Comprehensive Autoimmune Protocol

The Autoimmune Epidemic

Autoimmune diseases now affect roughly 50 million Americans — more than cancer and heart disease combined. The incidence keeps climbing. Something in our environment, our food, our stress loads is flipping switches in genetically susceptible people, and the immune system turns its weapons inward.

Conventional medicine treats autoimmunity with immunosuppression: steroids, methotrexate, biologics. These drugs can be life-saving, but they never ask the deeper question — why did the immune system lose tolerance in the first place?

Functional medicine asks that question. And the answers lead to root-cause protocols that can put autoimmune conditions into remission.

The Fasano Triad: Three Legs of the Autoimmune Stool

Dr. Alessio Fasano, the gastroenterologist at Harvard who discovered zonulin, proposed that autoimmune disease requires three simultaneous conditions:

1. Genetic susceptibility — HLA genes (HLA-B27, HLA-DQ2/DQ8, HLA-DR4, etc.) predispose but do not determine
2. Intestinal permeability — “leaky gut” allows large protein fragments into the bloodstream, triggering immune activation
3. Environmental trigger — the match that lights the fire: infection, toxin, food antigen, stress event, hormonal shift

Remove any one leg and the disease process stalls. This is the basis of the functional medicine approach: you cannot change the genes, but you can heal the gut and remove the triggers.

Zonulin, the protein Fasano discovered, is released in response to gluten and certain bacteria. It opens tight junctions between intestinal epithelial cells. In genetically susceptible individuals, this permeability becomes chronic, creating a highway for undigested proteins, bacterial endotoxins (LPS), and other antigens to reach the immune system.

Molecular Mimicry: When the Body Attacks Itself

Molecular mimicry is the mechanism by which a foreign antigen shares structural similarity with a self-antigen. The immune system mounts a response against the invader, but the antibodies or T-cells cross-react with the body’s own tissues.

Documented examples:

• Gluten and thyroid tissue — gliadin shares amino acid sequences with thyroid peroxidase. This is why Hashimoto’s thyroiditis and celiac disease so frequently co-occur. Remove gluten and thyroid antibodies (TPO-Ab, TG-Ab) often decrease over 6-12 months.
• Klebsiella pneumoniae and HLA-B27 — Klebsiella bacteria share epitopes with HLA-B27, driving ankylosing spondylitis. A low-starch diet (starving Klebsiella) has shown benefit in clinical studies. The London AS Diet pioneered by Dr. Alan Ebringer demonstrated this link.
• Proteus mirabilis and rheumatoid arthritis — Proteus bacteria share molecular sequences with type XI collagen. Urinary tract infections with Proteus often precede RA flares.
• Epstein-Barr virus (EBV) and lupus/MS — EBV nuclear antigen-1 (EBNA-1) cross-reacts with multiple self-antigens. Nearly 100% of MS and lupus patients are EBV-seropositive. Recent large-scale studies (2022, Science) showed EBV infection increases MS risk 32-fold.
• Campylobacter jejuni and Guillain-Barré syndrome — ganglioside mimicry attacks peripheral nerve myelin.

Common Autoimmune Conditions

The functional medicine approach applies across the spectrum:

• Hashimoto’s thyroiditis — most common autoimmune condition, often undiagnosed for years. Check TPO-Ab, TG-Ab, not just TSH.
• Rheumatoid arthritis — anti-CCP antibodies can appear 10 years before symptoms.
• Systemic lupus erythematosus (SLE) — ANA, anti-dsDNA, complement (C3/C4) monitoring.
• Multiple sclerosis — demyelination driven by neuroinflammation and immune dysregulation.
• Celiac disease — the only autoimmune condition with a known trigger (gluten) and a known cure (remove it).
• Type 1 diabetes — beta cell destruction, GAD65 antibodies.
• Psoriasis and psoriatic arthritis — skin as immune organ, gut-skin axis.
• Crohn’s disease and ulcerative colitis — IBD involves loss of tolerance to commensal bacteria.
• Sjogren’s syndrome — dry eyes, dry mouth, anti-SSA/SSB antibodies.
• Ankylosing spondylitis — HLA-B27 positive in >90% of cases.

The AIP Elimination Diet

The Autoimmune Protocol (AIP) elimination diet, developed and researched extensively by Dr. Sarah Ballantyne (The Paleo Mom), removes the foods most likely to drive intestinal permeability, immune activation, and inflammation. It is not a permanent diet — it is a diagnostic tool.

Phase 1: Elimination (30-90 Days Minimum)

Remove completely:

• Grains — all grains, including gluten-free (rice, corn, oats, quinoa). Prolamins and agglutinins in grains damage the intestinal lining.
• Legumes — beans, lentils, peanuts, soy. Lectins and saponins increase intestinal permeability.
• Dairy — all forms. Casein (especially A1 beta-casein) cross-reacts with gluten and is independently inflammatory. Whey and lactose also problematic.
• Eggs — lysozyme in egg whites penetrates the gut barrier. Egg yolks are less reactive and reintroduced first.
• Nuts and seeds — phytic acid, enzyme inhibitors, and high omega-6 content.
• Nightshades — tomatoes, peppers, eggplant, white potatoes, goji berries. Alkaloids (solanine, capsaicin, tomatine) increase intestinal permeability.
• Coffee — cross-reacts with gluten in many people. Also stimulates cortisol.
• Alcohol — directly damages the intestinal barrier.
• Refined sugars — feed pathogenic bacteria, drive insulin resistance and inflammation.
• Food additives — emulsifiers (polysorbate 80, carboxymethylcellulose), artificial sweeteners, carrageenan — all shown to damage the mucus layer and increase permeability.
• NSAIDs — ibuprofen, naproxen, aspirin. These directly cause intestinal permeability within hours. A major and often overlooked trigger.
• Seed-based spices — cumin, coriander, mustard, nutmeg initially removed.

Include generously:

• Organ meats — liver (vitamin A, B12, folate, copper, iron), heart (CoQ10), kidney. 2-4 servings per week. The most nutrient-dense foods on the planet.
• Bone broth — collagen, glycine, proline, glutamine. 1-2 cups daily. Directly nourishes the intestinal lining.
• Fermented foods — sauerkraut, kimchi (nightshade-free), coconut yogurt, water kefir, kombucha. Start small (1 tablespoon) and increase slowly.
• Wild-caught fatty fish — salmon, sardines, mackerel, anchovies. Omega-3 rich. 3-4 servings per week minimum.
• Vegetables — all non-nightshade vegetables. Emphasize leafy greens, cruciferous vegetables (cooked for thyroid conditions), root vegetables, alliums.
• Fruits — moderate amounts, emphasizing berries (polyphenols). 1-2 servings per day.
• Healthy fats — olive oil, avocado oil, coconut oil, rendered animal fats (tallow, lard from pastured animals).
• Fresh herbs and non-seed spices — turmeric, ginger, garlic, basil, oregano, thyme, rosemary, cinnamon (Ceylon).
• Collagen-rich foods — skin-on poultry, pork rinds, tendon, bone broth.

Phase 2: Reintroduction

After 30-90 days of strict elimination (or when significant symptom improvement is noted), reintroduce foods one at a time, every 3-5 days. Keep a detailed food and symptom diary.

Order of reintroduction (least to most reactive):

1. Egg yolks (cooked)
2. Seed-based spices (black pepper, cumin, coriander)
3. Ghee (clarified butter — casein removed)
4. Nuts and seeds (start with soaked/sprouted)
5. Cocoa/chocolate
6. Egg whites
7. Coffee
8. Nightshade spices (paprika, chili)
9. Legumes (lentils first, well-cooked)
10. Nightshade vegetables (cooked first)
11. Dairy (butter → aged cheese → fresh dairy)
12. Grains (white rice first if at all)
13. Gluten-containing grains (often permanent removal for autoimmune)

Reaction signs to watch: joint pain, fatigue, brain fog, skin breakouts, digestive symptoms, headache, mood changes, sleep disruption. Reactions can be delayed 24-72 hours.

Key Supplements for Autoimmune Protocol

Vitamin D3 + K2

Vitamin D is a hormone and a master immune modulator. Low vitamin D is found in virtually every autoimmune condition. Optimize serum 25(OH)D to 60-80 ng/mL (not the standard “sufficient” of 30). This often requires 5,000-10,000 IU/day of D3, always paired with K2 (MK-7, 100-200mcg) to direct calcium into bones and away from arteries. Retest every 3 months until stable.

Omega-3 Fatty Acids

EPA and DHA are potently anti-inflammatory, resolving inflammation through specialized pro-resolving mediators (SPMs). For active autoimmune flares, dose 4-6g combined EPA+DHA per day. Maintenance: 2-3g/day. Use triglyceride-form fish oil or wild-caught fatty fish. Monitor omega-3 index (target 8-12%).

Curcumin

The most studied anti-inflammatory botanical. Inhibits NF-kB, COX-2, TNF-alpha, IL-6. Use liposomal curcumin or Meriva (phytosome) form for absorption — standard curcumin has <1% bioavailability. Dose: 1000-2000mg/day of enhanced-absorption form. Equivalent to roughly 20-40g of turmeric powder.

SPMs (Specialized Pro-Resolving Mediators)

SPMs (resolvins, protectins, maresins) are the molecules your body makes to actively resolve inflammation — they are the off-switch. Supplemental SPMs (from fish oil) at 1000-2000mg/day can accelerate the resolution phase of inflammation.

Glutathione and NAC

Glutathione is the master antioxidant and critical for immune regulation. Autoimmune patients are typically depleted. Liposomal glutathione 500-1000mg/day or N-acetylcysteine (NAC) 600-1800mg/day as a precursor. NAC also thins mucus (helpful in respiratory autoimmune) and supports detoxification.

Low-Dose Naltrexone (LDN)

LDN at 1.5-4.5mg taken at bedtime is one of the most promising interventions in autoimmune medicine. At full dose (50mg), naltrexone blocks opioid receptors and is used for addiction. At low dose, it has a paradoxical effect:

• Briefly blocks opioid receptors, causing a rebound increase in endorphin and enkephalin production
• Upregulates opioid growth factor (OGF) and its receptor, modulating immune function
• Blocks toll-like receptor 4 (TLR4) on microglia and macrophages, reducing neuroinflammation and systemic inflammation
• Published evidence in MS, Crohn’s disease, fibromyalgia, Hashimoto’s

Start at 0.5-1mg and titrate up over 4-8 weeks. Must be compounded. Side effects are minimal — vivid dreams early on.

Vitamin A (Retinol)

Preformed vitamin A (retinol, not beta-carotene) is essential for mucosal immunity, regulatory T-cell development, and gut barrier integrity. Dose: 5,000-10,000 IU/day from cod liver oil or supplemental retinyl palmitate. Liver is the richest food source.

Gut Healing: The Central Strategy

The gut is the epicenter of autoimmunity. Over 70% of the immune system resides in the gut-associated lymphoid tissue (GALT). Healing the intestinal barrier is non-negotiable. Follow the 5R protocol:

1. Remove — infections (SIBO, parasites, Candida, H. pylori), food triggers, toxins, NSAIDs
2. Replace — digestive enzymes, HCl (betaine HCl with pepsin), bile salts if needed
3. Reinoculate — diverse probiotics (Lactobacillus, Bifidobacterium, Saccharomyces boulardii), prebiotic fibers
4. Repair — L-glutamine (5-10g/day), zinc carnosine (75mg 2x/day), DGL licorice, aloe vera, collagen, butyrate
5. Rebalance — sleep, stress management, vagal tone, movement

Infection Screening

Chronic infections are frequently the “match” that lights the autoimmune fire. Screen for:

• EBV — VCA IgG, EBNA IgG, Early Antigen IgG. Reactivation (EA IgG positive) is clinically significant.
• CMV, HHV-6 — often co-reactivate with EBV
• Mycoplasma pneumoniae — associated with RA, autoimmune hemolytic anemia
• Lyme disease — Borrelia burgdorferi drives molecular mimicry; co-infections (Babesia, Bartonella, Ehrlichia) compound autoimmunity
• Parasites — comprehensive stool testing (PCR-based like GI-MAP), not standard O&P
• H. pylori — associated with ITP, autoimmune gastritis, low B12
• Yersinia enterocolitica — shares epitopes with thyroid tissue

Treatment varies by organism but must be addressed. You cannot heal a leaky gut while an active infection persists.

Environmental Triggers

Heavy Metals

Mercury (dental amalgams, fish), lead (old paint, water pipes), arsenic (rice, well water), cadmium (cigarettes). Test with provoked urine challenge (DMSA or DMPS) or whole blood/RBC levels. Heavy metals displace zinc, selenium, and other minerals critical for immune regulation.

Mold and Mycotoxins

Chronic mold exposure (water-damaged buildings) produces mycotoxins (ochratoxin A, aflatoxins, trichothecenes, gliotoxin) that are potent immune disruptors. Screen with urinary mycotoxin testing (RealTime Labs, Great Plains). Treatment involves removal from exposure, binders (cholestyramine, activated charcoal, bentonite clay), and glutathione support.

Pesticides and Chemicals

Glyphosate damages the microbiome and tight junctions. BPA and phthalates are endocrine disruptors that affect immune tolerance. Eat organic when possible, filter water, avoid plastic food containers.

Stress and Autoimmunity

Chronic psychological stress is a documented trigger for autoimmune flares. The mechanism:

• Cortisol dysregulation — initially elevated cortisol suppresses immune balance. Over time, HPA axis dysfunction leads to cortisol resistance, and the immune system “escapes” suppression, attacking with increased Th1/Th17 activity.
• Vagus nerve dysfunction — reduced vagal tone impairs the cholinergic anti-inflammatory pathway. The vagus nerve directly dampens TNF-alpha and IL-6 production. Low vagal tone = higher inflammation.
• Interventions: vagus nerve stimulation (cold exposure, gargling, singing, humming), meditation, yoga, breath work (especially slow exhalation), HRV biofeedback, adequate sleep.

Testing and Monitoring

Baseline autoimmune panel:

• ANA (antinuclear antibody) with reflex to pattern and titer
• Anti-dsDNA (lupus-specific)
• RF (rheumatoid factor) and anti-CCP (cyclic citrullinated peptide)
• Complement C3 and C4 (consumed in active lupus)
• ESR and hs-CRP (general inflammation)
• Specific antibodies: TPO-Ab, TG-Ab (Hashimoto’s), anti-SSA/SSB (Sjogren’s), GAD65 (type 1 diabetes)

Gut assessment:

• Comprehensive stool analysis (GI-MAP or equivalent)
• Zonulin (serum or stool) for intestinal permeability
• Lactulose-mannitol test (gold standard for permeability)
• Food sensitivity panel (IgG/IgA — Vibrant Wellness, Cyrex Array 10)

Monitor every 3-6 months:

• Antibody titers (TPO, anti-CCP, ANA titer) — tracking trends is more important than single values
• Inflammatory markers (hs-CRP, ESR)
• 25(OH) vitamin D
• Omega-3 index
• Symptom scores (validated questionnaires for each condition)

Timeline and Expectations

Autoimmune healing is slow. The immune system does not reset overnight.

• Weeks 1-2: AIP elimination, supplement introduction. May experience temporary worsening (“die-off” or “detox” reaction).
• Weeks 3-6: Energy often improves first. Digestive symptoms begin resolving. Joint pain decreasing.
• Months 2-3: Skin clearing, brain fog lifting, measurable reduction in inflammatory markers.
• Months 3-6: Begin careful food reintroduction. Antibody titers starting to trend down.
• Months 6-12: Significant antibody reduction possible. Many patients achieve low-level antibodies or remission. Some can reintroduce many foods without reaction.
• Ongoing: Maintain core dietary principles. Continue key supplements. Monitor labs annually. Stay vigilant for triggers.

Autoimmune disease can go into deep remission. The body wants to heal. Give it the conditions it needs — remove the interference, heal the barrier, calm the immune system — and it will do the rest.