Nutrition and Mental Health: Using PureSYNAPSE Supplements to Optimize Outcomes in Clinical Practice*

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Nutrition and Mental Health: Using PureSYNAPSE Supplements to Optimize Outcomes in Clinical Practice* Kelly C. Heim, Ph.D.

Speaker Disclosure Kelly Heim, Ph.D I am a paid medical advisors for Pure Encapsulations. I have no other conflicts of interest to disclose. The Company assumes no liability for presenter s information, whether conveyed verbally or in these materials. All presentations represent the opinions of the presenter and do not represent the position or the opinion of the Company. Reference by the presenter to any specific product, process or service by trade name, trademark, or manufacturer does not constitute or imply endorsement or recommendation by the Company. Seminars, teleconferences and webinars such as this are for educational purposes only and are intended for licensed health care practitioners. These therapies are not substitutions for standard medical care. Practitioners are solely responsible for the care and treatment provided to their own patients.

Learning Objectives 1. Learn about the significance of neurotransmission and the various neurotransmitters that influence our mind and body. 2. Understand how key neurotransmitters are synthesized 3. Learn how implementing supplements can support the synthesis of neurotransmitter and promote healthy mood, memory, behavior, cognition, sleep, stress and eating habits*

What is Neurotransmission? Synapse Neurotransmitter

The Role of Neurotransmitters Chemical messengers that allow communication between neurons Release of these chemicals causes electrical impulses throughout the brain and nervous system, resulting in thoughts, feelings, & behavior Key Neurotransmitters: Serotonin Dopamine GABA Glutamate Norepinephrine Healthy neurotransmitter levels support:* Sleep Stress Eating habits Mood Memory

Neurotransmitters: Supporting Synthesis Serotonin - Positive mood* SUPPOR TS - Relaxation and calming* - Moderate occasional stress* - Healthy eating behavior* Dopamine SUPPOR TS GABA SUPPOR TS - Alertness* - Cognitive function* - Mood* - Stress response* - Positive mood* - Sense of reward* - Sleep* - Relaxation*

How Neurotransmitters are Synthesized 1. Amino acids serve as precursors for neurotransmitters 2. Vitamins and minerals serve as cofactors for enzymes that synthesize neurotransmitters 1 Amino acid 2 Enzyme + Cofactor Neurotransmitter

Neurotransmitter Precursors

Amino Acids Intake is Critical for Healthy Neurotransmitter Synthesis* Adequate protein consumption is critical Available amino acids are dependent on healthy digestion of protein* Protein digestion requires adequate gastric hydrochloric acid (HCl) and various proteases Betaine HCl, pepsin and digestive enzymes supports amino acid bioavailability from dietary protein* Key Amino Acids Serotonin: Tryptophan Dopamine: Tyrosine Phenylalanine GABA: Glutamine Glutamate

Digestive Enzymes Ultra High-potency, broad spectrum vegetarian enzymes that support protein, carbohydrate, fat, fiber and dairy digestion and optimal nutrient bioavailability and absorption* Proteases provide optimal activity across a wide ph range, facilitating the breakdown of proteins as well as di- and tri-peptides* *These statements have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Amino-NR Provides a natural ratio of free-form amino acids to encourage healthy neurotransmitter synthesis and support cognitive function and mood* Also includes - Alpha lipoic acid and alpha ketoglutarate to support mitochondrial function and energy* - Vitamin B6 to support healthy neurotransmitter synthesis and energy metabolism*

Neurotransmitter Synthesis 1. Amino acids serve as precursors for neurotransmitters 2. Vitamins and minerals serve as cofactors for enzymes that synthesize neurotransmitters 1 Amino acid 2 Enzyme + Cofactor Neurotransmitter

The Importance of Cofactors Cofactors are vitamins and minerals Facilitate the function, stability and/or activity of the enzymes and receptors responsible for neurotransmitter synthesis and response* Cofactors are commonly depleted in individuals as a result of: Medications Dietary limitations Environmental exposures Key Cofactors - Zinc - Magnesium - Folate - Vitamin B6 - Vitamin B12

Neurotransmitter Cofactors

The Importance of Zinc Maintains the structure of the AADC enzyme involved in the synthesis of dopamine and serotonin* Moderates the activity of glutamate receptors to support both emotional wellness and long-term neuroprotection* Essential for digestion: Increases the activity of digestive enzymes (see table) By supporting healthy neurotransmission zinc supports: Mood Focus Calmness Healthy eating habits Necessary for carbonic anhydrase activity and the formation of acid salts in the gastric mucosa

Zinc Deficiency The Standard American Diet: - Low in zinc rich foods - High in foods with components that inhibit the absorption of zinc (e.g., iron ) Other causes: - Puberty - Stress - Vegetarianism - Exercise - Environmental toxins

Zinc: Clinical Trials Women who took a multivitamin and zinc showed significant benefit in measurements of anger-hostility and mood 1* Zinc supplemented patients had significantly improved scores for mood compared to placebo 2* Patients who are refractory to other approaches were recruited to a study, in which zinc provided significant support for mood, as evident in 4 different clinical scoring methods 3* Zinc supported mood, relaxation, healthy weight gain and taste recovery in patients with very low BMI, compared to placebo. 4* 1. Sawada and Yokol, Eur J Clin Nutr (2010) 64(3):331-3 2. Nowak et al, Pol J Pharmacol (2003) 55:1143-1147 3. Siwek et al, J Affect Disord (2009) 118(1-3):187-95 4. Katz et al., J Adolesc Health Care (1987)

Magnesium Maintains cytokine homeostasis and antioxidant protection in the brain and nervous system* Inverse relationship between serum cortisol and magnesium levels* Supports the calming actions of GABA* Binds to the NMDA receptor, keeping glutamate/nmda activity within healthy limits* GABA response GABA receptor

Magnesium (glycinate) Highly bioavailable Less likely to cause loose stools than other forms of magnesium* Available in capsules or a great-tasting liquid o 120 mg elemental Mg per capsule o 165 mg elemental Mg in two teaspoons *These statements have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Folate Folate A collective term referring to folic acid and its naturally occurring analogs (mainly 5-MTHF but also 125 other different forms of folate!) Directly utilized by the body Significantly more bioavailable than folic acid Folic Acid Oxidized form of folate Not naturally found in food Plays no direct role in any biochemical reaction, must be converted to an active form Stability makes it preferable for food fortification

8 Major Roles of Folate 1. Biosynthesis of neurotransmitters* 2. Myelination of neurons* 3. Regulation of gene expression (epigenetics)* 4. Amino acid metabolism* 5. Division of red blood cells* 6. Prevention of neural tube defects* 7. Reduction of homocysteine* 8. DNA replication* 5-MTHF SAMe B 12 Methionine Methylation Homocysteine - Neurotransmitters - DNA - Many other compounds

Folate and Mood Restoring healthy dietary folate is associated with:* Improved mood Improved response to traditional approaches Sustainable emotional health effects Enhanced efficacy of other psychiatric modalities Hundreds of studies support the relationship between folate and mood*

Causes of Folate Deficiency Inadequate intake: Dietary sources are heat labile and easily oxidized ( 50% lost during food storage and processing) Malabsorption Medications Genetic variations MTHFR polymorphism

EA: 34% MTHFR and Mood Patients who have MTHFR C/T genotypes have a 1.36 times greater chance of requiring medical support for mood T/T Polymorphism 14% C/C 30% EA: 100% The odds of having the T/T genotype is twice as great in depressed patients verses the normal population C/T Polymorphism 56% Kelly CB et al. J Psychopharmacol. Bottiglieri T et al. J Neurol Neurosurg Psychiatry Surtees R, Heales S, & Bowron. Clinical Science. Lanctôt KL, et al. Brain Inj. Gilbody S, et al. Am J Epidemiol. Słopien R, et al. Maturitas. Lok A, et al. Transl Psychiatry. EA: 71% EA = Enzyme Activity

Essential Fatty Acids: EPA and DHA EPA and DHA = omega 3 fatty acids Cognition Omega-3 fatty acids are important components of neuronal cell membranes and are essential to cognitive function* By supporting vascular health, fish oils promote oxygen and nutrient delivery to the brain.* Stress Markers Studies show that fish oil maintain healthy levels of: ACTH* Cortisol* Norepinephrine* Cytokines such as TNFα and IFNγ* Maintain normal NFκB activity* Mood Balance prostaglandin production* Both epidemiological and double blind placebo-controlled trials indicate that fish oil supports positive mood.*

Pure Encapsulation s Fish Oils Ultra-pure, molecularly distilled fish oil concentrate Rigorously tested for: Heavy metals PCBs Dioxins and furans Microbial contaminants Oxidation and rancidity EPA/DHA Essential Per capsule: - 300 mg EPA - 200 mg DHA EPA/DHA Liquid Per teaspoon - 740 835 mg EPA - 460 550 mg DHA - Lemon flavor

Regulating Neurotransmitters: Enzyme Modulation and Reuptake Balance Once neurotransmitters are synthesized, their activity and stability can be influenced by specific phytochemicals* Reuptake (inactivation) Reuptake balance* Rhodiola rosea Green tea Neurotransmitter Enzyme modulation* Taurine Curcuminoids Quercetin Degradation (inactivation)

Serotonin: Healthy Reuptake *These statements have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Serotonin: Healthy Receptor Activity - Inositol translates serotonin receptor activation into a cellular response, enhancing healthy sensitization to serotonin and nervous system function*

SeroPlu s 3 Comprehensive Serotonin Support* 1 Precursor - 5-HTP 2 Cofactors - L-5-MTHF - P5P (B6) - Vitamin C - Magnesium Healthy Enzyme Activity & Reuptake* - Taurine - Inositol Supports healthy serotonin production and reuptake which promotes: - Positive mood* - Moderate occasional stress* - Relaxation and calming* - Healthy eating behavior*

DopaPlus 3 Comprehensive Dopamine Support* 1 Precursor - Tyrosine - L-DOPA 2 Cofactors - Folate - P5P (B6) - Zinc Healthy enzyme activity & Reuptake* - Green tea leaf extract - Rhodiola rosea extract - Grape seed extract Supports dopamine production and healthy reuptake to enhance daily mental function and sharpness* - Alertness* - Positive mood* - Cognitive function* - Sense of reward*

NeuroPur e 3 Support for mental health & emotional well-being* 1 2 Precursor - dl-phenylalanine - 5-HTP Cofactors - Folate - P5P (B6) - Zinc Healthy enzyme activity & Reuptake* - Curcumin - Quercetin Offers key nutrients to support overall neurotransmitter function, neuronal health and emotional balance*

NeuroPure Supports emotional balance and mood stability* Promotes the production of both serotonin and dopamine* Enhances phenylethylamine (PEA) activity to support mood and alertness* Curcumin modulates the activity of the enzymes monoamine oxidase and indoleamine dioxygenase (IDO) to maintain healthy serotonin levels* Supports optimal serum levels of zinc and folate to promote positive mood*

PRESYNAPTIC NEURON Phenylalanine L-Tryptophan Cytokines Oxidative stress DopaPlus Dopamine degradation COM T NeuroPure Tyrosine L-DOPA NeuroPure 5-HTP DOPAMINE SEROTONIN SeroPlus Serotonin Reuptake ID O Quinolinic acid NeuroPure SYNAPSE MA O Serotonin & dopamine degradation MA O Dopamine Receptor Dopamine benefits Serotonin Receptor Serotonin benefits Glutamate Receptor POSTSYNAPTIC NEURON

Selecting the ideal product for your patient* Mood support* Support for alertness* Support for relaxation* Healthy eating behavior * Cognitiv e support* General support * DopaPlus SeroPlus NeuroPure

PureSynapse TM : Summary Proper neurotransmission is essential for healthy mood, memory, behavior, cognition, sleep, stress and eating habits* Neurotransmission is dependent on the release, receptor-binding and reuptake of neurotransmitters The synthesis of neurotransmitters is dependent on amino acid precursors and vitamin/mineral cofactors Digestive complications, medications, dietary choices and genetic polymorphism can lead to deficiencies in the building blocks and cofactors of neurotransmitters Pure Encapsulations PureSynapse TM offers a comprehensive line of individual and combination products to restore neurotransmitters to healthy levels and promote normal neurotransmission*

Visit www.puresynapse.com

Zero Compromises. Pure Results.