Last Menses: 01/25/2018 DOB: 12/29/1989 (28 yrs) Patient Ph#: David T. Zava, Ph.D. (Laboratory Director)

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1 Test Results 8605 SW CreekSide Place Beaverton, OR Phone: Fax: U ÌJ914NVV7Î Samples Arrived: 03/09/2018 Report Date: 03/15/2018 Samples Collected: Urine: 03/06/18 06:32 Urine: 03/06/18 08:30 Urine: 03/06/18 19:00 Urine: 03/06/18 22:15 Ordering Provider: Invivo Clinical LTD Unit 1 The New Warehouse Libby's Drive Stroud, Gloucestershire Gl5 1RN UNITED KINGDOM Menses Status: Pre-Menopausal Gender: Female Lucy Rothwell Last Menses: 01/25/2018 DOB: 12/29/1989 (28 yrs) Patient Ph#: BMI: 23.3 Height: 5 ft 5 in Weight: 10 st Waist: Unspecified Test Name 02/14/2018 Current Range Salivary Steroids Estradiol 0.9 L pg/ml Premenopausal (Luteal) Progesterone 20 L pg/ml Premenopausal (Luteal) Ratio: Pg/E2 22 L Optimal: when E pg/ml Testosterone pg/ml (Age Dependent) DHEAS ng/ml (Age Dependent) Cortisol ng/ml (morning) Urinary Inhibitory Neurotransmitters Serotonin µg/g Cr (Optimal ) 5-HIAA µg/g Cr (Optimal ) GABA µg/g Cr (Optimal ) Glycine 38 L mg/g Cr (Optimal ) Urinary Excitatory Neurotransmitters Glutamate µg/g Cr (Optimal ) Histamine µg/g Cr (Optimal ) PEA H µg/g Cr (Optimal ) Dopamine µg/g Cr (Optimal ) DOPAC 2512 H µg/g Cr (Optimal ) HVA µg/g Cr (Optimal ) Norepinephrine (pooled) µg/g Cr (Optimal ) Normetanephrine µg/g Cr (Optimal ) Epinephrine (pooled) µg/g Cr (Optimal ) Ratio: Norepi/Epi (Optimal ) VMA µg/g Cr (Optimal ) Urinary Creatinine Creatinine (pooled) mg/ml <dl = Less than the detectable limit of the lab. N/A = Not applicable; 1 or more values used in this calculation is less than the detectable limit. H = High, L = Low Therapies 03/06/2018: None Indicated 02/14/2018: None Indicated ZRT Laboratory, LLC. All rights reserved. Page 1 of 7

2 U Lucy Rothwell ZRT Laboratory Reference Ranges Disclaimer: Supplement type and dosage are for informational purposes only and are not recommendations for treatment. For a complete listing of reference ranges, go to Estradiol - pg/ml Progesterone - pg/ml Ratio: Pg/E2 Testosterone - pg/ml DHEAS - ng/ml Cortisol - ng/ml Serotonin - µg/g Cr 5-HIAA - µg/g Cr GABA - µg/g Cr Glycine - mg/g Cr Glutamate - µg/g Cr Histamine - µg/g Cr PEA - µg/g Cr Dopamine - µg/g Cr DOPAC - µg/g Cr HVA - µg/g Cr Test Name Norepinephrine (pooled) - µg/g Cr Normetanephrine - µg/g Cr Epinephrine (pooled) - µg/g Cr Ratio: Norepi/Epi VMA - µg/g Cr Creatinine (pooled) - mg/ml Women pg/ml Postmenopausal (optimal ); pg/ml Premenopausal (Luteal); pg/ml Estrogen Rplcmnt (optimal ); pg/ml (Synthetic HRT, BC); pg/ml Premenopausal (Follicular); Premeno-Ovulatory ( optimal) pg/ml Postmenopausal; pg/ml Premenopausal (Follicular); pg/ml Premenopausal (Luteal); pg/ml Oral Progesterone ( mg); pg/ml Topical, Troche, Vag Pg (10-30mg); pg/ml Synthetic Progestins (HRT, BC); pg/ml Premeno-Ovulatory Optimal: when E pg/ml pg/ml (Age Dependent) 2-23 ng/ml (Age Dependent) ng/ml (morning); ng/ml (noon); ng/ml (evening); ng/ml (night) µg/g Cr (Optimal ); µg/g Cr (w/5-htp tx); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); ,204 µg/g Cr (w/5-htp tx); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o mg/g Cr (Optimal ); mg/gr Cr 10-14y/o; mg/gr Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g Cr <10y/o (Optimal ); <15y/o µg/g Cr (Optimal ); µg/g Cr 10-14y/o; µg/g <10y/o mg/ml ZRT Laboratory, LLC. All rights reserved. Page 2 of 7

4 U Lucy Rothwell **Category Symptom 2/14/2018 3/6/2018 Hot Flashes Night Sweats Vaginal Dryness Incontinence Foggy Thinking Memory Lapse Tearful Depressed Heart Palpitations Bone Loss Sleep Disturbed Headaches Aches and Pains Fibromyalgia Morning Fatigue Evening Fatigue Allergies Sensitivity To Chemicals Stress Cold Body Temperature Sugar Craving Elevated Triglycerides Weight Gain - Waist Decreased Libido Loss Scalp Hair Increased Facial or Body Hair Acne Mood Swings Tender Breasts Bleeding Changes Nervous Irritable Anxious Water Retention Fibrocystic Breasts Uterine Fibroids Weight Gain - Hips Decreased Stamina Decreased Muscle Size Rapid Aging High Cholesterol Swelling or Puffy Eyes/Face Slow Pulse Rate Decreased Sweating Hair Dry or Brittle Nails Breaking or Brittle Thinning Skin Infertility Problems Constipation Rapid Heartbeat Hearing Loss Goiter Hoarseness Increased Urinary Urge Low Blood Sugar High Blood Pressure Low Blood Pressure Numbness - Feet or Hands Breast Cancer Metabolic Syndrome Hypometabolism High Cortisol Low Cortisol High Androgens (DHEA/Testosterone) Low Androgens (DHEA/Testosterone) Estrogen Dominance / Progesterone Deficiency Estrogen / Progesterone Deficiency **Category refers to the most common symptoms experienced when specific hormone types (eg estrogens, androgens, cortisol) are out of balance, i.e., either high or low ZRT Laboratory, LLC. All rights reserved. Page 4 of 7

5 U Lucy Rothwell Lab Comments INHIBITORY NEUROTRANSMITTERS SEROTONIN Serotonin is within reference range. Serotonin has calming effects and contributes to the feelings of well-being. Serotonin elevates mood, decreases anxiety, appetite, and libido, improves sleep and memory, eases depression, and helps regulate body temperature. Most of serotonin in the human body is produced in the gastrointestinal tract, where it stimulates gut motility. 5-HIAA 5-hydroxyindoleacetic acid (5-HIAA) is within reference range. 5-HIAA is the primary metabolite of serotonin via the actions of monoamine oxidase and aldehyde dehydrogenase enzymes. GABA GABA is high-normal (>80th percentile). The brain's major inhibitory neurotransmitter, GABA functions as the "off" switch in the brain, balancing glutamate's "on" switch. GABA is essential to limiting excitation so that nerve input signals are balanced and not overdone. GABA prevents anxiety, improves mood, promotes sleep, lowers blood pressure, acts as a muscle relaxant, aids in formation and storage of fear memories, increases insulin secretion and decreases blood glucose levels. Supplementation with GABA as well as supplementation with probiotics may increase GABA levels. Clinically, high GABA levels are suspected in anxiety, excessive need for sleep, foggy thinking, lethargy, inflammation, and sluggishness. High GABA is often associated with low serotonin. THERAPEUTIC CONSIDERATIONS: Taurine and DHEA supplementation have all modulated and lowered GABA. Caffeine has also been shown to inhibit GABA release. GLYCINE Glycine is lower than the reference range. Glycine is a neurotransmitter and a simple, nonessential (can be made in the body) amino acid that plays a role in the production of DNA, phospholipids, collagen, creatine, heme and glutathione. Glycine serves as an anti-inflammatory agent, calms aggression, improves sleep quality, stabilizes blood sugar, improves metabolic parameters and modulates excitatory signals in the brain. Low levels may be indicative of chronically increased demand for tetrahydrofolate (active folic acid) production, for which glycine serves as a precursor. Research shows that urinary glycine levels are reduced after intense exercise (Corsetti, et. al. 2016) and in patients with hypometabolic disorders, such as hypothyroidism (Friedrich, et. al. 2017), obesity (Ahmad, et. al. 2016), and diabetes (Sasaki, et. al. 1988). THERAPEUTIC CONSIDERATIONS: Glycine supplementation has been shown to improve metabolic response - such as cholesterol parameters and insulin sensitivity, reduce blood pressure, and aid with decreasing the levels of hemoglobin A1C and pro-inflammatory cytokines (Diaz-Flores, et. al. 2013; Perez-Torres, et. al. 2017). Additionally, vitamin B6, serine support, and MTHF may all support the production of glycine. EXCITATORY NEUROTRANSMITTERS GLUTAMATE Glutamate is within reference range. The brain's major excitatory neurotransmitter glutamate (also known as glutamic acid) functions as the "on" switch in the brain. Glutamate regulates appetite, thinking (cognition), increases gut motility, optimizes learning, modulates memory, mood and perception of pain, improves libido, and decreases sleep. The brain is the major contributor of glutamate in the body. HISTAMINE Histamine is high-normal (>80th percentile). Histamine is both a neurotransmitter and a modulator of the immune system that has anti-pain properties, plays a neuroprotective role in the brain, and contributes to optimal maintenance of cognition and memory. Histamine stimulates wakefulness and decreases sleep, stimulates gastric acid production, increases metabolism, suppresses appetite, and prevents weight gain. Histamine is a potent vasodilator and a pro-inflammatory agent. Research shows that urinary histamine is high in patients with burns (Johansson et al., 2012), flushing disorder (Myers et al., 1981), food allergies (Raithel et al., 2015), cystitis (el-mansoury et al., 1994), polycythemia (Horakova et al., 1977), and pregnancy (Harrison et al., 1974). Clinically, high histamine levels are implicated in allergies, depression, headaches, migraines, OCD, schizophrenia, sensitivity to chemicals, and sleep difficulties. THERAPEUTIC CONSIDERATIONS: Therapeutic strategies to reduce histamine levels may involve antihistamines and a low histamine diet. High histamine foods include but are not limited to beer, champagne, aged cheeses, eggplant, canned fish, ZRT Laboratory, LLC. All rights reserved. Page 5 of 7

6 fermented meat, red and white wine, sauerkraut, and spinach (Maintz and Novak, 2007). Additionally, flavonoids (green tea extract, quercetin, grape seed extract, gingko biloba, citrus bioflavonoids, bilberry extract, hawthorn extract) may be beneficial to ease the symptoms of high histamine (Murray et al., 2005). PEA PEA is elevated. PEA, also known as phenethylamine, promotes energy, elevates mood, and regulates attention. PEA also contributes to aggression, serves as a biomarker for ADHD, and prolongs the signaling of dopamine, norepinephrine, and serotonin. Urinary PEA levels increase after amphetamine use (Kusaga et al., 2002;Zametkin et al., 1984), exercise (Szabo et al., 2001), and in the following disorders: bipolar disorder (Karoum et al., 1982), phenylketonuria (Reynolds et al., 1978), schizophrenia (O'Reilly and Davis, 1994), postpartum period (Taylor et al., 1996), and in severe anxiety and insomnia (DeLisi et al., 1984). High PEA is suspected in the etiology of anxiety, inflammation, inability to focus (racing thoughts), sleep difficulties, and toxicity. THERAPEUTIC CONSIDERATIONS: Methylation cofactor support to aid metabolism may be beneficial. DOPAMINE Dopamine is within reference range. Dopamine improves attention, focus, and motivation, helps with decision making, modulates movement control, promotes lactation, increases blood pressure, urine output and sodium excretion, and allows for feelings of reward and pleasure. Additionally, dopamine plays a central role in the etiology of addiction. Dopamine also serves as the parent precursor to norepinephrine and epinephrine. DOPAC AND HVA DOPAC and HVA are above the optimal range, which is most likely due to use of a bioflavonoid supplement (e.g. quercetin, resveratrol, etc.), however this type of supplement was not listed on the requisition form. Research shows that intestinal bacteria break down quercetin and related flavonoids to liberate a variety of metabolites, including DOPAC and HVA (Weldin, et. al. 2003). DOPAC and HVA are dopamine metabolites. Research shows that DOPAC and HVA are elevated in patients with anorexia nervosa (Van Binsbergen et al., 1991). HVA can also be elevated in lead toxicity (Tang et al., 1995), obsessive compulsive disorder (de Groot et al., 1995), and stress (Frankenhaeuser et al., 1986). In rare cases, HVA is elevated in patients with carcinoid tumors and pheochromocytomas (Davidson, 2005). TREATMENT CONSIDERATIONS: Evaluate supplementation for bioflavoinoid content. Therapies that help slow the MAO enzyme may also be helpful. These therapies include but are not limited to passiflora, curcumin, Huperzine A, and kava. Imaging may be appropriate in some patients. NOREPINEPHRINE Norepinephrine is low-normal (<20th percentile). Norepinephrine functions both as a neurotransmitter and a hormone, participating in the body's "fight or flight" response. Norepinephrine increases alertness, focuses attention, fine-tunes vigilance, increases blood pressure, heart rate, and blood glucose, reduces digestive activity, pain and sleep, prevents bladder emptying, and regulates body temperature. The adrenal gland produces approximately 20% of norepinephrine with 80% produced by the sympathetic nerve fibers. Research shows that urinary norepinephrine is reduced in patients with Alzheimer's disease. Clinically, low norepinephrine is implicated in anorexia, attention impairment, depression, fatigue, low blood pressure, lack of motivation, lethargy, low mood, memory issues, slow pulse rate, and weight issues. THERAPEUTIC CONSIDERATIONS: Precursor supplementation with tyrosine or phenylalanine, or cofactor support with vitamin C, iron, tetrahydrofolate, and vitamin B6 may be beneficial. NORMETANEPHRINE Normetanephrine is high-normal (>80th percentile). Normetanephrine is a norepinephrine metabolite formed via the actions of catechol-o-methyl transferase due to stress. Levels may be affected by stress, drugs, smoking, stimulating drinks (e.g. caffeine) and alcohol. Research shows that normetanephrine is elevated in patients with depression (Koslow et al., 1983) and polycystic ovarian syndrome (Garcia-Rudaz et al., 1998) and high norepinephrine. EPINEPHRINE Epinephrine is within reference range. Epinephrine, also called adrenalin, functions both as a neurotransmitter and a hormone, participating in the body's fight or flight response. Epinephrine increases alertness, focuses attention, fine-tunes vigilance, increases blood pressure, heart rate, and blood glucose, reduces digestive activity, pain and sleep, prevents bladder emptying, and regulates body temperature. VMA Vanillylmandelic acid (VMA) is low-normal (<20th percentile). VMA is a norepinephrine and epinephrine metabolite formed via the ZRT Laboratory, LLC. All rights reserved. Page 6 of 7

7 actions of monoamine oxidase (MAO), catechol-o-methyl transferase (COMT), and aldehyde dehydrogenase. Research shows that in rare cases, VMA is reduced in patients with MAO deficiency (Sims et al., 1989) or on SSRI and SNRI combination therapy (Chalon et al., 2003). Creatinine is within range showing normal concentration of urine ZRT Laboratory, LLC. All rights reserved. Page 7 of 7

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