Urine neurotransmitter Testing

Our testing measures the following areas.  Combining this test with our BloodSpot 20 for amino acids, we are able to get a clear idea of the "input" of amino precursors and the "output" of neurotransmitters.

There are two main groups of neurotransmitters:
    1.   Excitatory neurotransmitters/neuromodulators (ie: uppers)
    2.   Inhibitory neurotransmitters/neuromodulators (ie: downers)

A proper balance between the excitatory and inhibitory neurotransmitters is essential.  For example, excitatory symptoms can be caused by either an excess of excitatory neuromodulators OR a deficiency of inhibitory neuromodulators.

EXCITATORY NEUROMODULATORS

Epinephrine - Excitatory neuromodulator

Epinephrine, also known as adrenaline, is an excitatory neurotransmitter and hormone essential for lipolysis, which is a process in which the body metabolizes fat. Epinephrine is derived from the amine norepinephrine. As a neurotransmitter, epinephrine regulates attentiveness and mental focus. Epinephrine is synthesized from norepinephrine.As a hormone, epinephrine is secreted along with norepinephrine principally by the medulla of the adrenal gland. Heightened secretion can occur in response to fear or anger and will result in increased heart rate and the hydrolysis of glycogen to glucose. This reaction, referred to as the “fight or flight” response, prepares the body for strenuous activity. Epinephrine is used medicinally as a stimulant in cardiac arrest, as a vasoconstrictor in shock, as a bronchodilator and antispasmodic in bronchial asthma, and anaphylaxis. Commonly, epinephrine levels will be low due to adrenal fatigue (a pattern in which the adrenal output is suppressed due to chronic stress). Therefore, symptoms can be presented as fatigue with low epinephrine levels. Low levels of epinephrine can also contribute to weight gain and poor concentration. Elevated levels of epinephrine can be factors contributing to restlessness, anxiety, sleep problems, or acute stress.

Norepinephrine - Excitatory neuromodulator

Norepinephrine is an excitatory neurotransmitter that is important for attention and focus. Norepinephrine is synthesized from dopamine by means of the enzyme dopamine beta-hydroxylase, with oxygen, copper, and vitamin C as co-factors. Dopamine is synthesized in the cytoplasm, but norepinephrine is synthesized in the neurotransmitter storage vesicles.; Cells that use norepinephrine for formation of epinephrine use SAMe as a methyl group donor. Levels of epinephrine in the CNS are only about 10% of the levels of norepinephrine.

The noradrenergic system is most active when an individual is awake, which is important for focused attention. Elevated norepinephrine activity seems to be a contributor to anxiousness. Also, brain norepinephrine turnover is increased in conditions of stress. Interestingly, benzodiazepines, the primary anxiolytic drugs, decrease firing of norepinephrine neurons. This may also help explain the reasoning for benzodiazepine use to induce sleep.

Norepinephrine acts as an excitatory neurotransmitter and modulates neuron voltage potentials to favor glutamate activity and neurotransmitter firing.

Dopamine - Excitatory neuromodulator

Dopamine is an excitatory and inhibitory neurotransmitter, depending on the dopaminergic receptor it binds to. It is derived from the amino acid tyrosine. Dopamine is the precursor to norepinephrine and epinephrine, which are all catecholamines. The function of dopamine is diverse but plays a large role in the pleasure/reward pathway (addiction and thrills), memory, and motor control. Dopamine, like norepinephrine and epinephrine, is stored in vesicles in the axon terminal. Dopamine plays a significant role in the cardiovascular, renal, hormonal, and central nervous systems. The dopaminergic neurons have dendrites that extend into various regions of the brain, controlling different functions through the stimulation of adrenergic and dopaminergic receptors (D1 –D5). Common symptoms with low dopamine levels are loss of motor control, addictions, cravings, compulsions, and loss of satisfaction. When dopamine levels are elevated symptoms may manifest in the form of anxiety or hyperactivity. Some therapies utilize L-DOPA for parkinsonian symptoms which can also cause elevations in dopamine.

Glutamate - Excitatory neuromodulator

Glutamate is the major excitatory neurotransmitter in the brain which is necessary for memory and learning. In fact, it is believed that 70% of the fast excitatory CNS synapses utilize glutamate as a transmitter. Excitatory neurotransmitters increase the activity of signal-receiving neurons and play a major role in controlling brain function. Glutamate exerts its effects on cells, in part, through three types of receptors that, when activated, allow the flow of positively charged ions into the cell. These include the ionotropic receptors: kianate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) receptors. There are also series metabotropic glutamate receptors that do not directly manipulate an ion channel.; Of the ionotropic receptors, the N-methyl-D-aspartate (NMDA) receptor plays a particularly important role in controlling the brain’s ability to adapt to environmental and genetic influences which is important for learning and memory.

An event or process that dramatically increases the activity of glutamate often induces the death of neurons. Such a scenario is believed to take place in e.g. ischemia, trauma, hypoxia, hypoglycemia, and hepatic encephalopathy.; More mild but chronic malfunctioning of glutamatergic systems may be involved in many neurodegenerative diseases such as Huntington´s disease, Parkinson´s disease, Alzheimer´s disease, vascular dementia, amyotrophic lateral sclerosis, AIDS-neurodegeneration, Tourette´s syndrome, and Korsakoff syndrome.It is unlikely that a disturbance of glutamate homeostasis is the sole initiator of these neurodegenerative diseases, but rather that excitotoxicity plays a pivotal executive role in events triggered by other processes such as energy deficits that facilitate the neurotoxic potential of endogenous glutamate.

PEA - Excitatory neuromodulator

Beta-phenylethylamine (PEA) is an excitatory neurotransmitter derived from the amino acid phenylalanine.Studies have found that PEA promotes energy and elevates mood. PEA also functions as a synaptic neuromodulator inhibiting the reuptake of dopamine and norepinephrine. Studies have discovered that patients with depression have decreased PEA levels while increased levels have been found in patients with psychopathic symptoms. It has also been implicated in headaches and the antidepressant effects of exercise.; One of the biochemical abnormalities resulting from phenylketonuria, the absence of the enzyme that helps to synthesize phenylalanine into tyrosine, is an increased production of PEA. This can cause an elevated level of PEA in the urine. Since PEA is lipid soluble and readily crosses the blood-brain-barrier, the administration of PEA or of its precursor, phenylalanine, has been found to improve outcome with some antidepressants. Also, supplementation to manipulate PEA can help increase focus and attention.

PEA acts as an excitatory neurotransmitter and modulates neuron voltage potentials to favorglutamate activity and neurotransmitter firing.

Histamine - Excitatory neuromodulator

Histamine is an excitatory neurotransmitter involved in the sleep/wake cycle and inflammatory response. Depending on the receptor histamine activates a wide array of biological actions can occur. For instance, one receptor helps regulate the sleep/wake cycle whereas another receptor helps regulates norepinephrine, serotonin, and acetylcholine release. There are also other receptors that may be activated to induce inflammatory response, which is commonly associated with the exposure to an allergen.

Interestingly, histamine containing neurons have been found to have a pacemaker function within the brain. The firing rates of these neurons correlate positively with brain activity levels and displays distinct day-night rhythms. Within the posterior region of the hypothalamus, there are a large number of neurons that synthesize and utilize histamine. These neurons provide the stimulation that maintains or modulates activity in many other regions of the brain.

Histamine, like the other biogenic amines (serotonin, dopamine, norepinephrine, epinephrine, and PEA) is stored in presynaptic vesicles and is released into the synapse. Also like other amine neurotransmitters, histamine binds to transmembrane G-protein coupled receptors on the post-synaptic neurons to exert its function.

INHIBITORY NEUROMODULATORS

Serotonin - Inhibitory neuromodulator

Serotonin is an inhibitory neurotransmitter synthesized by enzymes that act on tryptophan and/or 5-HTP. Serotonin is stored in presynaptic vesicles and released to transmit electrochemical signals across the synapse. Extensive research has been conducted surrounding serotonin and acts as a target for symptoms like low mood, compulsions, anxiousness, and headaches.

Serotonin acts, in most cases, as an inhibitory neurotransmitter and, like GABA, modulates neuron voltage potentials to inhibit glutamate activity and neurotransmitter firing. Serotonin neurons have large numbers of axons and are important in integrating neural circuits. This also provides an explanation for serotonin’s role in so many health concerns.

GABA - Inhibitory Neuromodulator

GABA is a true neurotransmitter and is the major inhibitory neurotransmitter of the brain, occurring in 30-40% of all synapses. GABA is second only to glutamate, the brain’s major excitatory neurotransmitter. The GABA concentration in the brain is 200-1000 times greater than that of the monoamines or acetylcholine. The primary function of GABA is to prevent overstimulation. It does so by compensating for glutamate activity.; When GABA activates its receptor it causes negative ions to flow into the cell preventing depolarization. Glutamate can depolarize the cell and form an action potential by causing positive ions to flow into the cell when it activates its receptors. Overall, GABA regulates the activity of glutamate by preventing depolarization of the cell, therefore, preventing overstimulation.

Glycine - Inhibitory neuromodulator

Glycine is a principal inhibitory amino acid in the brainstem and spinal cord that regulates excitatory neurotransmission in much the same way as GABA. Glycine, much like GABA and taurine, can become elevated to compensate for elevations in excitatory neurotransmitters, primarily, glutamate and aspartic acid. This non-essential amino acid is common in protein-based foods, and can be synthesized metabolically from a number of different amino acids, including serine and threonine.; Curiously, glycine is a necessary cofactor in the activation of the glutamate receptor, NMDA. It seems paradoxical that a primarily inhibitory amino acid facilitates the activation of an excitatory receptor. It has been postulated that glycine’s inhibitory and excitatory actions are part of the many checks and balances the body has for regulating neurotransmission.

Taurine - Inhibitory neuromodulator

Taurine is an inhibitory neurotransmitter involved in neuromodulatory and neuroprotective actions. Supplementing with taurine can have a specific effect on GABA function.There are two primary ways in which taurine affects GABA.; First, it can inhibit GABA transaminase, an enzyme that metabolizes GABA. This allows GABA to stay in the synaptic cleft longer to bind to the postsynaptic receptor. Second, taurine can bind to the GABAAreceptor mimicking the effects of GABA. By helping GABA function, taurine is an important neuromodulator for prevention of excitoxicity. Excitability occurs when glutamate binds to its receptor, in this case, the NMDA receptor. Once glutamate activates the NMDA receptor there is an increase in intracellular Ca++ causing depolarization or cell excitability. With glutamate release, there is also simultaneous GABA and taurine release. When the inhibitory neurotransmitters, GABA and taurine, activate the GABAA receptor, the result is an increase in intracellular Cl- ions. This results in hyperpolarization which reduces cell excitability. Thus, the overall effect of taurine supplementation is to support GABA function. The relevance of GABA support is to prevent overstimulation due to high levels of excitatory amino acids. Therefore, taurine and GABA constitute an important protective mechanism against excessive excitatory amino acids. Similarly, taurine is increased in response to the exposure of free radicals elucidating its neuroprotective actions. Exposure to free radicals increases glutamate excretion, further potentiation NMDA receptor activation. Taurine modulates this effect to prevent cell excitability by keeping the cell hyperpolarized. The supplementation of taurine can help alleviate some excitability issues associated with elevated excitatory amino acids as well as play a role in regulating the effect of free radicals.

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Glutamine - GABA/Glutamate Precursor

Glutamine is an amino acid which acts as a precursor to glutamate. Glutamine aids in the maintenance of gut barrier function, intestinal cell proliferation and differentiation. Glutamine supplementation is commonly utilized to help repair the mucosal lining of the gut which can help with food sensitivities and other stomach/ intestinal issues. High levels may be a sign of inhibitory/excitatory imbalances in the neurotransmitter system.