CORRECTING DETOXIFICATION PATHWAYS IN THE BRAIN ORGANIC ACIDS Dr. Daniel Kalish, DC INTRODUCTION • 24 years of patient experience, with thousands of patients world wide • Trained over 1,000 practitioners in The Kalish Method of Functional Medicine • Principle investigator in a research study conducted with Integrative Medicine Dept., Mayo Clinic on The Kalish Method ORGANIC ACIDS TEST • Organic acid testing is a way to measure whether your body is getting and using nutrients to drive optimal health • It is designed to assess metabolic dysfunction, not diseases • Like a car’s gauges warn of potential problems, your body has certain chemical indicators, known as organic acids, that can alert you to potential problems • Always start with macronutrients, micronutrient deficiencies are a second tier issue Webinar in partnership with CORRECTING DETOXIFICATION PATHWAYS Ever increasing toxin exposure has become the plague of our time. Chemicals and heavy metals are disrupting the endocrine system and can also act as neurotoxins, damaging the brain. From neurological conditions and fatigue to weight loss resistance and depression, we are seeing the direct impact of toxic exposure to our patients every day. The Organic Acids test is one basic tool to incorporate in our assessment of oxidative stress, methylation and detoxification capacity. What we will cover today: • The connection between toxins, oxidative stress and Phase 1 or Phase 2 detox pathway problems • How to use Organic Acids testing as part of your basic patient work up • How the testing can guide you to detox programs for maximum clinical impact Webinar in partnership with OUR TOXIC WORLD • Nearly 80,000 new synthetic chemicals have been released into the environment • Over 350 different pesticides are used on the food we eat • Roughly 300 known harmful substances can be found in most blood samples these days • Newborn babies typically contain 50-70 dangerous toxins at birth • The average home contains 3 - 10 gallons of hazardous materials • In the U.S. alone, over 4 billion pounds of pesticides are used every year • There are at least 5,000 chemical ingredients in cosmetics • Prescription medications are now showing up in our water supply Webinar in partnership with CATEGORIES OF TOXINS ENVIRONMENTAL TOXINS PESTICIDES BIOTOXINS HERBICIDES INDUSTRIAL CHEMICALS HEAVY METALS GMO FOODS SOLVENTS BODY BURDEN The accumulation of toxic chemicals in the body, both naturally occurring and man-made Chemicals can be inhaled, swallowed, or absorbed through the skin When investigating body burden, you can include the total amount of chemicals, or the burden of a single chemical May be represented by breakdown products of chemicals that are stored within the body’s compartments and tissues U.S. Environmental Protection Agency paper from 1987 estimated that everyone alive carries within their body at least 700 contaminants, most of which have not been studied at all Webinar in partnership with BODY TOXICITY • Many toxins that we confront are lipophilic toxins, and they are made by their manufacturers specifically to be lipophilic • Lipophilic toxins love fatty tissue and will seek the fatty tissue in the body to attach themselves to • Largest collection of fatty tissue in the body is the brain - after that, all other fat stores are known repositories for lipophilic substances Webinar in partnership with INCREASE IN DIABETES AUTISM • The Centers for Disease Control and Prevention (CDC) estimates that about 1 in 88 children has been identified with an autism spectrum disorder (ASD) • This data comes from the Autism and Developmental Disabilities Monitoring (ADDM) Network, which estimated the number of 8-year-old children with ASDs living in 14 communities throughout the United States in 2008 • This new estimate marks a 23% increase since their last report in 2009, and a 78% increase since their first report in 2007 Webinar in partnership with DEPRESSION Courtesy of the National Institute of Mental Health DEPRESSION The Kynurenin Pathway Tryptophan, in addition to making serotonin, is the parent compound in the Kynurenin Pathway (see figure below). This pathway is very active in the liver and is the way that our bodies make niacin, a B- vitamin. NEUROTRANSMITTER METABOLISM NEURON DAMAGE CONDITIONS • Weight gain, fatigue, depression, eating disorders, binge eating and food cravings • Anxiety, panic attacks • Insomnia • Body pain, fibromyalgia, restless leg syndrome • Migraine headaches, ADD, ADHD • Parkinson’s • Drug dependency, drug depletion • Traumatic brain injury (TBI) Webinar in partnership with SEROTONIN PATHWAY • Tryptophan -> 5HTP ->serotonin • B3 is a cofactor of 5HTP synthesis • B6 is the most critical cofactor of serotonin synthesis. • Vitamin C is also a cofactor Webinar in partnership with DOPAMINE/CATECHOLAMINE SYNTHESIS PATHWAY Phenylalanine Tyrosine L-dopa Dopamine Norepinephrine Epinephrine LIVER DETOX PATHWAYS Phase One: B vitamins, glutathione, 1 antioxidants, vitamin C, vitamin E Phase Two: glycine, taurine, 2 glutamine, cysteine Webinar in partnership with OXIDATIVE STRESS • Free radicals cause severe damage to the normal cells of the body, which can manifest into diseases such as heart disease and cancer • DNA damage is induced by oxidative stress • Inflammation and free radical activity go hand in hand • Excessive oxidative stress can cause liver damage • Oxidation markers don’t tell you where the oxidation is coming from, but more how is the person handling the oxidative stress Webinar in partnership with HOW DO WE MEASURE LIVER DETOX FUNCTION? Organic acids detox markers : Arginine NAC Methionine Glycine Mg Antioxidants Deficiencies or elevations in these markers indicates abnormalities in Phase 1 & Phase 2 detoxification DETOXIFICATION MARKERS Webinar in partnership with DETOXIFICATION MARKERS: 2-METHYHIPPURATE High 2- Methyhippurate - specific detoxification byproduct from xylene environmental exposure. Xylene is a byproduct of petroleum and coal tar. Xylene is also used as a solvent in manufacturing chemicals, agricultural sprays, adhesives, coatings and gasoline. Can be caused by: • Paint • Airplane exhaust • Fuel and exhaust fumes • Paint thinners • Cleaning solvents • New carpet/new cars DETOXIFICATION MARKERS: OROTATE High Orotate: is a sensitive marker of your liver’s capacity to convert toxic ammonia to non-toxic urea that you can excrete. Can be caused by: • Intestinal dysbiosis • High protein diet • Arginine deficiency Symptoms: Impaired brain function, difficulty thinking, fatigue, headaches, increased food sensitivities DETOXIFICATION MARKERS: GLUCARATE High Glucarate: is an indicator of overall liver detoxification function. Indicates that your liver is working hard to remove these toxins. Can serve as a biomarker for exposure to a wide array of potentially toxic chemicals including: Can be caused by: • Pesticides • Herbicides • Fungicides • Petrochemicals Symptoms: Chronic fatigue, headaches, mood disorders and muscle pains Webinar in partnership with DETOXIFICATION MARKERS: ALPHA-HYDROXYBUTYRATE High alpha- Hydroxybutyrate (AHB): marker for glutathione synthesis. Glutathione is the most important antioxidant our body produces - it is 5000 more powerful than anything we can consume. It’s used up by removal of toxic chemicals and prevention of free radicals. Can be caused by: • Toxic exposure • Oxidative stress DETOXIFICATION MARKERS: PYROGLUTAMATE High Pyroglutamate: reflects glutathione wasting. Glutathione is an important antioxidant that helps protect against free radicals. Glutathione is constantly used up in the removal of toxic molecules and prevention of oxidative damage. DETOXIFICATION MARKERS: SULFATE High Sulfate: an indication that total body glutathione may be low due to chronic demand. Can be caused by: • Excessive high sulfate intake • Toxin exposure • High glutathione demand Webinar in partnership with IMPORTANCE OF METHYLATION • Repairs DNA, keeps inflammation in check, replenishes the compounds needed for detoxification, and helps maintain a stable mood • Methylation is important in helping to maintain the integrity of myelin, which acts as a protective coating for nerves • Methylation aids in removing toxins from the body Webinar in partnership with METHYLATION ISSUES ANXIETY FATIGUE DEPRESSION OBESITY INFERTILITY INSOMNIA OXIDATIVE STRESS OXIDATIVE STRESS DOSAGES • Safe dosages of 5HTP = 300mg/day; tyrosine = 3,000 mg for relief of drug induced depletion and control of appetite and other easy to treat symptoms • Ten to one ratio best starting point, 1000 mg tyrosine with 100 mg 5HTP 3x day • You can increase to 600mg/day 5HTP with 4,000 mg/day tyrosine if needed, caution advised and lab work makes this safer, lots of side effects begin to occur at these dosages • Rules: 5HTP must be used with tyrosine (ratios vary) together and with B6, calcium, vitamin C, folate and cysteine as co-factors Webinar in partnership with RECAP • Use up to 300 mg 5HTP and 3000 mg Tyrosine and cofactors, you can start with 1000 mg tyrosine along with 100 mg 5HTP 3x day with or without meals (turns out it doesn’t matter!) never use a single amino acid, also always include nutrients below or you won’t get the conversion you are looking for: • Cysteine • Vitamin C • Vitamin B6 (FACTOID: TURNS OUT B6 IS MORE IMPORTANT VARIABLE THAN 5HTP IN SEROTONIN PRODUCTION) • Calcium • Selenium • Folate Webinar in partnership with PROTECT YOUR POST-SYNAPTIC NEURONS You only have one brain! STEP ONE: Remove the incoming load of toxins from your system by simple green