Consult Dr A Webinar NAD Paul S Anderson

CE Accreditation Note: Starting January 2018: • ALL of these webinars will have AANP CE Accreditation. • The certificate at the end (last slide) will have the total and Pharm ours. • Many States do not have specific regulation (i. e. WA). • Some are VERY specific (i. e. HI, CA…) • For example with AANP accreditation you can claim 15 hours if doing recordings BUT can claim ALL if listening live. (c) PS Anderson - www. Consult. Dr. A. com - 2018 2

Conflict of interest: • None • I have no financial connection to ANY lab, product or company mentioned • Specific products mentioned are examples of items I use commonly in practice (c) PS Anderson - www. Consult. Dr. A. com - 2018 3

Next Webinars All are Tuesday PM – 5: 30 – 7: 00 PM Pacific Time NOTE – All are third Tuesday of the month unless noted “*” *September 17, 2018 [MONDAY!!] October 16, 2018 November 20, 2018 December 18, 2018 (c) PS Anderson - www. Consult. Dr. A. com - 2018 4

Past Webinar Topics Available: 1. EBV diagnosis and Treatment 17. Cardiac Rx dosing and tapering 2. Histamine – CNS 18. Steroids and Respiratory Med’s 3. Cortisol 19. Autoimmunity-2: Management 4. Iodine & T 3 20. 5. Biofilms (#1) Chronic Infections – Testing, assessment and re-assessment 6. Desiccated Thyroid 21. 30. Low Dose Naltrexone – pharmacology, uses and cases 31. Medical Cannabinoids 32. Neurological Inflammatory Therapies Lyme Illness – A top down approach 33. Food Allergy and Sensitivity 22. Chronic Infection Bundle 34. Hyperbaric Oxygen Therapies 23. Oral Chelation 35. Kidney and Liver Functions – Effect on Rx and Labs 24. Pain Medication Weaning 36. Organic Acid Testing 25. Assessment of Chronic Cases 37. Migraine 26. Nutrigenomic basics 38. PCOS 39. Fluoroquinolone Toxicity 40. GI Absorption and Rx 41. Dysautonomia and EDS 42. Low Dose Immunotherapy 43. Detox of Unusual Metals 7. Autoimmunity 8. Histamine – Peripheral 9. Mitochondria 10. Re. Dox and Inflammation 11. IV and Injection Q&A 12. Sulfation Pathways 27. 13. IV Therapy Q&A and Latest Updates Antidepressant Rx and Taper 14. 28. Pediatric Rx and dose adjustment ADHD Medications and Weaning 15. Renal Rx and Dose adjustments 29. 16. Biofilms #2 Seizure Medications and Weaning (c) PS Anderson - www. Consult. Dr. A. com - 2018 5

NAD

NAD • Originally discovered in 1905 in yeast, NADH is also known as the reduced form of coenzyme 1, a complementary enzyme utilized in the production and regulation of energy via oxidative phosphorylation. • NADH is the reduced coenzyme form of vitamin B 3 • NAD is the oxidized coenzyme form of vitamin B 3. • NAD and NADH are converted into each other in numerous different metabolic activities. (c) PS Anderson - www. Consult. Dr. A. com - 2018 7

NAD • In some metabolic reactions, it is NAD which is the needed catalyst, with NADH a useful by-product; in other reactions the situation is reversed. (c) PS Anderson - www. Consult. Dr. A. com - 2018 8

NAD • NAD and NADH also serve to activate various enzymes. NADH is the first of five enzyme complexes of the electron transport chain where much of the ATP bioenergy that runs every biological process of the body is formed. (c) PS Anderson - www. Consult. Dr. A. com - 2018 9

NAD • NADH is necessary to oxidize all macronutrients into ATP. • All cells require energy to survive, NADH reacts with oxygen to form water and energy. • See below (c) PS Anderson - www. Consult. Dr. A. com - 2018 10

NAD • One molecule of NADH yields three molecules of ATP with the amount of NADH present dictating the amount of energy produced. • The heart muscle cells contain 90 mcg of NADH per gram of tissue, with brain and muscle tissue containing 50 mcg per gram. • Red blood cells contain NADH with 4 mcg per gram. • The more NADH present in cells, theoretically, the more efficient they function in energy production. (c) PS Anderson - www. Consult. Dr. A. com - 2018 11

The role of mitochondrial dysfunction in disease: Damage to cell organelles (mitochondria, nucleus, ER, membrane) disrupts active transport, enzyme production and function & cell reproduction. These changes disrupt cell osmotic balance, transporters and other factors causing degenerative changes in the cell, tissue and eventually the person. (c) PS Anderson - www. Consult. Dr. A. com - 2018 12

Mitochondria: ELECTRON TRANSPORT / OX-PHOS – 1 • TCA cycle and Glycolysis only form a few ATP molecules each. • Most of the ATP from glucose metabolism comes from the electron transport system. • The main function of all the earlier steps is to make the Hydrogen of the Glucose molecule available in forms that can be utilized for oxidation. (c) PS Anderson - www. Consult. Dr. A. com - 2018 13

Mitochondria: ELECTRON TRANSPORT / OX-PHOS – 2 • Oxidation of Hydrogen is accomplished by Splitting the Hydrogen Atom into: • Hydrogen Ion • Electron used to change dissolved O 2 from fluids to Hydroxyl ions. • Hydroxyl ions combine to form H 2 O • During these reactions, ATP produced. • Occurs in the Mitochondria • Occurs via Enzymatically Catalyzed Reactions (c) PS Anderson - www. Consult. Dr. A. com - 2018 14

Mitochondria: ELECTRON TRANSPORT / OX-PHOS – 3 SNP’s and Poisoning can disorder mitochondrial function: • Inhibition is Blocking the respiratory chain at places other than the ADP+P position. • Many poisons can do this: • • Barbiturates Rotenone (insecticide) Sulfuric Acid, CO, Cyanide Antibiotics: Oligomycin, Piericidin-A • Uncoupling (derailing) Ox-Phos: • Ox-Phos is the addition of ‘P’ to ADP = ATP • Uncoupling is the dissociation of oxidation from phosphorylation (Incr. permeability of mitochondria to protons / reduces electromechanical potential – short circuits ATP-synthase [ATPase]) • 2 -4 -dinitrophenol, dinitrocresol, pentachlorophenol (c) PS Anderson - www. Consult. Dr. A. com - 2018 15

Mitochondria: ELECTRON TRANSPORT / OX-PHOS SNP’s – 4 • The chemiosmotic mechanism of Oxidative Phosphorylation resulting in the formation of large amounts of ATP. • At the mitochondrial membrane. COX series NDUFS series UQCRC series ATP 5 etc series (c) PS Anderson - www. Consult. Dr. A. com - 2018 16

Mitochondrial Cofactors to consider: • Nicotinamide / NAD(H) • Co-Q-10 • Riboflavin-5 -phosphate • Iron • Proline • Ca, Mg, K, Zn, Cu, Cr [positive] • Cd [negative = mito poison] • Structure 19, 833– 843, June 8, 2011 • African Journal of Food Science Vol. 4(5) pp. 200 -222, May 2010 • J. Anim. Sci. Vol. 91, E-Suppl. 2/J. Dairy Sci. Vol. 96, E-Suppl. 1 (c) PS Anderson - www. Consult. Dr. A. com - 2018 17

Parenteral “B-3” Normally in the Niacinimide form: https: //www. google. com/url? sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0 ah. UKEwj. Wvbi 3 q. If. NAh. UBSGMKHcbu. Dfk. Qj. B 0 IBg&url=http%3 A%2 F%2 Fwww. medchemexpress. com%2 Fnicotinamide. html&psig=AFQj. CNGu_j. Qg. DOut 2 Sqh. Ttf. RVVuk. Sy 341 Q&ust=1464887248849319 (c) PS Anderson - www. Consult. Dr. A. com - 2018 18

NAD versus B 3 • Holds two “B-3” molecules AND • Two Ribose Molecules https: //www. google. com/url? sa=i&rct=j&q=&esrc=s&source=images&cd =&cad=rja&uact=8&ved=0 ah. UKEwj. O 7 Pncq. If. NAh. VBKGMKHbth. Ao. QQj. B 0 IBg&url= http%3 A%2 F%2 Fhyperphysics. phy-astr. gsu. edu%2 Fhbase%2 Forganic%2 Fnad. html&psig=AFQj. CNGy. QZy. Lme. Jt. Ux. FS 1 Mv Vun 2 Wrnwzjw&ust=1464887121181490 (c) PS Anderson - www. Consult. Dr. A. com - 2018 19

Some selected research: (c) PS Anderson - www. Consult. Dr. A. com - 2018 20

Cantó C, Menzies K, Auwerx J. NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus. Cell metabolism. 2015; 22(1): 31 -53. doi: 10. 1016/j. cmet. 2015. 023. Highlights • Adaptive cellular metabolism relies on NAD+ to mediate energy signaling • NAD+ therapeutics is showing its potential to treat disease • Metabolic syndrome, cancer and aging all involve NAD+ signaling (c) PS Anderson - www. Consult. Dr. A. com - 2018 21

Oral Studies • Samuel A. J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath, Frank Jaksch, Ryan W. Dellinger, Zhonggang Li, E. Dale Abel, Marie E. Migaud & Charles Brenner. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications volume 7, Article number: 12948 (2016) • Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J. 2004 Jun; 23(2): 89 -93. • Alegre J, Rosés JM, Javierre C, Ruiz-Baqués A, Segundo MJ, de Sevilla TF. [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. [Article in Spanish] Rev Clin Esp. 2010 Jun; 210(6): 284 -8. doi: 10. 1016/j. rce. 2009. 015. Epub 2010 May 5. • Castro-Marrero J, et. al. Effect of coenzyme Q 10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clin Nutr. 2016 Aug; 35(4): 82634. doi: 10. 1016/j. clnu. 2015. 07. 010. Epub 2015 Jul 17. (c) PS Anderson - www. Consult. Dr. A. com - 2018 22

A common oral supplement with Co. Q-10 (c) PS Anderson - www. Consult. Dr. A. com - 2018 23

Birkmayer JG, et al. Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application. Acta Neurol Scand Suppl. 1993. PMID 8101414 Abstract The reduced coenzyme nicotinamide adenine dinucleotide (NADH) has been used as medication in 885 parkinsonian patients in an open label trial. About half of the patients received NADH by intravenous infusion, the other part orally by capsules. In about 80% of the patients a beneficial clinical effect was observed: 19. 3% of the patients showed a very good (30 -50%) improvement of disability, 58. 8% a moderate (10 -30%) improvement. 21. 8% did not respond to NADH. Statistical analysis of the improvement in correlation with the disability prior to treatment, the duration of the disease and the age of the patients revealed the following results: All these 3 parameters have a significant although weak influence on the improvement. The disability before the treatment has a positive regression coefficient (t value < 0. 01). The duration of the disease has a negative regression coefficient (< 0. 01) and so has the age a negative regression coefficient (t value < 0. 05). In other words younger patients and patients with a shorter duration of disease have a better chance to gain a marked improvement than older patients and patients with longer duration of the disease. The orally applied form of NADH yielded an overall improvement in the disability which was comparable to that of the parenterally applied form. (c) PS Anderson - www. Consult. Dr. A. com - 2018 24

Birkmayer JG, et al. On the safety of reduced nicotinamide adenine dinucleotide (NADH). J Environ Pathol Toxicol Oncol. 2004. PMID 15312041 Abstract The objective of the study was to determine both the toxicity of the stabilized orally absorbable form of nicotinamide adenine dinucleotide (NADH) (ENADA) and the maximum tolerated intravenous dose (MTD) of beta NADH (the reduced form of NADH) in beagle dogs. The administration of the stabilized orally absorbable form of NADH to beagle dogs at dose levels of 20, 100, and 150 mg/kg for 14 days elicited no signs of a toxicological effect. A transitory change in stool formation was observed with the intermediate and high dose in males. There were also apparent increases in adrenal, heart, kidney, liver, brain, and thyroid weights, particularly in males, but none of these changes were considered to be toxicologically significant. In addition, four dogs (two of each sex) received intravenous infusions of 100 mg NADH/kg/day for 4 days, followed by 200 mg NADH/kg/day for 3 days, followed by 500 mg NADH/kg/day for 4 days, and 1000 mg NADH/kg/day on the final day. At the end of the MTD phase, the control animals that had received saline solution in the MTD phase were used to evaluate the potential toxicity of the established MTD. These animals received 500 mg NADH/kg/day for 14 days (fixed dose phase). There were no deaths. At dose levels between 100 and 1000 mg/kg/day, effects on the cardiovascular system and also some evidence of an effect on the central nervous system and on the adrenals were observed. At doses of 500 mg/kg/day and above, food consumption and body weight were reduced. On the basis of the observed changes, the maximum intravenous dose of NADH tolerated by beagle dogs was considered to be 500 mg/kg/day. There were no gross histological findings indicative of toxicity in the organs of tissues examined. Based on these findings, the stabilized orally absorbable form of NADH (ENADA) can be regarded as safe. (c) PS Anderson - www. Consult. Dr. A. com - 2018 25

Kuhn W, et al. Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. J Neural Transm (Vienna). 1996. PMID 9013405 Abstract Exogenous application of levodopa is conventionally used to equalize the striatal dopamine deficit in idiopathic Parkinson's disease (PD). The stimulation of endogenous biosynthesis of levodopa via activation of tyrosine hydroxylase (TH) has been proposed as new therapeutic concept in PD. This may be achieved by exogenous supply with the reduced coenzyme nicotinamide adenine dinucleotide (NADH). Aim of this open prospective study was to investigate (1) the efficacy of a new developed, parenteral application form of NADH on Parkinsonian symptoms and (2) the influence of bioavailability of levodopa. 15 patients, suffering from idiopathic PD (11 male, 4 female, age: 61. 40[mean] +/- 10. 27[SD] range: 44 -74 years, Hoehn and Yahr stage: 3. 03 +/- 0. 69, range 2 -4) received intravenous infusions of NADH (10 mg a' 30 min) over a period of 7 days in addition to conventional Parkinsonian pharmacotherapy. Parkinsonian symptoms were scored before (day 1) and after NADH treatment (day 8). Levodopa plasma levels were estimated over a period of four hours on the day before and on the first day of NADH application by HPLC. Parkinsonian patients showed a significant response, evaluated by the Unified Parkinson's Disease Rating Scale Version 3. 0 (p = 0. 025; Wilcoxon test). Moreover application of NADH significantly increased bioavailability of plasma levodopa (AUC, p = 0. 035; Cmax p = 0. 025). In conclusion NADH in used galenic form may be a potent stimulator of endogenous levodopa biosynthesis with clinical benefit for Parkinsonian patients. (c) PS Anderson - www. Consult. Dr. A. com - 2018 26

Parenteral NAD Uses: 1. As a “B-3” donor 2. As a therapy in neurodegenerative conditions 3. As a therapy in fatiguing states 4. As a high dose therapy in addiction medicine (c) PS Anderson - www. Consult. Dr. A. com - 2018 27

Mitochondrial Support / Energy / Healing • Some preparations are fully water soluble and mix with the following. • Some are not and need to be administered in their own bag • Only the compounding pharmacy that makes it can tell you. • IV use is safe in other water soluble therapies. • Vitamin and mineral IV’s • Amino Acid IV’s (c) PS Anderson - www. Consult. Dr. A. com - 2018 28

Mitochondrial Support / Energy / Healing • IV Use for these purposes are generally 100 -500 mg NAD total. • As it can be stimulating and cause cardiovascular activity test dose at 50 -100 mg then ramp up. • Excess NAD or fast administration can lead to tachycardia, chest pain etc. (like T-3 therapy). (c) PS Anderson - www. Consult. Dr. A. com - 2018 29

Mitochondrial Support / Energy / Healing • Administration rate (at doses under 500 mg): • Commonly 100 -200 mg of NAD per hour. • Generally not more than 250 -300 mg of NAD per hour maximum. (c) PS Anderson - www. Consult. Dr. A. com - 2018 30

NAD – Lower Dose Uses This is generally given with other Re. Dox nutrient support and appropriate amino acids per patient need [see below]. (c) PS Anderson - www. Consult. Dr. A. com - 2018 31

NAD – Lower Dose Uses For fatigue, mitochondrial support etc. : • Infuse up to 500 mg (in 500 m. L normal saline) over 4 hours, or not faster than 100 mg per hour. • We will often add 50 – 200 mg NAD to a 500 m. L Vitamin. Mineral IV bag. (c) PS Anderson - www. Consult. Dr. A. com - 2018 32

NAD For Alcohol and Opioid detox: For every 250 mg of NAD, mix with 250 to 500 m. L of normal saline. Drip very slowly (250 mg every 2 hours or 2 m. L/min). (c) PS Anderson - www. Consult. Dr. A. com - 2018 33

NAD - Addiction A common detox (drug & ETOH) protocol: DAILY: • 1500 mg (in 1500 m. L normal saline) in 12 hours: day 1 and 2 • 1000 mg (in 1000 m. L normal saline) on day 3 • 750 mg (in 750 m. L normal saline) on day 4 • 500 mg (in 500 m. L normal saline) QD after for 7 -14 days depending on patient (c) PS Anderson - www. Consult. Dr. A. com - 2018 34

NAD -- I will add a vitamin-mineral-amino formula followed by GSH prior to this to provide co-factors. -- The specific amino acids added depend on the patient BUT usually include 200 -400 mg glycine; 200400 mg Taurine and 1 -2 grams Carnitine. (c) PS Anderson - www. Consult. Dr. A. com - 2018 35

NAD -- In many addicts the addition of 100 m. L 8. 5 -10% Mixed Amino Acid is useful. -- The base formula is similar to my GSH Preload formula (posted on Academia under glutathione support) https: //www. academia. edu/21925456/Glutathione_Augment ation_in_a_nerve_injury_model (c) PS Anderson - www. Consult. Dr. A. com - 2018 36

NAD IV Cautions • Dilute as indicated • Overdose or speed shock can lead to excessive mitochondrial activity • Tachycardia • Arrhythmia • Neuro-psych issues • Tremor • And more (c) PS Anderson - www. Consult. Dr. A. com - 2018 37

And: (c) PS Anderson - www. Consult. Dr. A. com - 2018 38

Past Webinar Topics Available: 1. EBV diagnosis and Treatment 17. Cardiac Rx dosing and tapering 2. Histamine – CNS 18. Steroids and Respiratory Med’s 3. Cortisol 19. Autoimmunity-2: Management 4. Iodine & T 3 20. 5. Biofilms (#1) Chronic Infections – Testing, assessment and re-assessment 6. Desiccated Thyroid 21. 30. Low Dose Naltrexone – pharmacology, uses and cases 31. Medical Cannabinoids 32. Neurological Inflammatory Therapies Lyme Illness – A top down approach 33. Food Allergy and Sensitivity 22. Chronic Infection Bundle 34. Hyperbaric Oxygen Therapies 23. Oral Chelation 35. Kidney and Liver Functions – Effect on Rx and Labs 24. Pain Medication Weaning 36. Organic Acid Testing 25. Assessment of Chronic Cases 37. Migraine 26. Nutrigenomic basics 38. PCOS 39. Fluoroquinolone Toxicity 40. GI Absorption and Rx 41. Dysautonomia and EDS 42. Low Dose Immunotherapy 43. Detox of Unusual Metals 7. Autoimmunity 8. Histamine – Peripheral 9. Mitochondria 10. Re. Dox and Inflammation 11. IV and Injection Q&A 12. Sulfation Pathways 27. 13. IV Therapy Q&A and Latest Updates Antidepressant Rx and Taper 14. 28. Pediatric Rx and dose adjustment ADHD Medications and Weaning 15. Renal Rx and Dose adjustments 29. 16. Biofilms #2 Seizure Medications and Weaning (c) PS Anderson - www. Consult. Dr. A. com - 2018 39

CE Accreditation Note: Starting January 2018: • ALL of these webinars will have AANP CE Accreditation. • The certificate at the end (last slide) will have the total and Pharm ours. • Many States do not have specific regulation (i. e. WA). • Some are VERY specific (i. e. HI, CA…) • For example with AANP accreditation you can claim 15 hours if doing recordings BUT can claim ALL if listening live. (c) PS Anderson - www. Consult. Dr. A. com - 2018 40

(c) PS Anderson - www. Consult. Dr. A. com - 2018 41

(c) PS Anderson - www. Consult. Dr. A. com - 2018 42

Check out the new layout: WWW. Consult. Dr. A. com Tell your friends we have lots of free content… (c) PS Anderson - www. Consult. Dr. A. com - 2018 43

Next Webinars All are Tuesday PM – 5: 30 – 7: 00 PM Pacific Time NOTE – All are third Tuesday of the month unless noted “*” *September 17, 2018 [MONDAY!!] October 16, 2018 November 20, 2018 December 18, 2018 (c) PS Anderson - www. Consult. Dr. A. com - 2018 44

AAMP Portland – September 28 -30: 2018 • Dr’s. Ann Corson; Jacob Leone; Dietrick Klinghardt; Cory Tichauer • Advanced Approaches to Chronic Infectious Illness • • Diagnosis and assessment The autoimmune and allergic component Troubleshooting Natural and Rx agents LDI – LDN – Immune therapies Role of toxicants Co-infections (and some we don’t think of) etc… (c) PS Anderson - www. Consult. Dr. A. com - 2018 45

More Information: https: //aampportland. com/ (c) PS Anderson - www. Consult. Dr. A. com - 2018 46

CME Certificate This is to attest that: Dr. _____________ Attended the webinar “NAD-NADH” given online live or via recording on or after 08 -21 -2018. Duration: 1. 5 clock hours Pharmacology 1. 5 hours This event discussed NAD-NADH Pharmacology, Treatment Considerations and management. – AANP CE Credit Applied for. Faculty: Paul S. Anderson, ND (c) PS Anderson - www. Consult. Dr. A. com - 2018 47

Thank you! (c) PS Anderson - www. Consult. Dr. A. com - 2018 48