Editor’s Note: Parts of this article have been reprinted from Chapters 3 and 4 of Connie Strasheim’s book, Beyond a Glass of Milk and a Hot Bath: Advanced Sleep Solutions for People with Chronic Insomnia by permission of the author. No part of this article may be reprinted or copied without the author’s permission. Copyright 2017 by Connie Strasheim
One of the problems that chronic Lyme disease causes is neurotransmitter imbalances. Neurotransmitters are chemical messengers that coordinate the transmission of signals between nerve cells in the brain and throughout the body. They affect many processes including mood, memory, cognition, concentration, alertness, energy, appetite, pain, and sleep.
Therefore, if you are brain fogged, irritable, anxious, depressed, in pain, fatigued and/or have low energy, it may be because some of your neurotransmitters are out of balance. Other problems, such as hormonal imbalances and inflammation can also cause these symptoms, but neurotransmitter dysfunction can also be a major cause.
Other causes of neurotransmitter imbalance, in addition to Lyme disease, include stress, nutritional deficiencies and environmental toxicity. Unfortunately, it’s not uncommon for people nowadays—even those who don’t have Lyme—to have both deficiencies and excesses of a variety of neurotransmitters. Following I describe some common neurotransmitter imbalances found in people with Lyme, along with nutrients, especially amino acids, that support a healthy balance of each of these.
Glutamate is an excitatory neurotransmitter that is often found in excess in people with Lyme. When it's balanced in the brain, it plays a vital role in learning, cognition and memory. It is also the precursor for GABA, the brain's primary inhibitory, or calming neurotransmitter. Unfortunately, though stress, a poor diet, illness and other factors can disrupt the glutamate-GABA conversion, which can then result in elevated levels of glutamate in the body.
This can cause insomnia in people with Lyme, and also impair cognitive functioning. Over time, excessive levels of glutamate lead to neuron self-destruction, and ultimately, neurodegeneration. In fact, studies suggest that many neurodegenerative disorders such as autism, ALS and Parkinson’s, are caused at least in part by glutamate excess.
Throughout my recovery from Lyme disease, my neurotransmitter test results consistently revealed that my glutamate levels were high, and my pharmacist believed that this was disrupting my sleep, since glutamate is an excitatory neurotransmitter. At the time that I discovered this, I had already been using a couple of remedies to help me sleep, and while I had had some measure of success with these, I still wasn’t getting a solid seven or eight hours every night, which is what I needed.
I told my pharmacist this and he recommended that I take oxaloacetate, a compound that has been found to help decrease glutamate levels in the brain by activating an enzyme responsible for scavenging glutamate. One study, the results of which were published in The Journal of Neurological Anesthesiology in July 2009, showed treatment with oxaloacetate after traumatic brain injury to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain.
If neurotransmitter testing reveals that your glutamate levels are outside of the normal range, you may find that supplementing with oxaloacetate will help you to sleep and perhaps improve other symptoms associated with glutamate excess. As a side note, it must be taken on an empty stomach, away from other supplements. One study published in The Journal of Neurochemistry in 2003 showed that large doses of oxaloacetate could reduce levels of glutamate by 30-40% in lab animals, which indicates that it is a potentially potent neuroprotectant.
People with Lyme also tend to have excessive levels of histamine, a neurotransmitter that is involved in the body’s immune response and which is produced whenever you have an allergic response to something.
Because people with Lyme are often allergic to many things; foods, chemicals in the environment and so on, it's easy for their bodies to get overloaded with histamine and become stuck in a perpetual inflammatory, or allergic response, to things in the environment. The disease itself can also cause histamine overload and immune system over-activation, which results in inflammation.
High histamine levels and inflammation in turn cause all kinds of symptoms, including pain, fatigue, depression, and sleep disturbances—among others.
Histamine release is also implicated in mast cell activation disorder or disease (often abbreviated MCAD), a condition in which the body overproduces mast cells, and which is common in those with chronic health conditions of all kinds. Mast cells release histamine and cytokines, or chemicals that cause widespread inflammation throughout the body. Evidence for this is found in a study published in Oxford Medicine Online in April 2013, which reveals that substantial amounts of histamine are contained in, and can be released by, tissue mast cells.
Lawrence Afrin, MD, an expert in MCAD, cites all kinds of health conditions that are the cause or effect of MCAD in his book, Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity. The list is amazingly long and includes just about every chronic health condition that you can think of. Further, some integrative doctors of late have been finding that many conditions are caused in part or made worse by mast cell activation disorder, including Lyme.
If you haven’t been tested for MCAD and have undiagnosed symptoms or a chronic condition that you haven’t been able to successfully treat with the means that have been made available to you, I highly recommend talking to your doctor about MCAD. Proper treatment for MCAD can shut down a variety of symptoms caused by histamine.
Treatments for high histamine and MCAD include a low-histamine diet, ketotifen (a compounded antihistamine medication with a very low side effect profile), quercetin, vitamin C and diamine oxidase, an enzyme that’s involved in the metabolism and inactivation of histamine. Other nutrients that have anti-histaminic properties include: vitamin C, magnesium glycinate, curcumin and holy basil, all of which are believed to help the body to metabolize histamine.
One thing that I like about the medication ketotifen is that it is profoundly effective and, unlike other commonly known antihistamines like Benadryl, it isn’t anticholinergic; that is, it doesn’t block the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Some antihistamines do this, and it is why drugs like Benadryl have been associated with Alzheimer’s and memory loss, since acetylcholine plays a vital role in memory and cognition.
There are other medications out there, such as benzodiazepenes, that shut down histamine and mast cells but most of these have significant side effects so you’ll want to talk to your doctor about these if none of the supplements seem to work for you.
In the end though, there is no “one size fits all” approach for controlling histamine and MCAD, so it’s best to work with a doctor who understands it. For instance, Neil Nathan, MD and Wayne Anderson, ND, are two expert integrative medical doctors in northern California who understand MCAD and histamine release. Both contributed a chapter to my 2016 book, New Paradigms in Lyme Disease Treatment: 10 Top Doctors Reveal Healing Strategies that Work.
Fortunately, I believe that as MCAD becomes increasingly recognized within the medical community, more and more integrative doctors will be testing and treating their patients for it.
Quercetin, which may be one of the better-known natural remedies for treating MCAD, is described in Dr. Afrin’s book Never Bet Against Occam. In it, Dr. Afrin says, “It (quercetin) seems to result in reduced production of inflammatory mediators (e.g., leukotrienes and histamine). It may also serve as an inhibitor of tyrosine kinases and other regulatory proteins of interest in activated mast cells.” This means that it can reduce the inflammation that causes symptoms such as pain, fatigue, depression and brain fog-among others, in people with excessive histamine.
Perhaps the most important calming neurotransmitter in the body is GABA, or gamma-amino butyric acid. GABA promotes restful sleep and relaxation by decreasing neuron firing in the brain. Its calming properties can also reduce anxiety and balance blood pressure. GABA deficiencies are common in people with Lyme, perhaps due in part to the dysfunctional glutamate-GABA conversion mechanism caused by chronic illness. GABA is an amino acid in addition to a neurotransmitter, and taking supplemental GABA has been found to support a healthy relaxation response and sleep in some people with Lyme.
I have regularly used GABA for sleep, but not just any regular ol’ form of GABA has worked for me. I once tried some GABA straight off of the supermarket shelf and felt horrible the first morning after I took it. Little did I know, my body couldn’t metabolize it well and I needed to use a more bioavailable form. So for a long time, I concluded that I didn’t need GABA, until one day, I came across a great product that a friend had urged me to try, and which I found actually worked for me.
That product was Kavinace, made by Neuro Science. It contains bioavailable GABA, in addition to taurine, which is an amino acid that can also help to block the negative effects of glutamate upon the body.
You may find that Kavinace will work better for you than other GABA products as well, especially if you have methylation issues and genetic defects (more on this later) that prevent your body from effectively utilizing amino acids. Kavinace costs more than just plain ol’ GABA though, so you may want to try regular GABA first to see if it helps you.
Taurine is an amino acid that is found in high levels in the central nervous system. One of its roles is to help modulate and promote healthy levels of GABA. Taurine can support a healthy sleep response when you need just a little extra something to get by, and has been found to be useful for some Lyme sufferers.
Another benefit of taurine is that it helps to prevent neuron damage caused by excessive levels of glutamate. Experimental studies on rats have shown that taurine inhibits glutamate toxicity through a number of different mechanisms. This is good news for those of us who suffer from cognitive and other brain symptoms caused by neurodegenerative diseases like Lyme.
Theanine, which is another calming amino acid, is also believed to play an important role in modulating several neurotransmitters, especially GABA. Some people have found theanine to be helpful for supporting a healthy sleep response, although it tends to be less powerful and sedating than GABA.
You will most likely find that you and your doctor will need to experiment to determine what types of products and amino acids that your body needs. Doing amino acid and neurotransmitter urine testing through a reputable lab can be helpful (later I share the names of some labs that do this kind of testing), but even tests are imperfect and you and your doctor may need to experiment a little to discover what you will need.
5-HTP and L-Tryptophan
Tryptophan and 5-HTP are two other calming amino acids that are both precursors to serotonin, a neurotransmitter that powerfully affects mood, energy levels, sleep, digestion and cognitive function. Many people with Lyme disease have either too high levels of serotonin, or, more commonly, too low levels of serotonin.
Symptoms of serotonin deficiency include: depression and/or anxiety, lethargy, digestive issues, fatigue, pain and insomnia.
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Most of you have probably heard about 5-HTP and tryptophan, but what you may not know is that these amino acids don’t always work that well in the body unless you have all of the proper co-factors and/or methylation support that your body needs to synthesize serotonin from them.
For instance, you may find that if you have any methylation issues or genetic defects (which are relatively common in people with Lyme) you may not benefit from taking these amino acids unless you have the proper methylators, and/or nutrients to make them work in your body. Methylation is a process that occurs in all of our cells and is a key biochemical process that is essential for the proper functioning of nearly all of our body’s systems. One of its roles is to help make neurotransmitters, but some of us have methylation problems that keep us from being able to do that.
Later in this article I describe some methylators/nutrients that may help your body to synthesize neurotransmitters from amino acids. You’ll want to discuss these with your doctor and ideally, get tested to discover which ones you may benefit from. The company 23andMe offers genetic testing that can provide insights into your body’s potential ability to synthesize and break down neurotransmitters. For more information, see: 23andme.com.
If you can’t afford genetic or other types of testing, you can ask your doctor to give you a trial treatment of amino acid therapy, to see how you respond. This is less ideal, but can sometimes provide enough insight into what supplements you may need.
Some people have commented to me that they feel worse when they take amino acids. I have at times, too. This can be due to several factors. First, and as I just mentioned, your body may not be able to synthesize neurotransmitters from amino acids due to a methylation or other genetic problem. This means that your body won’t use the amino acids properly and you will either experience no discernible benefit after taking them, or you will end up feeling worse.
Secondly, if you are highly deficient in certain amino acids and/or neurotransmitters, you can also feel worse when you first start amino acid therapy. If neurotransmitter testing reveals that you are deficient in certain neurotransmitters, you may want to ask your doctor to prescribe you low doses of the appropriate amino acid precursors, and then you can slowly work your way up on the dosing. Taking a dose that is too high, too soon, can make you feel worse.
The first time that I took a 5-HTP product I became more brain fogged, depressed and fatigued. I mistakenly concluded that amino acids were not helpful for me. Unfortunately, I continued to sleep poorly for several years after that, until I realized that the problem wasn’t that my body didn’t need 5-HTP, but rather, that it couldn’t make serotonin from the 5-HTP without a little help. Once I discovered the nutrients and methylating substances that my body needed to synthesize serotonin from 5-HTP, I actually became more energetic, clear-headed, and happy, and my sleep improved.
L-Phenalalaline and L-Tyrosine
These amino acids are both precursors to dopamine, an excitatory neurotransmitter that supports healthy energy production, mood and cognition. I have personally found L-tyrosine to have just as profound mood-enhancing effects as 5-HTP or any other serotonin precursor. Doctors who treat depression often talk about the importance of serotonin for modulating mood, but dopamine is just as crucial. And as one of my former doctors, Jeremy Kaslow, MD, once taught me—serotonin and dopamine must be balanced in the body in order for both to work optimally.
Many people with Lyme disease have dopamine deficiencies, so taking an amino acid like L-phenalalaline or L-tyrosine may help to support healthy levels of dopamine, but I recommend working with your doctor to determine how much you need, as excessive levels of tyrosine can cause anxiety and heart palpitations. L-dopa, which is the closest precursor to dopamine on the amino acid chain, is used to treat Parkinson's (which some researchers believe is actually caused by Lyme disease). It can also be purchased as a compounded cream or powder, but is also found in low amounts in mucuna bean powder.
L-dopa should only be taken under physician supervision as it can cause side effects when taken in excess.
Acetylcholine is a neurotransmitter that is responsible for cognition, memory, learning and processing. It is another neurotransmittter that is often depleted in people with Lyme disease.
The body uses choline to make acetylcholine, so supplementing with a high-quality oral or transdermal choline product (especially GPC), or even better, taking choline via IV can help to restore some of the cognitive functions that are lost through chronic Lyme. Cell membranes are also composed partially of choline, so taking choline can also help to support healthy cell membranes, which is important as the cell membrane is responsible for the entire integrity of the cell. As one of its major functions, the cell membrane helps to shuttle nutrients into the cell, and is responsible for carrying waste out of the cell.
Methylators and Co-Factors Help the Body to Make Neurotransmitters
As I mentioned, amino acids may not work properly in your body if you take the wrong product, dosage or combination of nutrients; or if you need methylators and/or nutritional co-factors, which assist neurotransmitter synthesis. This is important to understand if you have tried amino acids before but not had good results from them.
I have found that many people, especially those who battle chronic neurological diseases may need methylation support, along with amino acids. Some common methylators that help the body to synthesize neurotransmitters from amino acids include:
• Methyl-folate (a bioavailable form of folate)
• P5P (pyridoxyl phosphate, which is a bioavailable form of Vitamin B-6)
• Vitamin B-12
In addition, your body needs an adequate supply of zinc, magnesium, vitamin C and vitamin B-6 to make serotonin from 5-HTP (and perhaps other vitamins and minerals to make the other neurotransmitters), so it may be worthwhile to get tested to find out which vitamins and minerals you may be deficient in, to determine which ones you need for optimal neurotransmitter function.
Ideally, to find out which methylators you may need, it’s best to have your doctor do a complete amino acid and neurotransmitter profile, which are available through many labs and compounding pharmacies such as:
• Sabre Sciences (SabreSciences.com)
• NeuroScience (WhyNeuroScience.com)
• Pharmasan (Pharmasan.com)
• BioHealth Diagnostics (BioHealthLab.com)
In addition, you’ll want to do the gene test from 23andMe.com, the results of which your doctor can use to determine whether you have genetic defects that may hamper your ability to properly synthesize and metabolize neurotransmitters and other chemicals.
Again, if you can’t afford lab testing, which can be expensive, and if your doctor approves, you might try a low trial dose of an amino acid or two. If you don’t notice that either amino acid improves your symptoms or you feel worse after taking them, consider adding a small dose of SAM-e, P5P and/or methyl-folate, according to your lab results and/or doctor’s recommendations. A small dose of SAM-e would be about 50 mg, taken in the morning (as it can disrupt sleep when taken at night). Even if you do lab testing, you may find that you need to experiment with the methylators and dosages to find the one(s) that will work best for you.
When I first started using methylators, I found that I could not tolerate more than half a capsule of SAMe. If I took more, it actually kept me up at night and worsened the insomnia. But a small amount helped my body to utilize the amino acids that I needed to function on all levels. I then introduced a small amount of P5P into my regimen, and finally, methyl-folate. I added them one at a time to gauge my response to each.
I highly recommend supplementing in this way and doing lab tests to determine what your body needs, as taking too much of any one methylator can actually cause your body to over-methylate, which can have an opposite effect and keep you up at night. In any case, it is always best to consult with a knowledgeable integrative doctor and/or compounding pharmacist for help in balancing your chemistry.
You may want to dose your amino acids in a similar fashion. For instance, if you want to try 5-HTP for mood or sleep support, ask your doctor about starting with one, say, 50 mg 5-HTP capsule or tablet (maybe even half a 50 mg capsule) and then increasing the dosage over time until you notice that you feel better. Typical dosages can range from 50 mg up to 300 mg, per your doctor’s recommendations. You can also try L-tryptophan, which is the amino acid precursor to 5-HTP and also works well for some people.
How to Determine Whether Amino Acid Therapy Is Right for You
First, if you take antidepressants, you’ll want to consult with your doctor before taking 5-HTP, L-tyrosine or L-tryptophan, as these amino acids are sometimes contraindicated for people who use anti-depressants and when combined, aminos and drugs can occasionally cause a condition known as serotonin syndrome. So if you are on an antidepressant, use amino acids with caution and only under the guidance of a qualified health care practitioner.
In summary, the steps that you’ll want to take to determine whether amino acid therapy is right for you, include:
1) Doing a complete amino acid and neurotransmitter profile through a reputable lab such as Sabre Sciences, NeuroScience, Pharmasan and/or BioHealth Diagnostics.
2) Doing a trial treatment of amino acid therapy to see if it is right for you and observing your response. I always recommend doing this under a doctor’s care, so that he/she can gauge your reactions to determine what you might need and how your regimen needs to be adjusted.
3) Supplementing with the appropriate co-factors that aid in neurotransmitter synthesis, such as zinc, magnesium and vitamin C (which are often depleted in people with chronic illness).
4) Supplementing with methylators that will help your body to make neurotransmitters from amino acids. (Take these only if your test results indicate that you need methylation support, you respond poorly to amino acids, and your doctor tells you that you need them).
Clues that you may have a methylation problem include: 1) Having a negative reaction or feeling worse when you take amino acids 2) Genetic testing indicates that you need methylation support or 3) Test results indicate that you have a deficiency of amino acids but taking the appropriate amino acids seems to produce no change in your symptoms or ability to sleep.
The most commonly used methylators that aid in neurotransmitter synthesis include:
• Vitamins B-6 (or pyridoxyl phosphate, P5P)
• Vitamin B-12 (methyl and/or adenosyl B-12 tend to be the most effective forms of these B vitamins). You may need one or more of these
By balancing your neurotransmitters, you can greatly improve the way that you feel during Lyme disease treatment and mitigate some of the symptoms associated with Lyme. Indeed, neurotransmitter balancing and repletion are a key piece of the puzzle for many with Lyme.
Connie Strasheim is the author or co-author of 11 wellness books, including the recently released New Paradigms in Lyme Disease Treatment: 10 Top Doctors Real Healing Strategies that Work. (October, 2016) and Beyond a Glass of Milk and a Hot Bath: Advanced Sleep Solutions for People with Chronic Insomnia. (March, 2017). She is also a medical copywriter and an editor at ProHealth.com, as well as Editor of the Alternative Cancer Research Institute (ACRI). Her passion is to help people with complex chronic illnesses find freedom from disease and soul-spirit sickness using whole body medicine, and she collaborates with some of the world's best integrative doctors to do this. In addition to Lyme disease and insomnia, Connie’s books focus on cancer, nutrition, detoxification and spiritual healing. To learn more about her work, see: www.ConnieStrasheim.org.