Going Deep Into Autoimmune Factors: Viruses, Complement & - - PowerPoint PPT Presentation

Going Deep Into Autoimmune Factors: Viruses, Complement & Vitamin D Metabolism

Michael McEvoy MetabolicHealing.com

About me

• Founder MetabolicHealing.com & TrueReport -
• Consulting Programs
• 5 Clinical Training Courses
• TrueReport -
• Client Management
• Blood Chemistry Analysis
• Symptoms & Tracking
• Genetics Analysis from 23andme
• Research & Writing - authored 500+ articles over past 8 years

Essential Steps: Working with Clients Who Have Autoimmune Conditions

• Dietary Refinement & Remediation -
• Identify & remove all antigenic foods & triggers
• Optimize organic, whole food nutrition
• Identify & Remove as Many Environmental Triggers as Possible -
• Toxins in the immediate environment: mold, chemical exposure, toxic metals, water, drugs, cosmetics,

pesticides

• Create a Strong Foundation -
• Hydration, sleep/circadian biology, diet, exercise
• Optimize:
• Digestion & absorption
• GI microbiome
• Liver & detoxification
• Hormones & Endocrine balance
• Identify & Address Infections:
• Viral
• Bacterial
• Parasitic
• Fungal

Viruses & The Immune System - The Oldest Cat & Mouse Game

Epstein Barr Virus (EBV): Linked to 7 Autoimmune Diseases

Systemic lupus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease and type 1 diabetes

Type 1 Diabetes

Lupus: EBV, Parovirus, CMV

EBV & Hashimoto’s

Autoimmune Susceptibility

• Loss of self tolerance
• Typically involves elevations in antibody to self tissues
• Genetic Predispositions - HLA 1-3 regions (examples)
• HLA B27 (AS, psoriasis, Crohn’s)
• C4, C4a, C4b, RCCX (Lupus, RA, T1D, MS, Grave’s, Crohn’s,

Hashimoto’s, Celiac, Autism)

• C2 (Lupus)
• Factor B (Celiac)
• SKIV2L & TREX1 (Lupus)
• C1q (Lupus, Hashimoto’s, Graves)
• Viral & other infections
• Dysbiotic terrain: loss of tight junctions in gut, food antigens, infections,

toxins (glyphosate, Hg, AI, Cd, etc)

• Joint hypermobility ??? Inflammasome/TLR’s

The Innate Immune System

The Innate Immune System

• Early responders to the threat of danger (viral, pathogenic, toxin, ECM

collagen tissues)

• Complement pathways: Lectin pathway, Alternative, Classical
• Inflammasome: TLRs, PAMP’s, DAMP’s
• Epithelial & mucosal barriers
• NK cells
• Dendritic cells (APCs)
• Mitochondria

Inflammasome Activation & Cell Danger Signaling: Mechanisms of Inflammation, Anti-Viral Activity & Autoimmune

• Danger signaling protein complex
• Modulates production of pro-inflammatory

cytokines IL1ß, IL18

• IL18 - Interferon gamma activation (most

notable anti-viral cytokine)

• IL1ß - Pain & COX-2 activation
• Inflammasome strongly linked to

autoimmune disease

Possible Indicators of Inflammasome Activation

• Active autoimmune disease
• Hashimoto’s, Lupus, T1D, Grave’s, RA, MS - IL18
• Sudden onset of hypermobile joints (breakdown of collagen leads to DAMPs

which stimulate TLRs)

• MCAS - mast cell activation syndrome is IL1ß dependent
• High pathogenic load
• Fever - IL-1
• Toxins that stimulate TLR’s - AI, Hg, Cd, silicon, asbestos

Modulation of Inflammasome

Inhibition of Inflammasome

• AMPK activation
• Fasting
• Calorie restriction
• Exercise
• Cold exposure
• Berberine, Bitter melon, Lipoic acid, L-Carnitine,

Astragalus, Resveratrol

• Ketosis
• ß-hydroxybutyrate
• Autophagy Activation
• Fasting
• Ketosis
• Resveratrol, green tea, coconut oil & MCTs, Reishi,

sulphoraphane

The Complement Immune System

Complement Immune Response

• Innate Immune System Pathways:
• Alternative pathway
• Lectin pathway
• Classical pathway
• Series of circulating “pre-proteins” produced by: liver, macrophages, epithelial cells (urinary

tract, GI tract) - C4, C3, C2, C1q etc.

• Create “adhesive bonds” (polysaccharides & ficolin) directly to: bacteria, fungi, viruses,

parasites, mold/mycotoxins

• Classical pathway uses antibodies but not lectin or alternative pathway
• Goals of Complement Pathways: Opsonization, antibody binding

The Complement Immune System

Common Complements

• C4
• C4a, C4b
• C3
• C3a
• C1q, C1R, C1S
• C2

Complement Immune Deficiencies & Autoimmune Disease

Deficiencies of Complement - Among the most common immune deficiencies worldwide -

• Lupus - C4, C1Q, C1r, C1s, C2
• MS - C4 deficiency in cerebrospinal fluid, but other complements in CNS of MS are high!
• RA - Deficiencies of C4, C4b, C1Q, C1R, C1S
• Celiac - Deficiency of C4, C3 - significantly lower C4 protein levels
• Type 1 Diabetes - C1Q, C4 & C3 protein deficiency common
• Mice bred to be deficient in C4 were shown to have decreased frequencies of TREGs cells

The significance of complement immune deficiencies indicates an impaired innate immune response to resolving the threat of danger.

• Hashimoto’s & Grave’s - Thyroid tissue features an increased expression of C4

Sugars: Powerful Immune Weapons Modulating the Complement Immune Response

• Polysaccharides & Other Sugars: Immune Glycosylation
• Beta 1,3 glucans: mushrooms (reishi, maitake, Lion’s mane, agaricus blazei, etc)
• Polymannan, mannose: Aloe vera
• Sulfated polysaccharides, Fucoidans: Marine red & brown algae, bladderwrack, kombu,

seaweeds

• Glucomannan - Konjac
• Arabinogalactan - Larch bark
• D-Mannose
• Manuka honey

Glycosylation & Immune Cells - Adhesive binding to pathogens Almost all of the key immune molecules of the innate & adaptive immune systems are glycoproteins

EBV Testing

Testing Epstein Barr Virus (EBV)

• Most people have been exposed to EBV in their lifetimes and will

show IgG antibodies

• The only 2 antibodies that are relevant for active EBV infection are:
• Early Antigen (EA) IgG
• IgM
• Armin Labs (Germany) - T-cell Elispot for EBV
• T-cell Lymphocyte reactivity test

Testing Epstein Barr Virus (EBV)

Active EBV: EA IgG Active EBV: Armin Labs T-cell Elispot

Testing Epstein Barr Virus (EBV)

Active EBV: VCA IgM

Key Anti-Virals

Key Anti-Virals

Product Dosage Effect Vitamin C (high dose) IV - 30-50 grams 1X weekly; Liposomal Na ascorbate 2-3 grams minimum Potent Bravo Yogurt (source of GcMAF & Immunomodulatory peptides) 1 teaspoon - 4 ounces daily

• Strong. Occasional intolerance

Baicalin from Chinese Skullcap 250-1,500mg with fat

• Strong. Taken orally or topically

BHT (butylated hydroxytoluene) 250-1,000mg

• Strong. Fast acting in cases of HSV-1&2,

CMV Andrographis paniculata Tincture (1/2 dropper 3X daily); Capsules 500mg X3

• Good. Pairs well with: Licorice, Isatis,

Goldenseal Bitter Melon 500mg X3 Good Foundational: Selenium, Zinc, Vitamin A, Vitamin E Other herbals worth noting: Monolaurin, Licorice, Astragalus, Isatis, Berberine, Olive Leaf

Case Study Female Age 60

• Celiac
• Hashimoto’s
• History of viral (HSV-2, EBV)

Additional Symptoms:

• Joint hypermobility
• Pain
• Extreme fatigue
• Poor stress tolerance
• SIBO-like bloating

Current Regimen

• Diet - paleo, low

FODMAPS

• NatureThyroid -

32.5mg

• Nacent Iodine -

400mcg

• LDN - 4.5mg
• CoQ10 300mg
• Vitamin D3 - 5,000IU
• Vitamin K2 - 120mcg
• Selenium - 200mcg
• L-Lysine - 1,000mg
• Omega 3
• Liposomal C -

2,000mg

• Antrantil - 9 daily
• Betaine HCL - 600mg

w/food

• Digestive enzymes

Case Study Female Age 60

• Improve hydration - Add electrolytes to drinking water

Viral Support Protocol - titrate slowly over 10-14 days

• Pure Vida CBD oil - 10-20 mg daily or as needed
• Monolaurin Lauricidin - 1/4-1/2 teaspoon daily
• Enzymedica Serrapeptase - 1 capsule 2X daily
• Baicalin - Start with 250mg (1 scoop). Titrate unto 4 scoops (1,000mg)
• Add later: BHT (butylated hydroxytoluene)

Female Age 60 - Initial Protocol

Updates after 2 weeks: CBD improves pain & fatigue Updates after 6 weeks: Fatigue has gone from an 8 to a 3

Female Age 60 - Follow-up Protocol: 3 months

New Protocol Additions Instructions Dosing Functional Effects Increase water & salt intake 3-4 tablespoons salt in 1 gallon of water and daily use 2 teaspoons 3X daily in drinking water

• Acting on ECM electrolyte gradient
• Acting on salt lost though

aldosterone deficient due to CYP21a2 Autoimmune-X Digestaqure Start with 4 capsules daily. After 3-5 days, workup to 8 capsules daily. The ceiling dosage is 12 capsules daily. (initial symptoms of gas, nausea has been reported by some people. Titrate up and down accordingly)

• Acting on Complement C4 to yield

lectin pathway activation

• Acting on growth factors by

modulating ECM Megasporebiotic 2 daily Immunomodulatory, Histamine Himalaya Ashwagandha 1X2 Attenuating CYP21a2 Modulating thyroid axis Berberine 500mg - experimental dosage to determine physiological effects. May be useful for reducing progesterone bottleneck, increasing tight junctions in gut, improving circulation Collagen Supplement Daily as needed Improving collagen structure & ECM

Immunomodulatory/Anti-Viral Pure Vida CBD 10-20 mg Baicalin 1,000 mg BHT 500-1,000 mg

Follow-Up Blood Work - 6-Months

Vitamin D

Vitamin D Testing

• Measuring 25OH Vitamin D by itself is futile
• Calcitriol (1,25) should be measured simultaneously with 25OHD
• Ratio should be close to 1:1
• Aberrations in 25OHD : Calcitriol ratio is associated with chronic

inflammation, autoimmunity, viral & pathogenic infection

Vitamin D, Immune Activation & Other Targets

• Vitamin D-Binding Protein is a GcMAF - activating macrophages
• Activates TREGs cells - critical in “self tolerance”
• Inhibits Mast Cells
• Modulate T & B-cell lymphocytes
• T-cell maturation
• Also:
• Activates CYP3a4
• Bile acid formation
• Neuronal growth
• Dopamine activation
• Testosterone, sperm count & fertility

ONLY Calcitriol (1,25 DihydroxyVitaminD) activates the VDR. NOT 25OHD

25OHD:Calcitriol Findings: Hashimoto’s with EBV

Foods UVB D3 Cholecalciferol CYP2R1 CYP27a1 25OH Vitamin D3 CYP27B1 Calcitriol (1,25 dihydroxyVitamin D3) VDR Inactive metabolites CYP24A1 RXR VDR Targets

VDR Inhibiting Factors

• Lyme
• Epstein barr virus (EBV)
• Cytomegalovirus (CMV)
• Wifi radiation
• Gliotoxin (aspergillus, penicillium, trichoderma)

EBV & VDR

Hair Loss (alopecia) & VDR Inactivation

Is this one explanation for hair loss in Hashimoto’s (and other autoimmune diseases)?

• Clean up the mess

Key Takeaways for Vitamin D Testing

• Testing 25OH Vitamin D by itself is of limited value
• 1,25 dihydroxyVitaminD (Calcitriol) should be tested with 25OHD
• Functional Ideal for 25OHD:Calcitriol 1:1
• Chronic Infections the ratio is often 1:1.5 - 1:2

Improving Vitamin D Metabolism

Supplementing with Vitamin D3 is often useless because it fails to address the Functional Changes of D metabolism, & subsequent VDR inactivation attributed to pathogenic influences

• Lower Inflammatory Burden
• Adequate sun exposure
• Subsequent use of therapies to address pathogenic & viral activity
• Boron - 10mg (enhances D metabolism, likely through inhibiting 24-

hydroxylase)

• Lactobacillus Reuteri NCIMB 30242 increases 25OHD by 25% - also T-REGS
• Use of Bravo Yogurt to activate macrophages & Vit. D-binding proteins
• Turn off the Wifi (at night especially)

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