BalancingNeuroChemistryPrimer LF LAW2015 · •2007: $25 billion dollars were spent on...
Transcript of BalancingNeuroChemistryPrimer LF LAW2015 · •2007: $25 billion dollars were spent on...
Balancing Neurochemistry: Identifying and Treating Neurotransmitter Imbalances
Lylen Ferris, NDLabrix Clinical Services
• 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.
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 40‐59 take antidepressants (more than any other age‐sex group)
Center for Disease Control and Prevention. Health, United States. Available at: http://www.cdc.gov/nchs/data/hus/hus10.pdf . Accessibility verified October 24, 2012. OlfsonM, Marcus SC. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009; 66: 848–56.
Numerous chief complaints/many functional conditions...Where to begin?
• Treat root causes: • Neuroendocrine imbalances• Hormonal• Adrenal• Neurotransmitter
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
Neurotransmitters
• Neurotransmitters are chemical messengers that regulate many physical and emotional processes including movement, stress response, cognition, emotions, energy, cravings, pain and more.
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.
Neurotransmitters
Inadequate neurotransmitter function disrupts the signal to target tissue and has a profound influence on overall health and well‐being.
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
REMEMBER... the consequences of neurotransmitter imbalances are not all in our head.
Medicalinsider.com
Signs and Symptoms Caused by Imbalanced NTs Beyond Mood and Behavioral Disorders
• Altered sleep• Decreased concentration• Fatigue• Irritable Bowel Syndrome• Altered mental clarity • Addiction
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: 175‐82.
• Pain• Sweating• Dizziness• Heart palpitations• Attention deficits• Etc.
Presentation Roadmap
• Neurotransmitters we test• General treatment concepts• Walk through each neurotransmitter
• Discuss what imbalances look like • Discuss treatment ideas
• Mechanics of testing
Labrix Tests These Basic Neurotransmitters:
SerotoninDopamine
NorepinephrineEpinephrine
GABAGlutamate
Neurotransmitter pathways
General treatment concepts
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
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
Hinz M. Depression. In Kohlstadt I, ed. Food and Nutrients in Disease Management. Boca Raton, FL: CRC Press: 2009.Birdsall TC. 5‐Hydroxytryptophan: a clinically‐effective serotonin precursor. Altern Med Rev. 1998; 3: 271–80.Pyle AC, et al. The role of serotonin in panic: evidence from tryptophan depletion studies. Acta Neuropsychiatrica. 2004; 16: 79–84.
Tryptophan 5‐HTPTyrosine GlutamineGABA L‐theanineTaurine
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: 471‐81.
Mucuna pruriens (200‐800 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: 79‐82.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: 279‐87.Vadivel V, et al. Nutritional and anti‐nutritional characteristics of seven South Indian wild legumes. Plant Foods Hum Nutr. 2005; 60: 69‐75.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;1:249‐55.
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: 146‐55.Medline Plus. St. John’s Wort. http://www.nlm.nih.gov/medlineplus/druginfo/natural/329.html. Accessibility verified December 2, 2013.
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.
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.
Cofactors
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
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
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 • Hops• Passion flower • California poppy• Chamomile • Lavender• Lemon balm • Kava • Oats
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.
www.mthfr.net
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)
www.mthfr.net
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
www.mthfr.net
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
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):21‐30. Wakabayashi C, et al. Behavioral and molecular evidence for psychotropic effects in L‐theanine. Psychopharmacology (Berl). 2012 Feb;219(4):1099‐109.Weeks, BS. Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: Relarian. Med Sci Monit. 2009 Nov;15(11)
L‐theanine (100‐500 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: 25–38. Kimura K, et al. L‐Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007; 74: 39–45.Haskell CF, et al. The effects of l‐theanine, caffeine and their combination on cognition and mood. Biol Psychol. 2008 ; 77: 113–22.
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. 1996 Feb;36(1):193‐6.Humble MB. Vitamin D, light and mental health. J PhotochemPhotobiol B. 1988 Jul; 2(1):1‐19.
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
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 stress‐related 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.
Probiotic resources
• Bercik P, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut‐brain communication. Neurogastroenterol Motil. 2011 Dec;23(12):1132‐9.
• Borre YE, et al. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol. 2014;817:373‐403.
• Cryan JF, Dinan TG. Mind‐altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci. 2012 Oct;13(10):701‐12.
• Foster JA, McVey Neufeld KA. Gut‐brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305‐12.
• Galland L. The gut microbiome and the brain. J Med Food. 2014 Dec;17(12):1261‐72.
• 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. 2014 Nov 30.
• Tillish K, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394‐1401.
• Vitetta L, Bambling M, Alford H. The gastrointestinal tract microbiome, probiotics, and mood. Inflammopharmacology. 2014 Dec;22(6):333‐9.
• Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain BehavImmun. 2014 May;38:1‐12.
Whitaker R. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness. New York, NY: Broadway Paperbacks; 2010. Maas JW, et al. Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. Am J Psychiatry. 1984; 141: 1159‐71.
Serotonin
• Functions include mood control, sleep, pain, GI motility
• Imbalanced serotonin levels (high or low) are associated with depression
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 2009‐12‐01.Berger M, Gray JA, Roth BL (2009). "The expanded biology of serotonin". Annu. Rev. Med. 60: 355–66.
Symptoms: Imbalanced Serotonin
• 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: 355‐66.
• 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
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.
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. 1995 Nov;3 Suppl 4:477S‐480S.
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‐myo‐inositol diet". Am. J. Clin. Nutr. 33 (9): 1954–67
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.
ChallacombeDN, Wheeler EE. Are the changes of mood in children with coeliacdisease due to abnormal serotonin metabolism? Nutr Health. 1987; 5: 145‐52.
Looking Downstream From Tryptophan
Supporting Serotonin
Low Serotonin
• Tryptophan• 500‐2,000 mg
• 5 HTP• 50‐600 mg
• L‐theanine (short half life)• 100‐500 mg bid
• Cofactors• Iron 25‐50 mg (citrate or bisglycinate)
• P5P 50‐200 mg• Vitamin C 4,000‐6,000 mg• Vitamin D 2,000‐10,000 IU• MTHF
High Serotonin
• L‐theanine• 100‐500 mg bid
• Co‐factors (to support metabolism and conversion)
• Vitamin B2: 50 mg• Vitamin B3: 50 mg• Iron: 25‐50 mg• SAMe: 250‐500 mg
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. 2007 November; 32960:394‐399.
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.
Excess dopamine
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
Dopamine Structure and Biosynthesis
As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline).
Looking Downstream From Tyrosine
Supporting Dopamine
Low Dopamine• N‐acetyl l‐tyrosine
• 250‐1,500 mg• Mucuna pruriens
• 200‐800 mg• L‐theanine
• 100‐500 mg bid• Vitamin D
• 1,000‐10,000 IU• Cofactors
• Vitamin C 4‐6 gm• Iron 25‐50 mg• Vitamin B3 50 mg• P5P 50‐200 mg• MTHF
High Dopamine• L‐theanine
• 100‐500 mg bid• Co‐factors (to support MAO/COMT)
• Vitamin B2: 50 mg• Vitamin B3: 50 mg• Iron: 25‐50 mg• SAMe: 250‐500 mg
• Co‐factors (if norepi low or low range)
• Vitamin C: 4‐6 gm• Copper: 0.5‐1 mg• Vitamin B3: 50 mg
Fight or Flight
Norepinephrine and epinephrine
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, ParadisoMA. Neuroscience. Exploring the Brain, second edition
Norepinephrine Synthesis
• Norepinephrine is released by stress events• Released from noradrenergic neurons in the locus coeruleusin 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
Epinephrine Synthesis
• Epinephrine is synthesized in the medulla of the adrenal gland in anenzymatic 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
Coordinated Fight or Flight ResponseIn 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. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2005.
What Do These People Have In Common?
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
Excess levels of norepinephrine and epinephrine may lead to...
• Palpitations• Tachycardia• Arrhythmia• Headache• Restlessness• Cold hands• Tremor• Hypertension• Acute pulmonary edema
Physical symptoms Mood/Cognitive• Irritability• Anxiety• Agitation• Sleeplessness• Inability to relax• Lack of mental focus
http://www.msnbc.msn.com/id/25060719/ns/health‐mental_health/t/debt‐stress‐causing‐health‐problems‐poll‐finds/#.T59‐XKttpRQ
Supporting Norepinephrine
Low norepinephrine• N‐acetyl l‐tyrosine
• 250‐1,500 mg
• Mucuna pruriens• 200‐800 mg
• L‐theanine• 100‐500mg bid
• Vitamin D• 1,000‐10,000 IU
• Co‐factors• Vitamin C: 4‐6 gm• Copper: 0.5‐1 mg• Vitamin B3: 50 mg
High norepinephrine• L‐theanine
• 100‐500 mg bid• Co‐factors (to support
MAO/COMT)• Vitamin B2: 50 mg• Vitamin B3: 50 mg• Iron: 25‐50 mg• SAMe: 250‐500 mg
• Co‐factors (if epi low or low range)
• SAMe: 250‐500 mg• Address hypoadrenia
Supporting Epinephrine
Low epinephrine• N‐acetyl l‐tyrosine
• 250‐1,500 mg
• Mucuna pruriens• 200‐800 mg
• L‐theanine• 100‐500mg bid
• Vitamin D• 1,000‐10,000 IU
• Co‐factors• Vitamin C 4‐6 gm• SAMe 250‐500 mg• Magnesium 150‐500 mg• Must address adrenal dysfunction (hypoadrenia)
High epinephrine• L‐theanine
• 100‐500 mg bid
• Co‐factors (to support MAO/COMT)
• Vitamin B2: 50 mg• Vitamin B3: 50 mg• Iron: 25‐50 mg• SAMe: 250‐500 mg
Glutamate
• The most common excitatory neurotransmitter in the brain
High/Low Glutamate
• Anxiety • Insomnia• ADHD/poor concentration• Seizure• ALS/MS• Autism• Alzheimer’s
High glutamate Low glutamate
• Depression• Fatigue• Brain fog• Addiction/ dependency• Slowed learning
Bear MF, Connors BW, ParadisoMA. Neuroscience. Exploring the Brain, second edition
GlutamateWe 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 Any “flavors” or “flavoring”
Dextrose
Anything “hydrolyzed” Barley malt or malt extract
Rice syrup. Brown rice syrup
Textured protein (anything “protein”)
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
Neurotransmitter Pathways
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
• 100‐500 mg bid
• Taurine• 500‐1,500 mg
• Co‐factors (to support metabolism and conversion)
• Vitamin B3: 50 mg• P5P: 50‐200 mg
• Magnesium (reduces glutamate toxicity)
• 150‐500 mg
• Assess and treat dysbiosis
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
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: 250‐54.
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):2040 –2048
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
Addressing GABA
Low GABA• L‐theanine
• 100‐500 mg bid
• GABA• 500‐2,000 mg
• Phenibut• 250‐1,500 mg bid
• Glutamine• 1,000‐3,000 mg
• Co‐factors• P5P: 50‐200 mg
High GABA• L‐theanine
• 100‐500 mg bid
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
http://www.neurophysiology.ws/bbb.htm. Accessibility verified 12/10/13Zengo G. Neurotransmitters & GI Health Testing & Treatment. PracticalCMEMedical Training, 2013. Accessed 12/10/13
Supplementation References
• Abdou AM, et al. Relaxation and immunity enhancement effects of gamma‐aminobutyric acid (GABA) administration in humans. Biofactors. 2006; 26: 201‐8.
• Fernstrom JD. Dietary effects on brain serotonin synthesis: relationship to appetite regulation. Am J Clin Nutr. 1985; 42: 1072‐82.
• Fernstrom, J and Fenrstorm M. Tyrosine, Phenylalanine and catecholamine synthesis and function in the brain. J. Nutr June 2007; vol. 137 no. 6 15395‐15475
• 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: 802–809
• Receptors. PLoS ONE 8(4): e61733. doi:10.1371/journal.pone.0061733
• 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: 31‐30.
• 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; 1503 24‐2
• Yokogoshi H, et al. Effect of theanine, r‐glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998; 23: 667‐73.
• Young S. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007 Nov: 32(6): 394‐399
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
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.
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
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.
Sample NT test report
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
Metabolism
Metabolism
• MAO enzyme supported by:• Vitamin B2: 50 mg (ideally riboflavin 5 phosphate)• Vitamin B3: 50 mg• Iron: 25‐50 mg
• COMT enzyme supported by:• SAMe: 250‐500 mg• Mg: 150‐500 mg (or bowel tolerance)• MTHF: 400‐5,000 mcg• Methylcobalamin: 1,000‐5,000 mcg
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.
Summary
In most cases, neurotransmitter imbalances can be effectively addressed with amino acids, nutrients and botanicals, which are less toxic than pharmaceuticals.