Eliminate Fatigue, WCA Part I. Addressing the 9 Underlying Causes of Fatigue Digging Deeper for Clinical Solutions

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1 Addressing the 9 Underlying Causes of Fatigue Digging Deeper for Clinical Solutions ELIMINATE FATIGUE WHAT DOES CLINICAL/CHRONIC FATIGUE LOOK LIKE? 1

2 Fatigue is different than being tired. When you are tired, you know that if you can just get some sleep you will feel better, but fatigue is still there when you wake up, it stays with you all day, it is a lack of energy, a feeling of mental, emotional and physical exhaustion. I couldn t think straight. I had days where I couldn t spell my name. And such complete exhaustion you can t describe it it s like you just ran a marathon, are hungover, and have the flu all at once. 2

3 WHAT DOES CLINICAL FATIGUE LOOK LIKE? What if you got the flu, and it never left? What would your life be like? FATIGUE IS VERY COMMON ~20% of Americans have fatigue intense enough to interfere with living normally Physical cause: 20-60% of time Emotional/mental cause 40-80% Adequate rest is not restorative 3

4 SYMPTOMS ASSOCIATED WITH FATIGUE Extreme fatigue Tiredness & lethargy Heavy limbs Brain fog Cognitive dysfunction Chemical sensitivities Poor concentration Impaired memory Forgetfulness confusion Food cravings Insomnia Unrefreshing sleep Chronic allergies Joint pain Night sweats Gastrointestinal imbalances/ibs Muscle pain Frequent illness Persistent low-grade fever Swollen/tender lymph nodes Recurrent sore throat Headache Post-exertional malaise (>24 hrs) HOW YOUR PATIENTS DESCRIBE IT: Lethargic Listless Lack of energy Tired Worn out Weary Exhausted Feel run down All. The. Time. 4

5 CHRONIC FATIGUE SYNDROME (CFS) Complex disorder Overwhelming fatigue + many other symptoms No improvement with bed rest Muscle pain, impaired memory or mental concentration, insomnia, and post-exertion malaise lasting more than 24 hours. Can persist for years No specific cause or test to diagnose Diagnosis of exclusion DIAGNOSTIC CRITERIA FOR CFS Unexplained, persistent fatigue present for > 6 months that is not due to ongoing exertion; is not substantially relieved by rest, is of new onset (not lifelong) and results in a significant reduction in previous levels of activity PLUS at least 4 of the following symptoms present > 6 months : Impaired memory or concentration Sore throat that s frequent or recurring Tender cervical or axillary lymph nodes Muscle pain Multi-joint pain without swelling or redness Headaches of a new type, pattern or severity Unrefreshing sleep Post-exertional malaise lasting > 24 hours 5

6 CFS PREVALENCE 1-4 million people in US 200,000 new cases each year Most common in yo women Latino, African American & Caucasian Now common in adolescents Often after infection (i.e., mononucleosis) Usually recover https://www.gstatic.com/healthricherkp/pdf/chronic_fatigue_syndrome.pdf CHRONIC FATIGUE SYNDROME (CFS) Chronic Fatigue is a clinical diagnosis when everything else is ruled out. 6

7 WHERE TO START? Fatigue is a symptom, not a disease PRIMARY CONCERN VS. UNDERLYING CAUSE Primary Concern (PC) Presenting with acute symptoms What they are coming in for No explanation necessary Underlying Cause May or may not exhibit acute symptoms NEED to correct in order to address PC May be able to discern from interview Usually requires additional testing Will need to explain why it s important to address 7

8 UNDERLYING CAUSES OF FATIGUE Research shows chronic fatigue associated with: Nutritional insufficiency/imbalance B-complex, amino acids, EFAs, vitamin D3, CoQ10, L- carnitine, Mg, Zn Mitochondrial Dysfunction Detoxification Imbalances Hormone Imbalances Adrenal, thyroid, sex hormones, blood sugar GI Imbalances Immune dysfunction King MS. Adrenal insufficiency: an uncommon cause of fatigue. The Journal of the American Board of Family Practice / American Board of Family Practice. Sep-Oct 1999;12(5): Brown BI. Chronic fatigue syndrome: a personalizedintegrative medicine approach. Alternativetherapies in health and medicine. Jan-Feb 2014;20(1): WojcikDP, Godfrey ME, Christie D, Haley BE. Mercurytoxicitypresenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand generalpracticesetting ( ). Neuroendocrinology letters. Aug 2006;27(4): Bell IR, Baldwin CM, Schwartz GE. Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia. The American journal of medicine. Sep ;105(3A):74S-82S. Nater UM, Maloney E, Boneva RS, et al. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. The Journal of clinical endocrinology and metabolism. 3/ ;93(3): Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutrition &metabolism. 2010;7:79. UNDERLYING CAUSES OF FATIGUE 1. Diet Insufficiency Allergy/sensitivity 2. Adrenal fatigue 3. Mitochondrial dysfunction 4. GI Imbalances Poor digestion Malabsorption Food hypersensitivity Dysbiosis 5. Inflammation 6. Sleep disturbance 7. Immune Imbalance Chronic infection Hypersensitivity 8. Toxicity Detoxification Imbalance Heavy metal toxicity 9. Hormone Imbalances Adrenal Thyroid Insulin Sex hormones 8

9 OTHER UNDERLYING CAUSES OF FATIGUE Medications Antidepressants Anti-anxiety medications Sedative medications Proton-Pump Inhibitors Antihistamines Statins Anti-hypertensives Antipsychotics Antibiotics Diuretics Medication/drug withdrawal Psychiatric conditions Depression Anxiety Grief/bereavement Chemotherapy/radiation Cancer Rheumatic conditions Cardiac condition Pulmonary conditions MEDICATIONS THAT CAUSE FATIGUE Blood Pressure Medications Why prescribed: There are at least 8 categories of them all are used to try and lower the pressure inside the blood vessels, so the heart doesn t have to work as hard to pump blood throughout the body. ACE inhibitors: Lisinopril (Prinivil, Zestril) Calcium channel blockers: amlodipine (Norvasc) Thiazide diuretics: hydrochlorothiazide (HCTZ) Loop diuretics: furosemide (Lasix) Beta-blockers: metoprolol (Lopressor, Toprol), atenolol, propranolol How: Blood-pressure medications slow down the pumping action of the heart as well as depress the entire CNS, or in the case of diuretics, deplete vitamins and minerals your body needs for energy. Beta blockers, such at atenolol and propranolol can also decrease endogenous melatonin levels. 9

10 MEDICATIONS THAT CAUSE FATIGUE Statins and fibrates Why prescribed: used to treat high cholesterol. Statins: Atorvastatin (Lipitor), rosuvastatin (Crestor), simvastatin (Zocor) Fibrates: fenofibrate (Tricor) How: Statins stop the production of satellite cells in the muscle, stopping muscle growth; statins also block the production of coenzyme Q10, dramatically decreasing cellular energy production MEDICATIONS THAT CAN CAUSE FATIGUE Proton pump inhibitors Why prescribed: Used to treat GERD and other similar disorders. PPIs: esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix) How: People that take PPIs for as little as three months are at risk of low blood levels of magnesium, which can cause loss of appetite, fatigue and weakness. 10

11 MEDICATIONS THAT CAN CAUSE FATIGUE Benzodiazepines Why prescribed: Used to treat a variety of anxiety disorders, agitation and muscle spasms, insomnia and prevent seizures. Alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), temazepam (Restoril) Zolpidem (Ambien) is not a benzodiazepine but interacts with the same neurotransmitters in the brain and has many of the same pharmacological effects, including fatigue How: Benzodiazepines can cause sedation and fatigue by dampening activity in key parts of the CNS; It can take weeks to months to clear these drugs out of the system and withdrawal can also cause fatigue. MEDICATIONS THAT CAN CAUSE FATIGUE Antihistamines Why prescribed: used to relieve or prevent symptoms of allergic reactions or the common cold. Some also used to prevent motion sickness, nausea, vomiting and dizziness, and to treat anxiety or insomnia. Diphenhydramine (Benadryl), fexofenadine (Allegra) How: Antihistamines are CNS depressants; most cause tiredness and drowsiness and can cause dizziness and weakness. 11

12 MEDICATIONS THAT CAN CAUSE FATIGUE Antipsychotics Why prescribed: Antipsychotics are used to treat schizophrenia, bipolar disorder and other psychiatric conditions. They are also often used off label to treat agitation and depression, among other conditions. Aripiprazole (Abilify), haloperidol (Haldol), olanzapine (Zyprexa), risperidone (Risperdal), ziprasidone (Geodon) How: Antipsychotics are powerful CNS depressants, with side effects of fatigue, lethargy and weakness. Many also lower dopamine levels, which can lead to drowsiness and sleepiness as well. MEDICATIONS THAT CAN CAUSE FATIGUE Antibiotics Why prescribed: Antibiotics are used to treat health conditions caused by bacteria, including ear and skin infections, urinary tract infections, food poisoning, pneumonia, meningitis and other illnesses. They are also used to treat or prevent infection that can complicate surgery or other medical procedures. Amoxicillin, azithromycin (Zithromax), ciprofloxacin (Cipro), levofloxacin (Levaquin), sulfamethoxazole/trimethroprim, cephalexin How: Clinical trials and research has long shown that antibiotics cause tiredness and extreme fatigue, but the mechanism is still unclear. It is likely due to alterations in gastrointestinal microflora and/or immune dysfunction. 12

13 MEDICATIONS THAT CAN CAUSE FATIGUE Diuretics Why prescribed: Diuretics (often referred to as water pills ) are used to treat high blood pressure, glaucoma, edema and other conditions. How: Diuretics interfere with electrolyte balance in your body; this can cause series health issues, including extreme fatigue, muscle weakness, and achy joints, bones and muscles. MEDICATIONS THAT CAN CAUSE FATIGUE Antidepressants Why prescribed: Used to treat depression, anxiety disorders, eating disorders, obsessive compulsive disorder, chronic pain, smoking cessation and some hormone-mediated disorders, such as severe menstrual cramps and hot flashes. There are many different kinds of antidepressants, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), dopamine antagonists, monoamine oxidase inhibitors (MAOIs) and lithium, amongst others. Abilify (ariprazole), Adapin (doxepin), Anafranil (clomipramine), Aplenzin (bupropion), Asendin (amoxapine), Aventyl HCI (nortriptyline),brintellix (vortioxetine), Celexa (citalopram), Cymbalta (duloxetine), Desyrel (trazodone), Effexor XR (venlafaxine), Emsam (selegiline), Etrafon (perphenazine and amitriptyline), Elavil (amitriptyline), Endep (amitriptyline), Fetzima (levomilnacipran), Khedezla (desvenlafaxine), Latuda (lurasidone), Lamictal (lamotrigine), Lexapro (escitalopram), Limbitrol (amitriptyline and chlordiazepoxide), Marplan (isocarboxazid), Nardil (phenelzine), Norpramin (desipramine), Oleptro (trazodone), Pamelor (nortriptyline), Parnate (tranylcypromine), Paxil (paroxetine), Pexeva (paroxetine), Prozac (fluoxetine), Pristiq (desvenlafaxine), Remeron (mirtazapine), Sarafem (fluoxetine), Seroquel XR (quetiapine), Serzone (nefazodone), Sinequan (doxepin), Surmontil (trimipramine), Symbyax (fluoxetine and the atypical antipsychotic drug olanzapine), Tofranil (imipramine), Triavil (perphenazine and amitriptyline), Viibryd (vilazodone), Vivactil (protriptyline), Wellbutrin (bupropion), Zoloft (sertraline), Zyprexa (olanzapine) How: All antidepressant medications alter neurotransmitter (and often hormone levels) which can lead to fatigue. In addition, many can lower potassium levels, which in turn can lead to muscle weakness. 13

14 MEDICATIONS CAN CAUSE FATIGUE Always get a complete current (and recent) medication list Check for medications that can cause fatigue May need to correct the underlying imbalances necessitating the medication in order resolve fatigue Also check for nutrient depletions due to medications Augment as needed NUTRIENT DEPLETION BY MEDICATIONS Type of Drug Name Brand Examples Nutrients Depleted Potential Solutions Antacids H2 blockers: Axid, Pepcid, Tagemet, Zantac PPI: Nexium, Prevacid, Prilosec Vitamin B12, folic acid, vitamin D, calcium, iron, zinc, protein Intrinsi B12-Folate or Hemagenics 1 tablet BID Multi-Min Chelate 1 tablet TID Antibiotics General Aminoglycosides (gentomycin, neomycin, streptomycin), Cephalosporins, Penicillins B-vitamins, vitamin K, Friendly Intestinal Bacteria UltraFlora Spectrum 1 capsule BID on empty stomach Tetracyclines Glycogenics 1 tablet BID Calcium, zinc, magnesium, iron, vitamin B6 Anti-diabetic drugs Micronase, Tolinase CoQ10 CoQ10 (100 mg) 1 gelcap BID Glucophage, Metformin CoQ10, vitamin B12, folic acid Intrinsi B12-Folate 1 tablet BID Anti-depressants Adapin, Aventyl, Elavil, Tofranil, Pamelor, Sinequan, Norpramin Vitamin B12, CoQ10, neurotransmitters Intrinsi B12-Folate 1 tablet BID CoQ10 (100 mg) 1 gelcap BID Amino acid therapy as needed Anti-Convulsion drugs Dilantin, Tegretol Folic acid, Vitamin D, B12, B6 IntrinsiB12-Folate 1 tablet BID D capsules daily Anti-Inflammatories Aspirin & Salicylates NSAIDs: Advil, Aleve, Motrin, Naprosyn, Ibuprofen Vitamin C, folic acid, potassium Folic acid Ultra Potent C 1 tsp 1-2x/day Folapro 1 tablet/day Glutagenics 1 tsp TID Corticosteroids: Cortisone, Hydrocortisone, Prednisone Vitamin C, folic acid, calcium, magnesium, potassium, selenium, zinc Multi-Min Chelate 1 tablet TID Folapro 1 tablet BID From Drug-Induced Nutrient Depletion Handbook, 2 nd Edition and References 14

15 NUTRIENT DEPLETION BY MEDICATIONS Type of Drug Name Brand Examples Nutrients Depleted Potential Solutions Antihypertensives / High Blood Pressure Apresoline Atenolol, Lopressor/Toprol-XL, Propranolol/Inderal Vitamin B6, CoQ10 CoQ10, melatonin CoQ10 (100 mg) 1 gelcap BID Glycogenics 1 tablet BID Lotensin, Vasotec, Lisinopril/Prinivil, Captopril/Capoten CoQ10, sodium Diuretics Hydrochlorothiazide/HCTZ, Metalzaone/Zaroxolyn Lasix, Bumex Magnesium, potassium, zinc, CoQ10, sodium Vitamins B1, B6, C; magnesium, calcium, potassium, zinc, sodium Multi-Min Chelate 1 tablet TID CoQ10 (100 mg) 1 gelcap/day Glycogenics 1 tablet BID Multi-Min Chelate 1 tablet TID Cholesterol Lowering Agents / Statins Lipitor, Zocor, Mevacor, Pravachol, Crestor, Lescol Colestid, Questran CoQ10 Vitamins A, B12, D, E, K, betacarotene, folic acid, iron CoQ10 (100 mg) 1 gelcap BID Multigenics Intensive Care 2 tablets TID with meals Hormone Replacement Therapy (HRT) Evista, Prempro, Premarin, Estratab Vitamins B2, B6, B12, C, folic acid, magnesium, zinc Oral Contraceptives (BCP) Norinyl, Ortho-Novum, Triphasil, etc. Vitamins B2, B3, B6, B12, C, folic acid, magnesium, selenium, zinc Wellness Essentials for Women 1 packet QD Wellness Essentials for Women 1 packet QD QD = 1x/day with meals (unless stated otherwise) BID = 2x/day with meals (unless stated otherwise) TID = 3x/day with meals (unless stated otherwise) FINDING ANSWERS 15

16 TEST, DON T GUESS Provides an objective measure of progress Helps client understand their condition Improves quality of care PRIMARY CONCERN VS. UNDERLYING CAUSE Primary Concern (PC) Presenting with acute symptoms What they are coming in for No explanation necessary Underlying Cause May or may not exhibit acute symptoms NEED to correct in order to address PC May be able to discern from interview Usually requires additional testing Will need to explain why it s important to address 16

17 GETTING ANSWERS Research shows that conventional testing for chronic fatigue identifies abnormal results in only 5%-8% of cases Moses S. Fatigue. [Electronic]. 2012; Accessed September 25, Lane TJ, Matthews DA, Manu P. The low yield of physicalexaminations and laboratory investigations of patients with chronic fatigue. The American journal of the medicalsciences. May 1990;299(5): Nijrolder I, van der Windt D, de Vries H, van der Horst H.Diagnoses during follow-up of patients presenting with fatigue in primary care. CMAJ : Canadian Medical Association journal = journal de l'association medicale canadienne. Nov ;181(10): CLIENT PACKET Health Appraisal Questionnaire Detoxification Questionnaire Identi-T Stress Assessment Insulin Resistance Questionnaire Health History Diet Journal Exercise Log 17

18 OFFICE FLOW Provide the Client Packet before or at your first meeting Have your patient complete at home and bring to next appointment Have office staff total and score all questionnaires Provide you with summaries Indicate where to start HEALTH APPRAISAL & HISTORY 18

19 HAQ GRAPH 19

20 HAQ GRAPH AND KEY -> RECOMMENDATIONS Reassess every 2-6 months to document progress INTRODUCING IDENTI-T THE PERSONALIZED STRESS RELIEF PROGRAM 20

21 IDENTI-T STRESS ASSESSMENT Provides information on 3 layers of stress response: 1. The intensity of perceived stress 2. HPA over- or under-responsiveness to stressors 3. The relationship between stress type and the appropriate nutraceuticals and lifestyle support STEP 1: IDENTIFYING STRESS TYPE Add up the points in each Section A through E Section A: Wired Section B: Worried Section C: Adrenal cortisol Section D: Mental fatigue Section E: Tired 21

22 DETERMINE STRESS INTENSITY Eustress (35 or less in both Sums) Mild to Moderate (36-70) Chronic (71-105) INTERPRETING IDENTI-T SCORES & PROTOCOLS The Flow Transfer individual Section and Sum scores to the Score Card Determine stress intensity Determine HPA Over- or Underresponsiveness Determine Stress Type within HPA path chosen Check adrenal function Check sleep questions Eustress recommendations Protocols 22

23 HEALTH HISTORY HEALTH HISTORY CHECKLIST Current health conditions Current health goals Current symptoms (frequency/intensity) Current medications & supplement Laboratory procedures & outcome Hospitalizations, surgeries, injuries Stress/stressors Occupation Personal medical history Women: menstrual history Familial Health History Health habits (tobacco, alcohol, soda, caffeine, water) Exercise Eating habits/restrictions 23

24 KEEP A JOURNAL Diet/Exercise/Sleep/Stress Use online journal or other tracking forms Look over the journal with client at each visit to determine if the diet and lifestyle modifications are happening and to what extent Identify issues surrounding lifestyle changes Their resistance to change Discuss emotional responses to making changes DIET/EXERCISE/SLEEP LOG Name: Day 1 Date: Please complete your "Diet Diary / Exercise Log" every day. Wake up: Morning Meal 1.) Make note of the time you wake up. 2.) List and describe in detail all foods Time: and drinks including the amount of Snack each. Make note as to whether the Time: food was fresh, frozen, canned, raw, cooked, baked, fried, etc. Note the Mid-Day time of each meal or snack. Be Meal sure to list everything you eat or drink, Time: Snack 3.) Keep track of how much water you Time: drink and list the amount in ounces in the section provided. Also note the type and amount of any other drinks you consume. Evening Meal 4.) Write down any activity or exercise Time: 24

25 DIET/EXERCISE/SLEEP LOG FOOD JOURNAL PAGE DATE Daily Goal Breakfast 1 st Lunch 2 nd Lunch Dinner Protein: Fat: Fruit/Whole Grain/Starchy Vegetable: Non-starchy Vegetable: Protein: Fat: Fruit/Whole Grain/Starchy Vegetable: Non-starchy Vegetable: Protein: Fat: Fruit/Whole Grain/Starchy Vegetable: Non-starchy Vegetable: Protein: Fat: Fruit/Whole Grain/Starchy Vegetable: Non-starchy Vegetable: Water (in cups) Exercise (activity/duration) Sleep (in hours and quality) Supplements Obstacles Encountered Morning: Noon: Night: Taken as directed? Obstacles Overcome 80/20 Options Used (6/week) Notes (stress level, mood, energy, etc) 25

26 FOOD JOURNAL Makes eating conscious Free Takes little time Can do on paper or online If weight loss is a goal, they will lose 2x more Kaiser Permanente (2008, July 8). Keeping A Food Diary Doubles Diet Weight Loss, Study Suggests. Science Daily. Retrieved September 13, 20011, from ONLINE FOOD JOURNAL OPTIONS My Fitness Pal (www.myfitnesspal.com) Fit Day (www.fitday.com) My Calorie Counter (www.my-caloriecounter.com) 26

27 LISTEN & EXPLORE It is more important to know what patient has the disease than to know what disease the patient has. - Sir William Osler Studies show: Patients spoke, uninterrupted, an average of 12 seconds after the doctor enters the room Doctors interrupt patients 25% of the time before they finish speaking Average time with patients ~11 min; patients speaks ~4 min Fam Med Jul-Aug;33(7): Speaking and interruptions during primary care office visits. Rhoades DR 1, McFarland KF, Finch WH, Johnson AO. POTENTIAL AREAS TO EXPLORE Client goals - you may have to articulate Health history (have them provide summary) Energy/pain levels/fluctuations (scale 1-10) Bowel habits Sleep habits/patterns Stress level & major stressors Diagnosed conditions Current medication use (Rx & OTC)& current providers Dietary patterns/preferences Line of work, hours/shift, stress Physical activity Support network/relationships How to make recommendations most useful to them 27

28 USING LAB TESTS TO CREATE PATIENT FOCUSED NUTRITIONAL STRATEGIES Biochemical Individuality Everyone s needs are different Everyone expresses nutrient insufficiency in different ways One nutritional imbalance can affect numerous systems TESTING In-house testing Lab work Functional Tests 28

29 IN-HOUSE (OR AT HOME) TESTING Blood pressure Orthostatic (adrenals) Barnes Basal Temperature Test (thyroid) Bioelectrical Impedance Analysis (BIA) Zinc Tally Iodine Stain (thyroid) LAB WORK CBC w/ WBC diff Comprehensive metabolic panel Glucose, liver function, kidney function, electrolytes, proteins Thyroid panel (TSH, Free T3, Free T4) If suspect adrenal involvement: rt3 If suspect immune involvement: TPO AB, thyroglobulin AB 25 OH Vitamin D Hs-CRP / SED Rate Ferritin/Iron Homocysteine EBV/CMV titers HbA1C GTT/ITT Urinalysis/culture 29

30 COMMONLY USED FUNCTIONAL TESTS Genova/Metametrix Adrenal Stress Organix Profile Fatty Acid Bloodspot CDSA 2.0 Comprehensive Parasitology Small Intestine Bacterial Overgrowth Toxic Element Clearance Menopause/Plus Rhythm/Plus Male Hormone/Plus SpectraCell LPP+ Micronutrient Profile Elisa/Act LRA DBS Labs OCT2 Assay Interpretation IN-HOUSE (OR AT HOME) TESTING Blood pressure Orthostatic (adrenals) Barnes Basal Temperature Test (thyroid) Zinc Tally (zinc status) Iodine Stain (thyroid) Bioelectrical Impedance Analysis (BIA) 30

31 VITALS: BLOOD PRESSURE Orthostatic Normal Take lying blood pressure after supine for 5-10 min Have patient stand; take blood pressure immediately and again 1 minute later Orthostatic Hypotension Systolic should increase 5-10 mmhg Systolic decreases Diastolic should increase 5mmHg Diastolic decreases A drop of more than 5-10 mmhg upon standing is suggestive of adrenal stress/fatigue If BP does not recover at 1 min post-standing test is suggestive of long-term adrenal fatigue BARNES BASAL TEMPERATURE TEST Upon waking, take your axillary (armpit) temperature BEFORE rising Record the temperature for at least 3 mornings Menstruating women: perform days 2-4 of cycle ideally Take the average; any number below 97.6F is an indication of subclinical hypothyroidism 31

32 ZINC: FUNCTIONS Found in over 300 enzymes Only metal which appears on all enzyme classes Metabolism of carbohydrates, proteins and lipids Protein and DNA synthesis Anti-oxidant (component of Cu-Zn SOD) Plays a role in taste, smell, hormone production, immune health, prostate and reproductive organ health, GI health, detoxification, eye health, learning, neurotransmission, gene expression, programmed cell death, etc 32

33 ZINC TALLY Quick, effective zinc status assessment 2 tsp of Zinc Tally in mouth; swish for 20 sec If no metallic taste/astringency very deficient Recommend 150 mg/zn/day Some metallic taste/astringency deficient Recommend 100 mg/zn/day Strong metallic taste/astringency sufficient Recommend no or 25 mg/zn/day Retest in 1 month IODINE STAIN Quick iodine assessment Apply 2% iodine solution to inner forearm About the size of quarter Cover with Band-Aid once dry Observe length of time until disappears > 6 hours sufficient iodine status < 6 hour indicates need for iodine Repeat every 2 weeks until sufficient, then conduct monthly 33

34 BIOELECTRICAL IMPEDANCE ANALYSIS (BIA) BIA measures: Body fat Lean muscle mass Total body water Intracellular water Extracellular water Basal metabolic rate Phase angle Daily energy needs BIA AND FATIGUE Use to determine: Hydration status crucial for energy production Loss of 2.5% BW in water = 25% reduction in mental and physical abilities TBW/TBW%; ICW/ICW% Protein needs customize dietary guidelines SMM grams protein/lb SMM Overall health status/metabolic function ICW/ECW balance/shifts Phase angle Gopinathan P.M., Pichan G., Sharma M.A. Role of dehydration in heat stress-induced variations in mental performance. Arch. Environ. Health. 1988;43: Cian C., Barraud P.A., Melin B., Raphel C. Effects of fluid ingestion on cognitive function after heat stress or exercise-induced dehydration. Int. J. Psychophysiol. 2001;42: Cian C., Koulmann N., Barraud P.A., Raphel C., Jimenez C., Melin B. Influences of variations in body hydration on cognitive function: Effects of hyperhydration, heat stress, and exercise-induced dehydratio. J. Psychophysiol. 2000;14:

35 BIOELECTRICAL IMPEDANCE ANALYSIS (BIA) BODY COMPOSITION Ratio of Fat to FFM Obesity, heart disease, diabetes, insulin resistance, cancer Weight loss Healthy or not / Long term or not BCM/LBM daily protein needs grams protein/lb of BCM or LBM Metabolic/mitochondrial function 35

36 BODY COMPOSITION Risk of disease associated with excess fat Weight loss Healthy: Fat, ICW, SMM Long-term or short-term SMM protein needs grams protein/lb of SMM Metabolic/Mitochondrial function Exercise beneficial/enough Best biomarker of healthy aging Ideal body fat %: Female = 20-25% Males = 10-15% WATER DISTRIBUTION TBW low = insufficient water intake Water needs; eliminate diuretics ICW low / ECW high= functionally dehydrated Electrolyte (K/Mg), EFA &/or detoxification need Inflammation, mitochondrial dysfunction, sex hormone imbalance(s),food hypersensitivity, kidney impairment Exercise 36

37 Hydrated cells vs. Dehydrated cells 37

38 BIA: OPTIMAL VALUES Data from Robert Rakowski, DC BIA BENEFITS Simple, objective, in-office procedure Early detection of imbalances Reliable progress monitor Inexpensive and solid ROI 38

39 BIA ORDERING INFORMATION Contact: Charles Hughes W / C Code: OLERSEMINAR Get lowest clinical price on new units Receive free training materials with new units BIA ORDERING INFORMATION Contact: Susan Stauffer Code: OLERSEMINAR Get lowest clinical price on new units Receive free training materials with new units 39

40 LAB WORK CBC w/ WBC diff Comprehensive metabolic panel Glucose, liver function, kidney function, electrolytes, proteins Thyroid panel (TSH, Free T3, Free T4) If suspect adrenal involvement: rt3 If suspect immune involvement: TPO AB, thyroglobulin AB 25 OH Vitamin D Hs-CRP / SED Rate Ferritin/Iron Homocysteine EBV titers HbA1C GTT/ITT Urinalysis/culture LAB WORK: CBC WITH WBC DIFF Red Blood Cells RBC Low: blood loss; hemolytic rxn, bone marrow disorder High: dehydration, polycythemia Hgb/Hct Low: anemia, hemolytic rxn High: polycythemia MCV classify anemias Low: microcytic need iron High: macrocytic need B12/Folate Test Result Unit Reference Range RBC 5.28 M/mm Hgb 15.6 g/dl Hct 45.7 % MCV 86.5 fl MCH 29.5 Pg MCHC 34.1 g/dl

41 RBC CASE STUDY #1 Test Result Unit Reference Range RBC 3.5 M/mm Hgb 11.6 g/dl Hct 36.0 % MCV 78.2 fl MCH 29.5 Pg MCHC 34.1 g/dl Next Steps? Look for cause of low RBC Trauma (recent) Internal bleeding GI tract, bladder/uterus Hemolytic reaction Medication(s) Autoimmunity Hemoglobinopathy Sickle cell anemia Chronic inflammatory condition/disease Support RBC formation Iron, succinic acid, glycine, folic acid, B6, B12 Hemagenics 1 BID cf RBC CASE STUDY #2 Test Result Unit Reference Range RBC 4.62 M/mm Hgb 11.6 g/dl Hct 36.0 % MCV fl MCH 29.5 Pg MCHC 34.1 g/dl Next Steps? Supplement Iron Folate B12 Hemagenics 1 BID cf 41

42 LAB WORK: CBC WITH WBC DIFF White Blood Cell Differential WBC Critical levels <2500 or >30,000 >10K: active infection, inflammation (acute) <4K: viral/chronic infection, bone marrow disorder Differential Counts Test Result Unit Reference Range WBC 6.1 K/mm LY 27.7 % MO 4.8 % EO 2.5 % BA 1.0 % LY# 1.6 K/mm MO# 0.4 K/mm GR# 4.5 K/mm EO# 0.2 K/mm BA# 0.1 K/mm LAB WORK: CBC WITH WBC DIFF Neutrophils High: acute bacterial infection, inflammation Low: viral/overwhelming infection, drug reaction Eosinophils High: allergic rxn, parasite, IBD Monocytes High: acute/resolving immune response; IBD Lymphocytes High: acute viral infection, lymphoma/leukemia Basophils High: Inflammation, allergic rxn Test Result Unit Reference Range WBC 6.1 K/mm NE 58.0 % LY 27.7 % MO 4.8 % EO 2.5 % BA 1.0 % LY# 1.6 K/mm MO# 0.4 K/mm NE# 4.5 K/mm EO# 0.2 K/mm BA# 0.1 K/mm

43 WBC CASE STUDY #1 Test Result Unit Reference Range WBC 3.2 K/mm NE 42.0 % LY 52.0 % MO 6.0 % EO 0.2 % BA 0.1 % Analysis? Viral infection, possibly chronic Next Steps? Health history recent and past Additional testing EBV, CMV, etc. WBC CASE STUDY #2 Test Result Unit Reference Range WBC 10.0 K/mm NE 54.0 % LY 28.0 % MO 6.0 % EO 8.6 % BA 0.1 % Analysis? Allergic reaction Next steps? Health history Asthma, hay fever, seasonal allergies, known allergies/exposure Testing Food allergy testing IgE and hypersensitivity Environmental allergy testing 43

44 CBC WITH WBC DIFFERENTIAL: THERAPEUTIC CONSIDERATIONS Fatigue Chronic infection/illness Guidance on type of infection Pallor/pale skin Suspect iron, B12 and/or folate deficiency Chronic inflammation LAB WORK: METABOLIC PANEL Fasting glucose Optimal: mg/dl High: (pre)diabetes Low: hypoglycemia BUN Low: malnutrition, malabsorption Creatinine & BUN High: impaired kidney fxn 44

45 LAB WORK: CMP - ELECTROLYTES Calcium High: hyperparathyroid/thyroid, cancer, excess vitamin D Low: malabsorption, vitamin D deficiency Chloride High: dehydration, hyperparathyroid Low: severe vomiting, diuretic medications Magnesium High: dehydration, kidney disorder Low: chronic diarrhea/sweating, malabsorption, liver disease Potassium High: dehydration, cell damage, Addison's disease Low: diarrhea/vomiting/sweating, malabsorption, malnutrition, diuretic, excess licorice ingestion Sodium High: dehydration, Cushing s disease Low: diarrhea/vomiting/sweating, malabsorption, diuretics, excess body water LAB WORK: CMP Protein/Albumin High: dehydration, vomiting, diarrhea, poor kidney fxn Low: malabsorption, malnutrition, severe liver disease, alcoholism Alk Phos High: obstructive jaundice, cirrhosis, hepatitis; osteomalacia, bone disease, celiac Low: malnutrition AST/ALT High: myocardial infarction, liver disease, pancreatitis 45

46 CMP: THERAPEUTIC CONSIDERATIONS Blood sugar imbalance Kidney function Liver function Drug effects Electrolyte balance Parathyroid imbalance Severe dehydration VITAMIN D: 25-OH VITAMIN D Normal range: ng/ml Optimal range Healthy: ng/ml Auto-immune, chronic pain, osteoporosis: ng/ml Toxic: >200 ng/ml Adults: IU/day Children: IU/day Hathcock JN, Shao A, Vieth R, Heaney R (January 2007). "Risk assessment for vitamin D". Am. J. Clin. Nutr. 85 (1): "Dietary Reference Intakes Tables [Health Canada, 2005]". Retrieved21 July2011. Vieth R (December 2007). "Vitamin D toxicity, policy, and science".j. Bone Miner. Res. 22 Suppl2: V

47 VITAMIN D: HOW MUCH DO I TAKE? Kennel, Kurt A. et al. Vitamin D Deficiency in Adults: When to Test and How to Treat. Mayo Clinic Proceedings, Volume 85, Issue 8, Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status. Osteoporosis International. July 2005, Volume 16, Issue 7, pp LAB WORK: HS-CRP High sensitivity C-Reactive Protein Nonspecific, acute phase reactant protein which increases with inflammation, infection or cell injury high sensitivity lower limits of detection than CRP Normal: < 1.0 mg/dl High risk: > 3.0 mg/dl: risk of CV event 300% > 15 mg/dl indicates non-cardiovascular specific inflammation High hs-crp associated with insulin resistance, metabolic syndrome, VAT, CVD & systemic inflammatory states/disorders 47

48 LAB WORK: ESR (SED RATE) Erythrocyte (RBC) Sedimentation Rate Measures rate at which RBCs settle out of blood in one hour Increased during inflammatory states and infection RBCs become sticky, clump together and settle faster Normal: Male: < 15 mm/hr; Female: < 20 mm/hr LAB WORK: FERRITIN Ferritin is the major iron-storage protein Test when suspect iron deficiency Normal: Male: ng/ml; Female: ng/ml Fatigue can arise < 35 ng/ml Decreased with iron deficiency, chronic bleed Increased with macrocytic anemia (B12, Intrinsic factor, folic acid deficiency); iron overdose, inflammation 48

49 LAB WORK: HOMOCYSTEINE Intermediate amino acid formed during methionine metabolism HOMOCYSTEINE 49

50 LAB WORK: HOMOCYSTEINE Intermediate amino acid formed during methionine metabolism Important predictor of coronary, cerebral and/or peripheral vascular disease Promotes the progression of atherosclerosis (by causing endothelial damage, & LDL oxidation High homocysteine = 5x risk of stroke, dementia and Alzheimer s disease Associated with deficiency of B6, B12, folic acid and/or trimethylglycine (TMG) Optimal is ~6.2 μ/l (<10 μ/l acceptable) OPTIMAL LAB VALUES Triglycerides HDL Glucose: Fasting Glucose: 2 hour Insulin: Fasting Insulin: 2 hour Homocysteine LabTest < 150 mg/dl Male: > 40 mg/dl Female: > 50 mg/dl mg/dl mg/dl Optimal Values (U.S.) < 15 μ/ml (4 μ/ml ideal) < 30 μ/ml HbA1C 5.0% Hs-CRP Blood pressure < 8 mmol/l < 0.7 mg/l < 130/85 mm Hg Waist Circumference (WC) Male: < 40 Female: <

51 Blood Glucose (mg/dl LAB WORK: HGA1C Hemoglobin A1C is the component of hemoglobin that most strongly binds with glucose % HgA1C is a strong indicator of blood glucose levels over past o days (life span of RBC) Normal values 2.0%-4.9%: Non-diabetic adult 2.5%-5.9%: Good diabetic control > 6.0%: Diabetes/poor diabetic control In Control A1c(%) 6% 5% % 150 Out-of-control 10% 9% 8% % % 300 GLUCOSE TOLERANCE TEST (GTT) & INSULIN RESPONSE Patient drinks 75 gram glucose solution after fasting 12 hrs Blood drawn fasting and at 2-hr post-glucose Test glucose and insulin LabTest Glucose: Fasting Glucose: 2 hour Insulin: Fasting Insulin: 2 hour Optimal Values (U.S.) mg/dl mg/dl < 15 μ/ml (4 μ/ml ideal) < 30 μ/ml 51

52 COMMONLY USED FUNCTIONAL TESTS Genova/Metametrix Adrenal Stress Organix Profile Fatty Acid Bloodspot CDSA 2.0 Comprehensive Parasitology Small Intestine Bacterial Overgrowth Toxic Element Clearance Menopause/Plus Rhythm/Plus Male Hormone/Plus SpectraCell LPP+ Micronutrient Profile Elisa/Act LRA DBS Labs OCT2 Assay Interpretation GENOVA/METAMETRIX ACCOUNT SET-UP Contact: Client Services: OR website: Go to Getting Started box OR https://www.gdx.net/customer-support/client-infoform CDSA Parasitology, Toxic Elements, Adrenal Stress, Hormones, Organic acids Code: OLERSEMINAR Ask for educational & personal testing options 52

53 SPECTRACELL ACCOUNT SET-UP Contact: Chris Nordeen Micronutrient Testing Lipoprotein Particle Testing LPP+ GETTING THE DATA: WHERE TO START Give everyone the Client Packet Health Appraisal, Detoxification, Identi-T Stress, Insulin Resistance Questionnaires Health History, Diet Journal, Exercise Log Have office staff score/summarize all Review medical records (if possible) Use this information to identify most probable/top 3-4 underlying causes 53

54 UNDERLYING CAUSES OF FATIGUE 1. Diet Insufficiency Allergy/sensitivity 2. Adrenal fatigue 3. Mitochondrial dysfunction 4. GI Imbalances Poor digestion Malabsorption Food hypersensitivity Dysbiosis 5. Inflammation 6. Sleep disturbance 7. Immune Imbalance Chronic infection Hypersensitivity 8. Toxicity Detoxification Imbalance Heavy metal toxicity 9. Hormone Imbalances Adrenal Thyroid Insulin Sex hormones GETTING THE DATA: WHERE TO START Nutritional/Diet Testing: Food diary, medication use BIA, Zinc Tally, CBC, 25-Hydroxy Vitamin D, Homocysteine, Ferritin/Iron Organix Profile, Fatty Acid Bloodspot, Micronutrient Profile Adrenal Testing: HAQ: Part IIIB Identi-T Stress Assessment Adrenal Stress test Orthostatic blood pressure Mitochondrial Dysfunction HAQ: Mountain range BIA, Zinc Tally, CBC, 25-Hydroxy Vitamin D, Homocysteine, Ferritin/Iron, Packed RBC Mg Organix Profile, Fatty Acid Bloodspot 54

55 GETTING THE DATA: WHERE TO START Gastrointestinal Imbalances Health history; previous diagnoses; medical records HAQ: Part I BIA, CBC with WBC diff, Zinc Tally Saliva ph > 6.8 CDSA 2.0 w/ Parasitology, Organix Profile, Fatty Acid Bloodspot, Micronutrient Profile Inflammation Health history; medical records HAQ: Part IX BIA, CBC w/ WBC diff, hs-crp, 25-OH Vitamin D Fatty acid bloodspot Insulin Resistance Health history; Food journal; medical records; Rx use HAQ: Part IV; Insulin Resistance Questionnaire BIA, WHR, Fasting glucose, GTT/ITT, HgbA1c, Triglycerides, Blood pressure, hs-crp WHERE TO START 1. Determine need for additional testing (gaps in the data) and get testing/labs completed 2. Review data and formulate recommendations for top 1-3 underlying causes 3. Initiate dietary change 55

56 STANDARD AMERICAN DIET (SAD) We are digging our graves with our teeth. - Thomas Edison REALLY SAD DIET 92% do not eat enough vegetables 93% do not eat enough legumes 96% do not eat enough whole grains Over 90% over-consume solid fats, added sugars and alcoholic beverages Smith, et al. Americans Do Not Meet Federal Dietary Recommendations. The Journal of Nutrition. Doi: /jn released Sept

57 SAD SAD DIET 45% do not eat ANY fruit or fruit juice 22% do not eat ANY vegetables ¼ of all vegetables consumed = French fries 20-25% of Americans eat fast food/day 70% of all foods consumed are highly processed Average only 2-3 servings vegetables/day B H Patterson, G Block, W F Rosenberger, D Pee, and L L Kahle. Fruit and vegetables in the American diet: data from the NHANES II survey. American Journal of Public Health December 1990: Vol. 80, No. 12, pp WE ARE PLANT DEPRIVED U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, th Edition, Washington, DC: U.S. Government Printing Office, December

58 WHAT AMERICANS EAT Dairy products: lbs Ice Cream: 24 lbs. Cheese: 31.4 lbs. Pizza: 23 lbs.. Red meat: 110 lbs. Fats & Oils: 85.5 lbs. Coffee, Cocoa & Nuts: 24 lbs. Vegetables: lbs. French fries: 29 lbs. Corn: 56 lbs. Caloric sweeteners: lbs. Artificial sweeteners: 24 lbs. Soda: 53 gallons 2700 calories/day https://visual.ly/what-americans-eat SUGAR SWEET INFLAMMATION The average American consumes 156 lbs of sugar each year = 31 5-lb bags of sugar per person/year 44 tsp of sugar EVERY DAY 58

59 SOFT/ENERGY DRINKS Account for more than 27% of total beverage consumption in the US Average American drinks over 54.5 gallons of soft drinks per year (almost oz. cans) 36% of added sugar intake comes from soda Single largest source of refined sugar in US diet! PH OF LIQUIDS Remember that the body must maintain an alkaline (ph>7.0) chemistry, so a low ph is BAD! Substance ph Substance ph Pure water 7.0 Diet Mountain Dew 3.34 Cow s milk 6.5 Mountain Dew 3.22 Barq s 4.61 Orange Slice 3.12 Beer 4.4 Nestea 3.04 Diet 7Up 3.67 Gatorade 2.95 Wine 3.5 Coke / Pepsi 2.50 Diet Coke 3.39 Battery Acid 1.0 Ditch the soda! 59

60 BUT I NEED CAFFEINE TO FUNCTION Avoid if possible Causes stress on the adrenals, which can prolong adrenal fatigue and resolution of fatigue Start with adrenal support, increase sleep/rest and foundational nutrition If needed use the following: Green tea Yerba Mate SAD SAD DIET Most Americans eat foods that will kill them and avoid foods that will help them thrive 60

61 TREAT OR CHANGE? Think of your body as a fish tank Cells, organs and tissues as the fish Pollute the water, put in too much or the wrong kind of food, slow down filtration/elimination = sick fish Will you treat them or change the water and give them what they need to thrive? We need to change our internal environment to heal and thrive THE NEED FOR DIETARY CHANGE Optimal nutrition starts and ends with what we eat and drink on a daily basis Most daily nutrients come from food NEED a constant, daily supply Progress/healing will depend on it Not a race, but sooner the better Balance is key progress not perfection Tastes will change; give them time & pay attention All in for days 61

62 OPTIMAL NUTRITION An adequate diet (USDA Food Pyramid) prevents gross nutritional deficiency An optimal diet improves performance and promotes health and longevity HOW DOES EATING THIS WAY EFFECT YOU? 62

63 WHAT IS THE MESSAGE I M SENDING? Food is information NUTRITION & FATIGUE A single nutritional deficiency can lead to fatigue >9 out of 10 Americans are nutritionally deficient https://milklife.com/sites/default/files/field_pdf/nutrition/2013/08/08/what_americas_missing.pdf 63

64 NUTRITION & FATIGUE NUTRITION & FATIGUE REFERENCES Marquezi M, Roschel H et al. Effect of aspartate and asparagine supplementation on fatigue determinants in intense exercise. Int J Sport Nutr Exer Metab 2003;13: Lancha A, Recco M et al. Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise. Physiol Behav 1995;57: Efthivoulou M, Phillips J, Berry M. Abolition of the inhibitory effect of ethanol oxidation on gluconeogenesis from lactate by asparagine or low concentrations of ammonia. Biochim Biophys Acta 1995;1244: Bounous G, Molson J. Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome. Med Hypotheses 1999;53: Nicolson G, Conklin K. Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis 2008;25: Suh S, Bae W et al. Intravenous vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial. Nutr J 2012;11:7 Osada K, Komai M et al. Experimental study of fatigue provoked by biotin deficiency in mice. Int J Vitam Nutr Res 2004;74: Acin-Perez R, Hoyos B et al. Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis. FASEB J 2010;24: Jin G, Kataoka Y et al. Changes in plasma and tissue amino acid levels in an animal model of complex fatigue. Nutrition 2009;25: Vecchiet J, Cipollone F et al. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett 2003;335: Prada P, Hirabara S et al. L-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity. Diabetologia 2007;50: Berkovitz S, Ambler G et al. Serum 25-hydroxy Vitamin D Levels in Chronic Fatigue Syndrome: a Retrospective Survey. Int J Vitam Nutr Res 2009;79: Greenfield J, Farooqi I et al. Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 2009;89: ShinchukL, HolickM. Vitamin D and rehabilitation:improving functional outcomes.nutr Clin Pract 2007;22: Heap L, Peters T, Wessely S. Vitamin B status in patients with chronic fatigue syndrome. J R Soc Med 1999;92: Head K, Kelly G. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep. Altern Med Rev 2009;14: Shimizu T, Hoshino H et al. Anti-fatigue effect of dicethiamine hydrochloride is likely associated with excellent absorbability and high transformability in tissues as a Vitamin B(1). Eur J Pharmacol 2010;635: Starks M, Starks S et al. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr 2008;5:11. Nozaki S, Mizuma H et al. Thiamine tetrahydrofurfuryl disulfide improves energy metabolism and physical performance during physical-fatigue loading in rats. Nutr Res 2009;29:

65 NUTRITION & FATIGUE REFERENCES Mizuno K, Tanaka M et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition 2008;24: Engels A, Schroer U, Schremmer D. Efficacy of a combination therapy with vitamins B6, B12 and folic acid for general feeling of ill-health. Results of a non-interventional post-marketing surveillance study. MMW Fortschr Med 2008;149 Suppl 4: Maes M, Mihaylova I et al. Coenzyme Q10 deficiency in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardi. Neuro Endocrinol Lett 2009;30: Lundell K, Qazi S et al. Clinical activity of folinic acid in patients with chronic fatigue syndrome. Arzeimittelforschung 2006;56: Logan A, Wong C. Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev 2001;6: Malaguarnera M, Cammalleri L et al. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86: Vermeulen R, Scholte H. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med 2004;66: Guery M, Douillard C et al. Doctor, my son is so tired... about a case of hereditary fructose intolerance. Ann Endocrinol 2007;68: Litherland G, Hajduch E et al. Fructose transport and metabolism in adipose tissue of Zucker rats: diminished GLUT5 activity during obesity and insulin resistance. Mol Cell Biochem 2004;261: Werbach M. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 2000;5: Cefalu W, Rood J et al. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus. Metabolism 2010;59: Maes M, Mihaylova I et al. In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol Lett 2005;26: Cordova A, Alvarez-Mon M. Behaviour of zinc in physical exercise: a special reference to immunity and fatigue. Neurosci Biobehav Rev 1995;19: For more references, go to Huskisson E, Maggini S, Ruf M. The role of vitamins and minerals in energy metabolism and well-being. J Int Med Res 2007;35: Moorkens G, Manuel Y et al. Magnesium deficit in a sample of the Belgium population presenting with chronic fatigue. Magnes Res 1997;10: Maes M, Mihaylova I et al. Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. Neuro Endocrinol Lett 2007;28: DIETARY RECOMMENDATIONS 65

66 PROVIDE SUPPORT & GUIDANCE It s not because things are hard that we lose confidence; things are hard because we lack confidence. Seneca DIETARY RECOMMENDATIONS Assess readiness/ability to change May need to start VERY slowly 66

67 DIETARY RECOMMENDATIONS - OVERVIEW We are going to include foods that speed up the healing process, and pull foods out that slow it down. DIETARY RECOMMENDATIONS - OVERVIEW Change the quantity and quality of carbohydrates Focus on whole foods Foods that don t need a label Know the ingredients Small balanced meals 4-6x/day Space meals evenly every 3-4 hours Balanced = Complex carb + protein + healthy fats 67

68 QUANTITY AND QUALITY OF CARBS FOCUS ON WHOLE FOODS 68

69 FOCUS ON WHOLE FOODS LOTS OF NON-STARCHY VEGGIES Organic preferred (Dirty Dozen especially) More color the better Starchy veggies: white potato, corn, parsnip 69

70 THE DIRTY DOZEN & CLEAN 15 PROTEIN NEEDS Determine the right amount of protein BIA = 1 gram for every lb. LBM/SMM Add grams if trying to gain muscle Divide by # meals to get amt for each meal Ex: need 80 grams protein, 4 meals/day 20 grams protein at each meal Use legumes, fish and protein powders AMAP 70

71 PROTEIN GRAMS IN FOODS Meats Grams of Protein Serving Sizes Red Meat 7-9g per oz. Veal 8-9g per oz. Pork Loin 9g per oz oz. portion of meat = 1 deck of cards Turkey White Meat Dark Meat Chicken White Meat Dark Meat 9.5g per oz. 9g per oz. 9.5g per oz. 8.5g per oz. Fish and Seafood Fish 7-9g per oz. 3 oz. of grilled fish = 1 checkbook Shellfish 6-7g per oz. Eggs Whole 6.2g per egg 1 egg = 6 grams White 3.5g per oz. PROTEIN GRAMS IN FOODS Cheese and Dairy Feta 4g per oz. Cream Cheese 2g per oz. 1 oz. of cheese = 2 dice Ricotta (1/2 c) 14g per oz. Cottage Cheese (1/2 c) 14g per oz. 1/2 half c of ricotta or cottage cheese = 1/2 baseball Milk 8g per oz. Most Cheeses 6-7g per oz. Yogurt 12g per 8 oz. Soy Products Tempeh Miso Tofu Soybeans (1/4 c) 6g per oz. 3.5g per oz. 5g per oz. 14g per oz oz. of tofu or tempeh = 1 deck of cards Nuts/Beans/Legumes Nuts (1oz) 4-6g per oz. 1 oz. of nut butter = 1 ping pong ball or 2 tbsp Beans (1/2 c) 6-8g per oz. 1 oz = 20 almonds Legumes (1/2 c ) 6-8g per oz. 1/2 cup of beans or legumes = 1/2 baseball 71

72 FAT MATTERS It s not the total amount of fat in the diet that matters, it s the kind of fat Quality matters as much or more than quantity Polyunsaturated fats are good for us when we have the correct balance of -6: -3 Monounsaturated fats and some saturated fats (like those found in coconut) are good for us Most saturated fats, along with all trans fats (hydrogenated or partially hydrogenated) are deadly HYDROGENATION & PARTIAL HYDROGENATION Hydrogenation is a chemical process to add more hydrogen to natural fats to decrease the number of double bonds to increase shelf life Become saturated with hydrogen Partial hydrogenation turns natural fats into Trans fats 72

73 CIS VS. TRANS FATS Cis = on the same side Natural / Good Trans = on the other side Unnatural / Very, very BAD TRANS FATS The body cannot properly break down trans fats Incorporate into cell membranes alter function In ALL partially hydrogenated & some hydrogenated oils NAS concluded in 2005: there is no safe level of trans fat consumption LDL Cholesterol Effects of Trans Fats on Health risk of cardiovascular disease HDL Cholesterol Triglycerides Insulin resistance risk of diabetes risk of hypertension mental performance risk of multiple sclerosis (MS) risk Parkinson s Disease risk Alzheimer s Disease Can pass through breast milk! 73

74 TRANS FATS = MUST READ LABELS GETTING THE FATTY ACID BALANCE RIGHT If you choose to eat animal protein, choose fish high in omega-3s: Anchovies, herring, mackerel (Atlantic), salmon (wild), sardines, trout, tuna (albacore) Eggs organic, pasture fed Meat organic, pasture/grass fed or wild Remember 1 deck of cards sized flesh protein = ~20-25 grams protein Choose the right oils for cooking 74

75 ANIMAL FAT Comparison of Animals Muscle Fatty Acid Concentrations (mg fatty acids/100 g sample) Fatty Acid Elk Mule Deer Antelope Pasture-Fed Steer Grain- Fed Steer Saturated Monounsaturated Total Polyunsaturated Omega-3 PUFA Omega-6 PUFA Ratio -6: :1 2.3:1 2.5:1 2.3:1 5.3:1 Organic, 100% pasture fed ideal OMEGA-3 CONTENT OF FOODS Food LNA (mg) EPA (mg) DHA (mg) Total -3 (mg) Mackerel, Atlantic Herring (ocean) Lake Trout Tuna, Albacore Salmon, Chinook Salmon, Pink Sardines, canned Egg yolk Walnut Flaxseed Flaxseed oil *per 100 gram edible fish tissue or food 75

76 COOKING WITH OILS Oil Usage at a Glance Best for Baking Coconut oil Palm oil Safflower oil-high oleic Sunflower oil-high oleic Best For Sautéing Canola oil Coconut oil Olive oil Safflower oil-high oleic Sesame oil Sunflower oil-high oleic Best For Frying Coconut oil Avocado oil Palm oil Sesame oil Best For Dressing, Marinades And Dipping Flax Oil Udo's Oil Hemp Oil Olive oil Toasted sesame oil Olive, coconut and flax/udo s Store oils in cool, dark place Do NOT heat flax or Udo s oil store in fridge Use a bit more flax than olive oil daily Do not use soybean (vegetable oil), wheat germ or peanut oils Contain lectins that can adversely affect GI, immune and heart health NUTS AND SEEDS Nut -6:-3 ratio % MUFA % PUFA Walnuts Macadamia nuts Pecans Pine nuts Cashews Pistachios Sesame seeds Hazelnuts (filberts) Pumpkin seeds Brazil nuts Sunflower seeds Almonds High Eat raw if possible preserves -3 Soaking nuts improves digestion Soak overnight, drain and store in fridge for up to a week Flaxseeds grind in coffee grinder; eat ~1 Tbsp/day Enjoy nuts/seeds as a snack/side dish, not a main dish 76

77 SOAKING NUTS/SEEDS Easy way to improve digestibility and nutritional value Put nuts or seeds in a bowl, cover with purified water and let sit overnight Drain water, rinse thoroughly with fresh water Store in refrigerator for up to a week Almonds Sesame seeds Best Nuts & Seeds to Soak Macadamia nuts Pumpkin seeds EFA DEFICIENCY Standard American Diet ~25:1 omega 6:omega 3 should be ~2-4:1 Fatigue! Dry skin, hair, nails, follicular hyperkeratosis Foggy brain, inability to concentrate, psychological disturbances Compromised immune system Neuropathy Reduced visual acuity High total cholesterol/hdl ratio High triglycerides 77

78 FATTY ACID BLOODSPOT Identifies imbalances with omega-3 and omega-6 fatty acids Inflammation, free radical production, immune function Also measures trans-fatty acids Easy to implement in any practice Simple finger stick, can be done at home Cost-effective 78

79 FATTY ACID BLOODSPOT: CASE STUDY FAT SUMMARY Fats are necessary for optimal health; it s the type of fat that is important Avoid ALL trans fats and foods that have partially hydrogenated oils; limit animal fats High heat cooking Coconut oil Medium/low heat cooking olive oil Salad dressings/marinades Flaxseed/olive oil Eat raw nuts and seeds, especially walnuts If you eat animal protein choose wild caught fish, chicken, turkey, lamb, wild game or grass fed beef Get 1-2 Tbsp per day Flaxseed oil Get 2-10 grams EPA/DHA per day 79

80 THE BALANCED PLATE BALANCED MEAL What your plate should look like 80

81 IF SOMEONE IS EAT JUST TO STARTING HEAL OUT Eat Food. Not too much. Mostly Plants Strictly avoid: alcohol, soda, sugar, white flour products, artificial sweeteners, trans fats (will need to read labels) Eat: vegetables, fish, whole fruits 75%+ (3/4 plate) alkaline foods: deep colored vegetables/fruit 25% MAX (1/4 plate) HEALTHY acidic foods: fatty fish, raw nuts/seeds & some whole grains (~1-2 servings/day) Chew, chew chew! (At LEAST 30 times) Drink pure water throughout the day ½ body weight in ounces every day in divided doses DIETARY STRATEGIES GLYCEMIC CONTROL Skip the sugar Refined carbs sodas, white breads, candies, cookies Increase fiber, especially soluble fiber Legumes (beans, peas, lentils), whole fruits and vegetables, whole grains; supplement PRN (Fiber Plus or Fibersol-2) Eat meals/protein regularly Breakfast within 60 min of waking 4-5 meals/day, grams protein every meal Stay hydrated ½ body weight in ounces daily Increase phytonutrients eat the rainbow Avoid alcohol, tobacco and caffeine 81

82 WHEN THEY ARE READY Modified Anti-inflammatory diet WHEN THEY ARE READY Modified Anti-inflammatory diet Artificial sweeteners 82

83 AVOID SUGARS AND ARTIFICIAL SWEETENERS ARTIFICIAL SWEETENERS Many names: Saccharin: Sweet and Low, Sweet Twin, Sweet N Low, Necta Sweet Aspartame: Nutrasweet, Equal, Sugar Twin Sucralose: Splenda Acesulfame K: acesulfame potassium, Ace-K, Sunett Now, starting to blend them together NO studies have been done on safety 83

84 ARTIFICIAL SWEETENERS LEAD TO WEIGHT GAIN Animals fed artificially sweetened foods/liquids tended to eat more, consume more calories and gain more weight than animals fed glucose sweetened foods You can t fool Mother Nature Body expects calories with sweet-foods Increases temperature, metabolism, activity and naturally decreases calorie intake Artificial sweeteners trick the body When no calories, temp doesn t rise, metabolism slows, activity slows, hunger/food intake and fat accumulation Findings match emerging data in humans Swithers SE; Davidson TL. A role for sweet taste: Calorie predictive relations in energy regulation by rats. Behavioral Neuroscience, Vol 122(1), Feb 2008, Davidson TL, Martin AA, Clark K, Swithers SE. Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: Implications for the learned control of energy and body weight regulation. Yang Q. Gain Weight by going diet? Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med Swithers, SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in Endocrinology & Metabolism, Volume 24, Issue 9, EFFECTS OF ARTIFICIAL SWEETENERS Similar to sugar-sweetened beverages, artificially sweetened beverages (ASB) are linked to obesity Regular ASB consumption induces metabolic derangements Alters gut microbiota Induces insulin resistance ASB increase risk of diabetes, metabolic syndrome & CVD ASB can increase cravings for sugar and promote over-consumption of calories Suez J, KoremT, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, (09 October 2014). Yang Q. Gain Weight by going diet? Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med Swithers, SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in Endocrinology & Metabolism, Volume 24, Issue 9,

85 ELIMINATE SUGAR & ARTIFICIAL SWEETENERS MANAGING FATIGUE - DIET Dietary recommendations: Anti-inflammatory diet Determine/eliminate food hypersensitivities and any other food triggers, especially dairy, gluten & sugar Lymphocyte Response Assay (LRA) If have significant muscle/joint pain: Avoid nightshade vegetables (tomatoes, white potatoes, eggplant and bell peppers) Avoid grapefruit slow down detoxification Get plenty of EFAs (fatty fish, flax) Eat an alkaline (at least 50-75%) & varied diet (stress deep colored vegetables and fruits) 85

86 TRANSITION DIET Checklist get them from where they are to where they want to be ASAP Start where they are and build from there Use each Phase a unit in time (i.e., 1 week) Can be modified as needed for life circumstance Check off items when completed TRANSITION DIET: PHASE 1/8 Start reading labels know what you are eating. Give yourself an hour or so for 1-2 shopping trips to really get to know the foods you are eating If you use tobacco, coffee, soda/pop, and alcohol cut down to one or less serving a day. Help is available at the npc, just let us know. Eliminate all added salt. Do not buy products with high sodium content. Experiment with other spices and salt-substitutes. Consume a minimum of five (5) 8 oz. glasses of pure water (spring, distilled or reverse osmosis) daily (you may want to buy your water in refillable gallon containers at a health food store) If you eat animal flesh, consume only one serving daily. Have at least one piece of fruit and two vegetables each day. These are preferably fresh and raw, but may be lightly steamed or stir-fried. Buy and eat as much organic produce as possible. 86

87 TRANSITION DIET: PHASE 2/8 Eliminate margarine, vegetable shortenings, and baked goods containing hydrogenated or partially hydrogenated oil of any kind. You will have to read and begin to understand the labels if you need help, please ask us. Eliminate fried foods of all kinds, including French fries and any deep-fried foods. Stir-frying is okay. If you use tobacco, coffee, soda/pop, and alcohol cut down to one or less serving a day. Help is available just ask us! Add another piece of fruit and another vegetable to your diet. Buy and eat organic produce when possible, otherwise by sure and wash the produce with FIT or another natural produce cleanser. Eat a large salad full of raw vegetables everyday. Rotate what you include in your salads so that they are always new and enjoyable. Try some herbal and/or green teas. Buy a sampler pack and experiment. Eat a wide variety of foods daily, varying what you eat from day to day. Ideally, you should not eat the same food until four days have passed (this does not count for your salad vegetables). TRANSITION DIET: PHASE 3/8 Eliminate coffee, soda/pop and tobacco. Consume a minimum of eight (8) 8 oz. glasses of pure water (spring, distilled or reverse osmosis) daily. Try some new cereal grains this week, such as millet, quinoa, amaranth, teff or brown rice. Go to a health food store and try some soy and rice based products. Pick several and give them a whirl ask us for suggestions if you like! Reduce dairy consumption (milk, cheese, ice cream, yogurt) to a maximum of one serving daily. Try and eat only fruit in the morning at least three days this week. Eat as much fruit as you would like, but eat only fruit until noon. 87

88 TRANSITION DIET: PHASE 4/8 Do not consume any more refined supermarket vegetable oils, which are vegetable oils that are on the shelves in clear containers (corn, sunflower, safflower or canola oils) they have been stripped of many vital nutrients. Consume only virgin or cold-pressed flax, canola, Udo s and olive oils that are stored in opaque containers from organic sources. Eliminate white flour, bleached flour, bromated flour, even wheat flour. It has to say 100% whole wheat or 100% whole grain. If it does not, one look at the label will show you that you shouldn t eat it. Find out which foods you are sensitive to and eliminate them. Wheat, gluten-containing grains, dairy products, and yeast-containing foods are common offenders. Help is available at the NPHC if needed! Eat 1-2 servings of steamed vegetables at lunch or supper. TRANSITION DIET: PHASE 5/8 Eliminate processed sugars, including high-fructose corn syrup, barley malt, fruit juice concentrate, and processed honey, molasses and rice syrup. Avoid baking powder that contains aluminum, aluminum foil, and aluminum pots and pans. Aluminum is implicated in causing Alzheimer s disease. Eliminate all dairy products, including milk, cheese and ice cream. Try some healthier alternatives instead. Go to a health food store and try at least three new things this week; pick from the following categories: meat/dairy alternatives, raw nuts/seeds or produce. Add another piece of fruit to your diet and another vegetable. You should now be eating at LEAST 3 pieces of fruit and 4 vegetables daily. More is better! If you eat animal flesh, eat a maximum of five servings/week. One serving of animal flesh is about 4 oz., which is equivalent to the size of a deck of cards. 88

89 TRANSITION DIET: PHASE 6/8 Relax!! Buy foods that do not have chemical preservatives, artificial colors, artificial flavors, emulsifiers, or other synthetic agents. Avoid peanuts or peanut butter unless the manufacturer certifies them as aflatoxin-free and raw. Try some other nut butters, including raw cashew butter, almond butter and organic, aflatoxin-free peanut butter. Add another piece of fruit and another vegetable to your diet. You should now be having at least 4 pieces of fruit and 5 vegetables every day. TRANSITION DIET: PHASE 7/8 Go to a health food store and try at least three new things this week; pick from the following categories: meat/dairy alternatives, produce, cereal grains. Eat only free-range, organic animal flesh products such as chicken, turkey, meat and eggs; they have more essential fatty acids, less total fat and do not contain the hormones and antibiotics given to other animals. Avoid fish from polluted waters. Fresh, wild-caught fatty cold water fish are the best (salmon, halibut, mackerel, herring, sardines); farm raised fish are usually less desirable as they are fed diets deficient in omega-3 EFA. Raw or undercooked fish should also be avoided as it can harbor parasites. Add another vegetable to your diet. You should now be having at 4-5 servings of fruit and 6-7 vegetables daily. Remember your large salad daily and have another small salad with lunch or supper. 89

90 TRANSITION DIET: PHASE 8/8 Go to a health food store and try at least three new things this week; pick from the following categories: meat/dairy alternatives, raw nuts/seeds, cereal grains or produce. Listen to your body what kinds of foods is it telling you to eat? TELL US! At this point, we need to adapt your diet to your specific needs and activity levels. Congratulations!!! You have officially transitioned into a health-promoting diet that provides all the vitamins and minerals your body needs for optimal functioning. USING THE TRANSITION DIET Have client read over phases to determine where they are Begin with earliest phase not completed Check off each completed action Celebrate completion of each phase! Alter pace as needed, but if not progressing through a phase every 2-3 weeks CALL! Progress, not perfection is the goal 90

91 SIMPLE CHANGES TO JUMP START Eat a breakfast of alkalizing fruits or veggie juice Eat at least 2 cups of alkalizing vegetables at both lunch and dinner Drink the juice of ½ a lime/lemon or 1 tsp of apple cider vinegar in 6-8 oz. water a few times daily Eat at least 2 cups of alkalizing greens (kale, mustard & turnip greens, collards or endive) daily Add miso and seaweed to soups and other dishes Enjoy liberal amounts of fruit, especially watermelon If gas/bloating a problem, cook vegetables/fruit and have small amounts of fresh vegetable juice DIETARY RECOMMENDATIONS Follow any dietary recommendations you are going to use BEFORE recommending them Experience Overcoming obstacles Connection Credibility 91

92 WATER Your body is about 70% water. You lose water every day (through sweat, urine, normal metabolism and breathing); if you don t replace it every day, you will become dehydrated. Most people are dehydrated; in fact, we have found less than 1% of the people we ve tested are properly hydrated. Nothing limits physical and mental performance faster than dehydration. If you lose just 2.5% of your body weight from water loss, you will lose 25% of your mental and physical abilities. Jeukendrup A, Gleeson M. Sport Nutrition: An Introduction to Energy Production and Performance. 2 nd Ed Benton D. Dehydration Influences Mood and Cognition: A Plausible Hypothesis. Nutrients May; 3(5): Coulston AM, Boushey C. Nutrition in the Prevention and Treatment of Disease. 2 nd Ed p FUNCTIONS OF WATER IN THE HUMAN BODY Improves oxygen delivery to the cells Transports nutrients Enables cellular hydration Cushions and lubricates bones and joints Absorbs shocks to joints and organs Regulates body temperature Removes wastes and flushes toxins Improves cell-to-cell communications Maintains normal electrical properties of cells Allows immune system to function properly Reduces Inflammation & Fatigue! 92

93 THE DEHYDRATION EPIDEMIC Water 4.6 Coffee 1.8 Milk 1.3 Juices 1.4 Soda with caffeine 1.3 What America Drinks Servings per day in order of quantity Tea 1.0 Soda without caffeine 0.6 Beer 0.5 Wine or other alcoholic beverage 0.3 Coffee, soda, caffeinated beverages, and alcohol are all diuretics which means they are dehydrating Net is that the average American consumes only ~3 eight (8) oz. servings of hydrating beverages daily! Report from Nutrition Information Center at the New York Hospital-Cornell Medical Center, May 11, Table: Cornell University Medical Center, Nutrition Information Center. Survey conducted by Yankelovich Partners. Underwritten by the International Bottled Water Association (IBWA). Reported in Alternative Medicine Magazine. June 3, 2000 DETRIMENTAL EFFECTS OF DEHYDRATION Early Signs of Dehydration Mature Signs of Dehydration Fatigue Anxiety Irritability Depression Cravings Cramps Headache Heartburn Joint and back pain Migraine headaches Fibromyalgia Constipation/colitis Anginal pain Asthma and allergies Adult onset diabetes Hypertension Autoimmune disorders Skin disorders (psoriasis, eczema, etc.) 93

94 HYDRATION MYTHS If my urine is clear, I am hydrated well. FALSE If your urine is clear, it simply means that you drank more water than your body could absorb and it is flushing it out. It has no bearing on your hydration status. HYDRATION MYTHS Thirst response is a reliable indicator of when I need to drink water FALSE Thirst response is NOT a reliable gauge of hydration/need for water Thirst response will decrease if ignored over time Thirst response often mistaken for hunger Thirst response decreases with age 94

95 HYDRATION MYTHS If I drink a lot of water at once, I am getting rehydrated. FALSE Your body s cells can only absorb so much water at once, no matter how much water you drink. While exceeding that capacity isn t harmful, you will be making more trips to the bathroom and you won t be any better hydrated. HYDRATION MYTHS I drink plenty of other liquids during the day including milk, black tea, coffee, soda and alcohol that all counts as water FALSE Tea (caffeinated), coffee, alcohol, soda and caloric beverages are NOT substitutes for water They are all diuretics, which means they make you MORE dehydrated 95

96 HYDRATION MYTHS Dehydration isn t that big of a deal. FALSE If you lose just 2.5% of your body weight from water loss, you will lose 25% of your mental and physical abilities. That means if a 100 pound person loses just 2.5 pounds or a 200 pound person loses 5 pounds of water (which can easily be done in a 1 hour workout or a day of yardwork), you will already be operating at 75% maximum capacity! That is a VERY BIG DEAL! HYDRATION FACTS We lose 2-3 quarts of water per day through normal perspiration, respiration, urination and metabolism Can increase dramatically with exercise, changes in temperature, humidity, altitude, stress & body size. 96

97 HYDRATION FACTS You can get dehydrated in a couple hours, but it can take 2-3 weeks to become properly hydrated once you become dehydrated. OUR BODY S WATER NEEDS Drink ½ your body weight in ounces every day + water lost during excessive sweating Example: 150 lb person should drink ~75 oz. of water throughout the day + water lost through sweating Sweating: 2-3 hours yardwork can cause 2-3 lbs of water loss 1 hour hard workout/practice can cause 2-5 lbs water loss 2 lbs water loss = 1 quart extra water needed Must drink in divided doses 2-4 oz. every minutes ideal; water lost from sweating should be replaced over next hrs Drink the purest water available distilled, reverse osmosis, filtered bottled water (glass or hard plastic), bottled spring water (glass or hard plastic) 97

98 EATING OUT It is likely that they are eating out the majority of the time 83% of Americans eat fast food at least 1x/week Average American eats out 4.5x/week People in US spend more on dining out than groceries It s not ideal/desired, but they are likely going to do it, at least at first Transition them to other options/cooking ASAP Give them healthier options for when they eat out https://www.zagat.com/b/the-state-of-american-dining-in-2015 EATING OUT - RECOMMENDATIONS Fast (American) food Choose: None of them unless absolutely necessary Grilled chicken/fish; sauce on side (use 1 Tbsp); no bun; extra veggies (toppings) Green salad with dressing on side AVOID: McDonalds, Burger King, Hardees, Culvers If HAVE TO eat here, see above Deep-fried anything; red meat/hamburger 98

99 EATING OUT - RECOMMENDATIONS Mexican Choose: Chipotle Fajitas with grilled meats or beans + vegetables Salads/burritos with beans, chicken or lean meat Add black beans, salsa and guacamole Avoid: Taco Bell Cheese, anything deep fried, refried beans, large bowl(s) of tortilla chips, pitchers of margaritas EATING OUT - RECOMMENDATIONS Asian or Thai Choose: Noodles, Chins, Sai Bai Thong, Bahn Tai Stir-fried shrimp, chicken + veggies (+ little brown rice) Avoid: Buffets Dishes with thick, sweet/sour sauces (Kung Pao chicken), large bowls of rice, fried eggo rolls, lo mein Breaded or deep fried foods 99

100 EATING OUT - RECOMMENDATIONS Subs and sandwiches Choose: Jimmy John s unwich Veggies especially sprouts, spinach, olives, etc. Can add chicken or turkey Salads or have open-faced sandwich (1/2 bun) Avoid: Blimpie s, Quiznos, Subway Cheese, mayo, lots of sauces EATING OUT Pizza Choose: Papa John s Thin crust, lots of veggies, hint of cheese (or none) Vegan/vegetarian pizza Salad bar as a meal or side Avoid: Pizza hut, Dominos, Toppers, Rocky s Loads of cheese, meat lovers (aka cardiac arrest) Alfredo/creamy sauces Eating more than 1-2 slices 100

101 EATING OUT - TIPS Limit menu extras Drinks, appetizers, soups, sides, desserts, sauces Always choose salad/veggies for sides; limit sauces Eat slow and enjoy your food Put your fork down between bites Chew your food until it is a liquid before swallowing Make it two meals Eat only ½ your plate; get a to-go box with meal Don t eat more to be polite Dining with another - intake 35%; 2 others - 75% Be the last to start eating and leave food on your plate EATING OUT BEST CHOICES Salad bars/deli at co-ops and/or Whole Foods Always choose options with LOTS of veggies Protein: legumes, fish, chicken, turkey Always get sauces/dressings on the side Use about ¼-1/2 of what you are given Consider eating something healthy before you go Avoid drinking alcohol before eating Will eat 20-33% more if consume alcohol 101

102 QUICK MEAL IDEAS Get salads/meals at co-op/whole Foods/grocery salad bar/deli Purchase frozen food entrees and compliment with salad bar Stir fry: buy pre-chopped veggies (salad bar), choose sauce, add protein; high heat 2-5 min Go Mediterranean: pick up some hummus, veggies (salad bar), olives, goat cheese QUICK MEAL IDEAS Super-soups add canned beans, fresh/frozen veggies, herbs and/or salsa to soups put in crock pot and let simmer Mexican chopped lettuce, mixed veggies, salsa, beans, avocado/guacamole Lettuce wraps use toppings from salad bar Omelets use leftover veggies/protein SALADS salad bar or pre-washed; try different veggies/toppings Nuts/seeds, dried fruit, herbs, oil/vinegar, veggies 102

103 THE NEED FOR SUPPORT They will NEED other people to help them They are TIRED Have support come with them Review plan of action Establish who can do what, when Get verbal/written commitment Ask if they have any questions or concerns Reiterate that they will offer support/encouragement Don t become discouraged themselves; this is not easy Acknowledge them for their support DIETARY RECOMMENDATIONS SUMMARY Use their food journal to get an overview Help them understand the NEED for dietary change Ask them if they want to go fast/slow Eat to Heal Transition Diet Anti-Inflammatory Diet CHEW food until liquid (at least 30 times) Increase water intake throughout the day 103

104 DIETARY RECOMMENDATIONS SUMMARY Give simple/easy meal ideas Help them make better choices when eating out Help them line up support needed Significant other, friend, other Plan for eating where, when go/shop, how Keep in close contact for the first 4-8 weeks Most crucial time to get them positioned for success DIETARY FOLLOW UP Ask if they have any questions Follow up within 1-2 weeks Better to catch problems NOW In-house follow up 4 weeks Review dietary recommendation step-by-step Identify issues and determine solutions together Ask them how they can do it BEFORE offering solution Come up with a plan/specific goals Subsequent follow ups 2-8 weeks 104

105 QUESTIONS: DIETARY RECOMMENDATIONS THE NEED FOR SUPPLEMENTATION Nearly the entire U.S. population consumes a diet that is not on par with recommendations conclusion of a report published online on August 11, 2010 in the Journal of Nutrition. J Nutr Aug;140(8):

106 Two case studies presented here indicate the need for supplementation as improvement in nutritional behavior could not replenish already exhausted nutrient reservoirs. Only supplementation was able to significantly boost nutrient levels and confer beneficial effects on general welfare, physical performance, and resistance to infections. Therefore, it appears that nutritional supplements are advisable for everyone. Advances in Natural Therapy Sept./Oct Functional Nutrient Deficiency in Chronically Multi-symptomatic People A Pilot Study Laraine C. Abbey, R.N., M.S. 1 This pilot study was done in partial fulfillment of the M.S. degree requirements at the University of Bridgeport. Abstract Functional vitamin testing utilizing in vitro enzyme stimulation assays was performed on 22 office clients, many of whom had no evidence of organic disease, but who had sought nutritional assessment for help with various multiple chronic symptoms unresolved by traditional medical treatment. These 22 clients with identified underactivity of various vitamin dependent enzymes (functional vitamin deficiency), despite use of multivitamins, were supplemented with pharmacological dosages of the functionally deficient nutrients). The supplementation was associated with significant symptom reduction or elimination and enhanced feelings of well being. The client Nutrients, improvement was as concomitant in food with changes and in enzyme in activity supplement demonstrated through form, follow-up as enzyme therapeutic stimulation assays. These assays demonstrated normalization after a period of pharmacological vitamin supplementation. The data agents indicates an may apparent relationship be among between chronic, the non-specific most symptoms powerful (including the tools so-called available psychoneurotic symptoms to us like fatigue, in anxiety, depression, and muscle tension) and nutritional-biochemical imbalance. Many such imbalances are now measurable and appear to be responsive to dietary and nutrient manipulation often requiring pharmaco-logical doses of specific B-vitamins to normalize the functionally vitamin deficient assay and reduce or manipulating biochemistry to prevent, modify, or eliminate eliminate the symptoms. Introduction We are various quite literally the symptoms, product of ourown nutrition signs,... built and and maintained chronic by the progressive diseases. breakdown of food into various metabolites which are in turn ultimately transported in and out of cells.this process of intermediary metabolism, regulated by enzymes, is subject to manipulation by various factors including vitamins. University Such manipulation of Brideport, is possible, even 2010 in the absence of classical vitamin deficiency, since vitamins form coenzymes and many enzymes are not fully saturated with coenzymes under physiological conditions (Holtzman, 1980; Dakshinamurti, 1977; Martin, 1981). The author has observed that multi- symptomatic people who institute dietary changes often experience symptom reduction, including behavioral change, along with an enhanced sense of well-being. Many individuals who fail to experience significant symptom reduction with dietary changes and routine vitamin therapy do experience marked improvement from pharmacological levels of various specific nutrients following functional vitamin testing (Abbey, 1982). Various chronic symptoms in people with or without diagnosable disease were associated with underactivity of various vitamin dependent enzymes which were responsive to pharmacological vitamin supplementation. This can be the result of the vitamin's effect upon a particular enzyme system's activity rather than because the total body vitamin pool was low as in a deficiency. An understanding of enzyme kinetics helps to clarify the role of vitamins in increasing an enzyme's reaction product through increasing the percentage of functioning apoenzymes and holoenzymes and further by increasing the rate or velocity of its reaction (Partridge, 1977). It is well documented that depriving individuals of certain vitamins may result in a variety of symptoms and personality RNA LifesStyle, Warren Plaza West, Route 130, East Windsor. N.J

107 THE NEED FOR SUPPLEMENTATION Especially true with chronic fatigue and illness Increased need Genetics Metabolic imbalances Chronic stress/adrenal support Gastrointestinal imbalances Deficiency/imbalance likely Past dietary habits Genetics Metabolic imbalances Chronic stress/adrenal support Gastrointestinal imbalances Improper proportion of nutrients in foods Impractical SUPPLEMENTATION FOR OPTIMAL HEALTH The RDA (U.S. Government Recommended Daily Allowance) is the nutritional equivalent of the minimum wage. - Joel Evans, MD, The Center for Women s Health 107

108 THE FABULOUS Fabulous 5 The Fabulous Five The Fabulous 5 The The 5 Essential Essential Nutritional Nutritional Supplements Supplements The Essential Nutritional The Five Essential Nutritional Supplements Supplements FOUNDATIONAL NUTRITION: FABULOUS 5 PhytoNutrient Multi - Vitamins, Minerals & phytonutrients Broad spectrum, plant-based antioxidant protection; bioavailable forms of vitamins; nutrients for cellular/mitochondrial health EPA-DHA Pharmaceutical grade Ω-3 fatty acids Support for inflammation, body composition, cardiovascular health, blood sugar, brain development/health, mood, hormone balance, soft tissue, Less expensive & safer than eating fish Vitamin D3 (5000 IU) - Vitamin D 3 Support for fatigue, hormone function, muscle weakness, mood Impossible to get enough from sun exposure; essential for health Full Spectrum Probiotic - Probiotics Essential for GI function, nutrient assimilation, immune health Powdered Phytonutrient Blend - Broad spectrum plant phytonutrients Plant-based antioxidant support & phytonutrients 108

109 PhytoNutrient Multi EPA-DHA 720 mg Full Spectrum Probiotic Powdered PhytoNutrient Blend 109

110 FOUNDATIONAL NUTRITION: FABULOUS 5 PhytoMulti - Vitamins, Minerals & phytonutrients Broad spectrum, plant-based antioxidant protection; bioavailable forms of vitamins; nutrients for cellular/mitochondrial health OmegaGenics EPA-DHA Pharmaceutical grade Ω-3 fatty acids Support for inflammation, body composition, cardiovascular health, blood sugar, brain development/health, mood, hormone balance, soft tissue, Less expensive & safer than eating fish D Vitamin D 3 Support for fatigue, hormone function, muscle weakness, mood Impossible to get enough from sun exposure; essential for health Ultra Flora Spectrum - Probiotics Essential for GI function, nutrient assimilation, immune health Dynamic Fruits & Greens - Broad spectrum plant phytonutrients Plant-based antioxidant support & phytonutrients PHYTOMULTI CELLULAR SUPPORT Bioavailable forms of vitamins Folate (L-5-methyltetrahydrofolate) B12 (methylcobalamin) Ultra-Potent C (fat & water soluble mineral ascorbate) Suite of essential vitamins and minerals for cellular/mitochondrial health Blend of concentrated plant extracts & phytonutrients High antioxidant potential 110

111 SMART EVALUATIONS: TOTAL ORAC FN 10 servings of fruits & vegetables= ORAC 3,000 to 5,000 USDA Cell Protection and DNA Stability Nucleus COMET Cell Total ORAC FN Free radicals attacking the cell DNA Proprietary PhytoMulti phytonutrient blend Total ORAC FN Oxygen Radical Absorbance Capacity COMET Assay Single Cell Gel Electrophoresis Assay 111

112 Text EPA&DHA: THE SUPER NUTRIENTS Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Long-chain polyunsaturated fatty acids from fish Essential because humans are unable to synthesize them, so they must be obtained by diet A Question of Balance The average American diet is at least 20 times higher in omega-6 EFAs (plant oils) to omega-3 EFAs. This imbalance can lead to numerous health complications. 112

113 FISH OIL TO FIGHT INFLAMMATION & FATIGUE Omega-6 Fatty Acids Omega-3 Fatty Acids (Corn, safflower, sunflower, soybean oils) Linoleic Acid Alpha-Linolenic Acid (ALA) (Flaxseed, soybeans, green leafy vegetables, spirulina) (Borage seed, Evening Primrose) Gamma-Linoleic Acid (GLA) EPA DHA (Fish, fish oils) (Meat, eggs, organs) COX Arachidonic Acid (AA) LOX COX LOX PGE2 LTB4 PGE3 LTB5 Pro-Inflammatory Compounds Anti-Inflammatory Compounds -6 : -3 in US ~25:1; we need a ratio ~2:1 113

114 QUALITY OMEGA-3 SUPPLEMENTS: HIGHER PURITY AND SAFETY THAN FISH Summary PCBs in farmed salmon Government studies show that one of every six pregnant July women 2003 in -the Results U.S. will from give tests birth of store-bought a baby whose farmed blood salmon is show contaminated seven of with 10 fish mercury were so at levels contaminated above the with federal PCBs safety that they standard. raise Emitted cancer risk from -- coal-fired Salmon power farming plants has made and other salmon the third sources, most the popular pollutant fish builds in America up in and some comprises types of seafood, 22 percent of all retail including seafood canned counter tuna. sales. Nutrients However, in fish research are vital for shows a baby's that brain farmed development, salmon but are too likely much the mercury most PCB-contaminated can cause lasting protein brain source damage. for (Source: people in Environmental the U.S. (Source: Working Environmental Group) Working Group) EVERY BATCH OF OIL SHOULD BE THIRD-PARTY PURITY- CERTIFIED Third-party certified by the world s leader in in chemical analysis, Wertz Laboratories in Hamburg, Germany Assays available online listed by product and date tested 114

115 EVERY BATCH SHOULD BE THIRD-PARTY TESTED For over 250 contaminants including: 220 pesticides 6 heavy metals 7 markers of PCBs 15 dioxins & furans 12 dioxin-like PCBs VITAMIN D Vitamin D deficiency is associated with fatigue, cognitive dysfunction, muscle weakness and depression Important for calcium absorption Up- and down-regulates immune functions Anti-inflammatory Heidari B, Shirvani JS, Firouzjahi A, et al. Association between nonspecific skeletal pain and vitamin D deficiency. Int J Rheum Dis2010;13: Montero-Odasso M, Duque G. Vitamin D in the aging musculoskeletal system: An authentic strength preserving hormone. Mol Aspects Med2005;26: Barnard K, Colón-Emeric C. Extraskeletal effects of vitamin D in older adults: Cardiovascular disease, mortality, mood, and cognition. Am J Geriatr Pharmacother 2010;8:4-33. Walsh D, Rybicki L. Symptom clustering in advanced cancer. Support Care Cancer 2006;14: American Journal of Clinical Nutrition, Vol 51, Vitamin D: its role and uses in immunology The FASEB Journal. Hector F. Deluca and Margherita T. Cantorna 2001;15:

116 VITAMIN D: FUNCTIONS May be involved in: Depression and mood Cognition and dementia Pregnancy deficiency associated with: Gestational diabetes, pre-eclampsia and small birth weight Testosterone production Improving body composition Decreasing VAT Better overall health and mortality VITAMIN D: SOURCES Hormone-like in action D3 results from UV irradiation (sunlight) of 7-dehydrocholesterol, which is then converted in the liver and kidneys to active form 10 minutes of sun exposure to face and hands = 400 IU Supplementation with D3 116

117 SUN EXPOSURE NOT ENOUGH Researchers at University of Wisconsin investigated vitamin D status of healthy males living in Hawaii Mean of 11.1 hours/week of total body sun exposure with no sunscreen 51% had low vitamin D levels Ability to convert vitamin D in the skin becomes significantly diminished with age Binkley N, Novotny R, Krueger D, et al. Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab Jun;92(6):

118 VITAMIN D: THERAPEUTIC CONSIDERATIONS Ideal levels (healthy): ng/ml Autoimmunity/Inflammation: ng/ml SAD/Depression Fractures, Osteoporosis/Osteopenia Dark skin Research shows that dark-skinned people living in temperate climates have lower vitamin D levels Melanin hinders vitamin D synthesis Sunscreen blocks vitamin D synthesis HOW MUCH VITAMIN D DO YOU NEED? Have blood tested: 25-hydroxyvitamin D Optimal levels ng/ml Daily Vitamin D Dose Increases blood levels by: 1,000 IU 11.6 ng/ml 10,000 IU 58.5 ng/ml 50,000 IU ng/ml BMI important larger people need more D Example: target 60 ng/ml 154 lb person, baseline level: 20 ng/ml Need ~5,000 IU/day Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int. 1998;8(3):

119 VITAMIN D: HOW MUCH DO I TAKE? Kennel, Kurt A. et al. Vitamin D Deficiency in Adults: When to Test and How to Treat. Mayo Clinic Proceedings, Volume 85, Issue 8, Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status. Osteoporosis International. July 2005, Volume 16, Issue 7, pp The Human Microbiome - The enormous population of microbes, including bacteria, fungi, and viruses, that live in and on the human body, but predominantly in the gut. There are 20 times as many of these microbes as there are cells in the body, up to 200 Trillion in an adult, and each of us hosts at least 1,000 different species. Discover Magazine March

120 HEALTH BENEFITS OF FLORA BALANCE Support vitamin and short chain fatty acid production Promotes healthy intestinal tissues, energy production and repair processes Support the assimilation of nutrients Facilitate digestion (lactose) Support healthy mucosal and systemic immune response Help to protect the intestinal mucosa from increased permeability and toxins GI CONDITIONS: DYSBIOSIS - CAUSES Antibiotics, antifungals, antacids/ppis/h2 antagonists, NSAIDS, steroids Viral, bacterial, fungal and/or parasitic infection Poor diet nutrient/fiber, allergens Low stomach acid/digestive enzymes Stress Significant changes in 1-6 days Environmental toxins 120

121 GI CONDITIONS: DYSBIOSIS - SYMPTOMS GI Symptoms Nausea/vomiting Loose stools Diarrhea Constipation Gas Bloating Heartburn/acid reflux Belching/burping Indigestion Non-GI Symptoms Bad breath Cravings Runny nose Itchy eyes/skin Rashes/skin disorders Joint pain Hyperactivity Fatigue Sinus congestion Headache Mood swings Acne Muscle aches Flu-like symptoms WHAT TO LOOK FOR IN A PROBIOTIC Potency: billion CFU at expiration Stain-identified: targeted support Each probiotic strain supports specific activities within the body. Beneficial properties of each probiotic strain verified by scientific and clinical research Viability: documented; refrigeration Expiration date: at most 1 year after manufacture; guarantee potency at expiration 121

122 PHYTONUTRIENTS & SUPERFOODS phyto means plant in Greek Responsible for color and smell of many foods ~4,000 phytonutrients Have biological significance but are not established as essential nutrients i.e., carotenoids and flavonoids Many act as potent antioxidants 122

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125 PHYTONUTRIENTS Eat as many deep colored foods as possible daily ANTIOXIDANTS SUPERFOODS Nutrient-dense, high in antioxidants Fruit and Nut Superfoods Acai berry, Goji berry, Pomegranate, Mangosteen, Cacao (raw), Maca, Noni, Coconuts, Acerola cherry, Grape seed extract Greens Barley grass, Wheat grass, Blue-green algae, Spirulina, Chlorella, Alfalfa, Green leafy vegetables Seaweed: Kelp, Nori, Dulse, Wakame, Kombu 125

126 ANTIOXIDANTS SUPERFOODS Benefits Very high in antioxidants counter free radical damage Enhance immune function Improve detoxification Improve metabolism Improve recovery/repair Improve digestion Look for: Organic, whole-food ingredients, no added sugar/artificial anything, dairy/gluten-free FREE RADICAL DAMAGE 126

127 FREE RADICAL DAMAGE Disorders caused by free radical damage Alzheimer s disease and senility/dementia Atherosclerosis Cancer Heart disease Inflammation Joint disease Stroke Cataracts/vision loss Chronic fatigue Diplock AT. Antioxidant nutrients and disease prevention: an overview. Am J Clin Nutr 1991:53;189S-93S. Harman D. Free radical involvement in aging: pathophysiology and clinical implications. Drugs Aging 1993;3: FREE RADICAL DAMAGE 127

128 ANTIOXIDANTS REDUCE FREE RADICAL DAMAGE THE BENEFITS OF ANTIOXIDANTS 128

129 FABULOUS FIVE RECOMMENDATIONS Recommendation Dosage PhytoNutrient Multi 1 capsule BID with food D (per testing) 1 capsule 1-3x/day with food EPA-DHA 720 Full Spectrum Probiotic Powdered Phytonutrient Blend OR PhytoNutrient Health Drink (added protein) Provides foundational support 1-2 gelcaps BID with food 1 capsule before bed (empty stomach) 1 scoop in 8-12 oz. liquid Vitamin, minerals, phytonutrients, EPA/DHA, D High levels of plant-based antioxidants Supports proper immune and GI function QUESTIONS: FABULOUS FIVE??? 129

130 UNDERLYING CAUSES OF FATIGUE 1. Diet Insufficiency Allergy/sensitivity 2. Adrenal fatigue 3. Mitochondrial dysfunction 4. GI Imbalances Poor digestion Malabsorption Food hypersensitivity Dysbiosis 5. Inflammation 6. Sleep disturbance 7. Immune Imbalance Chronic infection Hypersensitivity 8. Toxicity Detoxification Imbalance Heavy metal toxicity 9. Hormone Imbalances Adrenal Thyroid Insulin Sex hormones FATIGUE: ADRENAL STRESS/FATIGUE Extremely common Clinical presentation can vary dramatically Anxiety, nervous, fidgety Physical tired and/or exhausted Depression, lethargy, malaise Cognitive decline, emotionally/mentally spent 130

131 CHRONIC STRESS THREATENS OUR HEALTH 75% of US adults experience moderate to high levels of stress every month 54% are concerned about the level of stress in their everyday lives Nearly 4 in 5 U.S. adults regularly experience physical symptoms associated with stress Over 7 in 10 American adults commonly suffer stressrelated psychological symptoms Nearly 1 in 2 report that stress has had a negative impact personally and professionally Accounts for 75%-90% of all primary care visits in the U.S. Stress in America: American Psychological Association; I AM SOOOOO STRESSED! 131

132 THE STRESS RESPONSE Chronic stress inappropriate stress experienced frequently for a duration of time Physiological responses to chronic stress allow an individual to adapt to the heightened level of stress = allostasis A person s response to the stressors in their lives (based on perception) determine how/whether they adapt THE STRESSFUL THINGS IN LIFE (STRESSORS) THAT TRIGGER THE STRESS RESPONSE DON T MAKE US SICK. The body s unique response to those stressors does. Center for Studies on Human Stress, Sonia Lupien PhD 132

133 A healthy stress response is short lived Stressors: Novel Unexplained Threatening Sense of control 2 Hypothalamus Perceived Stressor 1 Sympathetic ALARM Response (SNS*) (norepinephrine noradrenalin ) Pituitary Gland ACTH Resolution turns off stress response Facilitates Negative Feedback Loop Adrenal Glands 1.*Sympathetic Nervous System 2. Adrenocorticotrophin hormone 3. Corticotrophin releasing hormone 3 Cortisol Kidneys Resolution STEROID HORMONE PRINCIPLE PATHWAYS Cholesterol Pregnenolone 17-OH Pregnenolone DHEA Progesterone 17-OH Progesterone Androstenedione Estrone Aldosterone Cortisol Testosterone Estradiol DHT Estriol 133

134 HOW STRESS AFFECTS EVERYTHING Dotted lines = inhibition; solid lines = activation 134

135 WHY STRESS/CORTISOL IMPACTS EVERYTHING HOW CHRONIC STRESS CAUSES DISEASE The sympathetic response (HPA hyperactivation) utilizes tremendous energy & resources Designed to be a transient state If stress is prolonged, it can create an overactive stress response Chronic release of cortisol & catecholamines Symptoms: insomnia, anxiety, impatience, irritability, difficulty relaxing, over-reaction McEwen BS, Kalia M. The role of corticosteroids and stress in chronic pain conditions. Metabolism. 2010;59 Suppl 1:S9-15. al-damluji S. Adrenergic control of the secretion of anterior pituitary hormones. Baillieres Clin Endocrinol Metab. 1993;7: Plotsky PM, Cunningham ET, Jr., Widmaier EP. Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev. 1989;10: Dunn AJ, Berridge CW. Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res Brain Res Rev. 1990;15: Polymeropoulos MH, Torres R, Yanovski JA, Chandrasekharappa SC, Ledbetter DH. The human corticotropin-releasing factor receptor (CRHR) gene maps to chromosome 17q12-q22. Genomics. 1995;28: Aguilera G, Millan MA, Hauger RL, Catt KJ. Corticotropin-releasing factor receptors: distribution and regulation in brain, pituitary, and peripheral tissues. Ann N Y Acad Sci.1987;512: Chrousos GP. The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. Int J Obes Relat Metab Disord. 2000;24 Suppl 2:S

136 HOW CHRONIC STRESS CAUSES DISEASE If stress continues, this can progress into a state of inadequate stress response HPA response becomes desensitized Often referred to/feels like burnout Body cannot react appropriately to stress with decreasing cortisol production Symptoms: apathy and extreme fatigue, suicidal thoughts, poor appetite, low self-esteem, psychomotor retardation or agitation, inflammation, decreased libido and hypersomnia Thyroid function often compromised Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25:1-35. O'Connor TM, O'Halloran DJ, Shanahan F. The stress response and the hypothalamicpituitary-adrenal axis: from molecule to melancholia. Qjm. 2000;93: Pedersen WA, Wan R, Mattson MP. Impact of aging on stress-responsive neuroendocrine systems. Mech Ageing Dev. 2001;122: Bryla CM. The relationship between stress and the development of breast cancer: a literature review. Oncol Nurs Forum. 1996;23: McEwen BS. Protective and damaging effects of stress mediators: the good and bad sides of the response to stress. Metabolism. 2002;51:2-4. BREAKDOWN HPA IMBALANCES AND ADRENAL FATIGUE HPA hyper-arousal CRH, ACTH, cortisol, glucose, insulin, free fatty acids Insulin resistance catecholamines, heart rate, blood pressure, heart rhythm Anxiety, CVD, insomnia TSH, T3 Thyroid hypofunction, weight gain HPA hypo-arousal CRH over time leads to downregulation of pituitary CRH receptors Can cause adrenal atrophy CRH, ACTH, cortisol, catecholamines Depression, auto-immunity, fatigue, pain, weight gain, non-restful sleep HPA - hypothalamic-pituitary-adrenal axis 136

137 CONTINUAL EXPOSURE TO STRESSORS IS A BIOCHEMICAL EVENT THAT EXCITES THE SYMPATHETIC NERVOUS SYSTEM, PUTTING THE ENTIRE BODY ON THE ALERT An individual s stressortolerance varies based on: genetics diet toxic burden health status occupation lifestyle social skills community network family and friends human experience Kyrou I Ann N Y Acad Sci 2006 WHEN WE EXCEED OUR PERSONAL THRESHOLD OF STRESSOR-TOLERANCE WE BREAK DOWN. Everyone s breakdown is unique Digestive upset Breathing difficulties Cardiovascular Physical problems Emotional & social challenges Mental impairment Sleep disorders 137

138 ASSOCIATED SYMPTOMS Pain/spasm in upper back & neck muscles Loss of libido Poor memory Light headed when standing Headaches Irritability/moodiness Alcohol intolerance Tenderness in low back Dry/thin skin Scanty perspiration Slow wound healing Cold intolerance Weakness Nervous/anxious Chronic inflammation Palpitations Weight gain Low blood pressure Sweet/salt cravings Unexplained hair loss Muscle wasting Poor concentration Frustration/confusion Low body temps Slow recovery from work outs CLINICAL SYMPTOMS OF ADRENAL FATIGUE HPA Over-responsiveness Excess SNS Hyper-aroused, hyper-vigilant anxious, worried Easily irritated/agitated Belly fat or weight loss Decreased appetite Decreased libido Difficulty concentrating Insomnia Hypertension, tachycardia Pain and inflammation Elevated cortisol HPA Under-responsiveness Excess PSN Lethargy and fatigue Apathy, low motivation Low cortisol Weight gain Variable appetite Hypersomnia excessive sleep Suicidal thoughts Low self-esteem Depressed immune activity Autoimmune disorders Chronic pain & inflammation 138

139 CONDITIONS LINKED WITH ADRENAL FATIGUE Over-production (excitatory) Cushing s syndrome Depression & OCD Anxiety Insomnia Diabetes Anorexia nervosa Myocardial ischemia, arrhythmia Hypertension Lipid disorders Hyper- & Hypo-thyroidism Osteopenia/osteoporosis Under-production (inhibitory)) Addison s disease Seasonal depression CFIDS and Fibromyalgia Myocardial infarction Allergies/Asthma Rheumatoid arthritis Post traumatic Stress Syndrome Hypothyroidism Atypical depression Chronic pain Hypersomnolance Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25:1-35. Appels A. Exhausted subjects, exhausted systems. Acta Physiol Scand Suppl. 1997;640: Nicolson NA, van Diest R. Salivary cortisol patterns in vital exhaustion. J Psychosom Res.2000;49: O'Connor TM, O'Halloran DJ, Shanahan F. The stress response and the hypothalamicpituitary- adrenal axis: from molecule to melancholia. Qjm. 2000;93: Fries E, Hesse J, Hellhammer J, Hellhammer DH. A new view on hypocortisolism. Psychoneuroendocrinology. 2005;30: Mayer EA, Berman S, Suyenobu B, et al. Differences in brain responses to visceral pain between patients with irritable bowel syndrom Romero LM, Raley-Susman KM, Redish DM, Brooke SM, Horner HC, Sapolsky RM. Possible mechanism by which stress accelerates growth of virally derived tumors. Proc Natl Acad Sci USA. 1992;89: Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999;99: Wales JK. Does psychological stress cause diabetes? Diabet Med. 1995;12: e and ulcerative colitis. Pain. 2005;115: ADRENAL STRESS CLASSIC SIGNS Waking up in the morning and not feeling refreshed? Feeling unusually tired most of the time? Needing coffee, soda or sugary snacks to get going and keep going? Feel physically exhausted, but your mind continues to race, filled with anxiety? The feeling that you are aging too quickly? Poor digestion? Struggling to lose weight in spite of dieting and exercise? Achy muscles and/or joints or tension in your body particularly, your neck and shoulders? Diminished sex drive? Feeling dark or depressed or having trouble concentrating and focusing and remembering things? The lack of motivation to accomplish even small tasks? Getting sick more frequently and taking longer to recover? Check off >3 Investigate Adrenal Fatigue 139

140 ADRENAL FATIGUE How do you know? Acute symptoms/primary concern Interview What would you rate your energy level on a scale of 1-10? Indenti-T Stress Assessment HAQ: Part III A & B Thyroid & Adrenal Part IV Glucose Regulation Part VI Mood Part VII Immune System Part IX C Muscle and Nerves Part X B Cognition Adrenal Stress Test DEFINING STRESS AND ADRENAL FATIGUE General Adaptation Syndrome (G.A.S) 140

141 STAGES OF ADRENAL FATIGUE Acute Adrenal Stress Mild High Adrenal Fatigue NORMAL DIURNAL RANGE 141

142 ABNORMAL CORTISOL RHYTHM IDENTIFY THE STRESS EXPERIENCE 142

143 IDENTI-T STRESS ASSESSMENT IDENTI-T STRESS ASSESSMENT Provides information on 3 layers of stress response: 1. The intensity of perceived stress 2. HPA over- or under-responsiveness to stressors 3. The relationship between stress type and the appropriate nutraceuticals and lifestyle support 143

144 IDENTIFYING STRESS TYPE/INTENSITY Add up the points in each Section A through E Section A: Wired Section B: Worried Section C: Adrenal cortisol Section D: Mental fatigue Section E: Tired IDENTIFYING HPA OVER/UNDER RESPONSIVENESS Add up the points in Sections A+B+C and C+D+E Hyper vs. Hypo function Lifestyle & Health Status indicates need for lifestyle counseling 144

145 3 ADD SCORES A+B+C & C+D+E LIFESTYLE AND HEALTH STATUS x 0 Difficult menopause, divorce 2 Sausage McMuffin when I eat 0 x 0 x osteoporosis 6/08 Boniva and HRT 145

146 INTERPRETING IDENTI-T SCORES & PROTOCOLS The Flow Transfer individual Section and Sum scores to the Score Card Determine stress intensity Determine HPA Over- or Underresponsiveness Determine Stress Type within HPA path chosen Check adrenal function Check sleep questions Eustress recommendations Protocols DETERMINE STRESS INTENSITY 40 Eustress (35 or less in both Sums) Mild to Moderate (36-70) Chronic (71-105)

147 DETERMINE HPA OVER-/UNDER-RESPONSIVENESS Determine HPA Over- or Under-responsiveness Difference >5 between the Sums determines the direction of shift Difference <5 review HPA profiles and determine via interview { } x Difference >5 between the Sums determines the direction of shift Difference <5 review HPA profiles described in LEFT column DETERMINE STRESS TYPE Choose the Stress Type section within the HPA path with the highest score Section C: Cortisol Metabolism. If >10 points, consider additional support Check sleep questions for a 3 response A12, A13 or B7; D6, E9, E12 Eustress? identify stress type sections with >10 points { 30 6 } 4 x

148 SECTION C: ADRENAL CORTISOL METABOLISM *>10 POINTS MAY REQUIRE ADDITIONAL ADRENAL SUPPORT *The score in section C is added to both the HPA Over and Under-responsive paths because adrenal gland function contributes to both scenarios. Adaptogens balance the HPA axis and relieve adrenal stress indirectly. Additional repair support may be required A chronic score (>21) may indicate the need for an Adrenal Stress Test to determine cortisol circadian rhythm dynamics and levels. 25 v INTERPRETING IDENTI-T SCORES & PROTOCOLS 148

149 ASSESSMENT OF ADRENAL FUNCTION Serum, saliva, or urine Serum: Protein bound vs. free fraction Salivary: Diurnal rhythm of Cortisol Salivary free-fraction best option: Correlated with serum free fraction Measures bioavailable hormone Easy at home collections throughout day/night or month Economical Adrenal Stress Profile STAGES OF ADRENAL FATIGUE Acute Adrenal Stress Mild High Adrenal Fatigue 149

150 STAGES OF ADRENAL FATIGUE Stage of adrenal fatigue Cortisol Levels DHEA Levels Average time to recovery Preferred Interventions I: Acute Adrenal Fatigue At least one cortisol level is high Total cortisol sum is high DHEA is borderline low, low or normal 1-6 months Lifestyle & dietary changes Supplementation PRN II: Mild Adrenal Fatigue AM, noon or afternoon cortisol is low or borderline low Total cortisol sum is normal DHEA is borderline low or low 6-12 months Adrenal Support Supplementation Targeted Lifestyle and dietary changes III: High Adrenal Fatigue Most cortisol levels are low or borderline low Total cortisol level is low DHEA levels are borderline low or low months Adrenal, Neurotransmitter and/or Hormone Supplementation Immediate lifestyle and dietary changes IV: Adrenal Failure All cortisol levels are low or borderline low Total cortisol is low DHEA level is low months Hospitalization/medical attention Adrenal, Neurotransmitter and/or Hormone Supplementation Immediate lifestyle and dietary changes ADRENAL STRESS PROFILE: CASE STUDY #1 150

151 ADRENAL STRESS PROFILE: CASE STUDY #2 VITALS: BLOOD PRESSURE Orthostatic Normal Take lying blood pressure after supine for 5-10 min Have patient stand; take blood pressure immediately and again 1 minute later Orthostatic Hypotension Systolic should increase 5-10 mmhg Systolic decreases Diastolic should increase 5mmHg Diastolic decreases A drop of more than 5-10 mmhg upon standing is suggestive of adrenal stress/fatigue If BP does not recover at 1 min post-standing test is suggestive of long-term adrenal fatigue 151

152 ADRENAL FATIGUE: LABS Cortisol/DHEA salivary test Orthostatic hypotension Thyroid panel (TSH, Free T3, Free T4, rt3) 25-hydroxy Vitamin D Fasting glucose Glucose and insulin tolerance test Sex hormone testing (salivary) MANAGING STRESS Only the individual is capable of defining what is and what is not stress. 1. Change the situation 2. Change the response 3. Build resistance 152

153 LIFESTYLE STRATEGIES Sleep, rest and recovery Exercise Stress management Reduce work-related stress Deep Breathing Stretching Meditation & Relaxation Response Progressive Muscle Relaxation Visualization Find FUN PHYSICAL REPAIR AND REGENERATION During sleep: Physical repair takes place from approximately 10PM-2AM Psychic regeneration occurs from approximately 2AM-6AM Under ideal circumstances, recommended bedtime is 9:00-10:00 pm 153

154 SLEEP AND REST Poor quality sleep and too little sleep causes Adrenal dysfunction Fat deposition Inflammation Get 8-10 hours/night The more before midnight the better Correct sleep apnea if necessary 60 min screen-free relaxation before bed If naps are restorative, take them Papanicolaou DA et al. The pathophysiologic roles of interleukin-6 in human disease. Ann Int Med 1998, 128: Vgontzas AN, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab 2004, 89: Irwin MR, Wang M, Ribeiro D, et al. Sleep loss activates cellular inflammatory signaling. Biol Psychiatry Sept 15;64(6): EXERCISE Stage I or II adrenal fatigue ONLY Only as energy & pain permit NEVER to failure Ideally, exercise before 2 PM Moderate exercise can reduce excess cortisol 70-75% of MHR for minutes 5x/week Gardening Walking Biking Dancing Playing with kids Sports Running Soccer Volleyball Yoga Tai Chi Lifting weights Hiking Skating Climbing Swimming Jumping rope House cleaning 154

155 DEEP BREATHING Incorporate into daily routine Helps you slow down Increase oxygen Eliminates CO2 Relaxes tense/tired muscles Calms the adrenal response 155

156 DEEP BREATHING Breathe deep whenever you Send/receive an /text/phone call Walk through a door Get to a stop light/sign Every time someone says your name DIETARY STRATEGIES GLYCEMIC CONTROL Skip the sugar Refined carbs sodas, white breads, candies, cookies Increase fiber, especially soluble fiber Legumes (beans, peas, lentils), whole fruits and vegetables, whole grains; supplement PRN Eat meals/protein regularly Breakfast within 60 min of waking 4-5 meals/day, grams protein every meal Stay hydrated ½ body weight in ounces daily Increase phytonutrients eat the rainbow Avoid alcohol, tobacco and caffeine 156

157 FOODS THAT SUPPORT ADRENAL FUNCTION Vegetables Nuts, grains, seeds Fruits Asparagus Almonds Blueberries All leafy greens Brown rice Coconut Legumes Flaxseed Figs Lima beans Millet Gooseberries Mushrooms Molasses Lemons Okra Pumpkin seeds Prunes Olive oil Whole grains Strawberries Onions Wild rice Sea vegetables Soybeans Sprouts ADRENAL FATIGUE: RECOMMENDATIONS Adaptogens (herbs) Non-toxic No change in normal physiology Helps the body adapt to stress Normalizes body function Benefits Improved blood sugar metabolism Less cravings Improved immunity Increased energy/stamina Better mood Improved focus/concentration Decreased anxiety Better sleep Improved motivation Increased productivity Improved muscle tone/strength Bryla CM. The relationship between stress and the development of breast cancer: a literature review. Oncol Nurs Forum. 1996;23: Romero LM, Raley-Susman KM, Redish DM, Brooke SM, Horner HC, Sapolsky RM. Possible mechanism by which stress accelerates growth of virally derived tumors. Proc Natl Acad Sci USA. 1992;89:

158 ADAPTOGENS Ayurvedic Herbs: Amla, Ashwagandha, Guduchi, Holy Basil, Licorice, Shatavari, Shilajit Chinese Herbs: Asian Ginseng, Astragalus, Codonopsis, Cordyceps, Eleuthero, He Shou Wu, Jiaogulan, Licorice, Lycium, Prince Seng, Reishi, Schisandra Western Herbs: American Ginseng, Rhaponticum, Rhodiola HPA UNDER-RESPONSIVE INVIGORATING & RESTORATIVE Ashwagandha Holy basil Bacopa Cordyceps Asian Ginseng Rhodiola Licorice root HPA OVER-RESPONSIVE CALMING & RESTORATIVE Rehmannia Schisandra ADAPTOGENS 158

159 ADRENAL FATIGUE: HPA UNDER-RESPONSIVE Ashwagandha (Withania somnifera) Ayurvedic herb used for more than 2500 years Enhances adaptability to physical, mental and chemical stress Improves endurance Can improve sleep quality/duration Supports immune function Can improve T3 & T4 concentrations Bhattacharya SK, Goel RK, Kaur R, et al. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res 1987;1(1): Singh N, Nath R, Lata A, et al. Withania somnifera (ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res 1982;20(1):29-35 Wagner H, Norr H, Winterhoff H. Plant adaptogens. Phytomedicine 1994;1: Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 2000 Aug;5(4): Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol 1999;67(2): Mol Cell Biochem May;260(1-2):39-47.Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Phytother Res May;17(5): Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Part II). J Med Food Summer;6(2): Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action. Life Sci Feb 21;72(14): Induction of nitric oxide synthase expression by Withania somnifera in macrophages. Phytomedicine Dec;7(6): Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytother Res Sep;15(6): Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice. ASHWAGANDHA BOOSTS BRAIN FUNCTION Cholinergic agonism - butylcholinesterase and acetylcholinesterase inhibitor, important in supporting cognitive function, reasoning and critical thinking. 159

160 HOLY BASIL (OCIMUM SANCTUM) Could be beneficial in the treatment of cognitive disorders such as dementia and Alzheimer s Hanumanthachar J et al. Indian Journal Experimental Biology,44:Feb 2006; Ocimum sactum (Holy Basil) appears to reduce serum concentrations of both glucose and cortisol providing antiperoxidative, hypoglycemic and hypocortisolemic activities Gholap S et al.pharmzi 59;2004: Anti-stress activity, including a normalizing affect on the CNS Samson J et al. Pharmacology, Biochemistry, Behavior 83;2006:

161 BRAMHI (BACOPA MONNIERA) Ayurvedic literature attributes its benefits to its ability to produce non-specific increased resistance. In animals: improves adaptations in sensory, motor, and motivational systems in animal testing. In humans: may decrease the rate of forgetting newly acquired information Antioxidant capacity may, in part, explain its anti-stress, immunomodulatory, cognition facilitating and antiaging effects in animals ADRENAL FATIGUE MENTALLY EXHAUSTED Mentally Exhausted Formula Holy Basil, Ashwaganda, Amla, Bacopa Profile: Prolonged stress Cognitive function decline Forgetful Poor concentration/focus Difficulty organizing thoughts/making decisions Impaired memory Dosing: 2 tablets 2-3x/day 161

162 Mentally Exhausted Formula CLINICAL SUMMARY EXHILARIN: FOR THOSE WHO ARE STRESSED & MENTALLY FATIGUED Suitable for daily use. Supports cognitive function under stress. Helps normalize glucocorticoid levels in a way that increases stress adaptation. Supports healthy immune function, antioxidant protection, prostaglandin production, blood glucose levels, and blood lipids all of which may help break the damaging stress cycle. Provides broad-range stress protection, unavailable with single-herb formulas. Suitable for vegetarians. 162

163 ADRENAL FATIGUE: HPA UNDER-RESPONSIVE Asian Ginseng (Panax ginseng) Traditionally used as/to: Tonic normalize the body Enhance stamina and capacity to cope with stress Person who is overwhelmed and exhausted Contain ginsenosides (isolated from root) Must be standardized Need ~30-60 mg/day ginsenosides Toxicity at doses >15 g/day Depression, hypertension, nervousness, sleeplessness Huang KC. The Pharmacology of Herbs 2nd Ed. New York: CRC Press; Bensky D, Gamble A. Chinese Herbal Medicine Materia Medica. Seattle: Eastland Press; Hsu HY. Oriental Materia Medica: A Concise Guide. New Canaan, CT: Keats Publishing, Inc; Hall T, Lu ZZ, Yat P, et al. Evaluation of consistency of standardized Asian ginseng products in the ginseng evaluation program. HerbalGram 2001;52: Cui J, Garle M, Eneroth P, et al. What do commercial ginseng preparations contain? Lancet 1994;344(8915):134. Non-specific strengthening properties normalize body functions, restore body s balance, enhance stamina and increase the body s resistance to stress and disease Overall, ginseng seems to have a balancing effect on the HPA axis by: Appropriate stimulation of adrenocorticotropic hormone (ACTH) in the pituitary gland during times of acute stress Improving cortisol sensitivity by increasing HPA sensitivity to glucocorticoids, possibly by promoting diffusion of corticosteroids across cell membranes in the hypothalamus Inhibiting cortisone-induced adrenal and thymic atrophy Possibly influencing the central opioid, GABA receptor and CRF mechanisms within the brain 163

164 ADRENAL FATIGUE: HPA UNDER-RESPONSIVE Cordyceps (Cordyceps sinensis) One of most valued medicinal fungi in Chinese medicine Strengthen and rebuild the body after exhaustion or long-term illness/stress Specific for excessive tiredness, persistent cough, impotence, debility and anemia Standardized to adenosine and cordyceptic acid Cordyceptic acid: mg/day; adenosine: 2-4 mg/day Exceptionally safe; possible mild side effects at high doses include stomach upset, dry mouth, nausea Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II. J Altern Complement Med 1998;4(4): Hobbs C. Medicinal Mushrooms. Loveland, Colorado: Interweave Press Inc.; Dai G, Bao T, Xu C, et al. CordyMax Cs-4 improves steady-state bioenergy status in mouse liver. J Altern Complement Med 2001;7(3): Cordyceps fulfills the criteria for a classic adaptogenic botanical Preliminary animal studies support traditional uses Possible mechanisms of action: May increase cortisone production; reduce blood glucose without reducing plasma insulin levels; reduce blood lipids; protect the kidneys from toxic insult; and stimulate immune function by increasing number of T-Helper and NK cells, depressed cytokines necessary for healthy immune response 164

165 ADRENAL FATIGUE: HPA UNDER-RESPONSIVE Rhodiola (Rhodiola rosea) More than 180 published clinical, pharmacological and phytochemical studies over 35 years showing: Increased work performance (physical and mental) Increased energy and athletic performance Improved cognitive function Increased resistance to stress (chemical, biological and physical) Improved attention and short-term memory No detectable toxicity Germano C, Ramazanov Z. Arctic Root (Rhodiola rosea): The Powerful New Ginseng Alternative. New York: Kensington; Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev 2001;6(3): Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000;7(5): Maimeskulova LA, Maslov LN. [Anti-arrhythmic effect of phytoadaptogens.] [Article in Russian] Eksp Klin Farmakol 2000;63(4): Maslova LV, Kondrat ev BI, Maslov LN, et al. [The cardioprotective and antiadrenergic activity of Rhodiola rosea in stress.] [Article in Russian] Eksp Klin Farmakol 1994;57(6): Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine 2000;7(2): FOR THOSE WHO ARE STRESSED & TIRED: DOSING CONSIDERATIONS Ginseng Crude main root: 2-9 grams of main root as decoction Standardized daily dose: ~23 to 150 mg total ginsenosides /day from the main root preparations Cordyceps Powder (not an extract) 3-9 grams taken three times/day Cultivated mycelial extract 1-3 grams/day Rhodiola (Phytomedicine. 2003;10(2-3): single dose research ) Start at 100 mg and increase to a maximum of 400 mg (200 mg 30 minutes before breakfast plus 200 mg 30 minutes before lunch) over a period of 1 to 2 weeks Possible stimulating effects in sensitive individuals between 50 mg or 100 mg. Conversely, treatment resistant depression and certain neurological disorders may require 600 mg a day or more. 165

166 ADRENAL FATIGUE: HPA UNDER-RESPONSIVE - RECOMMENDATIONS Stressed & Tired Formula Ginseng, Cordyceps, Rhodiola Profile: low energy; multiple organ/gland function Feels tired and weak Looks pale and feels puffy Wakes un-refreshed Appears apathetic and depressed Unexplained weight gain Long term chronic stress; may have other hormone issues Dosing 1-2 capsules BID Stressed & Tired Formula 166

167 CLINICAL SUMMARY ADRESET: FOR THOSE WHO ARE STRESSED & TIRED Asian ginseng root and cordyceps Enhance stamina, energy & resistance to stress Regulates ACTH production in pituitary in response to stress Improve cortisol sensitivity Inhibit cortisone-induced adrenal atrophy Rhodiola Increases energy and resistance to stress Improves cognitive function and memory Improve immune function Effects levels & activities of neurotransmitters and opiod peptides Prevents depletion of catecholamines in reaction to stress Stimulate specific immune defenses Modern research clarifying hundreds of years of traditional and clinical use ADRENAL FATIGUE: HPA OVER-RESPONSIVE Rehmannia (Rehmannia glutinosa) root Normalize production of adrenal hormones Anti-inflammatory Also used for asthma, skin diseases and arthritis Improves production of sex hormones Used for menopause, impotence & hormone deficiency No known drug interactions No documented toxicity levels Hson-Mou Chang and Paul Pui-Hay But (eds.), Pharmacology and Applications of Chinese Materia Medica, (2 vols.), 1986 World Scientific, Singapore. Shen Ziyin, et al., Kidney reinforcement regimen in the treatment of bronchial asthma, Journal of Traditional Chinese Medicine 1982; 2(2): Chen Shuanghou, et al., Pharmacological study of Bushen Shengxue No.1, Chinese Traditional and Herbal Drugs 1990; 21(6):

168 ADRENAL FATIGUE: HPA OVER-RESPONSIVE Schisandra Fruit (Schisanda chinensis) Increases concentration, coordination and endurance Has antioxidant and anti-inflammatory properties Increases energy and has a tranquilizing effect Increases resistance to illness and stress Helps to normalize blood sugar and blood pressure Improves liver function Upton R, ed. Schisandra Berry: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999;1-25. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, REHMANNIA & SCHIZANDRA Tian Wang Bu Xin Dan Used for centuries in traditional Chinese medicine (TCM) as a nourishing yin tonic- replenishes exhausted reserves and supports the kidneys and the circulatory system TCM Use and Indications Nervous tension, anxiety due to depletion of reserves and a tired heart and circulatory system. Palpitations, restlessness, uneasiness, insomnia, restless sleep, poor memory, short attention span, poor concentration, constipation, ulcers in the tongue and mouth, red/flushed appearance; a sense of feeling warm, overheated, hot flashes with or without thirst and dryness (skin and/or mucous membranes anywhere in the body) Rehmannia flowers and Prepared rehmannia 168

169 ADRENAL FATIGUE: HPA OVER-RESPONSIVE - RECOMMENDATIONS Stressed & Wired Formula Traditional Chinese Heart Calming Formula Contains Rehmannia, Schizandra, Jujube, Dong Quai Profile: stressed and nervous/anxious Feel burned out mentally/emotionally Anxious, apprehensive, irritable, edgy with persistent, high level psychological stress Difficulty sleeping Cardiovascular complaint ( blood pressure/heart rate) Nervous energy, can t calm mind down Dosing 2 tablets 2-4x/day (can use PRN) Stressed & Wired Formula 169

170 CLINICAL SUMMARY SERENAGEN: FOR THOSE WHO ARE STRESSED & WIRED Replenish exhausted reserves, nourish the blood, balance blood sugar Chinese foxglove root (Rehmannia glutinosa) Enhance stamina, support blood flow, oxygen transport, and cardiac contractility Ginseng root (Panax ginseng) Poria fungus (Poria cocos) Support circulation and therefore nutrition to the heart Dong Quai root (Angelica sinensis) Salvia Root (Salvia miltiorrhiza) Support the central nervous system; sedative Biota Seed (Biota orientals) Polygala Root (Polygala tenuifolia) Prevent exhaustion of reserves and support healthy detoxification Asparagus Root (Asparagus chochinchinensis) Ophiopogon Root (Ophiopogon japonicus) Scrophularia Root (Scrophularia ningpoensis) Maintain the integrity of heart tissue and function Schizandra Fruit (Schizandra Chinese) Jujube Fruit (Zizyphus spinosa) Has pulmonary affinity, ventilates the lungs, supports oxygen transport Platycodon Root (Platycodon grandiflorum) ADRENAL FATIGUE: CORTISOL METABOLISM Licorice Root (Glycyrrhiza glabra) Contains glycyrrhizin & glycyrrhitinic acid Can bind to glucocorticoid/mineralcorticoid receptors Increase the half-life of cortisol by inhibiting breakdown Increase availability of cortisol within the body Exhibit anti-inflammatory, antiviral, anticuler, estrogen-balancing and adaptogen qualities Especially for those with diminished adrenal function Can increase blood pressure/cause water retention Dosing: mg/day for 4-6 weeks or 100 mg/day ongoing Snow JM. Glycyrrhiza glabra L. (Leguminaceae). Protocol J Bot Med Winter1996:9-14. Kiso Y, Tohkin M, Nikino, et al. Mechanism of antihepatotoxic activity of glycyrrhizin. I: effect on free radical generation and lipid peroxidation. Planta Med 1984;50(4): Inoue H, Mori T, Shibata S, et al. Pharmacological activities of glycyrrhetinic acid derivatives: analgesic and anti-type IV allergic effects. Chem Pharm Bull 1987;35(9): Pompei R, Pani A, Flore O, et al. Antiviral activity of glycyrrhizic acid. Experientia 1980;36(3):304. Tamaya T, Sato S, Okada HH. Possible mechanism of steroid action of the plant herb extracts glycyrrhizin, glycyrrhetinic acid, and paeoniflorin: inhibition by plant herb extracts of steroid protein binding in the rabbit. Am J Obstet Gynecol 1986;155(5): Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice evaluation of health hazard. Food Chem Toxicol 1993;31(4): Ojima M, Satoh K, Gomibuchi T, et al. The inhibitory effects of glycyrrhhizin and glycyyrhetinic acid on the metabolism of cortisol and prednisolone in vivo and in vitro studies. Nippon Naibunpi Gakkai Zasshi1990;66(5):

171 ADRENAL FATIGUE: CORTISOL METABOLISM Ashwagandha root extract (Withania somnifera) Supports normal hypothalamic-pituitary-adrenal axis (HPA) function, enhances adaptability to physical, mental and chemical stressors Supports immune function Sedative, tranquilizing (cholinergic), improves sleep quality/duration Antioxidant protection of mucous membranes against free radical injury Rehmannia root (Rehmannia glutinosa) Can stimulate the production of adrenal hormones Anti-inflammatory Improves production of sex hormones Chinese yam root (Dioscoria batatas) Tonic - support digestion, assimilation, possible participation as substrate in hormone production, possible influence on estrogen brain receptors ADRENAL FATIGUE: CORTISOL METABOLISM - RECOMMENDATIONS Burned Out & Exhausted Formula Licorice, Ashwagandha, Rehmannia, Wild Yam Profile: Muscle and joint pain Crave salt and salty foods Get dizzy upon rising (from lying or sitting position) May use anti-inflammatory steroids Low salivary cortisol levels Dosage: 2 tablets 1-2x/day Contraindicated for those with hypertension, during pregnancy and/or for those on blood thinners 171

172 Burned Out & Exhausted Formula CLINICAL SUMMARY LICORICE PLUS: FOR THOSE WHO ARE STRESSED & HOT/EXHAUSTED Helps the body maintain a healthy level of circulating cortisol Restorative or tonic for stress-related adrenal fatigue Supports healthy immune function Supports mucous membranes throughout the body mouth, gut, lungs, urogenital system Polygala may influence glutamate, an exciting neurotransmitter. Concentrated and standardized licorice extract ensures accurate, safe and controlled delivery of glycyrrhizic acid, one the most important key actives that contributes to a positive outcome Do not use licorice if patient is hypertensive or on blood thinners Suitable for vegetarians 172

173 ADRENAL FATIGUE: RECOMMENDATIONS B-vitamins Pantothenic acid B5 often called anti-stress vitamin Essential for cellular energy production, hormone synthesis and neurotransmitter production Pyridoxine B6 required for proper neurotransmitter and hormone production Niacin B3 necessary for energy production and conversion of tryptophan into serotonin McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, Balanced B Complex Adrenal B Support 173

174 ADRENAL FATIGUE: RECOMMENDATIONS Stressed and tired Feel weak & fatigued due to stress Provide overall stress protection, increased energy, more restful sleep and enhanced mental clarity Cordyceps, Asian Ginseng, Rhodiola, B-vitamins Recommendation Dosage Stressed & Tired Formula Balanced B Complex Mentally Exhausted Formula (PRN - cognitive function decline) Sleep Support Formula (if needed) 1-2 tablets BID 1 BID/TID with food 2 tablets BID/TID 1-2 b4 bed PRN Exercise as energy/pain permits; focus on getting fresh air daily Improve stress management; implement strategies throughout the day Focus on proper sleep hygiene and maintaining blood sugar levels throughout the day Sleep Support Formula 174

175 ADRENAL FATIGUE: RECOMMENDATIONS Stressed and wired Overworked, sleep too little, have difficulty relaxing/resting, anxious, agitated, hectic lifestyle Promote inner balance and inner sense of calm Rehmannia, Schisandra Fruit, Asian Ginseng, B- vitamins Recommendation Dosage Stressed & Wired Formula 2 tablets BID/TID and PRN Balanced B Complex 1 BID/TID with food Sleep Support Formula (if needed) 1-2 b4 bed PRN Exercise as energy permits b4 2 pm ideal; focus on getting fresh air/grounded daily Improve stress management; implement strategies throughout the day (deep breathing) Focus on proper sleep hygiene and maintaining blood sugar levels throughout the day ADRENAL FATIGUE: RECOMMENDATIONS Stressed and hot (or burned out ): Cortisol Metabolism Prolonged stress, exhausted, muscle ache/stiffness, difficulty adapting & doing routine tasks Support immune system and improve cortisol levels Licorice Root, Ashwagandha, B-vitamins (esp B5 & B6), Vit C Recommendation Dosage Burned Out & Exhausted Formula 2 tablets BID/TID Balanced B Complex 1 BID with food Adrenal B Support (chronic/prolonged stress) 1 BID with food Sleep Support Formula (if needed) 1-2 b4 bed PRN Stretching/yoga as energy permits; focus on getting fresh air/grounded daily Improve stress management; implement strategies throughout the day (deep breathing) Focus on proper sleep hygiene and maintaining blood sugar levels throughout the day 175

176 CASE STUDY #1: CHRISTY Going through a long-drawn out divorce; spouse uncooperative/aggressive Symptoms: Restless, agitated, mood swings Trouble falling and staying asleep, wake up tired/unrefreshed Not hungry/forgets to eat Muscle/joint pain and weakness Lifestyle and Health Status: perceived stress rating 9; skips breakfast, no physical activity, no MVM/EFA, drinks coffee and smokes 1 pk daily, knee pain IDENTIFYING STRESS TYPE/INTENSITY Add up the points in each Section A through E Section A: Wired Section B: Worried Section C: Adrenal cortisol Section D: Mental fatigue Section E: Tired

177 IDENTIFYING HPA OVER/UNDER RESPONSIVENESS 13 Add up the points in Sections A+B+C and C+D+E Hyper vs. Hypo function Lifestyle & Health Status indicates need for lifestyle counseling SECTION C: ADRENAL CORTISOL METABOLISM *>10 POINTS MAY REQUIRE ADDITIONAL ADRENAL SUPPORT *The score in section C is added to both the HPA Over and Under-responsive paths because adrenal gland function contributes to both scenarios. Adaptogens balance the HPA axis and relieve adrenal stress indirectly. Additional repair support may be required A chronic score (>21) may indicate the need for an Adrenal Stress Test to determine cortisol circadian rhythm dynamics and levels. 25 v 177

178 CASE STUDY #1: CHRISTY Going through a long-drawn out divorce; spouse uncooperative/aggressive Symptoms: Restless, agitated, mood swings Trouble falling and staying asleep, wake up tired/unrefreshed Not hungry/forgets to eat Muscle/joint pain and weakness Lifestyle and Health Status: perceived stress rating 9; skips breakfast,no physical activity, no MVM/EFA, drinks coffee and smokes 1 pk daily, knee pain A - 22; B - 11; C - 25; D - 13; E - 14; Sleep responses yes A+B+C = 58, C+D+E = 53 HPA Over-Responsive, Issue with Cortisol metabolism, poor sleep quality CASE STUDY #1: CHRISTY A - 22; B - 11; C - 25; D - 13; E - 14; Sleep responses yes A+B+C = 58, B+C+E = 53 HPA Over-Responsive, Issue with Cortisol metabolism, poor sleep quality Benesom 178

179 CASE STUDY #1: CHRISTY: RECOMMENDATIONS Remedy/Supplement Upon rising Breakfast Mid morning Lunch Mid afternoon Dinner Before retiring PhytoNutrient Health Drink 1 scoop PhytoNutrient Multi 1 1 EPA-DHA Stressed & Wired Formula Burned Out & Exhausted Formula 2 2 Adrenal B Support 1 1 Sleep Support Formula take 60 min before bed 1-2 Dietary recommendations: 3-5 meals/day (use alarm); eat breakfast every day; grams protein at every meal, 50-75% of plate vegetables/fruit Deep breathing exercises throughout the day; reminder every hour to take 5-10 deep breaths Sleep get to bed between 9-10 PM; mediate and/or deep breathing for 10 min before bed Reduce cigarette smoking; do deep breathing exercises and/or go for a walk instead Exercise yoga 5-10 minutes every morning Get grounded every day meditation, yoga, walk in nature, walk bare-foot in the grass, read inspiring passage Speak with a counsellor/therapist regarding divorce CASE STUDY #2: ALAN Symptoms: Chronic fatigue, wake up feeling unrested Fatigue worse after physical activity; 2-4 days to recover Depression, lack of motivation Poor focus, concentration Joint/muscle pain, headaches A - 10; B - 8; C - 20; D - 21; E - 38; Sleep responses Yes A+B+C = 38, C+D+E = 79 Lifestyle and Health Status: Perceived stress rating 2; skips breakfast, no physical activity, MVM/EFA 3X, drinks coffee and alcohol daily 179

180 CASE STUDY #2: ALAN A - 10; B - 8; C - 20; D - 21; E - 38; Sleep responses Y A+B+C = 38, C+D+E = 79 HPA Under-Responsive, Issue with Cortisol Metabolism, poor sleep quality Benesom CASE STUDY #2: ALAN: RECOMMENDATIONS Remedy/Supplement Upon rising Breakfast Mid morning Lunch Mid afternoon Dinner PhytoNutrient Health Drink 1 scoop PhytoNutrient Multi 1 1 EPA-DHA D Stressed & Tired Formula 2 2 Mentally Exhausted Formula 2 2 Burned Out & Exhausted Formula 2 2 Sleep Support Formula take 60 min before bed Dietary recommendations: 5 meals/day (use alarm); eat breakfast every day; grams protein at every meal, 50-75% of plate vegetables/fruit; avoid sugars/simple carbohydrates Deep breathing exercises throughout the day; reminder every hour to take 5-10 deep breaths Sleep get to bed between 9-10 PM; mediate and/or deep breathing for 10 min before bed Get outside daily; short walks (never to fatigue) if possible Adrenal Stress Test if not improving in 4-6 weeks Before retiring

181 THE SERENITY PRAYER Perhaps the best general approach for treating stress can be found in the elegant passage by Reinhold Niebuhr "Grant me the courage to change the things I can change, the serenity to accept the things I can't change, and the wisdom to know the difference. The process of learning to control stress is life-long, and will not only contribute to better health, but a greater ability to succeed in one's own agenda. 181

182 QUESTIONS: ADRENAL FATIGUE??? UNDERLYING CAUSES OF FATIGUE 1. Diet Insufficiency Allergy/sensitivity 2. Adrenal fatigue 3. Mitochondrial dysfunction 4. GI Imbalances Poor digestion Malabsorption Food hypersensitivity Dysbiosis 5. Inflammation 6. Sleep disturbance 7. Immune Imbalance Chronic infection Hypersensitivity 8. Toxicity Detoxification Imbalance Heavy metal toxicity 9. Hormone Imbalances Adrenal Thyroid Insulin Sex hormones 182

183 FATIGUE: MITOCHONDRIAL DYSFUNCTION MITOCHONDRIA ARE ESSENTIAL TO LIFE Mitochondria 2001 ACE Powerhouse of cell Generate ATP Produce ~90% of total bioenergy mitochondria/cell Tissues that have a high energy requirement (ATP) have a higher density of mitochondria Brain Muscle (heart and skeletal) Liver Kidneys Reddy PH et al. Curr Alzheimer Res June ; 8(4): Vittorio CalabreseJournal of Nutritional Biochemistry 17 (2006)

184 METABOLISM: ATP PRODUCTION Lipids, Carbs, and Protein following digestion are processed and transported into the mitochondria Kreb s cycle continues the break down to high energy electrons Electron Transport Chain (ETC) utilizes oxygen (oxidative phosphorylation) to produce ATP for cellular energy MITOCHONDRIAL ENERGY PRODUCTION 184

185 MITOCHONDRIA: OTHER METABOLIC TASKS Hormonal signaling Energy production - (ATP & oxidative phosphorylation) Synthesis of useful compounds Regulation of cellular metabolism Control of apoptosis (cell death) Removal of unwanted compounds Regulation of cytosolic calcium THE BRAIN: METABOLIC MACHINE Uses ~70% of all ATP produced Billions of neurons depend on ATP to function Mitochondria in brain must regulate and control numerous electrical and chemical signals Sugar is the primary fuel source ~120 grams/day Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New York: W H Freeman;

186 MITOCHONDRIA ALSO GENERATE LOTS OF FREE RADICALS The production of ATP naturally generates oxidative stress reactive oxygen and nitrogen species (RONS), & other excitotoxins, like glutamate and cytokines Richter C, Park J, Ames BN (September 1988). "Normal oxidative damage to mitochondrial and nuclear DNA is extensive". PNAS 85 (17): Harman D (1956). "Aging: a theory based on free radical and radiation chemistry". J. Gerontol. 11 (3): Harman, D (1972). "A biologic clock: the mitochondria?". Journal of the American Geriatrics Society 20 (4): Tritschler HJ, Packer L, Medori R. Oxidative stress and mitochondrial dysfunction in neurodegeneration. Biochem Mol Biol Int 1994;34(1): Hagen TM, Wehr CM, Ames BN. Mitochondrial decay in aging. Reversal through supplementation of acetyl-l-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann N Y Acad Sci 1998;854: Mizuno Y, Ikebe S, Hattori N, et al. Role of mitochondria in the etiology and pathogenesis of Parkinson s disease. Biochimica et Biophysica Acta 1995;1271: Schapira AH. Mitochondrial involvement in Parkinson s disease, Huntington s disease, hereditary spastic paraplegia and Friedreich s ataxia. Biochim Biophys Acta 1999;1410(2): Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci 1998;95: Ozawa T. Mitochondrial genome mutation in cell death and aging. J Bioenerg Biomembr 1999;31(4): Tanaka M, Kovalenko SA, Gong JS, et al. Accumulation of deletions and point mutations in mitochondrial genome in degenerative diseases. Ann N Y Acad Sci 1996;786: MITOCHONDRIAL FITNESS REQUIRES OXIDATIVE STRESS Mitochondrial fitness requires oxidative stress to stimulate neuron resilience and repair Too much or too little oxidative stress impair function Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;9;408(6809): Chan DC. Mitochondria: Dynamic Organelles in Disease, Aging, and Development. Cell, Volume 125, Issue 7, , 30 June

187 TOO MUCH OXIDANT STRESS ACCELERATES MITOCHONDRIAL AGING Loss of membrane potential and function Reduced enzyme activity Increased mutations in mitochondrial DNA (mtdna) Reduced ATP synthesis Increased oxidant production and leakage A fall in the apoptotic threshold of neurons Decreased antioxidant defenses International Journal of Alzheimer s Disease Volume 2009, *mtdna mutation Increased RONS **mtdna depletion ***ETC dysfunction Cytochrome C Cytosol Capase activation Neuron Death *mitochondrial DNA mutation **mitochondrial DNA depletion ***electronic chain tranfer dysfunction (ATP) Cytochrome C (Cyt c) activation is the point of no return. One activated leads to neuronal cell death OUTCOMES OF EXCESSIVE MITOCHONDRIAL STRESS EARLY SIGNS Weakness Fatigue Exercise intolerance slow recovery Muscle tenderness Low mood lack motivation Poor glucose control Difficulty losing weight Joint and muscle pain Poor hepatic biotransformation ADVANCED DYSFUNCTION Chronic fatigue Fibromyalgia Neurodegenerative disorders Neuropathies Depression Liver dysfunction Cardiac dysfunction (cardiomyopathies) Pancreatic dysfunction (diabetes) Kidney dysfunction Acta Neuropathol (2012) 123: Transl Psychiatry (2012) 2, e187; doi: /tp Exp Med. 2009;2:

188 DISEASES ASSOCIATED WITH MITOCHONDRIAL DYSFUNCTION/STRESS Mitochondrial inefficiency causes fatigue Mitochondrial function appears to be directly related to fatigue, and when patients experience fatigue, their mitochondrial function is inevitably impaired. Nicolson GL. The Journal of the American Nutraceutical Association. 2003;6(3):

189 What disrupts mitochondrial function? Life is inflammatory excitotoxic triggers Unrelenting stress Standard American diet Alcohol and substance abuse Smoking Excess body fat and obesity Metabolic syndrome Chronic illness diabetes, cardiovascular disease, hypertension Prescription medications Transl Psychiatry (2012) 2, e187; doi: /tp & 2012 Macmillan Publishers Limited All rights reserved /12 SUPPORTING MITOCHONDRIAL HEALTH Support healthy mitochondrial energy production Dietary/lifestyle changes Supply necessary nutritional factors Limit/remove toxins Combat ROS/RNS production and damage Limit oxidative damage caused by diet/lifestyle Increase mitochondrial antioxidants Correct underlying imbalances/health conditions Inflammation, GI, Insomnia, Immune, Hormone imbalances 189

190 HEALTHY LIFESTYLE CHOICES Practice daily stress management and address adrenal fatigue Dramatically reduce/eliminate tobacco, alcohol, recreational drug use Improve/optimize body composition Regular/daily exercise Use the brain daily LEARN something new Eliminate & avoid toxins Anti-Inflammatory, antioxidant rich diet ADVANCED GLYCATION END PRODUCTS (AGES) Diverse group of compounds Formed from a non-enzymatic reaction between sugars and free amino acids in proteins, lipids and nucleic acids Pathogenic effects due to their ability to promote oxidative stress and inflammation Bind with cell surface receptors or cross-link Alter structure and function of cells URIBARRI J, WOODRUFF S, GOODMAN S, et al. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet. Journal of the American Dietetic Association. 2010;110(6): e

191 HOW AGES AFFECT HEALTH NFκB: nuclear factor kappa B RAGE: receptor for advanced glycation end products ROS: reactive oxygen species AGES AND MITOCHONDRIAL FUNCTION Majority of AGEs come from food Cooking (esp. dry heat) greatly increases the # of AGEs Grilling, broiling, roasting, searing and frying SAD is largely heat-processed AGEs increase inflammation and oxidative stress Promote chronic disease and mitochondrial dysfunction Vlassara H, Uribarri J. Glycoxidation and diabetic complications: Modern lessons and a warning? Rev Endocrin Metab Disord. 2004;5: O Brien J, Morrissey PA. Nutritional and toxicological aspects of the Maillard browning reaction in foods. Crit Rev Food Sci Nutr. 1989;28: Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc. 2004;104: Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Bueting C, Heitmann K, Vlassara H. Orally absorbed reactive advanced glycation end products (glycotoxins): An environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA. 1997;94: Lin RY, Choudhury RP, Cai W, Lu M, Fallon JT, Fisher EA, Vlassara H. Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis. 2003;168: Uribarri J, Cai W, Peppa M, Goodman S, Ferruci L, Striker G, Vlassara H. Circulating glycotoxins and dietary advanced glycation end-products: Two links to inflammatory response oxidative stress, and aging. J Gerontol A Biol Sci Med Sci. 2007;62: Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J. Protection against loss of innate defenses in adulthood by low AGE intake: Role of a new anti-inflammatory AGE-receptor-1. J Clin Endocrinol Metab. 2009;94:

192 FOODS HIGHEST IN AGES Food AGE (ku/100 grams) Serving size (g) AGE/Serving Chicken, skin, back or thigh, roasted then BBQ 18, ,668 Bacon, fried 5 min no added oil 91, ,905 Beef, frankfurter, broiled 450 F, 5 min 11, ,143 Chicken, skin, thigh, roasted 11, ,034 Chicken, skin, leg, roasted 10, ,897 Beef, steak, pan fried w/olive oil 10, ,052 Chicken, breast, breaded, oven fried, 25 min, with skin 9, ,965 Chicken, breast, breaded, deep fried, 20 min 9, ,750 Beef, steak, strips, stir fried with 1 T canola oil, 15 min 9, ,570 Chicken, (McDonalds) 9, ,331 Turkey burger, pan fried with cooking spray, 5 min, high heat, microwaved 13.5 sec, 8, ,044 Chicken, back or thigh, roasted then BBQ 8, ,922 Whiting, breaded, oven fried, 25 min 8, ,897 Big Mac (McDonalds) 7, ,801 Chicken, nuggets, (McDonalds) 8, ,764 Chicken, dark meat, broiled, inside, 450 F, 15 min 8, ,469 Turkey burger, pan fried with 5 ml canola oil, 3.5 min, high heat 8, ,426 Chicken, breast, with skin, 450 F, 45 min 8, ,420 Turkey burger, pan fried with cooking spray, 5 min, high heat 7, ,171 Chicken, crispy (McDonalds) 7, ,950 Pizza, thin crust 6, ,825 Uribarri J, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010;110: ; Goldberg T. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 2004;104: AGES & FOOD: KEY TAKEAWAYS Meat, especially when cooked with dry heat is high in AGEs Grilling, broiling, roasting, searing and frying Dry heat AGEs >10-100x over uncooked foods Processed meats and fast food are especially high in AGEs Cheese, especially when melted/heated is also high in AGEs Anything fried, burnt or charred is high in AGEs URIBARRI J, WOODRUFF S, GOODMAN S, et al. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet. Journal of the American Dietetic Association. 2010;110(6): e12. doi: /j.jada

193 LIMIT AGES EXPOSURE Limiting meat consumption & avoid meat that has been cooked with dry heat Grilled, broiled, roasted, toasted, seared or fried Do not eat anything (especially meat) that has been fried, charred or burnt Don t eat processed meats or fast food Avoid cow s dairy, especially cheese Cook food (especially meat) at lower temperatures, in an acidic environment (lemon juice or vinegar) or in water (boil or steam) when possible Maintain blood sugar control Avoid simple carbohydrates, eat balanced meals URIBARRI J, WOODRUFF S, GOODMAN S, et al. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet. Journal of the American Dietetic Association. 2010;110(6): e12. FOODS HIGH IN ANTIOXIDANTS Foods high in antioxidants Deep colored berries Blueberries, blackberries, cranberries, raspberries Apples Red/green grapes Green leafy vegetables Sprouts Pecans, walnuts, hazelnuts Green tea Raw best Effect of cooking Boiling can destroy up to 90% of antioxidants Steaming retains more Juicing Organic Variety Need a wide array of antioxidants 193

194 MITOCHONDRIAL RESUSCITATION Healthy lifestyle choices Metabolic reserve insulin sensitivity Adequate nutritional and antioxidant reserves to promote oxidative balance Vimani A Mol NeurobioL 2013 Jun 28. [Epub ahead of print] MITOCHONDRIAL RESUSCITATION L-Carnitine ( mg) mitochondrial ß-oxidation of fatty acids for ATP production, waste removal, antioxidant and supports insulin sensitivity Taurine ( mg) - crosses the blood-brain barrier and plays a role in supporting brain health, rescues neurons from excess glutamate Magnesium ( mg) ATP transport CNS, heart, skeletal muscle; calcium ion influx and apoptosis, muscle relaxation S.B. Sartori, N. Whittle, A. Hetzenauer, and N. Singewald. Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment Neuropharmacology January; 62(1): doi: /j.neuropharm McCully KK, et. al. Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients. Dynamic Medicine 2006;5:1 William J Rowe Correcting magnesium deficiencies may prolong life Clinical Interventions in Aging 2012: Riboflavin (B 2 ), Niacinamide, Vitamin C - mitochondrial function, nervous system support, electron chain transport Pryridoxine (B 6 )- Excitatory glutamate conversion to calming GABA, neuron life cycle, nervous system function, methylation, homocysteine metabolism Thiamin (B 1 )- oxidative metabolism of pyruvate, alpha-ketoglutarate, and branched chain amino acids Vitamin C and Selenium ROS scavenging, glutathione support Chromium insulin sensitivity 194

195 L-CARNITINE REQUIRED FOR ATP PRODUCTION Key role in cellular energy production Essential for beta-oxidation of long-chain fatty acids in mitochondria to make ATP CARNITINE, ADVANCED-GLYCATION END PRODUCTS (AGES) AND HAEMODIALYSIS 102 hemodialysis patients randomized to either oral administration of L- carnitine (900 mg/day) (N=51) or control (N=51). 70 completed. After 6 months, metabolic and inflammatory variables, including serum levels of carnitine were measured. Skin AGE levels were determined by evaluating skin autofluorescence with an AGE-reader. Conclusions: Oral L-carnitine supplementation significantly decreased skin AGE levels in hemodialysis patients with carnitine deficiency. Supplementation of L-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with hemodialysis. Fukami K et al. Rejuvenation Res Aug 4. [Epub ahead of print] 195

196 L-CARNITINE: THERAPEUTIC CONSIDERATIONS Hyperthyroidism Blocks entry of thyroid hormones into cell nuclei Can significantly improve symptoms Can reduce ALT, AST, GGT and ferritin Angina/heart attack/congestive heart failure Diabetes - Can improve insulin sensitivity Male infertility- increases sperm motility Hyperlipidemia can Lp(a), LDL and trigs Fatty liver Kidney disorders Improve exercise performance Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebocontrolled clinical trial. J Clin Endocrinol Metab 2001;86: Cavallini, G., Ferraretti, A. P., Gianaroli, L., Biagiotti, G., and Vitali, G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl 2004;25(5): Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002;13: Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J 2000;139:S Malaguarnera, M., Vacante, M., Avitabile, T., Malaguarnera, M., Cammalleri, L., and Motta, M. L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin.Nutr 2009;89(1): Mingrone G, Greco AV, Capristo E, et al. L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr 1999;18: L-CARNITINE VS. ACETYL-L-CARNITINE In the body, have a carnitine pool L-carnitine, acetyl-l-carnitine, propionyl-l-carnitine, etc. Research indicates that a combination of L- carnitine & acetyl-l-carnitine may be best Lessen oxidative stress and prevent oxidative damage 1:1 or 1:2 ratio of L-carnitine: Acetyl-L-carnitine Liu J, Head E, Kuratsune H, et al. Comparison of the effects of L-carnitine and acetyl-l-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann N Y Acad Sci 2004;1033: Pettegrew JW, Levine J, McClure RJ. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry 2000;5: Mayeux R, Sano M. Treatment of Alzheimer's Disease. N Engl J Med 1999;341: Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-l-carnitine metabolism. Ann N Y Acad Sci 2004;1033:

197 L-CARNITINE: SOURCES Food Sources: Grass fed red meat ~ mg per serving Supplementation Typically, 2-6 grams/day in divided doses L-carnitine: 1-3 grams Acetyl-L-carnitine: 1-3 grams No more than 2 grams at one dose SCAVENGING REACTIVE OXYGEN SPECIES (ROS) & STIMULATING CELLULAR ANTIOXIDANT PATHWAYS Vitamin C Selenium N-Acetylcysteine (NAC) Taurine α-lipoic Acid CoQ10 Vitamin E Melatonin Manji H, et al. Nature Reviews Neuroscience 2012; 13,

198 VITAMIN C ASCORBATE: FUNCTIONS Made internally by almost all organisms Except guinea pigs, most bats, monkeys and HUMANS Required in the diet Can only store a small amount Can develop deficiency symptoms in 1-6 months VITAMIN C ASCORBATE: FUNCTIONS Antioxidant Protects proteins, fats, carbohydrates, DNA & RNA from free radical damage Can regenerate other antioxidants and increase glutathione production Collagen synthesis Immune support Enhance iron absorption 198

199 VITAMIN C ASCORBATE: DEFICIENCY Easy bruising Impaired wound healing Vascular fragility Bleeding hemorrhoids, varicose veins Bleeding gums Impaired immune function Iron deficient anemia VITAMIN C ASCORBATE: THERAPEUTIC CONSIDERATIONS Easy bruising Impaired wound healing Vascular fragility Bleeding hemorrhoids, varicose veins Bleeding gums Impaired immune function Iron deficient anemia Detoxification support Vitamin C Calibration/Flush 199

200 VITAMIN C CALIBRATION Vitamin C Calibration/Flush Achieve tissue saturation Take ascorbate until achieve liquid BM speed healing Use ONLY 100% L-ascorbate, fully reduced, buffered mineral ascorbate Ultra Potent C powder Start on empty stomach, 1 st thing in morning Amount needed depends on body needs VITAMIN C CALIBRATION Dosing guidelines: Healthy: begin with ½ tsp dissolved in 1-2 oz. of water or diluted juice every 15 minutes Moderately healthy: begin with 1 tsp dissolved in 4 oz. of liquid every 15 minutes Ill: begin with 1.5 tsp in 8 oz. liquid every 15 min After four doses, if no gurgling/rumbling in gut, double the initial dosage and continue every 15 minutes 200

201 VITAMIN C CALIBRATION Record dosing on chart VITAMIN C CALIBRATION Continue dosing until reach watery stool Once reach watery stool, stop Calibration Use the Calibration dose to determine ongoing ascorbate needs Consume 75% of the total Calibration amount daily in 3 or more doses per day 201

202 VITAMIN C CALIBRATION Example: 1. Calculate amount of ascorbate consumed 2. Multiply the number of grams by the number of doses 3. 75% of this total is the approximate daily need Time Dosage Grams Ascorbate (Vit C) 8:00 1/2 tsp 2 grams 8:15 ½ tsp 2 grams 8:30 ½ tsp 2 grams 8:45 ½ tsp 2 grams 9:00 1 tsp 4 grams 9:15 1 tsp 4 grams 9:30 1 tsp 4 grams 9:40 Watery BM 20 grams to flush 20 x 0.75 = 15 grams 5 grams TID daily ~ 1 heaping tsp Ultra Potent C TID VITAMIN C CALIBRATION HELPFUL HINTS Consume adequate water with each dose Gas, cramps or fullness due to too little water Room temperature liquid is best People with hemorrhoids, IBS/IBD may need to increase Ultra Potent C slowly over time before doing the Vitamin C Calibration Start with ½ tsp BID; increase by ½ tsp per dose each week 202

203 VITAMIN C CALIBRATION HELPFUL HINTS Best to do 1 st flush when can stay home Most people take grams (3-8 tsp) to flush Some may need grams Some people remain bloated and/or have loose stools for a day or so after flush If a person wishes to stop, taper them off by reducing the dose by ~ 5-10 grams/day During times of stress/illness, Vitamin C needs Repeat the flush every 2-4 weeks VITAMIN C ASCORBATE: FOOD SOURCES Cherries Plums Peppers Kiwi Broccoli Berries Papaya Citrus Pineapple Leafy greens 203

204 SELENIUM: FUNCTIONS Antioxidant protection Cofactor for reduction of antioxidant enzymes Glutathione peroxidases in mitochondria 2 GSH + H 2 O GSH-Px GSSG + 2 H 2 O Protection against mercury toxicity Binds with methyl mercury Thyroid hormone production Activate and deactivatest4 & T3 SELENIUM: DEFICIENCY, TOXICITY & THERAPEUTIC CONSIDERATIONS Consider if: Hashimoto s disease 21% reduction in TPO AB with 0.2 mg/day Mercury toxicity/exposure Antioxidant need Toxicity Immune support, inflammatory conditions, detoxification >900 mcg/day Garlic breath, hair loss, fatigue, irritability, cirrhosis 204

205 SELENIUM: SOURCES Food sources: Brazil nuts, kidney, tuna, crab, lobster, nuts, whole grains, meat, eggs Supplements Selenomethionine, amino acid chelate, aspartate mcg/day N-ACETYL CYSTEINE (NAC) Antioxidant protection Precursor of glutathione Also acts as an antioxidant itself Support for detoxification and toxicity 205

206 NAC: FUNCTIONS GLUTATHIONE: THE MASTER ANTIOXIDANT Body s most powerful antioxidant Found in every cell in the body Made from cysteine, glycine and glutamine Master antioxidant Unique ability to maximize performance of all other antioxidants Protect mitochondria Essential for detoxification, energy utilization, preventing disease associated with aging Ability to produce decreases with age Can increase with Cysteine, glycine, glutamine Alpha-lipoic acid, vitamin D, N-acetyl cysteine, B6, B12 & folate Whey protein, milk thistle, curcumin Sulfur rich foods (garlic, onions, cruciferous vegetables) 206

207 NAC: FUNCTIONS Decrease inflammation Reduces cellular production of TNF-α and IL-1 Neurotransmitter function Increase uptake of cystine, which increases glutamate in the synapse This inhibits further release of glutamate, which can improve compulsive behaviors and addiction NAC: THERAPEUTIC CONSIDERATIONS Acetaminophen poisoning Inflammatory disorders RA, OA, chronic pain, GI disorders Compulsive behaviors OCD, trichotillomania, addiction Lung and heart disorders Reduces mucus viscosity Anti-inflammatory and antioxidant Allergies/upper respiratory congestion 207

208 NAC: THERAPEUTIC CONSIDERATIONS Supplementation Acetaminophen overdose Oral loading dose of 140 mg/kg of a 5% solution should be administered (through a straw) Seventeen additional doses of 70 mg/kg as a 5% solutions should be given every 4 hours, for a total dose of 1330 mg/kg over 72 hours Other conditions mg BID/TID TAURINE Many fundamental biological roles: Conjugation of bile acids Antioxidation Osmoregulation Membrane stabilization Modulation of calcium signaling Essential for: Cardiovascular function Development and function of skeletal muscles, retina and CNS Unusual because does NOT contain carboxyl group Derived from cysteine; synthesized in the pancreas 208

209 TAURINE: FUNCTIONS Inhibits glycation (AGEs) Protects against glutamate excitotoxicity Antioxidant & prevents oxidative stress Protects against toxicity/heavy metals Helps with electrolyte balance/conduction May help control blood sugar and decrease blood sugar levels Huang JS, Chuang LY, Guh JY, Yang YL, Hsu MS (2008). "Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells". Toxicology and Applied Pharmacology 233 (2): doi: /j.taap Leon R, Wu H, Jin Y, Wei J, Buddhala C, Prentice H, Wu JY (2008). "Protective function of taurine in glutamate-induced apoptosis in cultured neurons". Journal of Neuroscience Research 87: Gürer, H; Ozgünes, H; Saygin, E; Ercal, N (2001). "Antioxidant effect of taurine against lead-induced oxidative stress". Archives of Environmental Contamination and Toxicology 41 (4): Sinha, M; Manna, P; Sil, PC (2008). "Taurine protects the antioxidant defense system in the erythrocytes of cadmium treated mice". BMB Reports 41 (9): Zhang M, Izumi I, Kagamimori S, Sokejima S, Yamagami T, Liu Z, Qi B (2004). "Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men". Amino Acids 26 (2): utaka Nakaya, Asako Minami, Nagakatsu Harada, Sadaichi Sakamoto, Yasuharu Niwa and Masaharu Ohnaka (2000). "Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes". American Journal of Clinical Nutrition 71 (1): Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J (2008). "Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits". Biochimie 91: Effects of taurine on advanced glycosylation end products and expression of TGF-β in renal cortex of, TsingHua, 2005, Blaylock RL. Altern Ther Health Med 2008;14(6): TAURINE BIOLOGICAL ROLES Provides multi-dimensional support for mitochondrial-rich organ systems Taurine plays multiple roles in the CNS including acting as a neuro-modulator, an osmoregulator, a regulator of cytoplasmic calcium levels, a trophic factor in development, and a neuroprotectant. In neurons taurine has been shown to prevent mitochondrial dysfunction and to protect against endoplasmic reticulum (ER) stress associated with neurological disorders Essential for cardiovascular function, and development and function of skeletal muscle, the retina and the CNS Kumari et al. Taurine and its neuroprotective role Adv Exp Med Biol. 2013;775: Huxtable, RJ (1992). "Physiological actions of taurine". Physiol Rev 72 (1): Shao A, Hathcock JN (2008). "Risk assessment for the amino acids taurine, L-glutamine and L-arginine".Regulatory Toxicology and Pharmacology : RTP 50 (3):

210 TAURINE: THERAPEUTIC CONSIDERATIONS Congestive heart failure/arrhythmia Heart attack (reducing damage) Neurodegenerative diseases Alzheimer s/dementia, Parkinson s disease, ALS, head injuries Epilepsy Heavy metal toxicity Diabetes Chemotherapy Obesity (chronic low level inflammation) Vermeulen MA, et al. J Parenter Enteral Nutr 2016;40(2): Gebara E, et al. Stem Cells Res 2015;14(3): Shalbaraj MC, et al. Plos One 2012;7(8):e Suarez LM, et al. Amino Acids 2016;48(5) Del Olm N, et al. Eur J Neurosci 2004;19(7): TAURINE Occurs natural in fish and meat Omnivore diet mg/day (mean: 58 mg/day) High meat diet: <200 mg/day Vegans 0 mg/day No definitive therapeutic dose has been identified Studies done on up to 1000 mg/kg/day Congestive heart failure: 2-6 grams/day Acute hepatitis: 4 grams TID for 6 weeks Recommend: 1 gram TID to start (empty stomach) Often use 4-10 grams TID Bouckenooghe T, Remacle C, Reusens B (2006). "Is taurine a functional nutrient?". Current Opinion in Clinical Nutrition and Metabolic Care. 9 (6): Brosnan J, Brosnan M (2006). "The sulfur-containing amino acids: an overview". J Nutr. 136 (6 Suppl): 1636S 40S. Huxtable RJ (1992). "Physiological actions of taurine". Physiol Rev. 72 (1): "Opinion on Caffeine, Taurine and D-Glucurono g -Lactone as constituents of so-called "energy" drinks". Directorate-General Health and Consumers, European Commission, European Union EFSA adopts opinion on two ingredients commonly used in some energy drinks [dead link] efsa.europa.eu/ Shao A, Hathcock JN (2008). "Risk assessment for the amino acids taurine, L-glutamine and L-arginine". Regulatory Toxicology and Pharmacology : RTP. 50 (3): Matsuyama Y, Morita T, Higuchi M, Tsujii T. The effect of taurine administration on patients with acute hepatitis. Prog Clin Biol Res 1983;125: Azuma J, Hasegawa H, Awata N, et al. Taurine for the treatment of congestive heart failure in humans. Prog Clin Biol Res 1983;125:

211 ALPHA-LIPOIC ACID (ALA) Potent antioxidant ALA and metabolite DHLA both antioxidants Increases production of glutathione Water and fat soluble Can also regenerate other antioxidants ALA: FUNCTIONS Carbohydrate metabolism Improves glucose uptake and fasting blood sugar Improves insulin sensitivity Decreases postprandial glucose levels Modulates inflammatory response May suppress vascular inflammation Inhibits NF KB Involved in Kreb s Cycle to make ATP Enhances detoxification Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22: Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104: Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45: Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27: Porasuphatana S., Suddee S., Nartnampong A., Konsil J., Harnwong B., Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr 2012;21(1): Beitner H. Randomized, placebo controlled, double-blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoaging of facial skin. Br J Dermatol 2003;149:

212 ALA: THERAPEUTIC CONSIDERATIONS Diabetes/Insulin Resistance Peripheral neuropathy Weight loss Chronic alcohol use/liver disease Detoxification/chelation Brain health/injury Inflammatory disorders Cardiovascular disease Ischemia (cerebral)/brain injury ALA: TOXICITY AND DOSING Toxicity rare; more likely if thiamine deficient Alcoholics supplement with thiamine Supplementation Mitochondrial support: mg/day Diabetes and peripheral neuropathy: mg/day Peripheral arterial disease: 300 mg BID Ziegler D, Hanefeld M, Ruhnau K, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A 7-month, multicenter, randomized, controlled trial (ALADIN III Study). Diabetes Care 1999;22: Ziegler D, Schatz H, Conrad F, et al. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. Diabetes Care 1997;20: Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A 2-year, multicenter, randomized, double-blind, placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy [abstract]. Free Radic Res 1999;31: Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Alt Complement Med 2007;13:

213 COENZYME Q10 (COQ10) Three redox states COQ10: FUNCTIONS Vital for energy production Component of electron transport chain Generates ATP 95% of the human body s energy is generated this way Very important for heart, liver, kidney, brain and muscle function 213

214 COQ10: THERAPEUTIC CONSIDERATIONS Statin and beta-blocker use CoQ10 shares a biosynthetic pathway with cholesterol Statin use can reduce serum CoQ10 levels by 40% Can lead to heart attack, severe muscle pain, memory issues, fatigue COQ10: THERAPEUTIC CONSIDERATIONS Inflammation & Chronic Pain Diabetes, Cancer Brain health Dementia, Parkinson s disease, concussions Cardiovascular disease CHF, hypertension, MI Migraine headaches Fatigue issues Chronic fatigue, fibromyalgia Mitochondrial dysfunction 214

215 COQ10: THERAPEUTIC CONSIDERATIONS Has the potential to inhibit effects of warfarin (Coumadin) by reducing INR CoQ10 very similar structure to vitamin K Competes with and counteracts warfarin s anticoagulation effects COQ10: DOSING & TOXICITY Toxicity not observed Studies done at 3600 mg/day tolerated well Supplementation Oil emulsion Typical dosing: mg/day Statin/beta-blocker use: 200+ mg/day Migraines: 100 mg TID for 3 months Chronic disease: mg/day 215

216 VITAMIN E Tocopherols α-tocopherol β-tocopherol γ-tocopherol δ-tocopherol ε-tocopherol Tocotrienols α-tocotrienol β-tocotrienol γ-tocotrienol δ-tocotrienol ε-tocotrienol d-α-tocopherol most biologically active dl forms are synthetically derived VITAMIN E: FUNCTIONS Antioxidant Protects cell membranes from oxidation Inhibits lipid peroxidation Reduces inflammation Inhibits cyclooxygenase (COX) enzymes Can be recycled by other antioxidants Vitamin C, vitamin A Alpha-Lipoic-acid CoQ

217 VITAMIN E: FUNCTIONS Cardiovascular disease Gene expression Down-regulates CD36 scavenger receptor gene Inhibits atherogenic plaque formation Up-regulates CTGF gene Helps repair and regenerate tissue damaged during atherosclerosis Inhibits platelet aggregation Devaraj S, Hugou I, Jialal I; Hugou; Jialal (2001). "-Tocopherol decreases CD36 expression in human monocyte-derived macrophages". J Lipid Res 42 (4): Azzi A, Stocker A; Stocker (2000). "Vitamin E: non-antioxidant roles". Prog Lipid Res 39 (3): Villacorta L, Graça-Souza AV, Ricciarelli R, Zingg JM, Azzi A; Graça-Souza; Ricciarelli; Zingg; Azzi (2003). "α-tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells". Circ. Res. 92 (1): Muller DP (2010). "Vitamin E and neurological function. Review". Mol. Nutr. Food Res 54 (5): Dowd P, Zheng ZB; Zheng (1995). "On the mechanism of the anticlotting action of vitamin E quinone". Proc Natl Acad Sci U S A. 92 (18): Brigelius-Flohé R, Davies KJ; Davies (2007). "Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson". Free radical biology & medicine 43 (1): 2 3. Atkinson J, Epand RF, Epand RM; Epand; Epand (2008). "Tocopherols and tocotrienols in membranes: a critical review". Free radical biology & medicine 44 (5): VITAMIN E: DEFICIENCY Neuromuscular problems Spinocerebellar ataxia Myopathies Neurological problems Dysarthria Loss of deep tendon reflexes Male infertility Retinopathy Impairment of immune response 217

218 VITAMIN E: TOXICITY Toxicity is rare Can act as anticoagulant Increased risk of bleeding Caution/monitor when use with aspirin, anticoagulants (Warfarin, Coumadin) or surgery VITAMIN E: THERAPEUTIC CONSIDERATIONS Male infertility Cardiovascular disease Fat malabsorption often have greasy stools Gastric bypass IBD (Crohn s disease, Ulcerative colitis) Liver disease Pancreatic insufficiency 218

219 VITAMIN E: FOOD SOURCES Wheat germ oil Sunflower oil/seeds Almonds/Almond oil Flax oil Pecans and walnuts Avocado Dark leafy greens MAGNESIUM, BRAIN, AND MITOCHONDRIAL FUNCTION Magnesium is an essential element that catalyzes more than 300 enzymatic reactions, in particular those involving mitochondrial ATP Mitochondria 2001 ACE Mitochondrial Mg deficiency may increase excitatory events in the neuron Reduced ATP efficiency Calcium influx Excess glutamate Potentiate stimuli that trigger apoptosis (cell death) Miller S, et al. Effects of magnesium on atrial fibrillation after cardiac surgery: a meta-analysis, Heart May;91(5): Gums JG. Magnesium in cardiovascular and other disorders. Am J Health Syst Pharm Aug 1;61(15): J Clin Psychiatry. 2000;61 Suppl 12:22-7 Ahan SK. Metabolism of magnesium in health and disease. J Indian Med Assoc Sep;95(9):

220 MAGNESIUM: DEFICIENCY Mg deficiency is common: % of population Intracellular Mg can be deficient with normal serum levels Muscle twitches/cramps Especially calves, feet and toes Weakness/fatigue Heart irregularities Hypertension Headaches Ayuk J., Gittoes N.J. (Mar 2014). "Contemporary view of the clinical relevance of magnesium homeostasis" Ann". Clin. Biochem 51 (2): Excess glutamate, magnesium and oxidative stress Post-synaptic neuron A2 Glutamate Receptors S. Bleich et al. / Prog Neuropsychopharmacol Biol Psychiatry 28 (2004)

221 Ca ++ antagonized by magnesium MAGNESIUM: THERAPEUTIC CONSIDERATIONS Primary causes of Mg deficiency: Insufficient dietary intake only 32% of US population meet RDA PPI/antacid use Alcoholism Malabsorption/increased excretion Diarrhea, IBD, chronic laxative use Supplementation Citrate best for constipation Glycinate and/or amino acid chelate best for muscle pain, bone, spasm, relaxation 221

222 MAGNESIUM: FOOD SOURCES Legumes and nuts Green vegetables Whole grains MELATONIN AS AN ANTIOXIDANT Melatonin is a potent antioxidant Water and fat soluble Can cross BBB 2-10x more effective than Vit E at protecting cell membranes from lipid peroxidation 5x more effective than glutathione for neutralizing hydroxy radicals Responsible for more than half of all free radical damage in the body Up to 60x more effective than Vit C or Vit E in protecting DNA from DNA damage Karasek, M (2004). Melatonin, Human Aging, and Agr-related Disease. Experimental Gerontology. 39: Reiter RJ, Paredes SD, Korkmaz A, Jou MJ, Tan DX. Melatonin combats molecular terrorism at the mitochondrial level. Interdiscip Toxicol Sep;1(2): Sofic E, Rimpapa Z, Kundurovic Z, et al. Antioxidant capacity of the neurohormone melatonin. J Neural Transm. 2005;112: PHARMACOLOGY LETTERS; Pieri,C; 55(15): (1994) JOURNAL OF PINEAL RESEARCH; Khaldy,H; 29(2): (2000) ENVIRONMENTAL HEALTH PERSPECTIVES; Qi, W; 108: (2000) Mansouri A,Demeilliers C, Amsellem S. Acute Ethanol Administration Oxidatively Damages and Depletes Mitochondrial DNA in Mouse Liver, Brain, Heart, and Skeletal Muscles: Protective Effects of Antioxidants. Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) ; THE INTERNATIONIAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY; Martin,M; 34(4): (2002) Shamir E, Barak Y, Shalman I, et al. Melatonin treatment for tardive dyskinesia: A double-blind, placebo-controlled, crossover study. Arch Gen Psychiatry 2001;58:

223 MELATONIN AS AN ANTIOXIDANT Melatonin does not redox-cycle It undergoes molecular rearrangement Removes the free electron from the system Each of these products of rearrangement is also a potent antioxidant Facilitates to production & activation of other antioxidants One melatonin molecule can scavenge up to 10 radical species before being fully metabolized/eliminated D. X. Tan, R. Hardeland, L. C. Manchester, B. Poeggeler, S. Lopez-Burillo, J. C. Mayo, R. M. Sainz and R. J. Reiter, J. Pineal Res., 2003, 34(4), Reiter RJ, Tan D, Terron MP, et al. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. G. R. Martinez, E. A. Almeida, C. F. Klitzke, J. Onuki, F. M. Prado, M. H. Medeiros and P. Di Mascio, Endocrine, 2005, 27(2), R. Hardeland, D. X. Tan and R. J. Reiter, J. Pineal Res., 2009, 47(2), A Galano, D. X. Tan and R. J. Reiter, J. Pineal Res., 2013, 54(3), D. X. Tan, R. J. Reiter, L. C. Manchester, M. T. Yan, M. El-Sawi, R. M. Sainz, J. C. Mayo, R. Kohen, M. Allegra and R. Hardeland, Curr. Top. Med. Chem., 2002, 2(2), D. X. Tan, L. C. Manchester, M. P. Terron, L. J. Flores and R. J. Reiter, J. Pineal Res., 2007, 42(1), Reiter RJ, Tan DX, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol. 2003;50(4): Johns JR, Platts JA. Theoretical insight into the antioxidant properties of melatonin and derivatives. Org. Biomol. Chem., 2014, 12, MELATONIN AND MITOCHONDRIAL HEALTH Melatonin concentration high in mitochondria Can readily enter Induces antioxidant enzymes in mitochondria Protects mitochondrial DNA Also directly facilitates electron transport chain & reduces electron leakage ATP production free radical generation Melatonin is very important to mitochondrial health May be another reason why sleep deprivation accelerates aging Reiter RJ, Tan DX, Manchester LC, El-Sawi MR. Melatonin reduces oxidant damage and promotes mitochondrial respiration: implications for aging. Ann N Y Acad Sci Apr;959: Reiter RJ1, Tan DX, Leon J. When melatonin gets on your nerves: its beneficial actions in experimental models of stroke. Exp Biol Med (Maywood) Feb;230(2): Reiter RJ, Tan DX, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol. 2003;50(4):

224 MELATONIN: THERAPEUTIC CONSIDERATIONS Sleep disturbances Insomnia, jet lag, shift work, etc. Chronic fatigue Hypertension Anxiety Solid tumors (with or without chemotherapy) Especially breast, lung, kidney, liver, pancreatic, stomach and colon cancer Thrombocytopenia Grossman, E., Laudon, M., and Zisapel, N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc.Health Risk Manag. 2011;7: Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2): Wang, Y. M., Jin, B. Z., Ai, F., Duan, C. H., Lu, Y. Z., Dong, T. F., and Fu, Q. L. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother.Pharmacol. 2012;69(5): Seely D, Wu P, Fritz H, et al. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012;11(4): Mills, E., Wu, P., Seely, D., and Guyatt, G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res 2005;39(4): Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35: Lissoni P, Tancini G, Paolorossi F, et al. Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study. J Pineal Res 1999;26: MELATONIN DOSING For sleep disturbances: mg at bedtime Used in adults and children Use with Vit B6 ( mg) Improves biosynthesis, secretion and absorption If don t tolerate (i.e., restlessness, too stimulating) Take with 5 g L-glycine If awaken during the night, take mg Do not take within 1 hour of waking time Fatigue 3-10 mg at bedtime Hypertension 2-3 mg before bed for 4 weeks Anxiety 5-6 mg Solid tumors mg Start 7 days prior to start of chemotherapy and continue throughout the course of treatment Thrombocytopenia 20 mg at bedtime If tired/groggy in the morning, reduce dosage until awaken refreshed Brusco LI, Fainstein I, Marquez M, Cardinali DP. Effect of melatonin in selected populations of sleep-disturbed patients. Biol Signals Recept 1999;8: van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol 2006;13: Brzezinski A. Melatonin in humans. N Engl J Med 1997;336: Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35: Lissoni P, Tancini G, Barni S, et al. Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer 1997;5: Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2): Acil, M., Basgul, E., Celiker, V., Karagoz, A. H., Demir, B., and Aypar, U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur.J.Anaesthesiol. 2004;21(7):

225 CELLULAR ENERGY AND ATP PRODUCTION: KREB S CYCLE CO-FACTORS CELLULAR ENERGY AND ATP PRODUCTION: ELECTRON TRANSPORT CHAIN CO-FACTORS 225

226 MITOCHONDRIAL DYSFUNCTION : TESTING If they have chronic illness/fatigue Organic acids testing B-vitamins Antioxidants (vit A/C/E) L-carnitine CoQ10 Cr, V, Biotin Lipoic acid Mg, Mn, Fe, Se Glutathione/Cysteine Organix Profile (Metametrix) ORGANIX PROFILE Organic acid testing Way to measure whether the body is getting and using nutrients to drive optimal health Can alert to metabolic imbalances Organix Basic Test All B-vitamins (including methylation cofactors) Fatty acid metabolism Carbohydrate metabolism Nutrients involved in cellular energy production (Citric acid cycle) Neurotransmitter metabolism Nutrients involved in detoxification Antioxidant status Organix Comprehensive Test All markers in Organix Basic Markers of intestinal microbial activity Marker of cellular DNA damage (8-Hydroxy-2-deoxyguanosine) 226

227 ORGANIX PROFILE Useful anytime looking for root nutritional imbalances Simple, at home urine collection Comes with Interpretation and Patient Guides Can be combined with Fatty Acid Bloodspot Anxiety/Depression GI imbalances Autoimmune disorders Bloating and gas Hypertension Attention and memory disorders Weight loss issues Dermatitis Ear, nose & throat symptoms Mood imbalances Headaches Blood sugar dysregulation Detoxification imbalances Fatigue Multiple chemical sensitivities Muscle and joint pain Sleep issues Mental, emotional & behavioral problems 227

228 228

229 MITOCHONDRIAL DYSFUNCTION Testing: HAQ, Organic Acids (Organix Profile) BIA: BMR, PA, ICW/ECW Zinc Tally Additional labs: Packed RBC Mg CBC w/ WBC differential Ferritin Homocysteine 25-hydroxy Vitamin D Fatty Acid Bloodspot Micronutrient Profile (SpectraCell) 229

230 MITOCHONDRIAL DYSFUNCTION : TESTING HAQ Mountain range MITOCHONDRIAL DYSFUNCTION: RECOMMENDATIONS Ideally, based on testing HAQ, Metabolic Acids, Labs Provide foundational support Fabulous Five Anti-Inflammatory Dietary Guidelines Limit AGEs Anti-oxidant rich: 50-75% deep colored vegetable/fruits Quality protein throughout the day Supplements for mitochondrial support Stress management/rest 230

231 MITOCHONDRIAL SUPPORT: SUPPLEMENTATION B1 (Thiamin) B2 (Riboflavin) B3 (Niacin) B5 (Pantothenic acid) B6 (Pyridoxine) B7 (Biotin) B9 (Folic acid) B12 (Cobalamin) Vitamin C Vitamin E L-carnitine Taurine CoQ10 N-acetyl cysteine Alpha-lipoic acid Magnesium Potassium Selenium Chromium MITOCHONDRIAL SUPPORT: SUPPLEMENTATION Vitamin C (as ascorbic acid) 300 mg 500% Thiamin (as thiamin mononitrate) 30 mg 2000% Riboflavin 1.9 mg 112% Niacin (as niacinamide) 50 mg 250% Vitamin B6 (as pyridoxine HCl) 50 mg 2500% Folate (as calcium L-5- methyltetrahydrofolate) 150 mcg 38% Vitamin B12 (as methylcobalamin) 150 mcg 2500% Calcium (as dicalcium phosphate) 62 mg 6% Phosphorus (as dicalcium phosphate) 50 mg 5% Magnesium (as magnesium carbonate and magnesium glycinate) 300 mg 75% Selenium (as selenomethionine) 25 mcg 36% Chromium (as chromium picolinate) 50 mcg 42% Potassium (as potassium chloride) 55 mg 2% L-Carnitine (as L-carnitine fumarate) 1.5 g ** Mitochondrial Support Formula Provides multiple nutrients for mitochondrial support Energy production Increase mitochondrial antioxidants Stimulate cellular antioxidants pathways Modulate excitotoxicity: calcium flux and glutamate Powder for ease of use 1 scoop 1-2x/day Malic Acid 760 mg ** Taurine 600 mg ** 231

232 MITOCHONDRIAL SUPPORT: SUPPLEMENTATION Cellular Energy Formula Complements Mitochondrial Support Formula for mitochondrial energy support 1 capsule BID with food Ingredients Amount Daily Value Magnesium (as magnesium oxide) 100 mg 25% Manganese (as manganese sulfate) 2 mg 100% Acetyl L-Carnitine HCl 300 mg ** N-Acetyl L-Cysteine 300 mg ** Coenzyme Q mg ** Alpha-Lipoic Acid 150 mg ** Grape Seed Extract 150 mg ** MITOCHONDRIAL SUPPORT: SUPPLEMENTATION Recommendation Dosage PhytoNutrient Multi and/or Powdered PhytoNutrient Blend 1 cap BID / 1 scoop QD D cap QD-TID (based on testing) Mitochondrial Support Formula Cellular Energy Formula Melatonin N-acetyl cysteine (600 mg) Acetyl-L-Carnitine (500 mg) E-Complex 1:1 Buffered High Absorption Vitamin C powder 1 scoop 1-2x/day with food 1 capsule BID with food 3-10 mg before bed 1 capsule BID with food 1 capsule BID with food 1 gelcap BID with food Modify based on test results/needs Per Vitamin C Calibration or 1 tsp BID/TID 232

233 Buffered High Absorption Vitamin C powder CASE STUDY: SUSAN Symptoms: Chronic fatigue many years rates energy 2/10; always tired with no strength or energy; worse after exertion for 2-7 days; unrestful sleep; often has to lay down min in afternoon to recharge Chronic pain (Dx FMS) muscles, L shoulder, low back, pain with/after exertion Irritable bowel (Dx IBS) gas, bloating, alternating constipation & diarrhea, abdominal pain with food Chronic seasonal allergies cannot function in the fall ; allergy shots 10 years (discontinued 3 yr ago); unresponsive to OTC and Rx medications Unwanted weight gain - 15 lbs in last year 233