Neurotoxicity in the Brain

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Normal tryptophan metabolism with low levels of inflammatory stressors

• Quinolate path (verses melatonin path)- triggered by inflammation • Mitigation of pathway- estradiol, niacin, mitigating of inflammation • Branch chain amino acids can prevent tryptophan from getting into the brain

Neurotoxicity in the Brain

Treatment Considerations: • Controlled release* 5HTP (100-400mg in divided doses daily • Optimize B6 levels (P5P best) 50-100mg/day • Optimize methyl folate 5-10mg/day • Optimize methyl B12 (1-2mg/day) • Consider BCAA

*Some evidence suggest short acting 5HTP can cause cortisol spike

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Natural Anti-inflammatories and Dosing:

• Curcumin 750-1500mg/ d • Quercetin 1500-3000 mg/d • Alpha lipoic acid (ALA)- 300- 1800 mg/d • N-acetylcysteine (NAC) 500-3000 mg/d • Essential Fatty Acids- EPA/DHA 1gram-4gram/d • Bosweillia- 400-1200mg/d • Niacinamide 2,000-5,000 mg/d • Palmitoylethanolamide (PEA) 350mg 1-2x daily

Medication Tools for Glutamate Modulation Glutamate antagonists for neurological ecotoxicity (ASD, ADD, Parkinson, Alzheimer dementia, PANs, Tics, GAD mutations)

1. Amantadine- 50-200mg QD-BID with “holidays” ; Antiviral, NMDA receptor antagonist 2. Osmolex- ER Amantadine new on the market; ER TAB: 129 mg, 193 mg, 258 mg 3. Namenda- NMDA receptor antagonist; start with 2.5mg QD-BID, can move up to 5mg BID 4. Nuedexta (dextromethorphan/quinidine)- PBA (1/2-1 cap QD-BID)

Specialty compounding can help with accessibility and extreme savings if insurance does not cover. ***Warning with compounding pharmacies*** 50

Supplement Tools, Cont. 1. Palmitoylethanolamide(PEA) ; 350mg QD- BID; pain, inflammation, anything that can benefit from NSAID. Consider loading dose of 700mg BID X 2-3 weeks. 2. Cannabidiol (CBD)- 10-50mg up to TID PRN 3. Inositol- Myo (up to 18grams in OCD found effective)- D- Chiro for PCOS and metabolic and autophagy pathologies; 500mg QD-BID 4. GABA- 100-400mg up to BID 5. L-Theanine- 400mg up to QID 6. Magnesium- forms preferred are threonate or glycinate; 80 grams of elemental weight or up to 1 gram up to BID; toxicity is RARE 51

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*Check routine serum studies with iron, zinc, and D supplementation

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Functional Preferences with Thyroid Medications

• NP Thyroid • Nature Thyroid • Armour Thyroid • Compounded Thyroid* Caution • Recheck Q6-12 weeks 61

Heavy Metal Toxicity & Fatigue

How do we become toxic?

Total toxic exposure -Ability to biotransform -Ability to excrete toxins =TOTAL TOXIC LOAD

Toxic Metals

Sources: top 3 metals include lead, arsenic, mercury

Sources: dental implants, water, old construction, guns, fish, rice Effect: can cause burden to mitochondria and impairs autophagy

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Current Toxic Exposures Vs Net Toxic Exposures

Current= exposure happened within the last 1-3 months Detected in blood and urine

Net= Exposure over lifetime Detected via: Provoked urine (with DMSA) Hair metals Urine porphyrin Signed consent when using RX chelation agents, to provoke, and/or to treat.

Topical DMSA/ALA

• 5 mg/kg 3 x daily, applied for 3 days on/11 days off. • Benefits- bypasses gut absorption and may have less yeast symptoms/less side effects. • Risks- possible depletion of essential minerals which need to be monitored and repleted. • Labs recommended- Hair metal, urine, porphyrin, or blood test. Basic labs recommended to monitor liver and kidney function throughout therapy in addition to basic nutrients. • Support- Vitamin C, vitamin E, magnesium, zinc, milk thistle, NAC, and adrenal cortex extract.

Ethylenediaminetetraacetic Acid (EDTA)

• EDTA 500 -750 mg suppository, 1-3 x per week. • Benefits- efficient for lead and mercury removal. Typically less GI side effects or flares in yeast. • Risks- EDTA can be dangerous when it is used while the patient has a current exposure to mercury. Once the mercury is bound in the body, it is very unlikely that EDTA would make it more toxic. • Labs recommended-Hair metal, urine, porphyrin, or blood test. Basic labs recommended to monitor liver and kidney function throughout therapy in addition to basic nutrients. • Support- vitamin C, vitamin E, magnesium, zinc, milk thistle, iron, NAC, and adrenal cortex extract.

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Glutathione: Best IV Rectal 600mg daily Oral 600mg BID-TID NAC precursor

Mold/Mycotoxin Toxicity Testing: Mycotoxin testing through Great Plain Labs, Richie Shoemaker protocols, serum positive candida (IgM+). Known exposures in home by certified mold specialist. FIRST REMOVE PATIENT FROM SOURCE OF EXPOSURE Treatment: 6 weeks minimum- average 3 months • Nystatin 500-1M TID OR cholestyramine ½-1 packet BID-TID (magnesium to help mitigate constipation SE, watch lipids) • BEG spray x 3 weeks (compound contains mupirocin + EDTA + gentamicin; breaks up biofilm and MARCONs • Oral glutathione - 600mg BID-TID • NAC or glutathione nebulized • Binders for those who herx (bentonite clay, charcoal timed after antifungal) • Infrared sauna therapy, sweating • Retest biomarkers to ensure treatment efficacy esp if sx have not resolved 68

Biomarkers to Consider Gut: Parasitology X 3, PCR Cx, yeast/candida, food allergies (IgE, IgG, IgA) Thyroid: TSH, Free T3, Free T4, AB/TPO Nutrients: Iron/IBC, Vitamin D, MMA (B12), folate, ferritin, zinc, selenium, iodine, CoQ10, magnesium, carnitine, B1, B2 Metabolic/Inflammatory: A1C, insulin, HsCRP, homocysteine, GGT, CMP, cholesterol, organic acids Toxic: Lead, arsenic, mercury, mold (Mycotoxins), environmental allergies Infectious: EBV, strep (ASO, DNASE), candida, lyme 69

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Mindfulness Meditation

Mindfulness meditation often uses either slow, intentional breathing or imagery to help to focus the thoughts.

Benefits include: • Reduced insomnia • Deeper sleep • Fewer episodes of wakefulness during the night • Improved mood and resilience • Greater daytime energy • Less anxiety

Simplified Approach to Fatigue Management

Remove mediating stressors: Mitochondrial and inflammatory stressors Allergic stressors (food, environment) Balance dysbiosis: bacteria, parasites, yeast Toxic exposures (environmental, infectious, emotional) Excess of anything- food, stress, technology

Replace restorative therapies: Restorative Sleep Supplemental repletion of mitochondrial cofactors Healing and anti-inflammatory foods Mind and body therapies (meditation, fasting, exercise) Hormones 72

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Case Study #1 Hx: Mother of 3 children- vegan, moved into older home Tarrytown, statins x 5 years, recent infidelity in marriage (manages stress through over exercise). Sx: extreme fatigue, anxious, brain fog, muscle aches Labs: lead & serum candida +, MMA and homocysteine high, low CoQ10, low T3, TSH 6, thyroid US WNL. Surface testing in home + for mycotoxins Tx: Mold remediation and eradication of lead in old bathtub Adaptogenic herbs- ashwagandha, black cumin Methylated B vitamins, CoQ10, glutathione Mold detox with CSM and glutathione Limited exercise, Paleo diet, individual counseling, meditation 3 month F/U: labs normalized, energy 80% better, anxiety significantly reduced, working in couples counseling

Case Study #2 Hx: 6 year old boy with fatigue and developmental delay by 2 years, dx with ASD at 2.5 years, chronic OM and URIs, angry and oppositional mood Sx: Sleeps 13 hours a night and needs 1-2 naps per day, delayed speech, stimming, floppy tone, chronic constipation, refusal to eat anything that is not beige Labs: gluten sensitivity, organic acids showing mitochondrial insufficiencies, nutrient deficiencies in zinc, iron, carnitine, and B vitamins, candida cultured in stool Tx: GF diet, nutrient repletion with zinc, iron, B’s, and carnitine, Nystatin protocol x 6 weeks to remove fungal overgrowth in gut, Amantadine for glutamate modulation, 1 gram BID of magnesium threonate (brain and gut) 3 month F/U: No more naps are needed, wants to play more outside and for longer periods, mood is significantly improved, starting to try new foods, bowels are regular and soft, meeting goals in ABA faster than expected 74

COVID19 Integrative Response

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COVID19 Proposed Prevention & Treatment Support Protocol 4/4/20

Prevention: (for adults and older children) • Vitamin A- 5,000IU daily • Vitamin C (Liposomal preferred)- 500mg twice daily • Vitamin D3- 5,000-10,000IU daily • Zinc- 40mg daily • Quercetin 400-800mg daily • L-glutathione 350-600mg daily • N-Acetyl- L-Cysteine (NAC)- 600mg daily • Melatonin 3-5mg at night

For younger children and very low risk: • Vitamin D- 2,500-5,000 IU daily • Vitamin C- 250-500mg daily • Zinc- 20-30mg daily

Antiviral herbs to consider when exposure is high: • Andrographis paniculate- 375mg twice daily • Black elderberry (Sambucas nigra)- 250mg twice daily Over the counter blends: • Immunitone Plus by Designs for Health- 2 caps twice daily (also contains anti-viral mushrooms) • Viracid by Ortho Molecular- 2 caps twice daily 76

Treatment for adults and high-risk patients:

Medications: 1. Azithromycin- 500mg daily- This would be 1 tablet (250mg) twice daily x 5 days 2. Hydroxychloroquine- 1 tablet twice daily x 10 days (caution in cardiac patients due to QT prolongation). Only use in higher risk patients, not children young and healthy. 3. Acetylcysteine- SOL (20%): 200 mg per mL (or inhaled glutathione 200mg per respule) combined with Albuterol (0.083%) nebs; can help prevent vasoconstriction and pulmonary fibrosis after illness is over, give 3-4 x daily and as needed. Hill Country Apothecary is compounding combo and ships all over Texas. Standard RX is feasible for acetylcysteine, but glutathione needs to be specialty compounded.

Supplements: 1. Melatonin high dose (natural inflammasome) (5-10mg) 3x daily x 10 days 2. Magnesium Glycinate- 120mg given twice daily. This is very important especially for those taking hydroxychloroquine. 3. Vitamin C (ascorbic acid)- high dose 2-3 grams every hour while awake (averaging 8x day) x 1-2 days, then 2 grams 3x daily for the next 8 days. IV vitamin C preferred if accessible. 4. NEO 40- NOS (nitric oxide) inducers- 1 tablet 4x daily x 10 days 5. D Hist by Ortho Molecular- 2 caps 4x daily (quercetin and stinging nettles- for blood type A especially) x 10 days. If no sourcing of D Hist- Quercetin 400mg 4x daily is alternative 6. Zinc 80mg 4x daily x 5 days then 40mg 4x daily x another 5 days 7. Vitamin D 100K IU X 3 days once illness starts, then discontinue 8. N-acetyl cysteine (NAC)- 600-900mg 3x daily for duration of illness (likely 10 days) *

Other important measures directions and dietary guidance: 1. Salt Water (hypertonic saline rinses- 2 tbs of salt in 4 cups of boiling water to make; make a fresh solution daily)- Then use Neil Med or Netty Pot and so sinus rinses every 2 hours while awake, especially in the first several days of the illness, but at least 3x daily until fully well. After each sinus rinse, apply 1 spray in each nostril of colloidal or chelated silver into each nostril. 2. Use Ibuprofen only if fever >101 or severe body aches and pains (pneumonitis). Palmitoylethanolamide (PEA) would be a preferred alternative for body aches if accessible. Take 350mg 3-4x daily as needed. 3. Nutrition during this time: Eat with supplemental use to avoid stomach upset (especially zinc) even if it’s just a little. Avoid all grapefruit products due to interactions with medications. Incorporate things like green tea, nettle tea, tonic water, garlic, onions, and beets into the diet as often as possible. Drink to stay hydrated but don’t over hydrate. 4. If symptomatic bowel involvement- Use immunoglobulins as needed (1 packet of Enteragam or 4 scoops of SBI Protect by Ortho Molecular) every four hours as needed. Children and low risk patients consider- Medications: 1. Azithromycin dosed aged appropriate 2. NAC or Glutathione/Albuterol nebs 2-3x daily as needed

Supplements: 1. Melatonin- 3-5mg twice daily until illness has resolved 2. Vitamin D 50,000 IU daily x 3 days 3. Vitamin C- 1 gram every hour while awake on the first few days of illness (likely 6-7x), then 1 gram 3x daily until illness has resolved 4. Zinc 40mg 4x daily x 5 days, then 40mg twice daily x 5 more days 5. N-acetyl cysteine (NAC)- 600-900mg 2x daily for duration of illness* 78

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Other measures: 1. OTC Ibuprofen if needed for fever >101 or severe body aches. 2. Saline spray or Xylitol and blowing nose often throughout the day- follow twice daily with 1 spray in each nostril of colloidal silver spray 3. Use immunoglobulins such as Enteragam (1/2-1 packet) or SBI Protect (2-4 capsules or 1-2 scoops) to help with any bowel involvement 3x daily as needed 4. Keep children eating with supplemental use to avoid stomach upset (even if its just a few bites). Hydrate to ensure urination of at least 4x in 24 hours.

*Those with known history of poor conversation of NAC to glutathione should substitute glutathione instead (both orally and inhaled).

**This proposed therapeutic plan is not FDA approved and intended to be supportive throughout COVID-19. The medications were chosen off of the limited data we have to date for this novel virus and the supplements were chosen off historical evidence to support optimal immune response. These supplements have antioxidant, viricidal, mucolytic, anti- inflammatory, anti-inflammasome, NOS inducing, immune modulating, and furin cleavage inhibition properties that can support a patient with both prevention and treatment of COVID-19.

Additional Support Strategies: • Colloidal Silver Spray or Chelated Silver spray- use 3x daily in nose while exposure is high • HYPOCHLOROUS ACID Force of Nature: HOCL https://www.forceofnatureclean.com/the-science-electrolyzed-water-d/ • Briotech HOCL: Skin Spray :https://www.briotechusa.com/topical-skin- spray

Emerging Treatments: • IV Vitamin C • Ozone Therapy • Convalescent plasma • Antivirals (Japan) • NAC/Heparin Nebs- clinical trial in progress • Vaccine 80

My Give Away

Dosing: 2 caps in AM with food, 2 caps in PM with food First 5 first-line acute care responders get 3-month supply- ER, ICU NPs Email: [email protected]

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Provider resources:

• Emmerson Ecologics • Full Script • Compounding pharmacies- Hill Country Apothecary • O3 Plus Practice in San Antonio- Kim Engelman • Wally Taylor, MD- ozone in Austin • Institute of Functional Medicine- education • Mark Hyman/Cleveland Clinic- eduation

Avoid Amazon

COVID References Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non- randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949 "Microbicidal effect of weak acid hypochlorous solution on various microorganisms." Biocontrol science 17.3 (2012): 129-133. Lewis, M. R. "Novel Coronavirus (2019-nCoV) Scope for Aqualution Hypochlorous Acid Solution for Effective Prevention and Control Orthomolecular Medicine News Service, Feb 16, 2020 “Early Large Dose Intravenous Vitamin C is the Treatment of Choice for 2019-nCov infected Pneumonia” Richard Z Cheng, MD, PhD; Hanping Shi, MD, PhD; Atsuo Yanagisawa, MD, PhD; Thomas Levy, MD, JD; Andrew Saul, PhD. Basak, Ajoy, et al. "Inhibition of proprotein convertases-1,-7 and furin by diterpines of Andrographis paniculata and their succinoyl esters." Biochemical Journal 338.1 (1999): 107-113. (Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension | Cardiovascular Research | Oxford Academic https://academic.oup.com/cardiovascres/advance-article- abstract/doi/10.1093/cvr/cvz312/5644338? redirectedFrom=fulltext) https://pubmed.ncbi.nlm.nih.gov/26681113-same-molecule-but-different-expression-aging-and-sepsis-trigger-nlrp3- inflammasome-activation-a-target-of-melatonin/) https://clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-6-113.php?jid=jide https://pubmed.ncbi.nlm.nih.gov/7585069-high-nitric-oxide-production-in-humanparanasal-sinuses/?dopt=Abstract) https://www.townsendletter.com/article/online-covid-19-mers-sars-critical-care-blood- ozonation/?fbclid=IwAR1AKDYFCVuM3v5DGlsT2jfKPKbo5QDPW_o0MYgU1lqeGH93TrrMRjFOfR0

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