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Purpose of running this test:

This Neurotransmitter Test assays neurotransmitters that function in your brain and body in ways that define your personality and physical abilities. Low serotonin has been implicated in OCD, perseverative behavior, depression, anxiety, and GI dysfunction. Dopamine is critical for executive function, attention, focus, goal motivated behavior, and mood. Dopamine is further converted into nor-epinephrine and epinephrine, neurotransmitters in themselves that may be associated with hyperactivity and attention deficit. A higher ratio of norepinephrine relative to epinephrine appears to be associated with ADD/ADHD.

I use several tests to get a complete sense of neurotransmitter formation, balance, and breakdown. First, I look at the level of the starting material for the neurotransmitteritself. In the example of serotonin,I am looking atthe level of the amino acid tryptophan. For dopamine, I am looking at the phenylalanine and tyrosine levels. These are measured on a UAA.

I can then compare how much amino acid is present versus how much of it is converting into its neurotransmitter, that level being measured by this test. From these two values, I make inferences concerning the availability of BH4 in your body. BH4 is needed to convert tryptophan into the neurotransmitter serotonin. It is also needed to convert both phenylalanine into the amino acid tyrosine, and tyrosine into the neurotransmitter dopamine. If these conversions are not happening well, I consider that BH4 may be low.

Finally, the level of the breakdown products of these neurotransmitters are measured on the MAP test, the rate of neurotransmitter breakdown being a decisive factor in the final level of neurotransmitter present in your body.

So, in order to assess neurotransmitter status and performance, I first look at a UAA to determine the level of the starting amino acid for the neurotransmitter in question. Then, I look at the reported neurotransmitter level on this Neurotransmitter Test. Finally, I look at a MAP test to get the measurement of neurotransmitter breakdown products. From the UAA and the neurotransmitter test results, I may also draw conclusions about BH4 levels.

This method of evaluating neurotransmitter (NT) status gives me a more complete picture of the status of neurotransmitter formation, balance, and breakdownin your body, rather than looking at reported neurotransmitter levels alone.

Finally, remember that all values on a urine test are reported after correcting for the creatinine level. What this means is that the raw value for a particular NT is divided by the value of creatinine to give you the final number you see on the test. Sometimes, if a person has significant physical or psychological stressors in their body or life, the creatinine value can be very high. This will make your NT values look low. So keep in mind the creatinine number, and if it is above around 150, realize that your NT values may look lower than they actually are.

Conversely, if you used a very dilute urine sample for the test, then your creatinine may be very low. This means that all urine sample values are divided by a small number, which will make your NT values look higher than they actually are. If your creatinine level is below around 50, then be aware that your NT values may appear high.

Result This table contains the rationale behind my suggestions. These suggestions are for your consideration. Defer your choices to your own health care practitioner, as always.
5 Hydroxy Tryptophan (5HTP) 5HTP is formed from tryptophan in the process of synthesizing serotonin. High 5HTP on this NT test, along with high tryptophan, phenylalanine, and tyrosine on a UAA, may signal a need for more BH4. BH4 is needed to convert 5HTP to serotonin, as well as for the conversion of phenylalanine to tyrosine, and tyrosine to dopamine. For low BH4, consider natural support to reach a healthy normal range, including MTHFR A1298C Liver Support capsules, BH4, and Royal Jelly, if you have no bee allergies. When looking at 5HTP, be sure to look at the levels of the available starting materials for serotonin, which are tryptophan and 5HTP, in conjunction with the level of serotonin on a NT test, and then the level of serotonin breakdown on a MAP test. The goal is to have a healthy level of serotonin without levels of its starting materials, tryptophan or 5HTP, or its breakdown product, 5HIAA, being either too high or too low. For high 5HTP, use more BH4 support. For low 5HTP, consider AminoAssist and low dose SeroMood.Excessive breakdown of tryptophan and 5HTP may be due to a need for niacin or Niacinamide, vitamin B3, so consider using Ultimate B or extra Niacinamide.
Tryptamine There is a delicate balance in the body between the serotonin metabolites melatonin, 5HIAA, and tryptamine. Tryptamine may cause neurologically based symptoms affecting mood, appetite, emotions, sleep, OCD behaviors, and psychosis. In fact, the psychosis inducing impact of tryptamine has been compared to LSD and mescaline. Elevated tryptamine urinary excretion has been observed in schizophrenic patients, suggesting that tryptamine may be involved in the pathophysiology of schizophrenia. Ketosis increases tryptamine levels in animal models. Ketosis occurs when the body is breaking down its own stores of glycogen, stored carbohydrate, rather than using carbohydrates from food. A low carbohydrate diet, and/or significant long term exercise may cause the body to break down glycogen, generating ketone molecules and ketosis. In addition, lack of digestive enzyme support or biotin to help process fats for energy, or ACAT + status may also generate ketosis. Ketosis can be evaluated on a MAP test.Tryptamine-induced symptoms include vegetative states, athetoid movements, delusions, hallucinations, autistic-like behavior, language disturbances, spatial and temporal perception disturbances, euphoria, and anxiety.

The use of Yucca, along with GSH support, may help to process unwanted tryptamine. Also, Feverfew may help to keep a better balance among serotonin compounds, including tryptamine.

Serotonin/melatonin If your serotonin levels are low, check that copper is not high on a HMT and UEE, because copper works with the MAO enzyme to break down serotonin. Also, check 5HIAA levels on a MAP test, as 5HIAA is a breakdown product of serotonin. The use of Molybdenum, Manganese, and low dose EDTA may help if your copper levels are high and are thereby causing increased serotonin degradation. A number of toxic metals can bind to tryptophan or to serotonin, so if your serotonin levels are particularly low, run a HMT, UTM/UEE, and/or FMT to check on your levels of aluminum, lead, and iron. Serotonin is formed from tryptophan or 5HTP with the help of BH4. Check your 5HTP levels on this NT test, as well as your tryptophan levels on a UAA, to be sure that you have sufficient tryptophan to produce serotonin. Also, check the indicators on a UAA, MAP, and a Neopterin / Biopterin Profile Urine Test to see that you have sufficient BH4 for serotonin to be produced from tryptophan. High tryptophan along with high phenylalanine and tyrosine on a UAA may signal a need for BH4 support. Consider MTHFR A1298C Liver Support capsules, BH4, and Royal Jelly, if you have no bee allergies, to naturally support healthy levels of BH4. Low serotonin may also be due to increased breakdown rather than a lack of synthesis. Consider a MAP test to look at the breakdown product from serotonin, 5HIAA. The goal is to have balance among these three: 1) the levels of the available starting materials for serotonin production, ie, tryptophan and 5HTP; 2) the level of serotonin on this NT test; and, 3) the level of 5HIAA, the breakdown product of serotonin on a MAP.Pay special attention to aluminum on a HMT and a UEE, because aluminum interferes with the production of BH4. Check that bacterial imbalances are not an issue, as this may lead to high aluminum, which in turn decreases BH4 production. Consider MetalAway and EDTA soap or soak to help address aluminum.

Tryptophan breakdown can be increased by bacteria. There is a balance between tryptophan and vitamin B3 levels which helps to support tryptophan. Consider using Ultimate B, Niacinamide, and /or NADH.

Also, for low levels of serotonin, you can consider using low dose Mood S nucleotide blend.

Conversely, levels of serotonin that are too high may be due to decreased breakdown of this neurotransmitter by the MAO enzyme. Licorice can inhibit the action of MAO causing serotonin levels to climb. This is not optimal, because serotonin may then feedback and inhibit itself.

Also, if serotonin levels are high, do a UAA to check for excess CBS activity, which may be detected from elevations in taurine. Excess CBS activity can generate increased levels of H2S, which also inhibits MAO enzyme activity. Check your levels of sulfur on a HMT and UEE, because, in conjunction with other data, they may also indicate excess H2S.

Lack of copper may limit MAO activity, causing serotonin levels to climb. Ideally, your level of zinc should be higher than copper to support attention and focus, as well as for melatonin production, but it is important for copper to be available to work with MAO, especially if serotonin levels are high.

Serotonin converts to melatonin at night to support sleep. If needed, Melatonin Sleep Spray or other forms of melatonin can be used. Cherries are a natural source of melatonin, however cherries are also a source of quercetin. While quercetin may help with increased histamine and oxidative DNA damage, it also inhibits COMT, which may be an issue for those who are COMT ++. Zinc works with melatonin, so be sure zinc levels are in balance. Magnesium support can also be assessed as magnesium may stimulate melatonin release.

Serotonin also plays a role in platelet clotting. If bruising and bleeding is an issue for those with low serotonin, you can consider using Vitamin K, Myrrh, and Topical Arnica Gel as needed, along with supports to help balance low serotonin levels.

Imbalances in serotonin have been implicated in perseverative and OCD behaviors. In addition to balancing serotonin, the use of Fenugreek may also be helpful for these symptoms, along with TNF Support nucleotide blend.

L dopa L dopa is formed from tyrosine in the process of synthesizing dopamine. Low L dopa on this NT test, along with high phenylalanine, tyrosine, and tryptophan on a UAA, may signal a need for more BH4, since BH4 is needed to help convert tyrosine to L dopa. For low BH4, consider natural supports to reach a healthy normal range, including MTHFR A1298C Liver Support capsules, BH4, and Royal Jelly, if you have no bee allergies. When balancing tyrosine and L dopa, look at the available tyrosine on a UAA because it is the starting material for both L dopa and dopamine. Then look at the levels of L dopa and dopamine on this NT test. Then, finally look at the level of the breakdown product of dopamine on a MAP test. The goal is to have a healthy level of dopamine without excessive HVA, the dopamine breakdown product, or levels of tyrosine, the dopamine starting material, that are either too high or too low. For high tyrosine but low L dopa, consider more BH4 support. For low tyrosine and low L dopa, you can consider AminoAssist or other forms of amino acid support.
Dopamine Dopamine is formed from tyrosine in conjunction with BH4 to first produce L dopa, and then finally dopamine. Check L dopa levels on this NT test, as well as tyrosine levels on a UAA, to be sure that there is sufficient tyrosine to produce L dopa, and ultimately dopamine. Also, check for indicators on a UAA, MAP test, and a Neopterin / Biopterin Profile Urine Test that there is sufficient BH4 for the reaction to proceed. Low dopamine may be due to increased breakdown rather than a lack of synthesis. If dopamine levels are low, check that copper is not high on a HMT and UEE, because copper works with the MAO enzyme to break down dopamine. HVA represents the breakdown product of dopamine. Its level can be checked on a MAP test. The use of Molybdenum, Manganese, and low dose EDTA may help if copper levels are high and are causing increased dopamine degradation. Consider running a MAP test to look at breakdown products from dopamine such as HVA. The goal is to be sure that there is balance among the level of tyrosine on a UAA, the available starting material for dopamine, the reported levels of L dopa and dopamine on this NT test, and the level of HVA, the breakdown product of dopamine on a MAP test. Pay special attention to aluminum on a HMT and a UEE, as aluminum may reduce BH4 levels. Check on CSA / GI Effects testing that bacterial imbalances are not an issue, as this may generate high aluminum levels, which in turn inhibits the production of BH4. Consider MetalAway to help address aluminum in order to support healthy BH4 levels.If values of dopamine are very low, consider the use of low dose ginkgo biloba, mucuna pruriens, Mycoceutics, low dose Mood D nucleotide blend, and Mood Focus nucleotide blend, depending on your nutrigenomics.

Adequate ATP can support dopamine release. The use of MitoForce and/or ATP may help low levels of dopamine, especially if other markers for ATP indicate a need for ATP support, such as energy data from a MAP test and low phosphate levels.

High tryptophan along with high phenylalanine and/or tyrosine on a UAA may signal a need for more BH4. Consider MTHFR A1298C Liver Support capsules, BH4, and Royal Jelly, if you have no bee allergies, to naturally support healthy levels of BH4 if indicated.

Conversely, levels of dopamine that are too high may be due to its decreased breakdown. Licorice can inhibit the action of the MAO enzyme, causing dopamine levels to climb. This is non-optimal, as dopamine can then feedback and inhibit itself.

If dopamine levels are too high, consider a UAA to check for excess CBS activity, which may be indicated by elevated taurine. Excess CBS activity can generate increased levels of H2S, which also acts to inhibit the MAO enzyme. The levels of sulfur on a HMT and UEE may also indicate excess H2S levels, if this coordinates with other test data.

Lack of copper may limit MAO enzyme activity causing dopamine levels to become high. Ideally, the level of zinc should be higher than copper to enhance attention and focus, as well as for melatonin production. However, it is important that copper be available to catalyze MAO activity, especially if dopamine levels are high.

Finally, lithium may play a role in modulating dopamine levels, so run a HMT and UEE to be sure that lithium is in balance.

Some studies indicate that excessive dopamine and high norepinephrine are factors in Tourette’s Syndrome, which is characterized by spontaneous vocal and motor tics. TNF Support nucleotide blend may help in these circumstances.

3 Methoxytyramine 3-methoxytyramine is a partial breakdown product of dopamine that is formed by the action of COMT. 3-methoxytyramine is then processed by MAO to HVA. Thus, checking the level of 3- methoxytyramine on this NT test, and HVA on a MAP test, helps to distinguish the steps in dopamine processing between the step that is achieved by the action of COMT, and the step that is achieved by the action of MAO. Some NT tests give a measure of DOPAC, as opposed to 3-methoxytyramine. DOPAC is formed when dopamine is first acted on by MAO. Then, in a second step, COMT converts DOPAC to HVA. The MAP test reports only HVA, the final breakdown product of dopamine via either route. This NT test, which looks at 3- methoxytyramine, is also assessing the activity of COMT on dopamine. A NT test that looks at DOPAC is assessing the activity of MAO on dopamine. The combination of either a DOPAC value or a 3-methoxytyramine value, in conjunction with the HVA value on a MAP test, gives composite information about dopamine breakdown, and enables you to discern which steps in the dopamine breakdown process may be most active or may need additional support.
Norepinephrine High norepinephrine relative to epinephrine may interfere with focus and attention. High norepinephrine relative to epinephrine may be due to toxic lead which inhibits the enzyme PNMT that converts norepinephrine to epinephrine. See suggestions in the UTM/UEE, HMT and FMT chapters about addressing lead in your system. Supplements that may help with attention and your norepinephrine to epinephrine balance include low dose Attention Support nucleotide blend, NADH, MTHFR A1298C Liver Support capsules, BH4, DMGSAM-e, Phosphatidyl Serine Complex (PS/PE/PC) , Vitamin C with rose hips, Zinc Lozenges, and Royal Jelly, if you have no bee allergies. Acute stress may also increase norepinephrine. Consider using Phosphatidyl Serine Complex (PS/PE/PC), Stress Foundation nucleotide blend, and Fenugreek to help with the stress response. High levels of norepinephrine may lower BH4, so consider other testing to be sure that you have sufficient BH4 available. If other tests indicate a need for BH4 support, and/or you are concerned about your BH4 levels, use MTHFR A1298C Liver Support capsules, BH4, and Royal Jelly, if you have no bee allergies.Some studies indicate that excessive dopamine and high norepinephrine are factors in Tourette’s syndrome, which is characterized by spontaneous vocal and motor tics. Consider a CSA and GI Effects test to rule out Streptococcus as a causative factor in Tourette’s Syndrome. TNF alpha has been definitively associated with strep infection. Use supports to help balance excess TNF alpha, such as TNF nucleotide blend.
Normetanephrine Normetanephrine is a partial breakdown product of norepinephrine that reflects the action of COMT on norepinephrine. Comparing MHPG on a MAP test to normetanephrine on this NT test separates the action of COMT to form normetanephrine from the action of MAO that produces MHPG from norepinephrine.
Epinephrine Low epinephrine relative to norepinephrine may interfere with focus and attention. If relative epinephrine levels are too low, use Vitamin C with rose hips, as that may enhance epinephrine levels. Supplements that may help with attention and norepinephrine to epinephrine balance include low dose Attention Support nucleotide blend, NADH, MTHFR A1298C Liver Support capsules, BH4, DMG, SAM-e, Phosphatidyl Serine Complex (PS/PE/PC), Zinc Lozenges and Royal Jelly, if you have no bee allergies.
Glutamic Acid & GABA Glutamic acid, or glutamate, is an excitatory neurotransmitter. While I am thinking, talking, processing, and sharing with you, the glutamate receptors in my neurons are functioning actively to take glutamate in. You need glutamate for learning, attending, and functioning. In fact, the more intelligent you are, the more glutamate receptors you have on your cells. But too much glutamate being taken into your nerve cells may damage or destroy them. It would be like turning a light switch on and off continuously until it breaks. A number of other substances related to glutamate will also act as excitatory neurotransmitters at glutamate receptor sites. They include glutamine, alpha ketoglutarate, and monosodium glutamate or MSG. The aspartate family of molecules will do this also. They include aspartate, aspartic acid, and aspartame, commonly known as NutraSweet. Cysteine can also act as a mild excitatory neurotransmitter, but N-acetyl cysteine does not. However, N-acetyl cysteine contains an acetyl and a sulfur group and so must be used thoughtfully. Glycine is also a special case neurotransmitter. If the balance in your body is towards glutamate, glycine will be excitatory. If the balance is toward GABA, it will be inhibitory. So if you tend toward glutamate excess, avoid glycine. The number of glutamate receptor sites you have on your neuron surfaces is an important determinant of the level of glutamate in your cells. The more glutamate receptor sites you have, the more glutamate you take in, thus your resting level of glutamate is higher. In this case your balance tips to favor excitotoxicity. Glutamate excitotoxicity produces nerve damage or death by inducing inflammation. Increased numbers of glutamate receptors have been associated with neurologic disorders such as Lou Gehrig’s Disease or Amyotrophic Lateral Sclerosis (ALS), Fragile X, schizophrenia, and seizure disorder.It was initially thought that autistic children had fewer glutamate receptors, but subsequent studies, including one from the prestigious journal Neurology published in 2001, showed that autistic children, in fact, have more glutamate receptors than normal controls. Furthermore, they are genetically predisposed to have more. So autism is another hyper-glutamate condition.

If you keep the total amount of glutamate in your body under control, you can limit neurologic symptoms. One way you can do this is by eliminating gluten and casein from your diet. You also want to eliminate glutamate and anything that sounds like that, and aspartate and anything that sounds like that, from your supplements. Glutamine is a frequently recommended supplement, but glutamate and glutamine change back and forth into each other. This means that the administration of glutamine, say for gastro intestinal support, actually increases the level of glutamate. Increased glutamate may produce insomnia, decreased eye contact, and too much acetylcholine, which can lead to bladder contraction and abnormal eye movements called strabismus. Increased glutamate also causes an increase in self-stimulatory behavior, commonly called stims. In adults, too much glutamate may be a factor in heart palpitations, inability to fall asleep, and excessive urination.

One of the ways your brain deals with excitotoxin damage is to increase the level of opioids that are produced. Opioids are opium-like substances. Obviously, they will interfere with your ability to function.

Elevated levels of glutamate can deplete your levels of glutathione (GSH). GSH is a central antioxidant and metal detox molecule. Depleted GSH leads to increased inflammatory mediators, including TNF alpha. Depleted GSH and increased TNF alpha can exacerbate leaky gut, generate gastrointestinal inflammation, and mediate allergic intolerance to foods.

GABA is a calming NT that helps to balance out the impact of glutamate. GABA, gamma amino butyric acid, is an inhibitory neurotransmitter. Glutamate should convert into GABA when it is acted on by the enzyme glutamic acid decarboxylase (GAD), but several factors may interfere with this conversion, and you get stuck at glutamate. The rubella virus interferes with the activity of the GAD enzyme. This is the same virus that is in the MMR vaccination. It has been shown in Type 1 Diabetes that the rubella virus can cause the GAD enzyme to stop functioning. The body makes antibodies against it. In some studies, enzyme activity was decreased by 50%.

Viral issues are related to methylation. If you are producing insufficient methyl groups, then you cannot methylate viral DNA to silence the virus. In addition, the methylation cycle is involved in new DNA synthesis that makes immune cells such as T-cells, which deal with viral infection.

When someone speaks to you and you are not quite attending, you may turn to them and say, “What did you say?” Before they can answer you, your mind replays it, and you can recover what they said. GABA is the neurotransmitter involved with this function. GABA is very prominently involved with the neuronal connections of language. It actually puts the gaps between words. Decreased GABA leads to increased anxiety, increased aggressive behavior, decreased social behavior, decreased eye contact, and decreased bowel function. GABA is necessary to stimulate bowel contraction. Decreased GABA also causes eye-focusing problems, like both eyes focused in toward the nose or vertical or horizontal eye wavering.

Calcium is another factor in the glutamate GABA story. If glutamate is like a gun, then calcium is the bullet. Glutamate creates the scenario for excitotoxicity to happen, but the factor that actually destroys the nerve cell is the influx of calcium. The combination of excessive glutamate from any source and too much calcium is a major problem.

Evaluate calcium levels using a UEE. Vitamin D and Vitamin K are fat-soluble vitamins and are important for re-establishing calcium balance. Your body can store Vitamin D, but Vitamin K may need to be supplemented on a daily basis, unless you are eating dark leafy green organic vegetables and are able to absorb the nutrients from them.

Supplementing calcium be accomplished by using Chamomile and/or Nettle rather than by taking calcium directly. Increasing magnesium relative to calcium, using zinc to limit glutamate damage, and monitoring lithium, iodine and boron levels, all aid in reducing glutamate levels and reversing the flow of calcium into the neurons and back to the bones and teeth.

You can evaluate glutamate and GABA levels by running a UAA. The UAA has both of these neurotransmitters on it. You can supplement GABA directly, and also consider the glutamate GABA balancing BeCalm Spray.

In the presence of ammonia and ATP, glutamate is converted to glutamine. Your levels of both glutamine and glutamate should be considered as they convert into one another. If your level of phosphate is low, then leucine is increased, which in turn increases glutamate and alpha KG, and in addition can cause hypoglycemia.

Consider supplements that help with glutamate/GABA balance such as Nerve Calm nucleotide blend, BeCalm Spray, GABA Balance capsules, Pycnogenol, Grape Seed Extract, and Resveratrol. Consider using Carnosine if your levels on a UAA are low, as it may decrease glutamate transport. Jujube & CoQ10 may also help control excess glutamate. Eliminate sources of glutamate and other excitotoxins. Also, check a HMT and UEE for the levels of minerals that can help with glutamate and calcium balance, such as Zinc, Magnesium and Lithium.

According to the literature, creatine may help reduce glutamate, so consider Creatine support if your creatinine levels are low.

Consider checking hydroxyproline levels, as high hyrdoxyproline can increase glycine and increase glutamate. When glutamate is high, then glycine can exacerbate the effects of glutamate, so check glycine levels and use SHMT Spray and AHCY/SHMT compound as needed to help with glycine balance.

H2S increases NMDA responses, so it is important to check taurine levels to be sure there is not too much flow from taurine to H2S. See suggestions for balancing high taurine levels if this is an issue, and be sure you have sufficient Molybdenum and B12 to process sulfur groups. You can consider Black Bear Spray or Black Bear Drink for low doses of molybdenum and B12.

Low levels of GABA may play a role in spasticity and involuntary movement syndromes.

Toxic levels of manganese may impact both GABA and taurine levels and affect their transport. If an individual is intolerant to GABA supplementation in spite of symptoms that suggest a need for GABA support, then check manganese levels to be sure they are not high. The use of valerian root in conjunction with low dose GABA may be a consideration for you and your doctor, as valerian may aid in GABA transport. If high manganese is the issue, consider increased EDTA support. Working with, and deferring to your own doctor consider the use of MetalAwayDetoxAwayEDTA soap and soak, and additional EDTA capsules can be considered.

If GABA is not tolerated, consider ruling out high manganese in your home water supply by using the Water Elements Test. Some defective water filtration systems may be a source of higher than ideal levels of manganese in your drinking and bathing water supply. Since manganese is important for helping to process arginine, consider supporting with low dose Manganese if arginine is high on a UAA test. However, high levels of manganese are a concern for the reasons described below. Ideally, manganese levels should be in the lower range of normal so that they are sufficient to support reactions that require manganese without allowing levels to climb too high.

Excessively high levels of manganese can cause psychosis as well as seizures. Excessive accumulation of manganese causes a neurological condition called “manganism” that is characterized by psychosis and eventually followed by symptoms similar to those seen in Parkinson’s disease. High levels of manganese have also been associated with ALS, and biochemical changes similar to Alzheimer’s and Huntington’s disease (Sidoryk-Wegrzynowicz, 2013). High levels of manganese can cause increases in reactive oxygen species, so consider Ultifend; impair glutathione levels, so consider GSH; and increase inflammatory mediators, so consider General Support nucleotide blend and low dose TNF nucleotide blend. High dose manganese may also decrease dopamine levels.

Histamine The basic components of allergic inflammation include mast cells, basophils, and eosinophils. Specific IgE molecules that are generated due to very precise allergens bind to mast cells, eosinophils, and basophils, causing the release of histamine, which causes immediate, and sometimes very intense, hypersensitivity reactions.In addition to their activity in causing inflammation, mast cells, basophils, and eosinophils also play a protective role in immune function. Conversely, excessively high levels of mast cells, called mastocytosis, or high levels of mast cell degranulation and release of histamine can cause health problems. Mast cells are like water balloons filled with histamine. When your body reacts to an allergen, it is like sticking a pin in a water balloon, allowing the histamine to burst out. Mast Cell Activation Syndrome (MCAS) is a condition in which there may be excessive numbers of mast cells that are triggered even in the absence of a specific allergen. In either case, the goal is to both reduce the number of mast cells, as well as to mitigate the high histamine levels.First, realize that there is a relationship between histamine and the methylation cycle. Low tetrahydrofolate (THF) levels can cause elevated histidine. Elevations in histidine in turn cause increased levels of histamine. So, high histidine along with high histamine may indicate a need for THF. Consider All in One or Ultimate B to help support healthy natural THF levels. In addition, check FIGLU levels on a MAP test, as FIGLU will also climb If there is not sufficient THF. Thus, high FIGLU may be an indirect sign of excess histidine. High levels of histidine may depress the levels of other amino acids, as well as be related to high cholesterol. A GI function test can be run to look at cholesterol levels.

In addition to the need for adequate THF, the methylation cycle is also important in processing the histamine that is produced secondary to a lack of THF. FIGLU is an indicator for low THF. When FIGLU is elevated it leads to the formation of histidine, which can convert to histamine. You need methyl groups to process histamine. Working on basic methylation cycle support, as well as the use of SAM-e, may help you process histamine, because SAM-e may specifically help to lower histamine. Some reports also suggest that methionine may have a similar impact; however, the effect of methionine may be due to its conversion into SAM-e, which is the active agent in lowering histamine.

Histamine is broken down by the enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). The HNMT enzyme requires methylation cycle function in order to break down histamine. The DAO enzyme needs copper to function. High levels of copper can be an issue for other NTs, increasing the breakdown of serotonin and dopamine, as well as negatively impacting attention. So, the goal is to keep copper in a normal range, with zinc levels higher than copper. In this way, there is sufficient copper for DAO function without causing increased serotonin or dopamine breakdown or causing issues with attention.

In addition, rule out excess CBS activity on a UAA, as the high H2S that can be generated due to excess transulfuration activity can decrease MAO activity.

Licorice can also inhibit MAO enzyme activity, so low copper, high H2S, and licorice, may slow the breakdown of histamine and lead to higher levels of histamine. Limit licorice ingestion in this situation and in general.

Some patients with Postural Orthostatic Hypotension Syndrome (POTS) have co-existing complaints of episodic flushing. In about half of these cases there is an associated mast cell activation disorder. This can be diagnosed by collecting urine from individual 2-4 hour voids following a severe flushing spell for determination of methylhistamines

Acrocyanosis due to POTS is reported to be helped with Nerve Calm nucleotide blend, BH4 support, and MTHFR A1298C Liver Support capsules, as well as CBS/NOS Kidney Support capsules. A striking physical feature of POTS is the acrocyanosis that occurs in the legs of 40-50% of these patients. They experience a dark red-blue discoloration of their legs, which are cold to the touch.

In addition to supporting healthy histamine breakdown, and being sure that FIGLU does not climb too high allowing increased histamine synthesis, it is also important to pay attention to vitamin B6 levels. Vitamin B6, or P5P (pyridoxal 5 phosphate) helps to produce higher levels of histamine. This program uses only low levels of B6/P5P for reactions that need it, such as converting glutamate to GABA, without using the excessively high levels of B6/P5P that are employed by some other programs.

The reason I suggest Ultimate B as the B complex of choice is that it is specially formulated to have the most active forms of B vitamins, while at the same time only including low levels of B6/P5P. The same is true for the general vitamin this program uses, All in One. It does support B vitamins, while maintaining only low levels of B6/P5P, as higher doses of B6/P5P may produce increased levels of histamine.

You may be able to slow down some of the mast cell degranulation and histamine release of an IgE reaction by the use of quercetin. Quercetin is not optimal for those who are COMT + +. While it may be a help for high histamine, as well as for oxidative DNA damage, it is not ideal for those who are COMT ++ because it can inhibit COMT. Cherries are a natural source of quercetin, so while cherries may help with inflammation, gout, and some forms of arthritis, the quercetin levels in cherries may be an issue for those who are COMT ++.

Also, Butterbur, which is in Petadolex, blocks the action of histamine. In general, keeping inflammation in check by using General Support nucleotide blend, Cytokine Balance nucleotide blend, Nettle, Boswellia, and Curcumin or Inflammatory Pathway Support capsules, are other routes to consider.

Working on leaky gut to limit immune responses to food may also be useful. Bowel Support nucleotide blend and Leaky Gut nucleotide blend can be considered. In addition, mast cells are released in H.pylori infection. Be sure you do not have H.pylori, which may be causing eosinophilia or sarcoidosis. See Chapter 7 for a more complete discussion of H.pylori. Low dose Respiratory Support nucleotide blend may be a help, along with low dose Hyper-Balancing nucleotide blend, NOT Hypoimmune nucleotide blend. As always, defer to and work with your doctor. Cross check supplementation with your doctor.

In addition to the role played by IgE and allergies in triggering mast cell histamine release, the compound nitric oxide may also regulate mast cell function. According to Guzik et al, “Activation of nitric oxide producing cells in the tissue microenvironment may be important in the control of mast cell-dependent allergic reactions”. Since tetrahydrobiopterin (BH4) is important for all NOS reactions, it is important to support healthy natural BH4 levels with BH4 and MTHFR A1298C Liver Support capsules.

Finally, more traditional medications may be a help if natural approaches are not enough to address severe Mast Cell Activation Syndrome (MCAS). The antibiotic minocycline has been reported to limit certain inflammatory reactions and can be used for anti-inflammatory purposes rather than for its antibiotic properties. Minocycline has been a help for limiting excessive microglial activation that plays a role in chronic neurological inflammation. In addition, minocycline has been reported to reduce overall levels of IgE. The action of IgE specific allergens binding to mast cells allows for the massive release of histamine in allergic conditions. Limiting IgE levels while identifying and eliminating the allergy triggers may be a help in extreme conditions in which natural approaches have not been sufficient.

The combination of Claritin and Pepcid has been reported to lower the number of mast cells in skin reactions, as well as to decrease histamine levels. While I generally prefer to go the more natural route first, to work on the underlying causes, in extreme conditions of MCAS, the combination of medication with natural supplements may be considered. As always, work with and defer to your own doctor.

 

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Related Tests to Run

The MAP test gives information about the breakdown products of neurotransmitters such as serotonin, dopamine, norepinephrine, and epinephrine that is useful in conjunction with this NT test. Looking at tryptophan and tyrosine on a UAA, in conjunction with neurotransmitter levels on this test, and their breakdown products on a MAP test, gives you a more comprehensive picture of neurotransmitter balance. Run the Neopterin / Biopterin Profile Urine Test for BH4 levels if necessary. In this way, you look at starting materials needed to produce neurotransmitters on a UAA and biopterin test, levels of neurotransmitters on this NT test, and their breakdown products on the MAP test.

In addition, consider HMT and UEE testing to check on copper, manganese, and molybdenum, which can influence neurotransmitter processing.

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