Labrix Clinical Services, Inc.

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1 Labrix Clinical Services, Inc. The Labrix Neurotransmitter Advantage Clinical Utility: Neurotransmitter imbalances are associated with many of the most prevalent symptoms and conditions seen by healthcare providers today. Testing provides a tool to better understand each patient s specific imbalances, which are treatable with a combination of nutraceutical, diet, and lifestyle interventions. Assay Technology: Labrix is known for setting higher standards for accuracy, consistency, and reproducibility. We ve incorporated the latest HPLC Mass Spec technology for neurotransmitter testing, a level of gold standard assay not previously available for urinary neurotransmitters. Labrix HPLC Triple Quadrupole MS/MS is more sensitive than ELISA or HPLC Immuno Fluorescence used by other labs. The advantage of Labrix assay is higher sensitivity, which contributes to higher accuracy, which means higher confidence in the reported results. Sample Stability: Labrix requires sample to reach the lab within 7 days of collection. The sample is frozen if not shipped same day to retard bacteria growth, and prepaid 3-day shipping is provided. Some labs allow up to 14 days for the sample to reach the lab, saying the sample stability is fine for up to 30 days - risking sample degradation. The advantage of this strict criteria on sample collection and shipping reduces the opportunity for error and less accurate results. Turn-Around-Time: We know that time is of the essence for addressing your patient s needs. We have guaranteed fast TAT with hormone testing and we re now providing the fastest TAT available on neurotransmitter testing. Patient samples ship to Labrix in just 3 days. Lab TAT on neurotransmitter results is guaranteed 5 days or less, which is 2 to 10 days faster than other sources. The Neuroendocrine Connection: Adrenal hormones, sex hormones, and neurotransmitters are functionally interrelated. Changes in sex hormones and adrenal hormones can lead to neurotransmitter imbalances. In turn, neurotransmitter imbalances can affect hormone function. Labrix offers neurotransmitter/hormone combination panels that can provide a more comprehensive view of the body s functional neuroendocrine status, and can bring to light additional factors contributing to symptoms. Practitioner Only Service: Labrix offers testing for practitioners only. Labrix will not discuss test results directly with patients. Patients are referred back to the practitioner for consultation and follow-up. Education and Service: Provider education and patient outreach resources are available to help educate your patients about the importance of testing and balancing their neuroendocrine system. labrix.com P: F:

2 Which Panels Should I Use For My Patients? NT H Neurotransmitter and Hormone Combination Panels Determining what panels to test is the first step in understanding your patient s neuroendocrine requirements. Adrenal hormones, sex hormones, and neurotransmitters are functionally interrelated. Changes in sex hormones and adrenal hormones can lead to neurotransmitter imbalances. In turn, neurotransmitter imbalances can affect hormone function. Including neurotransmitters with hormone panels provides a more comprehensive view of the body s functional neuroendocrine status, this interrelationship, and the associated factors that may be contributing to symptoms. swings, fatigue, and pain. Because the research on the estrogen quotient and the protective properties of estriol has not been done with men, this panel is currently recommended for women only. This panel should be considered for patients who have: Increased risk of developing breast cancer History of breast cancer or other hormonally sensitive cancers Personal or strong family history of autoimmune disease PCOS Estrogen dominance related symptoms NeuroHormone Complete Panel: 6 Neurotransmitters*, E2, Pg, T, DHEA, 4 Cortisols This panel is the best starting point for initial assessment of hormonal status, adrenal function and neurotransmitter balance. This panel is important for both men and women, providing baseline and monitoring information for patients of all ages. It is especially useful in individuals who are experiencing any of the following symptoms: Mood disorders, depression, anxiety Addiction, dependency Fatigue, lack of stamina, insomnia Chronic illness, immune deficiency Cognitive confusion, learning challenges, declining memory Weight issues, appetite control Low libido, sexual dysfunction PMS, menopause, andropause Fibromyalgia, chronic pain NeuroHormone Complete Plus Panel: 6 Neurotransmitters*, E1, E2, E3, Pg, T, DHEA, 4 Cortisols The NeuroHormone Complete Plus panel includes estrone (E1) and estriol (E3) plus the estrogen quotient. The addition of neurotransmitters to the Comprehensive Plus hormoneonly panel provides insight on how HPA axis function may be contributing to symptom manifestation such as mood NeuroAdrenal Panel: 6 Neurotransmitters*, DHEA, 4 Cortisols This panel provides a comprehensive view of HPA axis function. Included is a full diurnal cortisol pattern, DHEA, and 6 primary neurotransmitters (inhibitory and excitatory). Symptoms that would indicate ordering this panel include those shown for the Adrenal Function panel plus: Mood disorders, depression, anxiety Addiction, dependency Chronic illness, immune deficiency Low libido, sexual dysfunction NeuroBasic Panel: Serotonin, GABA, Dopamine, Epi, Norepi, Glutamate The NeuroBasic panel is a good tool for monitoring therapeutic interventions of neurotransmitter imbalances previously tested, or when symptoms indicate an imbalance. Includes inhibitory and excitatory neurotransmitters. *Neurotransmitters tested: Serotonin, GABA, Dopamine, Epinephrine, Norepinephrine, Glutamate Health Disclaimer: All information given about health conditions, treatments, products and dosages are not intended to be a substitute for professional medical advice, diagnosis or treatment. This is provided only as a suggested guideline. LBX labrix.com I P: I F:

3 NT Neurotransmitters Fact Sheet Neurotransmitters are powerful chemicals that regulate numerous physical and emotional processes such as mental performance, emotional state, physical energy, and pain response. Functioning primarily in the Central Nervous System (CNS), neurotransmitters are the brain s chemical messengers, facilitating communication among the body s glands, organs, and muscles. Numerous clinical studies have shown that inadequate neurotransmitter function has a profound influence on overall health and well-being. In fact, imbalances in certain neurotransmitters are associated with most of the prevalent symptoms and conditions seen in doctors offices today. Mood Disorders; depression, anxiety Adrenal Dysfunction; fatigue, insomnia Loss of Mental Focus; ADD, ADHD, cognitive fog Addiction and Dependency Hormonal Imbalances; E2 dominance, E2 deficiency, low androgens Loss of Appetite Control; insulin resistance Compounding these symptoms of imbalance are the myriad of bioactive substances like caffeine, alcohol and nicotine and many of the medications used to manage these conditions as well as some cholesterol lowering medications. These substances and medications can contribute to neurotransmitter depletion and resulting symptoms by suppressing or artificially stimulating NT receptor function. When functioning properly the neurotransmission system has natural checks and balances in the form of excitatory and inhibitory neurotransmitters. These are classified according to their effects on postsynaptic membranes (Receptor sites). Excitatory neurotransmitters cause depolarization of the membrane and promote an action potential. Inhibitory neurotransmitters cause hyperpolarization and depresses or inhibit an action potential. This Fact Sheet provides an overview of six important neurotransmitters and their respective roles in various symptomatic conditions. SEROTONIN is an inhibitory neurotransmitter considered to be the master neurotransmitter. Adequate amounts of serotonin are necessary to balance any excessive excitatory (stimulating) neurotransmitter firing in the hypothalamus. Serotonin imbalance is one of the most common contributors to mood problems, which is considered by some as a virtual epidemic in the United States. It also regulates many processes such as carbohydrate cravings, sleep cycle, pain tolerance and appropriate digestion, and can be associated with decreased immune system function. High stress, insufficient nutrients, fluctuating hormones, and the use of stimulant medications or caffeine all contribute to the depletion of serotonin over time. When serotonin is out of range then depression, anxiety, worry, obsessive thoughts and behaviors, carbohydrate cravings, PMS, difficulty with pain control, and sleep cycle disturbances can result. Serotonin is key to feelings of happiness and very important for emotions because it helps protect against both anxiety and depression. GABA is an inhibitory neurotransmitter that is often referred to as nature s valium-like substance. GABA is a significant mood modulator, essential for regulating norepinephrine, epinephrine, dopamine, and serotonin. High levels of GABA may indicate excitatory overload, due to the increased demand for GABA to balance the surplus excitatory neurotransmitter activity. These high levels may result in a calming action that contributes to sluggish energy, feelings of sedation, and foggy thinking. Low GABA levels are associated with adrenal distress and Hypothalamus-Pituitary-Adrenal Axis (HPA Axis) feedback dysfunction. Without the inhibiting function of GABA, impulsive behaviors are not controlled, contributing to a range of anxious and/or reactive symptoms that extend from poor impulse control to seizure disorders. DOPAMINE is our main focus neurotransmitter, largely responsible for regulating the pleasure/reward pathway, memory and motor control. Its function creates both inhibitory and excitatory action depending on the dopaminergic receptor it binds to. When dopamine is either elevated or low, memory issues frequently occur: forgetting where items are, forgetting what a paragraph said immediately after reading, or simply daydreaming and not being able to stay on task. Stimulants such as medications for ADD/ADHD and caffeine will cause dopamine to be pushed into the synapse so that focus is improved. Unfortunately, stimulating dopamine Health Disclaimer: All information given about health conditions, treatments, products and dosages are not intended to be a substitute for professional medical advice, diagnosis or treatment. This is provided only as a suggested guideline. LBX labrix.com I P: I F:

4 continually can inhibit natural transmission, reducing demand and contributing to depletion of dopamine over time. Common symptoms with low dopamine levels include loss of motor control, addictive behavior, cravings, compulsions, and loss of satisfaction. These feelings lead to drug use, drinking alcohol, smoking cigarettes, gambling, and overeating. These actions are a result of an unconscious attempt to self medicate, looking for the satisfaction that is not occurring naturally in the body. When dopamine levels are elevated, symptoms may manifest in the form of anxiety or hyperactivity. High dopamine has been observed in patients with poor GI function, autism, mood swings, psychosis and children with attention disorders. L-DOPA is a precursor to dopamine, and may also cause elevations in dopamine. Some therapies utilize L-DOPA for parkinsonian symptoms. NOREPINEPHRINE (Nor-Adrenaline) is an excitatory neurotransmitter responsible for stimulatory processes for attention and focus. It is produced by the adrenal medulla or synthesized from dopamine. Norepinephrine plays a critical role in survival. First, it relays messages in the sympathetic nervous system as part of the autonomic nervous system s fight-or-flight response. Second, norepinephrine prepares the brain to encounter and respond to stimuli from the environment thereby facilitating vigilance. In both roles, norepinephrine mediates arousal. High levels of norepinephrine are linked to anxiety, stress, high blood pressure, and hyperactivity. Low levels are linked to lack of energy, focus, and motivation. EPINEPHRINE (Adrenaline) is synthesized from norepinephrine, and is an excitatory neurotransmitter that helps regulate metabolism, heart rate, and blood pressure. Epinephrine is involved in managing the body s metabolic fight or flight response, rapidly preparing the body for action, boosting the supply of oxygen and glucose to the brain and muscles, while suppressing other non-emergency bodily processes (digestion in particular). This stress preparation increases heart rate and stroke volume, dilates the pupils, and constricts arterioles in the skin and gastrointestinal tract while dilating arterioles in skeletal muscles. It also increases catabolism of glycogen to glucose in the liver, thereby elevating the blood sugar level. Elevated levels of epinephrine are associated with hyperactivity, ADHD, anxiety, sleep issues, and low adrenal function. Low levels are associated with decreased energy, fatigue, depression, insufficient cortisol production, chronic stress, burnout, poor recovery from illness, dizziness, and persistent adrenal stimulation. Long-term over-stimulation of the adrenal glands can cause epinephrine stores to be depleted, resulting in chronic low energy and weight gain. Norepinephrine:Epinephrine Ratio The Norepi:Epi ratio is an indicator of adrenaline conversion (Epinephrine is synthesized from norepinephrine). Low cortisol can inhibit this conversion process, leading to an elevated ratio. Anxiety, burnout, and poor blood sugar control are associated with an elevated Norepi:Epi ratio. GLUTAMATE is an excitatory neurotransmitter considered to be the major mediator of excitatory signals in the central nervous system, and is involved in most aspects of normal brain function including cognition, memory and learning. In fact, it is believed that 70% of the fast excitatory CNS synapses utilize glutamate as a transmitter. Consistently high levels of glutamate can be an indicator of excitotoxicity. Elevated glutamate levels are more commonly associated with panic attacks, anxiety, excess adrenal function, impulsivity, OCD and depression. Low glutamate levels have been associated with agitation, memory loss, sleeplessness, low energy level, insufficient adrenal function, and depression. The NeuroEndocrine Connection...DEPRESSION...INSOMNIA...ADDICTIONS...PREMENSTRUAL SYNDROME...ANXIETY...FATIGUE...SEXUAL DYSFUNCTION... HYPOTHALAMUS PITUITARY THYROID ADRENAL GONADAL Putting It All Together Identifying and managing neurotransmitter imbalances is facilitated with a noninvasive urinary test. Testing provides a tool to understand each patient s specific neuroendocrine imbalances, which can be corrected with nutraceutical, BHRT, diet, and lifestyle interventions. This Neurotransmitter Fact Sheet identifies numerous symptoms and conditions associated with neurotransmitter imbalances. It is especially important to understand that there are agonistic/antagonistic interrelationships of the neurotransmitters with adrenal hormones and sex hormones. Changes in sex hormones and adrenal hormones can lead to neurotransmitter imbalances. And at the same time, neurotransmitter imbalances will affect hormone production and function. Testing both neurotransmitters and hormones provides a comprehensive view of the body s functional neuroendocrine status, and brings to light additional factors that may be contributing to symptoms. For additional reference please see the condition based Fact Sheets and other educational support available from Labrix Clinical Services. HPT AXIS HPA AXIS HPG AXIS

5 Test Results: Neurotransmitter Report Report Number: -S0015 Provider: Sample Reports SE 130th Ave Clackamas, OR Patient Info: Anna Sample Age:30 Gender: F Menopausal Status: Pre-Menopause 9876 SW Balanced St Billings, MO Sample Collection Date/Time Urine 02/26/ Wake Up Time 0700 Samples Arrived 02/29/2012 Results Reported 12/14/2015 Neurotransmitter Test Result Units L WR H Reference Range Serotonin µg/gcr GABA 2.98 µmol/gcr Dopamine µg/gcr Norepinephrine µg/gcr Epinephrine 2.35 µg/gcr Glutamate µmol/gcr N/E Ratio <14.06 Creatinine mg/dl Specific Gravity Neurotransmitter Interpretations: The reported cognitive and mood concerns, stress, diminished drive, fatigue and sleep difficulties, cravings and pain issues are consistent with the reported neurotransmitter imbalance(s). Low serotonin may contribute to anxiety/depression and a sense of discontentment. Diminished serotonin may also be implicated in poor sleep quality and subsequent fatigue upon awakening as well as muscle and body aches and over-all lassitude. Tryptophan, L-theanine, and 5 HTP influence this pathway. Low range GABA may be associated with anxiety, worry, poor impulse control and/or decreased sleep quality. L-theanine, GABA, and glutamine influence this pathway, while phenibut exerts GABA like effects. Low epinephrine may be associated with depression and mood changes as well as fatigue, difficulty concentrating, decreased ability to stay focused on tasks and diminished sense of personal/professional drive. L-tyrosine, L-theanine, and Mucuna pruriens influence this pathway. Low glutamate may be associated with increased addictive tendencies including food seeking behaviors and can contribute to mental fatigue and diminished mental stimulation. L-glutamine is a precursor in this pathway. The elevated N/E (norepinephrine/epinephrine) ratio is indicative of poor conversion of norepinephrine to epinephrine. Low cortisol levels may be contributing to the symptom picture (cortisol stimulates the enzyme phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine). Therapeutic considerations include SAMe and magnesium supplementation. Diurnal cortisol levels may be warranted. Therapeutic considerations include: 5-HTP and/or L-tryptophan; GABA, L-glutamine, and/or phenibut; L-tyrosine, and/or Mucuna pruriens; conversion support. Additional considerations are nervine and adaptogenic herbs, supportive nutrients, vitamin D, methylation support, and L-theanine. Notes: *Creatinine has no diagnostic value and is measured solely for calculation of neurotransmitter levels. *Neurotransmitter test results are for investigational use only. Jay H. Mead MD FASCP Labrix Clinical Services, Inc Medical Director Testing Performed At Labrix Clinical Services, Inc SE 130th Avenue Clackamas, OR 97015

Your First Neurotransmitter Reports. Ruth Hobson, ND Staff Physician Labrix

Your First Neurotransmitter Reports Ruth Hobson, ND Staff Physician Labrix Sample NT Test Report Adult Reference Ranges Female 17+ Analyte Range Lower range Upper range Serotonin 52-155 72.6 134.4 GABA