The Autoimmune Protocol (AIP) — A Root Cause Approach

The Three-Legged Stool of Autoimmunity

In 2011, Dr. Alessio Fasano at Harvard published a paper that rewrote the autoimmune playbook. He proposed that autoimmune disease requires three simultaneous conditions — like a three-legged stool. Remove any leg and the stool falls:

1. Genetic susceptibility — HLA genes that predispose you (HLA-DQ2/DQ8 for celiac, HLA-B27 for ankylosing spondylitis, HLA-DR4 for rheumatoid arthritis)
2. Environmental trigger — infections, food antigens, toxins, stress
3. Intestinal permeability — “leaky gut,” the gateway that lets triggers reach the immune system

This was revolutionary. Genetics loads the gun. Environment pulls the trigger. But the gut opens the door. And here is the good news: you cannot change your genes, but you can absolutely seal that gut and reduce your environmental load. The stool collapses.

The Autoimmune Spectrum

Autoimmunity does not arrive overnight like a thief. It creeps along a spectrum over years — sometimes decades:

• Silent autoimmunity: Antibodies are present in blood, but you feel nothing. No symptoms. This is the whisper stage. Thyroid antibodies (TPO, TG) can be elevated 7-10 years before a Hashimoto’s diagnosis.
• Autoimmune reactivity: Symptoms appear — fatigue, joint pain, brain fog, skin changes — but conventional labs look “normal.” You are told it is stress. Or aging. Or depression. This is the shout stage.
• Autoimmune disease: Tissue destruction is now measurable. TSH is finally abnormal. Joint erosion shows on X-ray. You get your diagnosis — and a prescription for immunosuppressants.

Functional medicine intervenes at the whisper. We do not wait for the house to burn before calling the fire department.

Common Autoimmune Conditions

The body has roughly 80-100 recognized autoimmune diseases. The most common:

• Hashimoto’s thyroiditis — immune attack on thyroid (most common autoimmune disease, affects 5% of population)
• Graves’ disease — thyroid-stimulating antibodies (hyperthyroidism)
• Rheumatoid arthritis — synovial joint destruction
• Systemic Lupus Erythematosus (SLE) — multi-organ (kidneys, skin, joints, brain)
• Multiple Sclerosis — myelin sheath destruction in CNS
• Celiac disease — gluten-triggered intestinal villous atrophy
• Type 1 Diabetes — pancreatic beta cell destruction
• Psoriasis / Psoriatic arthritis — skin and joint
• Crohn’s disease / Ulcerative Colitis — inflammatory bowel
• Sjogren’s syndrome — exocrine glands (dry eyes, dry mouth)
• Scleroderma — skin and connective tissue fibrosis

What they all share: a confused immune system attacking self. The tissue target differs. The mechanism rhymes.

The AIP Elimination Diet

The Autoimmune Protocol is a targeted elimination diet lasting 30-90 days. It removes foods most likely to drive intestinal permeability, immune activation, and molecular mimicry — then systematically reintroduces them to identify personal triggers.

Foods to Remove

• All grains — wheat, rice, oats, corn, barley, rye (gluten and non-gluten). Gluten triggers zonulin release in everyone, not just celiacs (Fasano, 2015).
• Legumes — beans, lentils, peanuts, soy (lectins, phytates)
• Dairy — all forms including ghee initially (casein, whey, butyrophilin mimics thyroid)
• Eggs — especially egg whites (lysozyme crosses gut barrier)
• Nuts and seeds — including nut butters, nut milks, nut flours (phytic acid, enzyme inhibitors)
• Nightshades — tomato, pepper (all varieties), potato, eggplant, goji berries (alkaloids: solanine, capsaicin increase intestinal permeability)
• Refined sugar and sweeteners — feeds dysbiosis, spikes insulin, drives inflammation
• Alcohol — directly damages intestinal lining, burdens liver detox
• Coffee — cross-reacts with gluten antibodies in some individuals, stimulates cortisol
• Chocolate/cacao — cross-reactive, contains caffeine
• Food additives — emulsifiers (polysorbate 80, carboxymethylcellulose), carrageenan, artificial sweeteners (documented to disrupt tight junctions)
• NSAIDs — ibuprofen, aspirin, naproxen (directly increase intestinal permeability within hours)

Foods to Emphasize

• Vegetables — all non-nightshade varieties. Load the plate. Aim for 8-10 servings/day. Variety matters — different colors feed different microbes.
• Fruit — limited to 2-3 servings/day (berries preferred for polyphenols)
• Quality meats — grass-fed beef, pasture-raised poultry, wild game
• Organ meats — liver 2-3x/week (nature’s multivitamin: retinol, B12, folate, copper, CoQ10)
• Bone broth — daily (collagen, glycine, proline, glutamine for gut repair)
• Fermented foods — sauerkraut, kimchi (without nightshades), coconut yogurt, kombucha (start small — 1 tablespoon/day)
• Healthy fats — extra virgin olive oil, avocado, coconut oil, rendered animal fats
• Seafood — wild-caught fatty fish 3-4x/week (EPA/DHA, selenium, iodine)
• Herbs and non-seed spices — turmeric, ginger, garlic, basil, oregano, thyme, cinnamon (Ceylon)

The Reintroduction Protocol

After 30-90 days, reintroduce foods one at a time, every 5-7 days. This spacing matters — delayed immune reactions can take 72 hours to manifest.

Reintroduction order (least to most reactive):

1. Egg yolks (cooked) — less immunogenic than whites
2. Ghee (clarified butter) — casein/whey removed
3. Seed-based spices — cumin, coriander, mustard, fennel
4. Nuts and seeds — start with tree nuts, then seeds
5. Egg whites
6. Dairy — butter, then aged cheese, then fresh dairy
7. Nightshades — cooked, peeled, deseeded first
8. Legumes — lentils and chickpeas first
9. Grains — white rice (least reactive), then others
10. Coffee, chocolate — last

Track symptoms in a journal: energy, digestion, mood, skin, joint pain, sleep quality. Any flare = that food stays out for 3-6 more months.

Immune Modulation Supplements

While diet does the heavy lifting, targeted supplementation accelerates immune rebalancing:

• Vitamin D: 5,000-10,000 IU/day with K2 (MK-7, 200mcg). Target serum 25-OH-D of 60-80 ng/mL. Vitamin D is not just a vitamin — it is a secosteroid hormone that programs T-regulatory cells. The Coimbra Protocol uses 40,000-200,000 IU/day for MS under strict medical supervision with calcium-restricted diet and frequent monitoring.
• Omega-3 fatty acids (EPA/DHA): 3-4g/day pharmaceutical grade. EPA drives resolvin E1 production; DHA drives resolvin D1 and protectin D1. These are pro-resolving — they actively turn off inflammation, not just block it.
• Low-Dose Naltrexone (LDN): 1.5-4.5mg at bedtime (compounding pharmacy). Blocks opioid receptors briefly, causing a rebound upregulation of endorphins and enkephalins. This modulates T-regulatory cells and reduces pro-inflammatory cytokines. Evidence in Crohn’s, MS, Hashimoto’s, fibromyalgia. Start at 0.5mg, increase by 0.5mg weekly.
• Curcumin (bioavailable form — Meriva, Theracurmin, or Longvida): 1000mg/day. Potent NF-kB inhibitor. Comparable to corticosteroids for NF-kB suppression without immunosuppression.
• SPMs (Specialized Pro-Resolving Mediators): derived from omega-3, these actively resolve inflammation. Think of them as the cleanup crew that arrives after the fire department. Brands: Metagenics SPM Active, Nordic Naturals ProResolve.
• Glutathione: 500-1000mg liposomal form. Master antioxidant, supports T-reg cells, critical for detoxification. Depleted in virtually every autoimmune condition studied.
• Vitamin A (retinol): 10,000 IU/day from cod liver oil or preformed retinol (not beta-carotene). Essential for mucosal immunity (IgA production), immune tolerance, and gut barrier integrity.

Root Cause Investigation

The AIP diet is the foundation, but detective work finds the deeper triggers:

Molecular Mimicry

The immune system attacks self-tissue because a foreign protein looks structurally similar:

• Gluten → thyroid tissue: gliadin’s amino acid sequence resembles thyroid peroxidase. Every time a Hashimoto’s patient eats gluten, the immune system is reminded to attack the thyroid.
• Klebsiella pneumoniae → HLA-B27: bacterial protein mimics the HLA-B27 receptor — driving ankylosing spondylitis, reactive arthritis
• Proteus mirabilis → Rheumatoid factor: urinary tract infections linked to RA flares
• Yersinia enterocolitica → thyroid: gut infection that triggers Graves’ disease through TSH receptor mimicry

Other Root Causes

• Infections: EBV (Epstein-Barr Virus) is linked to SLE, MS, Hashimoto’s, RA. CMV and HHV-6 also implicated.
• Toxins: mercury (dental amalgams, fish), silicone (breast implants — ASIA syndrome), BPA, pesticides
• Stress: chronic HPA axis activation shifts immune balance toward Th1/Th17 dominance and suppresses T-regulatory cells

Gut Healing — The 5R Protocol

Refer to the full 5R protocol article, but in brief for autoimmunity:

1. Remove — pathogens, food triggers, toxins
2. Replace — digestive enzymes, HCl (if low stomach acid)
3. Reinoculate — probiotics, prebiotics, fermented foods
4. Repair — L-glutamine (5g 2x/day), zinc carnosine (75mg 2x/day), collagen/bone broth, aloe vera, DGL licorice
5. Rebalance — sleep, stress, movement, connection

The goal: reduce zonulin, restore tight junction proteins (occludin, claudin, ZO-1), rebuild the mucosal barrier. When the gut seals, the immune system calms.

Lifestyle — The Non-Negotiables

Supplements and diet address the biochemistry. Lifestyle addresses the terrain:

• Sleep: 8-9 hours minimum. Autoimmune patients need more, not less. Sleep deprivation increases IL-6, TNF-alpha, and CRP. Prioritize sleep hygiene: dark room, cool temperature (65-68°F), no screens 1 hour before bed.
• Stress management: chronic stress depletes cortisol over time (HPA axis dysfunction), which removes the brake on the immune system. Daily practice: meditation, breathwork (4-7-8 breathing), yoga nidra, time in nature.
• Gentle movement: walking, swimming, yoga, tai chi. Avoid overtraining — excessive exercise increases intestinal permeability and cortisol. The goal is movement that reduces inflammation, not creates it.
• Community and connection: loneliness is inflammatory. Social isolation increases NF-kB activation. Connection with others who understand your condition reduces perceived stress and improves outcomes.

The Bottom Line

Autoimmunity is not a life sentence of immunosuppression. Fasano’s three-legged stool gives us a map: seal the gut, reduce triggers, modulate the immune response. The AIP protocol is not forever — it is a therapeutic intervention. Most people can reintroduce many foods within 3-6 months. The ones they cannot tolerate become their personalized avoidance list.

The body wants to heal. Remove what is blocking it. Provide what it needs. Give it time. The immune system can learn tolerance again — if you stop confusing it.