Balancing Neurochemistry: Identifying and Treating Neurotransmitter Imbalances

Transcription

1 Balancing Neurochemistry: Identifying and Treating Neurotransmitter Imbalances Lylen Ferris, ND Labrix Clinical Services

2 2007: $25 billion dollars were spent on antidepressants and antipsychotics 2009:US doctors wrote more psychiatric prescriptions than there were people in the USA Whitaker R. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness. New York, NY: Broadway Paperbacks; 2010.

3 The rate of antidepressant use in the United States has increased nearly 400% over the last two decades. Currently: 11% of Americans (over age 12) take antidepressant medication 23% of women aged take antidepressants (more than any other age sex group) Center for Disease Control and Prevention. Health, United States. Available at: Accessibility verified October 24, Olfson M, Marcus SC. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009; 66:

4 Numerous chief complaints/many functional conditions... Where to begin? Treat root causes: Neuroendocrine imbalances Hormonal Adrenal Neurotransmitter

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6 Our Objectives Today Review the definition and role of neurotransmitters Learn to incorporate neurotransmitter (NT) evaluation and treatment into your practice Discuss strategies for treating the symptoms of neurotransmitter imbalances without prescription medications

7 Neurotransmitters Neurotransmitters are chemical messengers that regulate many physical and emotional processes including movement, stress response, cognition, emotions, energy, cravings, pain and more.

8 Neurotransmitters Functioning primarily in the central nervous system (CNS), neurotransmitters facilitate communication between the brain and the body s glands, organs and muscles. They are released from neurons and travel across a small space, called a synapse, to reach receptors on target cells.

9 Neurotransmitters Inadequate neurotransmitter function disrupts the signal to target tissue and has a profound influence on overall health and well being.

10 Neurotransmitter Testing Provides Successful Assessment and Treatment Interventions For: Anxiety Depression Fatigue Insomnia Addictions Weight loss Cravings and poor impulse control Cognitive impairment (poor memory, lack of mental clarity, inability to focus) Chronic pain Headaches IBS

11 REMEMBER... the consequences of neurotransmitter imbalances are not all in our head.

12 Medicalinsider.com

13 Signs and Symptoms Caused by Imbalanced NTs Beyond Mood and Behavioral Disorders Altered sleep Decreased concentration Fatigue Irritable Bowel Syndrome Altered mental clarity Addiction Pain Sweating Dizziness Heart palpitations Attention deficits Etc. Capuron L, et al. Chronic low grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms. Biol Psychiatry. 2011; 70:

14 Presentation Roadmap Neurotransmitters we test General treatment concepts Walk through each neurotransmitter Discuss what imbalances look like Discuss treatment ideas Mechanics of testing

15 Labrix Tests These Basic Neurotransmitters: Serotonin Dopamine Norepinephrine Epinephrine GABA Glutamate

16 Neurotransmitter pathways

17 General treatment concepts

18 Treatment for Neurotransmitter Imbalances After evaluation, the best course of action is to target the imbalances with precursors and nutrients which remedy the problem. Amino acids Co factors Nervine and adaptogenic herbs

19 Amino acid precursors Taken on empty stomach at least 30 minutes away from food Cross the blood brain barrier and interact with HPA axis and neurotransmitter regulation Tryptophan Tyrosine GABA Taurine 5 HTP Glutamine L theanine Hinz M. Depression. In Kohlstadt I, ed. Food and Nutrients in Disease Management. Boca Raton, FL: CRC Press: Birdsall TC. 5 Hydroxytryptophan: a clinically effective serotonin precursor. Altern Med Rev. 1998; 3: Pyle AC, et al. The role of serotonin in panic: evidence from tryptophan depletion studies. Acta Neuropsychiatrica. 2004; 16:

20 Phenibut (250 1,500 mg bid) A derivative of GABA which can cross the blood brain barrier Phenibut will bind to GABA B receptors and has anxiolytic effects Discovered in the Soviet Union in the 1960s, Phenibut is standard issue in a cosmonaut s medical kit. Phenibut is able to lower stress levels without adversely affecting performance (making them drowsy). Lapin I. Phenibut (beta phenyl GABA): a tranquilizer and nootropic drug. CNS Drug Rev. 2001: 7:

21 Mucuna pruriens ( mg qd) Cowhage (mucuna pruriens) seeds have been used in traditional Ayurvedic medicine Contains small amounts of L dopa a precursor to dopamine The bean portion of the plant has 3 6% L dopa Inner layer (endocarp) is 5.3% L dopa Proven to lessen symptoms of Parkinson s disease Prakash D, et al. Some nutritional properties of the seeds of three Mucuna species. Int J Food Sci Nutr. 2001; 52: Vadivel V, et al. Nutritional and anti nutritional composition of velvet bean: an under utilized food degume in south India. Int J Food Sci Nutr. 2000; 51: Vadivel V, et al. Nutritional and anti nutritional characteristics of seven South Indian wild legumes. Plant Foods Hum Nutr. 2005; 60: HP 200 in Parkinson s Disease study group. An alternative medicine treatment for Parkinson s disease: Results of a multicenter clinical trial. J Alt Comp Med 1995;1:

22 St. John s Wort Equivalent relief of depressive symptoms in mild/moderate depression compared to SSRIs. Clinical guidelines from the American College of Physicians American Society of Internal Medicine suggest that St. John s Wort can be considered an option along with antidepressant medications for short term treatment of mild depression. Caution: SJW causes many drug interactions. (Especially CYP P450 2C19 and 3A4) Linde, K. St. John s Wort an Overview. Forsch Komplementmed. 2009;16: Medline Plus. St. John s Wort. Accessibility verified December 2, 2013.

23 Cofactors Cofactors are substances essential for the activity of an enzyme. For example, the conversion of dopamine to norepinephrine is driven by the enzyme dopamine b hydroxylase, which requires vitamin C, copper and vitamin B3 (niacin) to fuel the conversion. Cofactors are often vitamins or minerals. B vitamins are especially important in neurotransmitter pathways.

24 Cofactors Clinically, cofactors become important when conversion is slow. For example, if norepinephrine is elevated, and epinephrine levels are low, there is likely an issue with the enzyme phenylethanolamine N methyltransferase (PNMT). This will result in the N/E ratio being elevated. The cofactors in this conversion are SAMe, Mg and cortisol. Treatments might include supplementing with SAMe or Mg, and addressing adrenal gland dysfunction.

25 Cofactors

26 Cofactors: Pearls Activated forms of vitamins are essential when providing cofactor support. For example, vitamin B6 should be given in the form of pyridoxal 5 phosphate Folate and B12 should be given in the form of methyltetrahydrofolate (MTHF) and methylcobalamin

27 Adaptogenic herbs Adaptogens do exactly what their name would suggest help the body resist and adapt to stress. To be officially called an adaptogen, a compound must be able to enhance the body s physiology without any adverse side effects. They promote a normalizing action, tonifying adrenal glands and improving the body s ability to handle stress. Adaptogens promote balance in the whole adrenal gland: the adrenal cortex which secretes cortisol, as well as the adrenal medulla which secretes norepinephrine, epinephrine, and a small amount of dopamine. Common adaptogens include: Rhodiola Ginseng Licorice Ashwaganda Eleutherococcus Astragalus Gingko Schizandra

28 Nervines Nervine herbs provide a restoring and balancing action to the nervous system. Practitioners often prescribe sedative nervine herbs in the form of teas, tinctures, extracts or capsules to help patients cope with stress, anxiety, insomnia, and mild depression. Some common nervines include: Valerian Passion flower Chamomile Lemon balm Oats Hops California poppy Lavender Kava

29 Methylation support MTHFR (Methyltetrahydrofolate reductase) is the name of both the gene and the enzyme that play an essential role in the processing of the folate we eat into the nutrient that our bodies can utilize. Methylation affects a great many metabolic processes in the body and when interrupted, many essential functions, including neurotransmitter creation, are disrupted.

30 Methylation Support People who have MTHFR gene mutations make faulty MTHFR enzymes and in turn experience interruptions in methylation pathways. If a MTHFR defect is suspected, consider genetic testing. The most common MTHFR gene mutations are found at position 677 and/or position 1298 on the MTHFR gene. (1298 is commonly linked to mental dysfunctions)

31 Methylation support Possible supplements to support methylation include: L Methylfolate (NOT folic acid. It is recommended to avoid folic acid when a MTHFR defect is present, as the patient is unable to convert folic acid to methylfolate) Methylcobalamin Pyridoxal 5 phosphate SAMe

32 Combination therapies BHRT and amino acids provide targeted therapy, and some supplements can support both hormone and NT imbalances: Adaptogenic herbs tonify both the adrenal cortex (cortisol) and the adrenal medulla (catecholamines) B vitamins support adrenal cortex secretion and also act as co factors for various NT pathways

33 L theanine As we discuss treatments for high and low neurotransmitter levels, you will see that L theanine is repeatedly recommended. Many functions Acts as a GABA agonist (neuroinhibitory and parasympathetic) Antagonistic effects on glutamate receptors Will increase serotonin, GABA and dopamine levels Nathan PJ, et al. The neuropharmacology of L theanine (N ethyl L glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2): Wakabayashi C, et al. Behavioral and molecular evidence for psychotropic effects in L theanine. Psychopharmacology (Berl) Feb;219(4): Weeks, BS. Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: Relarian. Med Sci Monit Nov;15(11)

34 L theanine ( mg bid) Amino acid found in green tea Produces a calming effect in the brain (boosts alpha waves) Helps modulate mood; creates a sense of well being Reduces mental and physical stress responses Improves cognition When combined with caffeine, has been shown to increase focus and attention. Mindful alertness. Recommend divided dosing as L theanine has a short ½ life (4 6 hours) Gomez Ramirez M, et al. The deployment of intersensory selective attention: A high density electrical mapping study of the effects of Theanine". Clin Neuropharmacol. 2007; 30: Kimura K, et al. L Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007; 74: Haskell CF, et al. The effects of l theanine, caffeine and their combination on cognition and mood. Biol Psychol ; 77:

35 Vitamin D Calcitriol activates the gene expression of the enzymes tyrosine hydroxylase and tryptophan hydroxylase (the rate limiting steps in the production of serotonin and the catecholamines) Puchacz E. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Brain Res Mol Brain Res Feb;36(1): Humble MB. Vitamin D, light and mental health. J Photochem Photobiol B Jul; 2(1):1 19.

36 Fish oil Two major components of fish oil are EPA and DHA EPA is a potent anti inflammatory DHA contributes to the fluidity of cell membranes DHA plays a vital role in the structure and function of the brain and is a significant component of nerve cells and myelin Fish oil is neuromodulatory Exhibits antidepressant effects

37 Probiotics An emerging concept Over the past decade, studies have demonstrated a bidirectional relationship between the gut microbiome and brain function, i.e. the microbiota gut brain axis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition. Dysfunction of the microbiome brain gut axis has been implicated in stressrelated disorders such as depression, anxiety, and irritable bowel syndrome and neurodevelopmental disorders such as autism. Although not fully elucidated, accumulating data indicated that the gut microbiota communicates with the CNS through neural, endocrine and immune pathways. Probiotics attenuate anxiety and depressive like behaviors in experimental animal and human models. This emerging concept suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders. Nutritional tools for altering the gut microbiome include changes in diet, probiotics and prebiotics.

38 Probiotic resources Bercik P, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut brain communication. Neurogastroenterol Motil Dec;23(12): Borre YE, et al. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol. 2014;817: Cryan JF, Dinan TG. Mind altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci Oct;13(10): Foster JA, McVey Neufeld KA. Gut brain axis: how the microbiome influences anxiety and depression. Trends Neurosci May;36(5): Galland L. The gut microbiome and the brain. J Med Food Dec;17(12): Slyepchenko A, et al. Gut Emotions Mechanisms of Action of Probiotics as Novel Therapeutic Targets for Depression and Anxiety Disorders. CNS Neurol Discord Drug Targets Nov 30. Tillish K, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology Jun;144(7): Vitetta L, Bambling M, Alford H. The gastrointestinal tract microbiome, probiotics, and mood. Inflammopharmacology Dec;22(6): Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun May;38:1 12.

39 Serotonin Functions include mood control, sleep, pain, GI motility Imbalanced serotonin levels (high or low) are associated with depression Whitaker R. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness. New York, NY: Broadway Paperbacks; Maas JW, et al. Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. Am J Psychiatry. 1984; 141:

40 Origins of Serotonin Biochemically derived from the amino acid tryptophan. Serotonin is primarily found in: Gastrointestinal (GI) tract Contains 80 90% of the body s serotonin Platelets and central nervous system (CNS) Make up the rest of the 10 20% King MW. "Serotonin. The Medical Biochemistry Page. Indiana University School of Medicine. Retrieved Berger M, Gray JA, Roth BL (2009). "The expanded biology of serotonin". Annu. Rev. Med. 60:

41 Symptoms: Imbalanced Serotonin Racing/troublesome thoughts Emotional numbness Crying and/or angry outbursts Thoughts of escaping your current circumstances Obsessive/compulsive traits such as paranoia about germs and disease Physical changes such as: Fluctuating body temperature Aches/pains Cramps Bowel/bladder issues Smothering sensations Depressed mood Thoughts of suicide Berger M, et al. The expanded biology of serotonin. Annu Rev Med. 2009; 60:

42 Loss of interest Lack of interest in social engagements or sexual activities may indicate low serotonin levels. It is important to track favorite activities to monitor changes.

43 Appetite Change Moderately low serotonin can cause your appetite to change. Symptoms may include a lack interest in eating or craving for sweets and carbohydrates. The brain tries to use sweets and carbohydrates to increase serotonin levels. Wurtman RJ, et al. Brain serotonin, carbohydrate craving, obesity and depression. Obes Res Nov;3 Suppl 4:477S 480S.

44 Fat and sad? Increasing insulin for a long period may trigger the onset of insulin resistance, obesity, type 2 diabetes, and lower serotonin levels. Grossman, Mary H.; Hart, Cheryle R. (2008). The Feel Good Diet. New York: McGraw Hill. p. 64. Clements RS, Darnell B (1980). "Myo inositol content of common foods: development of a high myoinositol diet". Am. J. Clin. Nutr. 33 (9):

45 Are the changes of mood in children with celiac disease due to abnormal serotonin metabolism? Abstract: Children with untreated coeliac disease are characteristically unhappy and after a few days of treatment with a gluten free diet their mood improves. This improvement in mood can be rapidly reversed by introducing gluten into their diet again which suggests that a humoral agent could be involved in this process. As serotonin is a neurotransmitter in the brain and abnormalities of serotonin metabolism have been reported in celiac disease, this biogenic amine could be the humoral agent that mediates the changes of mood in celiac disease. Challacombe DN, Wheeler EE. Are the changes of mood in children with coeliac disease due to abnormal serotonin metabolism? Nutr Health. 1987; 5:

46 Looking Downstream From Tryptophan

47 Supporting Serotonin Low Serotonin Tryptophan 500 2,000 mg 5 HTP mg L theanine (short half life) mg bid Cofactors Iron mg (citrate or bisglycinate) P5P mg Vitamin C 4,000 6,000 mg Vitamin D 2,000 10,000 IU MTHF High Serotonin L theanine mg bid Co factors (to support metabolism and conversion) Vitamin B2: 50 mg Vitamin B3: 50 mg Iron: mg SAMe: mg

48 How to increase serotonin in the human brain without drugs Positive mood induction Light therapy Exercise Nutrition Simon N Young. How to Increase serotonin in the human brain without drugs. J Psychiatry Neurosci November; 32960:

49 Dopamine Enhances the reward response, especially if the reward is perceived as greater than expected. Stimulates pleasure centers Enables us not only to see rewards, but to take action to move towards them Locomotion and coordination of movement Motivation Behavior and cognition Sleep Mood Attention and learning Inhibition of prolactin production (involved in lactation) Schultz W. Dopamine signals for reward value and risk: basic and recent data. Behav Brain Funct. 2010; 6: 1 9.

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51 Excess dopamine

52 Dopamine Deficiency Isolation Issues with motivation. Inability to finish tasks. Drop in sex drive. Forgetfulness People with low dopamine activity may be more prone to addiction (to food, drugs, gambling, etc.) Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder

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54 Dopamine Structure and Biosynthesis As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline).

55 Looking Downstream From Tyrosine

56 Supporting Dopamine Low Dopamine N acetyl l tyrosine 250 1,500 mg Mucuna pruriens mg L theanine mg bid Vitamin D 1,000 10,000 IU Cofactors Vitamin C 4 6 gm Iron mg Vitamin B3 50 mg P5P mg MTHF High Dopamine L theanine mg bid Co factors (to support MAO/COMT) Vitamin B2: 50 mg Vitamin B3: 50 mg Iron: mg SAMe: mg Co factors (if norepi low or low range) Vitamin C: 4 6 gm Copper: mg Vitamin B3: 50 mg

57 Norepinephrine and epinephrine Fight or Flight

58 Norepinephrine and Epinephrine Regulate flight or flight response Control attention and arousal Regulate heart rate and blood pressure Release glucose from energy stores Bear MF, Connors BW, Paradiso MA. Neuroscience. Exploring the Brain, second edition

59 Norepinephrine Synthesis Norepinephrine is released by stress events Released from noradrenergic neurons in the locus coeruleus in the CNS and from post ganglionic neurons in the SNS to stimulate fight or flight response. The locus coeruleus is involved with the physiological response to stress and panic. It is the principal site for brain synthesis of norepinephrine When norepinephrine is released from the adrenal medulla, it is released into the blood and acts as a hormone

60 Epinephrine Synthesis Epinephrine is synthesized in the medulla of the adrenal gland in an enzymatic pathway that converts the amino acid tyrosine into a series of intermediates and, ultimately, epinephrine. ACTH stimulates the adrenal cortex to release cortisol which increases expression of PNMT in chromaffin cells, enhancing epinephrine synthesis. Epinephrine may be used as a neurotransmitter by some neurons in the brain, but its most important role is in the periphery

61 Coordinated Fight or Flight Response In the periphery, norepinephrine and epinephrine act as regulators of carbohydrate and lipid metabolism. Norepinephrine and epinephrine are released from storage vesicles in the adrenal medulla in response to fright, exercise, cold, and low blood glucose levels. They increase the degradation of glycogen and triacylglycerol, as well as increase blood pressure and cardiac output. Champe P, Harvey R, Ferrier D. Biochemistry. 3 rd ed. Philadelphia: Lippincott Williams & Wilkins; 2005.

62 What Do These People Have In Common?

63 Low levels of norepinephrine and epinephrine may lead to: Poor attention and memory Decreased concentration Reduced socialization Loss of alertness Memory problems (brain fog) Depression Pain Lack of arousal and interest

64 Excess levels of norepinephrine and epinephrine may lead to... Physical symptoms Palpitations Tachycardia Arrhythmia Headache Restlessness Cold hands Tremor Hypertension Acute pulmonary edema Mood/Cognitive Irritability Anxiety Agitation Sleeplessness Inability to relax Lack of mental focus

65 mental_health/t/debt stress causing health problems poll finds/#.t59 XKttpRQ

66 Supporting Norepinephrine Low norepinephrine N acetyl l tyrosine 250 1,500 mg Mucuna pruriens mg L theanine mg bid Vitamin D 1,000 10,000 IU Co factors Vitamin C: 4 6 gm Copper: mg Vitamin B3: 50 mg High norepinephrine L theanine mg bid Co factors (to support MAO/COMT) Vitamin B2: 50 mg Vitamin B3: 50 mg Iron: mg SAMe: mg Co factors (if epi low or low range) SAMe: mg Address hypoadrenia

67 Supporting Epinephrine Low epinephrine N acetyl l tyrosine 250 1,500 mg Mucuna pruriens mg L theanine mg bid Vitamin D 1,000 10,000 IU Co factors Vitamin C 4 6 gm SAMe mg Magnesium mg Must address adrenal dysfunction (hypoadrenia) High epinephrine L theanine mg bid Co factors (to support MAO/COMT) Vitamin B2: 50 mg Vitamin B3: 50 mg Iron: mg SAMe: mg

68 Glutamate The most common excitatory neurotransmitter in the brain

69 High/Low Glutamate High glutamate Anxiety Insomnia ADHD/poor concentration Seizure ALS/MS Autism Alzheimer s Low glutamate Depression Fatigue Brain fog Addiction/ dependency Slowed learning Bear MF, Connors BW, Paradiso MA. Neuroscience. Exploring the Brain, second edition

70 Glutamate We all know that MSG can increase glutamate levels, but there are many hidden sources of glutamic acid in the foods that we eat Ingredients that ALWAYS contain free glutamic acid Ingredients that OFTEN contain or produce glutamic acid Ingredients SUSPECTED of creating glutamic acid in sensitive people MSG Bouillon and broth Corn starch, corn syrup Yeast extract Anything hydrolyzed Textured protein (anything protein ) Any flavors or flavoring Barley malt or malt extract Dextrose Rice syrup. Brown rice syrup Soy sauce Reduced fat milk (skim, 1%, 2%) Soy or whey protein Seasonings Most things low fat or no fat Gelatin Carrageenan Anything vitamin enriched

71 Neurotransmitter Pathways

72 Supporting Glutamate Low glutamate L glutamine 1,000 3,000 mg Low glutamate/low GABA May be of little clinical relevance High glutamate L theanine mg bid Taurine 500 1,500 mg Co factors (to support metabolism and conversion) Vitamin B3: 50 mg P5P: mg Magnesium (reduces glutamate toxicity) mg Assess and treat dysbiosis

73 GABA The major inhibitory neurotransmitter in the brain Relaxing and calming Synthesized from glutamate and P5P Predominant receptor GABA A Utilized by neuroactive drugs like benzodiazepines Often used to treat anxiety, seizures, act as sedative or muscle relaxant

74 GABA imbalances Low GABA levels have been found in: Panic/anxiety Depression Alcoholism Bipolar disorders Deficient GABA levels may be caused by Inadequate diet Prolonged stress Genetics Vaiva G, et al. Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder. Biol Psychiatry. 2004; 55:

75 GABA Elevated GABA may contribute to Drowsiness/lack of alertness Difficulty concentrating Diminished memory Dampened mood Decreased cognitive processing GABA levels may become elevated as a compensatory mechanism when excitatory neurotransmitters are high Mathews G and Diamond J. Neuronal glutamate uptatke contributes to GABA synthesis and inhibitory synaptic strength. J Neurosci, March 15, 2003; 23(6):

76 GABA Impact When Sufficient or Therapeutic May: reduce symptoms of alcohol withdrawal reduce symptoms of anxiety help some schizophrenics help to reduce high blood pressure suppress appetite help with premenstrual symptoms be helpful in some cases of depression

77 Addressing GABA Low GABA L theanine mg bid GABA 500 2,000 mg Phenibut 250 1,500 mg bid Glutamine 1,000 3,000 mg Co factors P5P: mg High GABA L theanine mg bid

78 GABA supplementation It is often stated that in healthy people, GABA does not cross the blood brain barrier Then why is it found in so many supplements? And why do many people feel a relaxing effect from taking it? When dysbiosis is present, anxiolytic effects of GABA are observed, suggesting ability to cross the BBB Additionally, certain areas of the brain do not contain a BBB: Hypothalamus, pineal gland, and the posterior pituitary. A change at the hypothalamus will project to other neurons that are behind the BBB Accessibility verified 12/10/13 Zengo G. Neurotransmitters & GI Health Testing & Treatment. PracticalCME Medical Training, Accessed 12/10/13

79 Supplementation References Abdou AM, et al. Relaxation and immunity enhancement effects of gamma aminobutyric acid (GABA) administration in humans. Biofactors. 2006; 26: Fernstrom JD. Dietary effects on brain serotonin synthesis: relationship to appetite regulation. Am J Clin Nutr. 1985; 42: Fernstrom, J and Fenrstorm M. Tyrosine, Phenylalanine and catecholamine synthesis and function in the brain. J. Nutr June 2007; vol. 137 no Kletke O, Gisselmann G, May A, Hatt H, Sergeeva OA (2013) Partial Agonism of Taurine at Gamma Containing Native and Recombinant GABAA Okiyama, K., Smith, D. H., Gennarelli, T. A., Simon, R. P., Leach, M. and McIntosh, T. K. (1995), The Sodium Channel Blocker and Glutamate Release Inhibitor BW1003C87 and Magnesium Attenuate Regional Cerebral Edema Following Experimental Brain Injury in the Rat. Journal of Neurochemistry, 64: Receptors. PLoS ONE 8(4): e doi: /journal.pone Nathan PJ, et al. The neuropharmacology of L theanine (N ethyl L glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006; 6: Tian X, Sun L, Gou L, Ling X, et al. Protective effect of l theanine on chronic restraing stress induced cognitive impairments in mice. Brain Res 2013 Mar; Yokogoshi H, et al. Effect of theanine, r glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998; 23: Young S. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci Nov: 32(6):

80 In your BHRT patients... Why guess when you can test? When pronounced mood complaint is part of their initial treatment request, or they are currently using an SSRI, SNRI, etc. When patient reports significant neurotransmitter symptoms on the Labrix requisition form. When symptoms do not improve after hormones are balanced: Persistent fatigue Sleep issues Mood swings and cognitive issues

81 The relationship between hormones and brain chemistry strongly influences the severity of symptoms. If optimal levels of neurotransmitters are not present due to decreased synthesis or increased consumption, their hormonal counterparts may not adequately modulate, enhance or sensitize their activity.

82 When to test neurotransmitters? Many neurotransmitter symptoms overlap with hormone symptoms, but not all. When these symptoms are reported, consider neurotransmitter testing: Cravings and addictive behavior Obsessive behavior Poor impulse control Movement disorders IBS

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87 Beware of the expired kit Expiration dates are printed on the side of the test kit box. Expired samples will be rejected by the lab.

88 Sample NT test report

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92 General treatments and pearls Adaptogenic herbs treat both the adrenal cortex and the medulla Can be beneficial to give tyrosine and Mucuna together, much like we give adaptogenic herbs when giving hydrocortisone May be important to give a little tyrosine or L dopa when giving 5 HTP, and vice versa

93 Metabolism

94 Metabolism MAO enzyme supported by: Vitamin B2: 50 mg (ideally riboflavin 5 phosphate) Vitamin B3: 50 mg Iron: mg COMT enzyme supported by: SAMe: mg Mg: mg (or bowel tolerance) MTHF: 400 5,000 mcg Methylcobalamin: 1,000 5,000 mcg

95 Summary Neurotransmitters transmit impulses that contribute to a variety of physiological areas including mood, cognition, sleep, pain, and A variety of disorders ranging from mood and cognitive issues to addictions, cravings, pain, fatigue and/or gastrointestinal upset can be attributed to neurotransmitter imbalances. Testing neurotransmitter levels will enable you, the practitioner, to better utilize targeted therapies and monitor patient response.

96 Summary In most cases, neurotransmitter imbalances can be effectively addressed with amino acids, nutrients and botanicals, which are less toxic than pharmaceuticals.

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