Methylation Cycle dysfunction a possible part of benzo withdrawal picture

Methylation cycle dysfunction a part of the picture of benzo wd?

 

My current pet theory on part of what goes wrong with benzo wd and the cascade of chronic illness. I copied and pasted bits and pieces cause I can't be stuffed fully unpacking everything, nor have I fully collected my thoughts on the matter.

 

Still there is I think something to this being related to severe protracted dysfunction in the methylation cycle.

 

One plus to the theory is it can explain just about every symptom, including its protracted nature. This may be though because methylation cycle dysfunction can be smooshed to cover just about every possible symptom in the body (possibly why it is also appealing to other chronic systemic illnesses like ME, CFS, Fibro and autism). Similarly some of the potential complicators away from, and some of the possible routes toward, healing fits anecdotal reports from benzo wd sufferers - cutting glutamate, gluten, animal proteins, and healing gut. The other plus for it is there are very clear genetic polymorphisms that predispose to methylation cycle dysfunction at various different points (or indeed mean your methylation cycle has never worked very well). That is, some people will have fabulous functioning methylation cycles no matter what and others can easily fall into chronic dysfunction due to their genetics. That makes it appealing in the context of trying to make sense of why some people can walk away from benzo wd untouched and others get hurt badly and longly.

 

I possibly, maybe, have made progress cutting out the neurotoxins, and inflammatory foods, in diet - glutamate, gluten, reduction in protein, including high levels of histamine (histamine is broken down in the methylation cycle so increased histamine can be a sign of a disrupted methylation cycle) and healing the gut through diet as well as the right probiotics (in many cases not any probiotic will do for chronic illness and inflamed individuals).

I came to these things seperately and each improved the situation. Only later did I find out there were protocols for healing the methylation cycle that begin with the same steps.

The next stage following reduction of neurotoxin, histamine and improvement in gut health is to look at the methylation cycle itself. The daily green juice with the methyl folate may prove to be part of this too. I'll only know with some genetic testing.

 

Some history:

 

The idea of a trigger starting a cascade resulting in lowered glutathione levels is not new, by any means. I was taking glutathione injections back in 1999. A couple of docs, including Dr. Yasko, started looking upstream since patients would get a little better taking injections but would relapse as soon as the therapy was stopped. This lead to realizing that the biochemistry was 'broken' and fixing that would allow glutathione levels to rise naturally while reducing toxic loads on the body. Hence, Rich's use of the terminology of a “methylation cycle block”. The idea that dysfunction in the methylation cycle can be part of  a range of chronic body/mind illnesses like Fibro, ME, CFS and Autism is well established in those communities.

 

Dr. Yasko has identified the various stressors that can cause strain on the methylation cycle. These include viruses, bacterial infections, protozoa, chemicals, pesticides, mold, ciguatoxin exposure, head trauma, severe PTSD or psychological stress which all cause increased Nitrous Oxide which if left uncontrolled, initiates a chain reaction that results in chronic illness.

 

First, let's review methylation:

The Methylation Cycle is a biochemical pathway that manages or contributes to a wide range of crucial bodily functions, including:

 

    Detoxification

    Immune function

    Maintaining DNA - the switching on and off of DNA as well as general maintanence

    Energy production

    Mood balancing

    Controlling inflammation

 

All these processes help the body respond to environmental stressors, to detoxify, and to adapt and rebuild. That’s why lowered methylation function may contribute to many, major chronic conditions. Methylation is involved in almost every bodily biochemical reaction, and occurs billions of times every second in our cells.

 

Refer to the diagram below - taken from Dr. Yasko but this doctor labels the cycles with numbers and this is important to look at from a bird's eye view before digging into each cycle/mutations.

All these cycles interlink with each other like Olympic rings and getting one cycle going will drive another. The important cycles know to be major players include blood sugar wobbles, allergy problems, sleep cycles, mitochondrial function, anti-oxidant status, the NO/OONO cycle, thyroid and adrenal hormones cycles and de-toxification.

 

The 5 cycles of the methylation pathway are, from left to right

1. The Urea cycle

2. The Neurotransmitter cycle

3. The Folate cycle

4. The Methionine cycle (erroneously called the methylation cycle)

5. The Transulfuration cycle

 

The Krebs Cycle feeds into the Urea cycle so while it is not a part of the Methylation pathway, it gets sluggish or broken when the methylation is blocked - ergo, fatigue!

 

1. The Urea Cycle deals with an imbalance of ammonia and the creation of free radicals, excess nitrous oxide - ergo, inflammation, toxicity from ammonia, and excess NO leading to smooth muscle issues (gut dysmotility and possible dysautonomia from relaxed blood vessels)

 

2. The Neurotransmitter cycle or BH4 cycleshows an imbalance of seratonin and dopamine - ergo, OCD, mood disorders, sleep issues, bipolar and other psychological issues as well as central nervous system dysfunction.

 

3. The Folate Cycle demonstrates an imbalance or deficiency in folate and B12. This cycle directly affects the 4th cycle, the methionine cycle.

 

4. The Methionine Cycle when out of balance leads to elevated homocysteine (usually) which leads to cardiovascular disease, more inflammation, DNA/RNA changes,

 

5. The Transulfuration Cycle leads to out of balance sulfur, elevated homocysteine, low glutathione levels - ergo, reduced immunity to bacteria/viruses, cardiovascular disease, increased toxicity from excess sulfur.

 

These 5 cycles plus Krebs cycle work as a set of gears - when one is sluggish or broken, the next one is affected and on down the line. This is difficult to address and change.

 

 

 

Description of Dr. Yasko's Phases or Steps:

 

Phase I is preparing the body, correcting the foundation, primarily reducing inflammation caused by excess glutamate and excess ammonia. The first part of Phase I includes dietary changes (primarily, no excitotoxins in order to balance the GABA/glutamate levels (no MSG, glutamate, vitamins ending in “ates”, lowered calcium and protein (in the beginning), no gluten, no casein. Then balancing CBS/Ammonia (lowering sulfur by-products). There are several gene mutations that cause increased ammonia such as MTHFR A1298C as well as CBS). The next step of Phase I is gut health, lowering bacterial/viral loads, organ support to prepare for detoxification, supporting thyroid, Vit D levels, addressing parasites.

 

Step 1 of Phase I:

Removing all toxins possible and reducing toxic loads on the body from food or your environment.

 

The GABA/glutamate balance is usually the first step. GABA is calming and glutamate is stimulating. The brain needs both in the right balance. Glutamate is needed to lay down memories and is important for learning. Excess glutamate levels are toxic to the brain as the excess becomes an excitotoxin. See/read Dr. Russell Blaylock "Excitotoxins: The taste that kills". Read his book and/or view his YouTube seminar. Or google excitotoxins, glutamate, etc.

 

Glutamines comes from food so learn which foods contain it and eliminate or restrict: no MSG, no glutamine supplements, no gluten, no casein, no artificial flavors, (controversy about natural flavors). Unfortunately, this means most processed foods. Gluten free processed foods are not a good substitute. Going grain-free/carb free for a short while may make you feel better anyway so use that time to learn how to bake gluten free. I will post some tips and recipes soon.

 

Reducing calcium (especially for autism) and re-introducing it during Phase III.

Reducing protein (in order to reduce ammonia) by sprinkling Yucca when consuming protein. Adults with ME/CFIDS can't always do this because our carb metabolism is faulty so reduction might be more beneficial then elimination. But some people do feel better by not eating animal protein.

Reducing sulfur until you know if you have the CBS mutations or not.

Consider stopping all supplements unless they are essential until you get your genetics, especially those containing calcium, amino acids, chelated minerals, cysteine and mineral forms ending in "ate" such as glycinate or aspartate which can be excitotoxins.

 

Phase II is first stages of genetic bypass, getting systems working again by helping the body to release toxins – toxic metals which are released when bacteria and viruses are reduced. This Phase is laying the groundwork for Phase III: healing damaged neurons and helping the body to generate new ones. It may include chelation but balancing of essential minerals is an important part of this step, supporting the Krebs cycle, balancing amino acids, increasing methyl groups, controlling urea cycle. This is the longest phase since it addresses each mutation/mutation group one-at-a-time and slowly.

 

Phase III is for nerve growth and myelination - healing of the neurological damage and starts when the body has stabilized, systems are working better due to the genetic bypass where needed. This step usually allows re-introduction of calcium and reduction of the various supplements that are used for detoxification. The supplements that are kept are the ones needed for genetic bypass of mutations and the supplements for supporting nerve growth.

Very interesting. My doc talked about it a little and told me to go on a low carb paleo diet and drink water only. Does that cover it gor the most part? Oh and to take vitamin D.

Very interesting. My doc talked about it a little and told me to go on a low carb paleo diet and drink water only. Does that cover it gor the most part? Oh and to take vitamin D.

 

Vitamin D is part of it I think. Low carb paleo diet wouldn't necessarily fit because protein can be problematic using up BH4 which can lead to a build up of ammonia and less serotonin. If you have leaky gut/high gut permeability - which a lotta people with inflammed gut probably do - you could get some of the free glutamates from digesting protein too. Both GABA and serotonin rise after eating carbohydrates also. Having said that I'm not eating much carbohydrates cause I'm gluten free - and this particular protocol for treating methylation cycle calls for gluten free.

But sugar doesn't seem to get along with people in benzo wd so in that sense paleo and only water is good. The problem is the bounces in blood sugar. Low blood sugar from bouncing blood sugar releases glutamate and adrenaline which are obviously not good for us. So having a steady blood sugar is a possible up side of paleo.

 

This video has some general things on blood sugar and methylation

I stopped eating gluten actually all grains a few months ago. I have to say that my stomach is leaps and bounds better. In fact my stomach never felt so good. I ate some bread a few days ago and my trigger finger came back! I also got rid of anything from the nightshade family. I still consume dairy and I have a casein allergy. I still eat eggs sometimes even though I have an egg white allergy. I still eat sugar but have come down a lot. I just can't seem to quit sugar. I'm very hooked on it and I think that metabolic syndrome is a big part of it for me. I have been trying all my life to eat low carb but never can. I go through a protracted withdrawal from sugar too. I was off sugar for 6 months and low carb but still having the same withdrawal I had a week after stopping the sugar!

Smiff, have you had your genetic testing done? So important to know your mutations!

 

Great information! I've been working on this for quite some time, but it confusing information!

 

http://mthfr.net

 

Hey smiff what test fo u recommend? I see 23 and me and one by Dr amy yasko.

Cool, 23andme is who I went through! Then you can run your raw data through Yasko's site! There's also Promethease, Livewello and others!

 

I saw that 23 and me was not very accurate. Don't know if it's true or not and also that it doesn't test for 5 snp's that yaskos test does. Yasko test is almost 500 bucks though! I'll try 23 and me since it's cheaper. Did you figure out your results?

Yes, it's very simple once you get the raw data! I've not heard that 23andme is not accurate!

smiff, wow thanks for the info, I have lots of questions now, will keep up with this post.

http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/

 

 

What up G!

Awesome you've been thinking about this too! I am waiting on my 23 and me test but yes I agree: find out your mutations!

Did your snps come back with some methylation impairment?

Have you been following Dr Yasko protocol and if yes where are you up to? Have you started adding 'methylation vitamins'?

 

 

Cool, yes I've heard 23 and me is the best, easiest and cheapest really. You can then put the data through Dr Yasko's site or MTHFR.net Dr Ben Lynch's site.

If you want some practitioners who know how to read your test and advise can be found on MTHFR.net, or beyondMTHFR or Dr Yasko.

 

 

Sweetpea ask away.. I'm still kind of trying to get my head around it but G, myself and maybe someone who knows their stuff on CFS forums or MTHFR.net or beyondMTHFR can trrryy to answer

http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/

 

Wow G! That is awesome. I'm copy and pasting it cause it is so good

 

How to Increase GABA and Balance Glutamate

May 28th, 2014 · 2 Comments ·

 

You can’t really talk about how to increase GABA without talking about glutamate, because they have a complex and interconnected relationship. Both are very important neurotransmitters that have a profound impact on many different aspects of our physical, mental and spiritual health with the former being inhibitory and the latter being excitatory. Excitatory neurotransmitters stimulate brain cells, while inhibitory ones reduce stimulation. Like all neurotransmitters, too much or too little of either one leads to problems.

 

When all is working as it should, they keep each other in balance. However, there are many factors that can easily disrupt this delicate balance and result in too much glutamate and not enough GABA, which can wreck havoc on your mental and physical health.

What is Glutamate?

 

Glutamate is one of your primary excitatory neurotransmitters. It has many important roles like stimulating your brain cells so you can talk, think, process information, learn new information, pay attention, and store information in short and long term memory. As a matter of fact, studies suggest that the more glutamate receptors you have the more intelligent you are. High levels of glutamate receptors are correlated with superior abilities in learning and memory. Unfortunately, they also correlated with an increased risk of stroke and seizures.

 

Although glutamate is one of the most abundant neurotransmitters found in the brain, it exists in very small concentrations. If the concentration level rises, then neurons become too excited and don’t fire in a normal manner. Glutamate becomes an excitotoxin when it is in excess; meaning it overstimulates brain cells and nerves and results in neurological inflammation and cell death.

 

An excess of glutamate is a primary contributing factor to a wide variety of neurological disorders like autism, ALS, Parkinson’s schizophrenia, migraines, restless leg syndrome, tourettes, pandas, fibromyalgia, multiple sclerosis, Huntington’s chorea, and seizures. As well as atrial fibrillation, insomnia, bedwetting, hyperactivity, OCD, anxiety disorders, and STIMS (repetitive self-stimulatory behaviors like rocking, pacing, body spinning, hand-flapping, lining up or spinning toys, echolalia, repeating rote phrases or other repetitive body movements or movement of objects that are commonly seen in autistic children) and an increased risk of stroke.

 

Too much glutamate can also increase eosinophils (a particular type of white blood cell) which results in inflammation, impair blood vessels that lead to migraines and blood pressure irregularities, and impair other areas of the brain like the hypothalamus, hippocampal neurons and purkinjie neurons which affect speech and language.

 

Mercury in the body becomes more toxic in the presence of high levels of glutamate.

 

Excess glutamate also makes cancer cells proliferate and increases tumor growth and survival.

 

Elevated levels of glutamate trigger the brain to release its natural opioids (endorphins/enkephalins) in order to protect the brain from damage, which can result in feelings of spaciness and eventually contribute to depletion of your natural opioids, and it also depletes glutathione levels, which is vital for detoxification, controlling inflammation and gut health. Additionally, glutathione also assists in protecting neurons from damage, so when it is depleted it is not available to do this job and thus contributes to more cell death.

 

High levels of glutamate may increase the survival of unfriendly microbes in the gut and contribute to problems like excess acid and heartburn.

 

Too much glutamate can lead to too much acetylcholine, and too much acetylcholine has a stimulating effect as well and puts one into a perpetual state of sympathetic stress with high levels of anxiety, fear, insomnia, restlessness, nervousness etc.

What is GABA?

 

GABA, which is short for gamma-aminobutyric acid, is your primary inhibitory neurotransmitter. Its primary role is to calm the brain, slow things down and relax you. One of the ways that it assists in this process is by increasing alpha wave production. It is also vital in speech and language. GABA puts the pause or space between words when you speak. The brain uses it to support sensory integration. Without adequate GABA production, our conversations would consist of lots of run on sentences, slurred speech or loss of speech, and we would have trouble with comprehending language.

 

Your gastrointestinal tract is packed with GABA receptors and it is critical for contraction of the bowel.  Insufficient levels can result in abdominal pain, constipation, and impaired transit. It also supports healthy levels of IgA, (antibodies that protect your gut and other mucous linings from harmful invaders) which means it contributes to immune health.

 

Insufficient levels of GABA result in nervousness, anxiety and panic disorders, aggressive behavior, decreased eye-contact and anti-social behavior, attention deficit, problems with eye-focusing (like that seen in autistic children when both eyes are focused inward towards the nose or waver back and forth in a horizontal or vertical movement), chronic pain syndromes and much more. It may also contribute to GERD as it is needed to help regulate the lower part of the esophagus.

 

Low levels of GABA play a vital role in alcoholism, drug addiction, and cravings for sugar and carbs, as these substances will temporarily and artificially increase GABA, so one is unconsciously drawn to them. However, these substances also deplete neurotransmitters, so they will perpetuate the problem.

 

Gamma-aminobutyric acid is found in almost every area of the brain, but the hypothalamus contains a very high level of GABA receptors, so it is vital for its many functions like regulating sleep, body temperature, appetite, thirst, sexual arousal and desire, and action of the pituitary, HPA axis, and the autonomic nervous system. The primary role of the hypothalamus is to maintain homeostasis throughout the body, and without enough GABA production this will not happen.

 

Like all neurotransmitters GABA and glutamate play a vital role in regulating the autonomic nervous system (stress response system), maintaining balance between the sympathetic and parasympathetic nervous systems. Too many excitatory neurotransmitters and we are in sympathetic nervous system mode and not enough inhibitory and we are unable to return to the parasympathetic mode. Thus, depletion of GABA can be a major contributing factor to autonomic nervous system disorders of all kinds like adrenal fatigue, insomnia, chemical sensitivities, chronic fatigue, panic attacks, etc. Maintaining sufficient levels  is crucial in the recovery of these conditions.

GABA and Glutamate Balance

 

When GABA is low, glutamate is high and vice versa. So in order to increase gamma-aminobutyric acid it’s not simply a matter of bringing it up, you must also focus on reducing the excess glutamate. The goal is to achieve balance between the two. You might think of glutamate as the accelerator and GABA as the brakes. Both are equally important.

 

Glutamate (also referred to as glutamic acid) is actually the precursor to gamma-aminobutyric acid, and any excess is supposed to be converted automatically into GABA. This is the way it maintains balance; anytime glutamate levels start to build up too high, then it is converted to GABA to calm things down. However, sometimes the body cannot regulate glutamate properly for a variety of reasons which we will discuss, then glutamate can build up into excessively high levels.

 

An enzyme called glutamic acid decarboxylase (GAD) is needed for glutamate to make the conversion to GABA, but there are several factors that may interfere with this enzyme and impede the conversion process, which means a build up of glutamate and inhibited formation of GABA. Response time may be delayed or capacity to convert may be impaired. It is believed that problems with the GAD enzyme may be the primary underlying issue that results in too much glutamate.

 

For example, the rubella virus, which is found in the MMR vaccination can decrease activity of glutamic acid decarboxylase (GAD)by as much as fifty percent. Thus, one of the reasons children begin to exhibit some of the symptoms of autism immediately after vaccination, as we mentioned earlier GABA is critical in speech and brain function.

 

Other chronic viral infections interfere with the GAD enzyme and some microbes like streptococcus flourish in a glutamate rich environment, thus many children with pandas and autism carry an ongoing infection with strep.

 

Methylation also plays a role in the GABA and glutamate balance in a variety of ways. For one, if their is impairment in the methylation pathway, then folate doesn’t get utilized and it can break down into glutamate. Additionally, if you are not methylating properly you may not be able to suppress microbes like viruses or make enough T cells to fight them off, which means they will linger around to interfere with the GAD enzyme.

 

Methylation may be impaired due to nutritional deficiencies, toxins, genetic mutations, or Candida overgrowth. Methylation is also heavily influenced by the Krebs cycle and vice versa, so a problem in this cycle can also impede methylation, and consequently GABA production. If methylation is impaired, then it is even more important to manage glutamate levels.

 

Additionally, the syntheses of GABA itself is also dependent on the Krebs cycle, so it is vital in more ways than one that this system be working properly to have sufficient levels. The Krebs cycle can become impaired in a variety of ways like deficiency in B vitamins or the presence of heavy metals.

 

The GAD enzyme is generated by the pancreas, so problems with the pancreas may impair production of the enzyme.

 

People with type 1 diabetes produce antibodies against the GAD enzyme, which may impair its response time or ability to convert.

 

Lead also interferes with GAD activity. Lead also inhibits another enzyme involved in the heme synthesis pathway which results in an accumulation of an intermediate that competes with GABA.

 

Some substances like allylglycine (a derivative of glycine) are potent inhibitors of GAD.

 

B6 is also needed as a cofactor with GAD to convert glutamate into GABA, so if B6 levels are not sufficient, the conversion won’t happen either. Much of the population is deficient in B6.

 

Additionally, glutamate receptors also pull in other excitatory substances into the cell besides glutamate, including all of the following:

 

    Aspartate (can also be converted into glutamate)

    Aspartame

    Aspartic acid

    Glutamate

    Glutamic acid

    Glutamine

    Monosodium glutamate (MSG)

    Cysteine (But not n-acetyl-cysteine. However, does contain sulfur and too much sulfur can be counterproductive as well, so should be used mindfully.)

    Homocysteine

 

Therefore, each of these can bind with glutamate receptors, which also results in excessive stimulation and contributes to the imbalance in GABA and glutamate and the wide array of symptoms that are generated. The more glutamate receptors you have the more excitatory substances that will be pulled in.

 

To complicate things further, glutamate has the ability to bind with six other receptors in the brain, like the NMDA receptor, which assists in delivering calcium to the cell and plays a vital role in memory function and synaptic plasticity. Calcium is used by glutamate as the agent that actually inflicts the harm on the cell. So, if there is an excess of calcium in the body for any reason, it too will contribute to the GABA and glutamate imbalance.

 

Glutamate and calcium together cause ongoing firing of the neurons, which triggers the release of inflammatory mediators, which leads to more influx of calcium. It becomes a vicious cycle that results in neural inflammation and cell death. Glutamate has been described as the gun, while calcium should be seen as the bullet, says Dr. Mark Neveu, a former president of the National Foundation of Alternative Medicine. It’s important to note that activation of the NMDA receptor also involves glycine, D-serine or D-alanine, which means either one of these could allow for more influx of calcium as well.

 

Magnesium will help regulate calcium levels and so can zinc. However, higher doses of zinc (more than 40mg per day) can also activate the release of glutamate through non-NMDA glutamate receptors, so one must exercise caution with zinc. However, if calcium is excessively high, other herbs or nutrients may be used to bring it down, like lithium orotate, Boswalia or wormwood. Lithium, as well as iodine and boron, can also assist in lowering glutamate. Calcium intake in food may need to be reduced or limited if calcium is too high.

 

If one exhibits low levels of calcium, Dr. Amy Yasko recommends using nettle or chamomile to increase calcium levels, rather than supplementation of calcium itself, if we are dealing with someone who has an imbalance in GABA and glutamate. Vitamin K & D would be important as well. If supplemental calcium is used it should be accompanied by magnesium, both in citrate form, which will help control the excitotoxin activity.

 

Glycine can be inhibitory or excitatory, and in people who tend to lean towards excess glutamate it typically becomes excitatory, so it may need to be avoided.

 

Glutathione contains glutamate, so supplementing too heavily may contribute to excess glutamate.

 

The amino acid taurine increases the GAD enzyme and consequently GABA levels. Additionally taurine doubles as an inhibitory neurotransmitter and can bind directly to GABA receptors, so it can help provide balance naturally in that manner as well. Higher levels of any inhibitory neurotransmitter help lower high levels of any excitatory neurotransmitter. Taurine is found in high levels in the brain and cardiac tissue, indicating its importance in these areas. Taurine is found most abundantly in seafood and animal protein, so it is often deficient in one’s diet.

 

If taurine is deficient, then the GAD enzyme may be low as well, therefore, supplementing with taurine can be used to manage the GABA and glutamate balance and protect from neuron death. However, there are a couple genetic polymorphisms (particularly CBS and SUOX gene mutations) that can result in negative effects from taurine supplementation, because these mutations result in excess levels of sulfur in the body and taurine is sulfur based. If one has these gene mutations, they may also need to avoid other supplements that are high in sulfur and limit sulfur based foods. These mutations can also impair ammonia detoxification as well. B6 and SAMe increases the activity of these gene mutations, so supplementation with these substances may compound the problem too.

 

Serotonin, another vital inhibitory neurotransmitter is also needed in order for GABA to work properly. If one is deficient in serotonin, then even if you have sufficient levels of gamma-aminobutyric acid, it may not be able to perform its inhibiting effects adequately.

 

A diet that does not contain enough of the nutrients needed to make inhibitory neurotransmitters like animal protein and fat plays a vital role in an imbalance between glutamate and GABA. Furthermore, proper transmission of any neurotransmitters can’t happen without adequate levels of fat and most people are not consuming enough fat in their diet. Additionally, many foods and substances like sugar, whole grains, any high starch food, caffeine, chocolate, artificial sweeteners and flavorings, food additives and dyes can deplete GABA levels or disrupt transmission, so they should be removed from the diet. Grains (including whole grains) can bring about an excitoxic effect by causing excessive glutamate formation in some people. Following the Paleo diet would be the ideal diet for maintaining balance between gamma-aminobutyric acid and glutamate. You may want to note, that some fish like mackerel have high levels of naturally occurring GABA.

 

Environmental toxins like pesticides, herbicides, air pollution, heavy metals, and chemicals found in your common every day household cleaning products, cosmetics, perfumes and colognes, air fresheners, personal care products, dish soap, laundry soap and fabric softeners, all deplete and disrupt normal production and function of all neurotransmitters. Therefore, another critical component for maintaining sufficient levels of GABA is reduce your exposure to these toxins by living an environmentally friendly lifestyle and eating organic.

 

Supplementing directly with GABA is effective for some people. However, I frequently work with people who get a stimulating effect from supplementation, so be sure to monitor your response.

 

Glutamate and insulin have an intimate relationship. On one hand, high glutamate will trigger the release of insulin, which means insulin will then lower glucose levels; but glucose is needed to help regulate glutamate levels at the synapses, so if it goes to low, then glutamate is going to increase. This means hypoglycemia or low blood sugar will result in both triggering high levels of glutamate and impairing your ability to reduce the build up.

 

Therefore, not eating foods that spike insulin and keeping blood sugar levels stable are a vital element of keeping glutamate and GABA in balance. At the same time, keeping your glutamate balanced would be a vital aspect of keeping your insulin levels healthy, which would be important if you are trying to lose weight, have insulin resistance, type 2 diabetes, compulsive overeating, obesity, and the many other insulin related conditions. Again, demonstrating how the Paleo diet would be the most beneficial diet for this issue.

 

Some people have a genetic mutation (VDR/Fok gene) that impairs their ability to regulate their blood sugar levels sufficiently. Dr. Amy Yasko, says there are a variety of pancreatic supplements that may be needed to support this issue.

 

There are many drugs that target your GABA receptors like Ativan, Xanax, Klonapin, Valium, and Neurontin and others. These drugs look similar in chemical structure as gamma-aminobutyric acid so they can fit in your GABA receptors, which artificially stimulates them, but they do not actually increase production. Therefore they do not address the underlying problem of not producing enough, because there must be some level of GABA present in order for these drugs to have an effect. Anytime a substance is used to artificially stimulate a neurotransmitter the brain responds by reducing production or responsiveness, which results in more depletion of the neurotransmitter, which in this case is GABA. Therefore, any drugs that target GABA receptors will inhibit your ability to acquire and maintain balance with glutamate.

 

Some people may have a genetic predisposition to have more glutamate receptors than others, and the more glutamate receptors you have, the more you will take in. In this case, you will likely be someone who always tends to lean toward excess glutamate activity and will need to engage in life-long ongoing monitoring and maintenance to prevent overstimulation, cell death and neurological symptoms. However, if there is excess glutamate in the system due to genetic mutations, methylation problems, etc., then more glutamate receptors will be generated as well.

 

As is true for all neurotransmitters, ensuring that you get adequate sleep is vital for normal function, because sleep deprivation causes neurons to lose sensitivity to neurotransmitters, thus impairing communication.

Excitotoxins in the Diet

 

One of the biggest contributors to an imbalance in GABA and glutamate is the presence of excitotoxins in the diet. Many foods and nutritional supplements contain the excitotoxins (glutamate, glutamic acid, glutamine, aspartate/aspartic acid, and cysteine) or they contains substances that can prompt the body to produce them. These foods and substances should be avoided by anyone trying to balance their GABA and glutamate levels and anyone who tends to generally lean towards excess glutamate.

 

Dr. Amy Yasko explains that “excitotoxins in food overexcite neurons to the point where they become inflamed and begin firing so rapidly they become exhausted or die.” This results in a wide array of neurological symptoms that are found in autism, OCD, anxiety disorders, insomnia, hyperactivity, attention deficit, nervousness, aggressive behavior, restless leg syndromes, tourettes, migraines, seizures, and more. Excitotoxins increase other excitatory neurotransmitters as well like norepinephrine, which compounds these symptoms.

 

Dr. Amy Yasko, an expert in autism, tells parents with children who have autism that if they take only one step in her recovery program that the most important element is to eliminate excitotoxic foods that increase glutamate levels. This one step alone can provide dramatic improvements in STIMS. Thus, demonstrating the profound impact that excitotoxins have on brain function.

 

Here are some of the most common sources of excitotoxins.

 

Monosodium glutamate. Keep in mind that MSG is found in numerous places you may not be aware of like most processed food, fast food restaurants, and it may be a binder in medications, supplements, prescription drugs, over the counter drugs, IV fluids, vaccines, and as a growth enhancer sprayed on crops of food and produce called Auxigrow.

 

Aspartame (Nutrasweet)

 

Glutamate and aspartate are naturally occurring in wheat gluten, hydrolyzed yeast, and milk casein.

 

Other common food sources that contain excitotoxins include hydrolyzed protein, hydrolyzed oat flour, or anything hydrolyzed, sodium caseinate, calcium caseinate, disodium caseinate, autolyzed yeast, yeast extract or anything else autolyzed, gelatin, glutamic acid, carageenan or vegetable gum, guar gum, bouillon, kombu extract, anything malted, maltodextrin, many seasonings and spices, soy extract, soy protein or soy protein concentrate, or soy protein isolate, and soy sauce, textured protein, whey protein, whey protein concentrate or isolate.

 

The words natural flavor or natural flavoring on a package typically means it contains MSG or some other excitotoxin because they are used to stimulate your taste buds and artificially intensify flavor.

 

Other foods or substances that contain excitotoxins and can damage nerves include anything fermented, protein fortified, or ultra-pasteurized, or vitamin enriched, corn syrup, body builder formulas or protein formulas, caramel flavoring or coloring, flowing agents, dry milk, L-cysteine, egg substitutes, cornstarch and some brands of corn chips, citric acid if it is processed from corn, certain brands of cold cuts, hot dogs and sausages (even the ones in health food stores), many canned foods, pectin, pickles, any processed food, meats in mainstream grocery store are often injected with them, tofu or other fermented soy products, xanthan gum or other gums.

 

Any nutritional supplement that contains glutamine. Glutamine is often recommended to heal the gut and increase GABA, but it first increases glutamate, and if you aren’t converting your glutamate to GABA for any of the many reasons we listed above, then you end up with nothing but a bunch of excess glutamate. Anyone who has an issue with excess glutamate should avoid supplementation with glutamine. Glutamine and glutamate convert back and for into one another.

 

It can also be a matter of potency. For example, I can consume yogurt or butter every once in a while with no glutamate problems, but if I consume whey protein then I have immediate excess glutamate. This is because the level of glutamate in whey protein is much more concentrated than it is in butter or yogurt. Anything that has a concentrated level of glutamate is going to be more problematic than something that has less potency.

 

Bone broth, which is commonly recommended for healing the gut is very high in glutamate, especially chicken bones. For example, I get an instant migraine from taking a little sip of bone broth from the glutamate content. I can’t even cook chicken with the bone, or the chicken will absorb the glutamate and give me a migraine. I can sometimes eat beef or buffalo cooked with the bone, but it varies. I do best if the bone is removed. So you should experiment to see if your meat cooked with bone is contributing to your glutamate imbalance and be aware that bone broth will increase your glutamate levels.

 

Protein powders and amino acid formulas are high in glutamate. Branch chained aminos (leucine, isoleucine and valine) can be used to prevent excess glutamate.

 

You may also have a genetic polymorphism that inhibits your ability to form GABA itself. When that is the case, then supplementation may be needed ongoing.

 

Pyroluria is a genetic problem in hemoglobin synthesis that can result in deficiencies in B6 and zinc, both of which are critical for the production of GABA or the management of excess glutamate. Therefore, if you have pyroluria it can indirectly contribute to a GABA and glutamate imbalance.

 

Chronic stress is a major contributing factor to depletion of GABA and other inhibitory neurotransmitters. High levels of inhibitory neurotransmitters like gamma-aminobutyric acid and serotonin are needed to modulate the stress response system. They help the mind and body return to the parasympathetic state when the stressful event is over. If the stressful event is never over, then they are called upon repeatedly and over time this will drain their levels. Therefore, managing chronic stress is a vital element for the GABA and glutamate balance.

 

Vitamin K is very important for GABA and glutamate balance as well, as it is needed for healthy calcium metabolism where it reacts with glutamate and calcium to deliver calcium to the bones and teeth, and it prevents accumulation of excess calcium which would contribute to cell death. Vitamin K is a fat-soluble vitamin; however, unlike other fat soluble vitamins, it is not stored in the body and must be consumed on a daily basis. Typically, vitamin K is produced when the friendly flora in our gut process leafy greens, but if dysbiosis is present or you’re not eating leafy greens, then vitamin K is not produced in sufficient numbers and deficiency may develop.

 

The pancreas uses Vitamin K abundantly for sugar regulation. In addition to the brain, the pancreas is also very vulnerable to accumulation of excessive glutamate or other excitotoxins, which will further impair regulation of sugar. As we discussed previously, too much or too little insulin or glucose can both contribute to excess glutamate Therefore, keeping glutamate and GABA in balance is critical for the health of the pancreas and all its functions and the health of the pancreas is vital for maintaining the balance.

 

You have most likely seen substances called l-theanine and phenibut for increasing GABA. I am not in favor of using either one of these, because they are artificial means of stimulating gamma-aminobutyric acid, and remember any artificial stimulation leads to depletion. Many people report that they get addicted to phenibut, thus demonstrating that it is indeed too stimulating which will perpetuate depletion.

 

Many manufacturers of nutritional supplements and health care practitioners have no knowledge or are not fully educated on the topic of glutamate. Therefore, it is very common for nutritional supplements, even some of the more respected brands, to contain excitotoxins. If you tend to lean towards excess glutamate, you must be very careful with your nutritional supplements.

 

It’s also important to take note that it is not possible to eliminate every single source of glutamate or other excitotoxin, nor do you want to. Remember that glutamate is vital for proper brain function in small concentrations; the goal is to prevent excess. Preventing overstimulation, cell death and neurological symptoms may sometimes be a matter of moderating accumulation. The more foods or substances that one consumes that are excitoxic the more it builds up. You may get away with a little consumption, but if consumption is high then it pushes you over the edge of the cliff and symptoms present.

 

One of the greatest aspects of GABA is that it also opposes norepinephrine, your other primary excitatory neurotransmitter which is also important for stimulation, but it sets off the stress response system. Like glutamate, norepinephrine is also toxic to the brain when it is in excess. Excess norepinephrine can produce many of the same kinds of symptoms that excess glutamate produces and it can sometimes be hard to tell the difference between the two. Fortunately, when you focus on increasing your gamma-aminobutyric acid then you help reduce excess norepinephrine in addition to excess glutamate.

 

So, to summarize the steps that should be taken to increase GABA, it is vital that one is eating the right diet, avoiding excitotoxins, managing stress, avoiding environmental toxins, addressing nutritional deficiencies and/or genetic polymorphisms, getting adequate sleep, supporting a healthy gut and possible supplementation. It’s very important that you don’t just start supplementing with everything you’ve read will be helpful, as this usually backfires and you get the exact opposite effect. The sicker you are the slower you need to go with supplementation. Only take one thing at a time and monitor your response before trying something else. Some people must start with very minute doses.

 

Working with neurotransmitters is a complex and difficult process that is best done with a practitioner who has expertise in this area. However, finding someone who has enough expertise to cover all the bases we have presented on this page is very difficult as well, so you serve yourself better by being very well informed before beginning the journey.

References

 

Abshire VM1, Hankins KD, Roehr KE, DiMicco JA. Injection of L-allylglycine into the posterior hypothalamus in rats causes decreases in local GABA which correlate with increases in heart rate. Neuropharmacology. 1988 Nov;27(11):1171-7.

 

L. Amoreaux WJ, Marsillo A, El Idrissi A. Pharmacological characterization of GABA receptors in taurine-fed mice. J Biomed Sci. 2010;17 Suppl 1:S14

 

El Idrissi A, L?Amoreaux WJ. Selective resistance of taurine-fed mice to isoniazide-potentiated seizures: in vivo functional test for the activity of glutamic acid decarboxylase. Neuroscience.2008 Oct 15;156(3):693-9.

 

Richard W Olsen and Timothy M DeLorey. GABA Synthesis, Uptake and Release – Basic Neurochemistry. 1999

 

http://www.ncbi.nlm.nih.gov/books/NBK27979/

 

Todd D. Prickett and Yardena Samuels. Molecular Pathways: Dysregulated Glutamatergic Signaling Pathways in Cancer. Clinial Cancer Research August 15, 2012 18; 4240

 

Dr. Amy Yasko, Autism: Pathways to Recovery. Neurological Research Institute, LLC 2004, 2007, 2009

G, did you have a GAD mutation?

 

Cool, the article above says paleo would be a good diet for balancing gaba and glutamate. I guess once again it comes down to an individual call on how you are tolerating anything

Smiff, I do not have a GAD mutation! I do have MTHFR 1298 (Homozygous)!

 

I recently had neurotransmitter testing and my GABA is on the high end. I had micronutrient testing and my glutamine is severely deficient!

 

I am taking methlys (B12 and folate) and doing well with them! Thought I had some methyl trapping there for a bit, but started niacin and everything is better!

 

Smiff, I do not have a GAD mutation! I do have MTHFR 1298 (Homozygous)!

 

I recently had neurotransmitter testing and my GABA is on the high end. I had micronutrient testing and my glutamine is severely deficient!

 

I am taking methlys (B12 and folate) and doing well with them! Thought I had some methyl trapping there for a bit, but started niacin and everything is better!

 

 

oo wow you are well on your way!

 

fascinating your GABA is on the high end. Just goes to show if you don't have the right receptors and/or other pathways to make use of it and/or just too much glutamate then it doesn't necessarily mean much.

 

It is exciting to meet someone who is also interested in this! I'll let you know what my 23 and me says when it comes back.

I'm guessing some GAD and MTHFR but we shall see 

 

What brand and dose of methyl b12 and folate are you taking? did you start slow or just dive in and when hit a bit started niacin?

I stopped eating gluten actually all grains a few months ago. I have to say that my stomach is leaps and bounds better. In fact my stomach never felt so good. I ate some bread a few days ago and my trigger finger came back! I also got rid of anything from the nightshade family. I still consume dairy and I have a casein allergy. I still eat eggs sometimes even though I have an egg white allergy. I still eat sugar but have come down a lot. I just can't seem to quit sugar. I'm very hooked on it and I think that metabolic syndrome is a big part of it for me. I have been trying all my life to eat low carb but never can. I go through a protracted withdrawal from sugar too. I was off sugar for 6 months and low carb but still having the same withdrawal I had a week after stopping the sugar!

 

Cool sorry I only just saw this

Ok so that is great no gluten is helping!

As for sugar, well I guess that video talks about the downsides of low blood sugar so that might be driving your sugar addiction - keeping out of the adrenaline and other crappiness of low blood sugar. I wonder if there is a way to keep a steady higher blood sugar without straight up sugar (simple glucose)? Have you thought about legumes, lentils etc? Or like a fruit smoothie with coconut milk that you sip on throughout the day when you start feeling funky/anxious/agitated from low blood sugar?

I take Natures Bounty Methyl B12 1000 mcg. This should be started at least two weeks prior to beginning the Methyl Folate! I take Jarrow Methyl Folate 400 mcg. One of each daily.

 

You need to know your COMT V158M and your VDR taq mutations to know the correct vitamin B12 to take! Methyl, Hydroxy, or Adenosyl!

 

http://media-cache-ec0.pinimg.com/1200x/09/80/91/098091f418be982446d06a879ff6a55f.jpg

 

I started very slow with each new thing I added!

 

It is nice to have someone else looking at this! How long (approximately) till you get your results? I'm excited to hear!

 

G, did you have a GAD mutation?

 

Cool, the article above says paleo would be a good diet for balancing gaba and glutamate. I guess once again it comes down to an individual call on how you are tolerating anything

 

I saw that. You mean to tell me my doctor might have been tight? She told me low carb paleo and drink only water. She was the one who also did the allergy tests and told me I was allergic to casein and egg whites. Told me to eliminate them and just to be safe grains and nightshade stuff too. I notice potatoes and tomatoes hurt my stomach and they are nightshade. I think I'll still do the 23 test just to see what else is wrong.

 

Thanks for this great post. I looked into this a while back but forgot about it.

G, did you have a GAD mutation?

 

Cool, the article above says paleo would be a good diet for balancing gaba and glutamate. I guess once again it comes down to an individual call on how you are tolerating anything

 

I saw that. You mean to tell me my doctor might have been tight? She told me low carb paleo and drink only water. She was the one who also did the allergy tests and told me I was allergic to casein and egg whites. Told me to eliminate them and just to be safe grains and nightshade stuff too. I notice potatoes and tomatoes hurt my stomach and they are nightshade. I think I'll still do the 23 test just to see what else is wrong.

 

Thanks for this great post. I looked into this a while back but forgot about it.

 

Well I think if a paleo is going to be any good it will have to have LOTS of variety. Tons of meat and protein, like I said earlier, will use up BH4 and potentially leak glutamate out from your stomach with inflamed leaky guts (glutamate is part of protein's long chain amino acids).

 

Interesting you should say potatoes and tomatoes hurt your stomach because that is another thing I've been looking into that is part of this picture: histamine. Potatoes and tomatoes are high in histamine. Beyond meds has quite a few articles now on histamine intolerance after psych med withdrawal. And it turns out that the methylation cycle is precisely what degrades histamine in your body. Add to that again a leaky gut - with histamines leaching out - and you can have a bunch of issues with excess histamine.

 

I reckon get the 23andme done but for you definitely start at the beginning of that protocol: reduce neurotoxins and irritants in diet - glutamate, gluten and histamine - and heal your gut. That sounds like where you are at. Reducing that stuff will be part of healing your gut. Really anything you get a reaction to you should try and avoid for at least a few months. Remember that everytime you make your body deal with an allergen you are taxing its crapped out resources. The methylation cycle, and anti inflammatory systems, of our bodies are stretched to max and screwed. We gotta take the pressure off. So a decent diet is the first thing.

Then I think adding slowly in the right probiotics to heal the gut wall and get the balance right again. Again we gotta be careful because some probiotics are high in histamine and highly inflammatory. That means to be safe we should start with mini doses, and work up, of D-Lactate free probiotics plus L.Rhamnosus and L.Plantarum.

 

All of this is my opinion and I'm not a dr 

I take Natures Bounty Methyl B12 1000 mcg. This should be started at least two weeks prior to beginning the Methyl Folate! I take Jarrow Methyl Folate 400 mcg. One of each daily.

 

You need to know your COMT V158M and your VDR taq mutations to know the correct vitamin B12 to take! Methyl, Hydroxy, or Adenosyl!

 

http://media-cache-ec0.pinimg.com/1200x/09/80/91/098091f418be982446d06a879ff6a55f.jpg

 

I started very slow with each new thing I added!

 

It is nice to have someone else looking at this! How long (approximately) till you get your results? I'm excited to hear!

 

 

It will be 6 weeks at least cause I only recently got it. I have had it on my 'to do' for ages but I was waiting till after daughter's birthday and all christmas presents were bought. We pay $70 more just to get it to and from Aus.

I'll definitely tell you though. I'm intrigued about what it will say too.

 

When did you start the methyl vitamins? Were you still in withdrawal? Do you think dealing with this stuff has helped heal your benzo wd at all?

Hi GMIT and Smiff

I have long suspected methylation issues and genetics regarding getting off these drugs!

 

I recently received my 23andme data. Husband put it through Yaskos site and it came back with CRAZY amounts of info. I had been tested for MYHFR earlier in the year and already knew I was c677t heterozygous. Just found out more today about the "right type of B12" to take and I found that I need the adenosyl or hydroxy which is NOT what I have been taking. I have struggled to get mobile for nearly 2 years.

Also some info about the BH4 I beleive Yasko said that it may not be relevant regarding protein but have to double check. But I do evidently have issues with ammonia.

I also had a Spectracell test done in June and those results showed I was deficient in Coq10 and glutathione among other things. My 23andme results confirmed this.

What I don't know is if the chicken and egg theory exists here or not. Some readings I have found regarding DNA testing (epigenetics) is that we have thousands of switches that are constantly turned off and on genetically  They can be turned off and on during stress, toxin exposure environment, nutrition etc.

so the theory is not to feel doomed with the results.

I have just gotten my results so am curious what more I can find out.

I did also find out that my CYP3a4 enzyme is a tad on the fritz. Doesn't surprise me as I my liver seems to have changed. In terms of metabolizing drugs... Other things I have read confirm this.

Also found out I am sensitive to l-glycine. (Had crazy reaction with that) Makes me wonder why some people are able to tolerate magnesium Glycinate while others can't. Same with why some can tolerate B vitamins and others can't.

Finally, I have spoken with one woman on here who was completely healed - have to look her up again. When she tried to treat her MTHFR she was thrown back into withdrawal and had to start over from scratch. So I am proceeding with GREAT CAUTION!

I am still in the midst of tapering and know that anything that potentially get fixed or contributes to my detoxing could be problematic.

I also think the right nutrients are critical I. Healing - and the right balance.

This is waaaay more complicated than just GABA / Glutamate receptors IMHO! Genetics environment and minerals/nutrients are huge players and that is why so many people react so differently I beleive.

Just praying for healing and taking one day at a time.

 

Blessings to you and all you great research! I have loads of info I keep sending to myself to read but many times don't have the brain capacity to look through it as there is no perfect answer. But every little bit helps!

With healing prayers

Selah

 

 

 

My doc told me if I test positive for the heart disease gene or other disease genes it doesn't really mean much. She said if I corrected the heart disease through diet and exercise I'd test negative for the gene at a later time. It's just a good tool to see what you need to correct.

Selah.. yes you are so right: if it is part of the picture it is only PART. Also I agree 100% that people would have to be very careful if they were to up their methylation.

 

Methyl trapping causes anxiety etc and this video outlines another few genetic variants that cause anxiety/sleeplessness/pain - aka would ramp up withdrawal - because certain parts of the methyl cycle is driving too hard

 

I won't be trying anything till a) I know what I'm doing b) I'm out of withdrawal c) only baby teeny tiny doses and work up.

 

We'll see though. I haven't even got my genetic testing back.

 

Yes Cool, genetics are just a sign of some of the things that can tend to happen in your body and genetics do change over time.

 

I take Natures Bounty Methyl B12 1000 mcg. This should be started at least two weeks prior to beginning the Methyl Folate! I take Jarrow Methyl Folate 400 mcg. One of each daily.

 

You need to know your COMT V158M and your VDR taq mutations to know the correct vitamin B12 to take! Methyl, Hydroxy, or Adenosyl!

 

http://media-cache-ec0.pinimg.com/1200x/09/80/91/098091f418be982446d06a879ff6a55f.jpg

 

I started very slow with each new thing I added!

 

It is nice to have someone else looking at this! How long (approximately) till you get your results? I'm excited to hear!

 

 

It will be 6 weeks at least cause I only recently got it. I have had it on my 'to do' for ages but I was waiting till after daughter's birthday and all christmas presents were bought. We pay $70 more just to get it to and from Aus.

I'll definitely tell you though. I'm intrigued about what it will say too.

 

When did you start the methyl vitamins? Were you still in withdrawal? Do you think dealing with this stuff has helped heal your benzo wd at all?

 

When I started I was, and still do, go into waves and windows. I do everything SOOOOO SLOW!

 

I've tested cortisol (way off), neurotransmitters (epinephrine way low, GABA on high end), and just got my micronutrient testing back (many deficiencies, even the doc was shocked)

 

I'm not trying to heal the wd, although it would be nice! I'm trying to get healthy, which could also aid in healing!

 

Unfortunately, I have a really bad cold right now, so nothing is good right now!