Neurotransmitter Assessment and Treatment Dr. Daniel Kalish
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INTRODUCTION 24 years of patient experience, with over thousands of patients world wide Trained over 1,000 practitioners in The Kalish Method of functional medicine 2 years monastic training in Japan and Thailand
WHY MENTORING & TEACHING Was trained by naturopaths, DC s and MD s and have integrated this information for ease of use by today s clinicians Working to pass on my clinical training to the next generation of functional medicine doctors
LEARNING OBJECTIVES Understanding neurotransmitters and neurotransmission How production of neurotransmitters can be determined with Organic Acids testing How to detect if inflammatory conditions are creating neurotransmitter related conditions Treatment options for correcting neurotransmitter imbalances
CORRECT BODY SYSTEMS IN ORDER THAT PROBLEMS OCCUR Neuroendocrine System Amino acid replacement NT support Healing diet Exercise Sleep Meditation Detox GI System Treat leaky gut Probiotics Enzymes Support liver cells Further improve detox
HEALING THE BRAIN Neuroendocrine System Dysfunction Three Types of Brain Issues Deficiency Neuron Damage Genetics Decreased immune response GI System: GI pathogen acquired, food intolerances, leaky gut TOXINS Detoxification System
SYNTHESIS & STORAGE OF NEUROTRANSMITTERS
INACTIVATION OF NEUROTRANSMITTERS
ORGANIC ACIDS TEST Evaluates neurotransmitters relating to: energy levels, response to stress, mood, sleep patterns and weight regulation Just like we determine the efficiency of a car s engine by measuring the exhaust, we measure the function of these neurotransmitters by measuring their metabolites, or breakdown products, in urine Baseline testing of actual neurotransmitters in urine reflects kidney production and is not directly related to brain production
ORGANIC ACIDS TEST The Stress Neurotransmitters: Norepinephrine, Epinephrine, and Dopamine When we encounter a stressor, our body produces norepinephrine and epinephrine that stimulate our fight or flight or stress response. The by-product in urine is vanilmandelate (VMA). Dopamine is also involved in the stress response as well as in memory, movement and mood, and its by-product is homovanillate (HVA).
PRODUCTION RELATED MARKERS
NEUROTRANSMITTER METABOLISM MARKERS: VANILMANDELATE Low Vanilmandelate: VMA is a breakdown product of both epinephrine and nor epinephrine. Low levels may indicate that these products are no longer being made. Can be caused by: Sluggish MAO/COMT fx from polymorphisms Stress Low protein consumption Poor protein absorption Symptoms: fatigue, anxiety, sleep disturbances and depression
NEUROTRANSMITTER METABOLISM MARKERS: VANILMANDELATE High Vanilmandelate: VMA is a breakdown product of both epinephrine and norepinephrine. High levels indicate a high turnover and over activation of the nervous system. Phenylalanine and tyrosine are the precursors. Can be caused by: Internal stressors External stressors Symptoms: headaches, anxiety, sleep disturbances, muscle aches, GI disturbances, high blood pressure
NEUROTRANSMITTER AND METABOLISM MARKERS
NEUROTRANSMITTER METABOLISM MARKERS: HOMOVANILLATE Low Homovanillate: is a breakdown product of dopamine, our excitatory neurotransmitter, amino acid precursors are phenylalanine and tyrosine Can be caused by: Sluggish MAO/COMT function due to Polymorphisms or simply decreased fx Long term antidepressant usage Amino acid deficiency Adrenal/HPA axis issues Poor absorption / missing co-factors Symptoms: profound fatigue or physical exhaustion, difficulty concentrating, compulsive behaviors, loss of satisfaction, addictions, cravings, need for sensation seeking behaviors, food compulsions and has also been linked to Restless Leg Syndrome and ADHD
NEUROTRANSMITTER METABOLISM MARKERS: HOMOVANILLATE High Homovanillate: The breakdown of dopamine Can be caused by: internal stressors external stressors
NEUROTRANSMITTER AND METABOLISM MARKERS
NEUROTRANSMITTER METABOLISM MARKERS: HYDROXYINDOLEACETATE High 5-Hydroxyindoleacetate: is a breakdown product of serotonin a calming neurotransmitter, controls mood, behavior, appetite, sleep and bowel contractions. If 5-HIA is high it indicates higher than normal turnover of serotonin with potential depletion of tryptophan. Can be caused by: SSRI usage Stress Sluggish MAO function
NEUROTRANSMITTER METABOLISM MARKERS: HYDROXYINDOLEACETATE Low Hydroxyindoleacetate: is a breakdown product of serotonin. Low levels may indicate inadequate production of serotonin. Can be caused by: Adrenal exhaustion Antidepressant usage Amino acid deficiency Poor absorption and/or missing cofactors Symptoms: depression, anxiety, panic attacks, insomnia, digestive imbalances, constipation and chronic pain
NEUROTRANSMITTER METABOLISM MARKERS
INFLAMMATION RELATED MARKERS
NEUROTRANSMITTER METABOLISM MARKERS: KYNURENATE High Kynurenate- abnormal levels can have direct effect on brain function in addition for showing a need for vitamin B6 Can be caused by: Inflammatory diseases Pathogen defense B6 deficiency
NEUROTRANSMITTER METABOLISM MARKERS: QUINOLINATE High Quinolinate: When levels are high it can make you feel flulike due to its neurotoxic effects, achey, tired Can be caused by: Inflammatory process induced by immune system Increased oxidative stress Viral, parasitic, fungal or bacterial infection Gastrointestinal fungal or bacterial overgrowth Autoimmune disorders IBS Symptoms: Insomnia, irritability and nervousness
NEUROTRANSMITTER METABOLISM MARKERS: PICOLINATE High Picolinate: Can be caused by: Chronic inflammation High protein intake Low Picolinate: Can be caused by: Excessively high fish oil intake
SECOND TIER OF OAT- MICRONUTRIENTS Organic acids test shows micronutrient depletion and can reveal micronutrient deficiencies: Depleting B6/B12/Folate leading to methylation problems Depleting sulfur amino acids leading to liver detox phase 2 as well as catecholamine imbalances Depleting antioxidants leading to oxidative stress being placed on DNA, energy production Depleting of good bacteria and imbalance of flora in GI tract Depleting of carnitine, CoQ10, free form amino acids, B vitamins and other Krebs cycle intermediaries
NEUROTRANSMITTER METABOLISM/ PRODUCTION AND SULFUR
TYROSINE Tyrosine is a non-essential amino acid synthesized in the body from the essential amino acid phenylalanine. Tyrosine is the precursor amino acid from which the body makes dopamine, which is converted to norepinephrine and then epinephrine. Tyrosine Supports: Fat loss Supports brain dopamine production Supports dopamine production by the adrenal gland Improves stamina for exercise Precursor to thyroid hormones Precursor to melanin
L-DOPA Increases the body s natural production of dopamine L-Dopa Supports: Neurological conditions affecting movement/ balance Behavioral disorders Sleep disorders Mood disorders Cognition issues Lack of motivation Low prolactin production
5-HYDROXYTRYPTOPHAN (5-HTP) Made from the amino acid L-tryptophan with the help of vitamin B6, is a precursor to serotonin production. 5-HTP Supports: Excessive appetite Binge eating Carbohydrate cravings Obesity Headaches Migraines Insomnia Depression Bipolar disorder
VITAMIN B6 Water soluble vitamin found in meat, vegetables and grain products Vitamin B6 Supports: Normal energy-yielding metabolism The production of neurotransmitters Support the production of red blood cells and immune cells Regulation of hormonal activity Healthy nervous system
B6 VITAMIN MARKER: XANTHURENATE High Xanthurenate- may indicate tryptophan catabolism and is a functional marker for B6 deficiency. Product of tryptophan catabolism. Can be caused by many things including: Excessively high protein diet or tryptophan supplementation B6 deficiency Oral contraceptives Antihypertensives Bronchodilators Smoking Commonly seen in individuals who have villous atrophy and/or gut damage. B6 is also a major co-factor in serotonin production. Symptoms may include: high homocysteine, balance issues, fatigue, anemia, skin disorders, PMS, ADHD, anemia and peripheral neuropathy Intervention: Improve digestion and absorption, supplement with B6 and/or B complex
VITAMIN C Vitamin C is water soluble and found abundantly in vegetables Unlike most animals, our body is unable to make its own vitamin C Vitamin C refers to both ascorbic acid and dehydroascorbic acid (DHA) A powerful antioxidant, supplying electrons to free radicals Vitamin C Supports: Healthy formation of collagen and elastin Activates white blood cells Supports metabolism of fats, folic acid and histamine Regulates cholesterol levels
CALCIUM Calcium is found in the human body as deposits in bone and teeth High sources of calcium can be found in milk, leafy green vegetables and fish like salmon Calcium Supports: Healthy bone development Dental health Protects cardiac muscle Ensures healthy ph levels Helps control blood pressure Reduces risk of kidney stones
FOLATE vs. FOLIC ACID Folate and folic acid are NOT interchangeable Folic acid is the synthetic form of folate Only found in supplements Not found in food supply Hard to convert folic acid to folate, so it s easy to get unmetabolized folic acid -> folate deficiency
FOLATE METHYLATION CO-FACTORS MARKER: FIGLU High Formiminoglutamate: Functional marker of folate insufficiency. High marker usually appears after 90 days of insufficient folate availability. Deficiency can lead to precursor for many diseases especially coronary heart disease and cancer. Responsible for repair of DNA and making of red blood cells. Can be caused by many things including: Insufficient dietary intake of leafy greens high in folate Insufficient absorption caused by celiac disease or gut damage Alcoholism Medication interaction Symptoms may include: severe hair loss, fatigue, insomnia, anemia, swollen or sore tongue, mouth ulcers, nerve damage (peripheral neuropathy), headaches, heart palpitations, cognitive issues such as, forgetfulness, brain fog or other cognitive decline, depression and behavioral disorders
FOLATE METHYLATION CO-FACTORS MARKER: FIGLU FIGLU is converted into glutamate by folate. Hi FIGLU in the urine indicates a functional need for more folate. There is a blood test for folate, but at times it comes back normal despite a functional need for more folate. In these cases the FIGLU marker serves as a functional assessment where the blood folate test does not. Intervention: Folate
SUMMARY KEY CONCEPTS: The organic acids test measures the function of neurotransmitters by measuring their metabolites or breakdown products in urine Neurotransmitter markers can be split into 2 groups: production related markers and inflammation related markers The organic acids test shows micronutrient depletion and can reveal micronutrient deficiencies
CASE STUDY History: 45 year old female, Mother to two autistic children, full time care giver, moved to new state, lost most of support network Chief complaints: depression and insomnia Triggers: Father died recently in battle with siblings over estate issues. Very high stress and stress to continue. Physical exam: normal Treatment: 5-HTP, tyrosine, mucuna, methionine, B complex, gluten free, blood sugar control diet, parasite protocol and mitochondrial energy support with magnesium, CoQ10, carnitine and co-factors Resolution: first month of treatment significant improvement in mood and energy levels, able to be more present for children, by month 6 able to stop supplements and maintain benefits of 80% improvement on fatigue, energy and mood
FOLLOW UP TEST AFTER 6 MONTHS TREATMENT
CASE STUDY History: 39 year old male, computer programmer Silicon Valley, poor diet, skips meals, protein powders for lunch, long commute works long hours, long history low grade GI complaints, heartburn, bloating Chief complaints: chronic fatigue, memory issues, emotionally worn down Triggers: Stress, work meeting melt downs Physical exam: normal, conventional medical labs normal Treatment: 5-HTP, tyrosine, NAC, B complex, increased whole foods diet, H. pylori protocol and meditation exercises and increase in physical activity of walking 30 minutes daily Resolution: Significant benefits accrued from lifestyle changes and starting to eat regular food for meals, elimination of H. pylori and treating GI tract also contributed to improvements in fatigue. Lights on again experience with use of high dose amino acids, 5-HTP 600 mg daily in divided dosages with tyrosine at 4,000 mg daily
FOLLOW UP TEST AFTER 6 MONTHS TREATMENT
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