online, I might have discovered that I could get the med I needed without a prescription. Maybe. Or maybe I would have been asked for a prescription as I got into the ordering process.

After the first dose of parasite meds, Babybear started to perk up… After the second dose, his stools normalized and he was looking like himself. After the third dose, he had so much energy and was feeling so good, that he was driving me crazy again. At this point six weeks later, he has put weight back on, developed muscle, and is finally growing some whiskers…

The moral of this story is, “If you hear hoofbeats, look for horses, not zebras…”

Do not give in to intimidation. The moment I get the feeling that some professional is trying to bulldoze me, I close right off and go with my own instinct. Legitimate professionals do not try to intimidate.

So, finally, click on my formerly sick puppy to hear more zany advice from a doctor who has pulled more than a few rabbits out of the hat for both her patients and her critters…

 

Posted in Uncategorized | Leave a comment

So, What’s Next?

After supporting the shortcut pathway to produce methyl groups, and putting in lithium to get B12 into the cell, next you turn to dealing with your gastrointestinal tract and mineral balance.

There are things you can do right away to deal with gastrointestinal balance.  You should recognize that it is very likely to be an issue, even if you think you do not have GI symptoms. If you are middle-aged or older, you probably need digestive enzymes. If you are younger than middle age and have GI symptoms, definitely take a digestive enzyme with your meals. Don’t wait for testing to get back. Even when you are eating plenty of protein, your amino acids may be low because of compromised digestion, and digestive enzymes should help that.

Protein is hard to digest. Protein is digested down into amino acids. Enzymes are made out of amino acids. People who are chronically ill often have impaired digestion and hence low amino acid levels. You can’t make the enzymes in the methylation process with low amino acids. Digestive enzymes help with this.

Your body’s production of digestive enzymes starts to decline in middle age. When that happens, undigested food goes through your GI tract, which slows the transit time of the material in your intestines. Anything you do not digest is left for problem organisms to use, which usually means trouble.

If you are chronically ill, you have an increased chance of having parasites. Parasitology testing from standard labs is high in false negatives. You need to use a specialty lab or a specific doctor who comes well-recommended for this. If you have a parasite, you can go around and around with your GI tract and never get it balanced.

Gastrointestinal transit time is also something that you can work on right away. You do not want material sitting in your GI tract. There should be only 12 – 18 hours between having eaten a food and having eliminated what is left of it. This means if you are eating three meals a day, you should be eliminating two or three times a day.  Constipation is deadly. One of the ways in which your body culls the organisms in your GI tract is by evacuating them. If evacuation is slowed down, the organisms have the chance to over grow.  What happens when you leave food in the refrigerator too long? It gets moldy. The same thing happens in your GI tract, and mold (yeast) there results in problems.

To read previous topics in the Treating Chronic Illness Series, click on the Blog button in the navigation bar of www.NancyMullanMD.com. The Treating Chronic Illness Series started in January 2016.

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.

Methylation_Pathway1

 

Posted in Treating Chronic Illness Series | Leave a comment

Open Forum Invitation

Dr. Mullan would like to invite you to her Open Forum which is held on Tuesday night at 5:00 PM Pacific Time (8:00 PM Eastern Daylight Time, 7:00 PM Central, 6:00 PM Mountain) in order to answer your questions and introduce you to her work. You may be checking her out to see if you would like to consult her. Or you may not have the option of working with her, but would still like to get her information.

The call in number is (605) 562-3140, and the access code is 691392#.

When you hear Dr. Mullan come on the line, press *6 to get into the question and answer line if you have a question.

This program is not recorded. International call in numbers are linked here.

Join us to inform yourself so that you can be proactive about your health!

Methylation_Pathway1

So excellent! I literally learn something on every single call 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, this was such an uplifting call. 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

This is brilliant. I hope a lot of people not doing methylation work will see this. I wish I’d seen this before I started doing daily injections of B12 and folic acid and ended up in a crisis. Maybe had I known to have the genetic methylation stuff going, the IV therapies I did that really helped would not have been so traumatic…
JB

JOIN US ON TUESDAY NIGHT!

Thank you for your interest in Dr Mullan’s work.

Nancy Mullan MD

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

2829 Burbank Blvd., Suite 202, Burbank, CA 91505
Telephone/Fax: (818) 954-9267

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

 

Posted in Uncategorized