Rheumatoid Arthritis: The Functional Approach

When the Body Attacks Its Own Joints

Rheumatoid arthritis is not wear-and-tear arthritis. It is not the gradual erosion of cartilage that comes with age and overuse. RA is an autoimmune assault — the immune system infiltrating the synovial membrane of joints, creating a destructive tissue called pannus that erodes cartilage and bone from the inside. It is symmetrical (both hands, both knees, both feet), systemic (fatigue, anemia, lung nodules, vasculitis), and progressive if untreated.

What makes RA remarkable from a functional medicine perspective is how clearly the disease connects to specific environmental triggers — and how powerfully those triggers can be addressed.

The conventional model treats RA as a disease to suppress. Functional medicine treats it as a fire to find the source of.

Pathophysiology: From Citrullination to Destruction

The story of rheumatoid arthritis begins not in the joints but in the immune system’s response to citrullinated proteins.

Citrullination is a post-translational modification where the amino acid arginine is converted to citrulline by peptidylarginine deiminase (PAD) enzymes. This normally happens during cell death and inflammation. In genetically susceptible individuals (HLA-DR4, HLA-DRB1 “shared epitope”), the immune system recognizes citrullinated proteins as foreign and mounts an antibody response.

Anti-CCP (anti-cyclic citrullinated peptide) antibodies are highly specific for RA and can appear years before joint symptoms manifest. Rheumatoid factor (RF) — an antibody against the Fc portion of IgG — is less specific but commonly measured.

These autoantibodies, along with activated T cells (particularly Th17 cells producing IL-17) and inflammatory cytokines (TNF-alpha, IL-6, IL-1), drive the synovial inflammation that defines RA. The inflamed synovium proliferates into pannus — an aggressive tissue that invades cartilage and bone, causing the joint destruction visible on imaging.

The Oral-Joint Connection: A Revolution in Understanding

One of the most striking discoveries in RA research is the connection between periodontal disease and joint disease.

Porphyromonas gingivalis — the bacterium most strongly associated with periodontitis — possesses a unique PAD enzyme (PPAD) that citrullinates human and bacterial proteins. Mikuls’s 2014 research demonstrated that P. gingivalis antibodies correlate with anti-CCP antibody levels and RA disease activity. The hypothesis: periodontal infection with P. gingivalis triggers citrullination in the oral mucosa, which in genetically susceptible individuals provokes the anti-CCP immune response that ultimately targets joints.

The clinical implication is profound: treating periodontal disease is part of treating rheumatoid arthritis. Studies show that periodontal treatment — scaling, root planing, and infection control — improves RA disease activity scores. Every RA patient should have a comprehensive dental evaluation, and periodontal disease should be treated aggressively.

This is not a minor sidebar. This may be the origin of the disease in many patients.

Diagnostic Testing

• RF (Rheumatoid Factor) — Present in ~70-80% of RA. Not specific (also seen in hepatitis C, Sjogren’s, chronic infections).
• Anti-CCP Antibodies — Highly specific (>95%). Can precede symptoms by years. Higher titers predict more aggressive disease.
• CRP (C-Reactive Protein) — Acute-phase reactant. Correlates with inflammation and joint damage progression.
• ESR (Erythrocyte Sedimentation Rate) — General inflammation marker. Useful for monitoring.
• Joint Imaging — Ultrasound (can detect synovitis before clinical examination), MRI (bone marrow edema, early erosions), X-ray (late — shows joint space narrowing and erosions after damage has occurred).
• CBC — Anemia of chronic disease is common. Platelet elevation reflects inflammation.

Functional additions: comprehensive metabolic panel, 25-OH vitamin D, iron studies, comprehensive stool analysis, food sensitivity testing (IgG panels — controversial but clinically useful in some patients), organic acids test.

Conventional Treatment

RA treatment has been transformed by disease-modifying therapy. Early aggressive treatment prevents irreversible joint destruction.

• Methotrexate — Cornerstone DMARD. Effective, well-studied, relatively inexpensive. Critical: always co-supplement with folate (folic acid 1-5 mg daily or folinic acid/methylfolate) to reduce side effects (mouth sores, nausea, liver toxicity, cytopenias). Many practitioners use methylfolate 5-15 mg on non-methotrexate days.
• Biologics — TNF inhibitors (adalimumab, etanercept, infliximab), IL-6 inhibitors (tocilizumab), T cell co-stimulation blockers (abatacept), B cell depletion (rituximab).
• JAK inhibitors — Tofacitinib, baricitinib, upadacitinib. Oral small molecules. Effective but carry cardiovascular and thrombotic risks in certain populations.
• Corticosteroids — Bridge therapy during flares. Long-term use avoided due to side effects.

Functional Root Causes

Gut Permeability and the Microbiome

The gut-joint axis is well-established. RA patients demonstrate increased intestinal permeability and specific microbiome alterations. Ebringer’s work on Proteus mirabilis showed that this urinary and gut bacterium shares molecular mimicry with HLA-DR4 — the genetic risk factor for RA. Proteus antibodies are elevated in RA patients, and UTIs may trigger disease flares.

Beyond Proteus, RA-associated dysbiosis includes expansion of Prevotella copri (Scher 2013 — enriched in new-onset RA) and reduced microbial diversity.

Food Sensitivities

Darlington’s 1986 elemental diet study was landmark: RA patients placed on an elemental diet (pre-digested nutrients, no intact food proteins) showed significant improvement. When individual foods were reintroduced, specific triggers were identified — different for each patient but commonly including grains, dairy, corn, and nightshades.

Nightshade sensitivity: Solanine and other glycoalkaloids in potatoes, tomatoes, peppers, and eggplant may increase intestinal permeability and promote inflammation in sensitive individuals. This is not universal, but a nightshade elimination trial (strict avoidance for 30 days, then systematic rechallenge) is warranted when standard dietary interventions are insufficient.

Infections

Beyond P. gingivalis and Proteus, EBV, parvovirus B19, and mycoplasma have been implicated in RA pathogenesis through molecular mimicry and chronic immune stimulation.

Stress

Psychosocial stress precedes RA onset and triggers flares through HPA axis dysregulation, increased intestinal permeability, and immune activation.

Diet: The Evidence

Mediterranean Diet

Skoldstam’s 2003 randomized controlled trial demonstrated that a Mediterranean diet in RA patients reduced CRP, improved physical function, and increased vitality over 12 weeks compared to controls. The mechanism: abundant omega-3 from fish, polyphenols from olive oil and vegetables, fiber for microbiome health, and reduced omega-6 from processed oils.

Vegetarian/Vegan Diet

Kjeldsen-Kragh’s 1991 landmark study used a dramatic protocol: 7-10 days of supervised fasting (which rapidly reduces inflammation), followed by a vegan, gluten-free diet for 3.5 months, then transition to lacto-vegetarian for 9 months. The intervention group showed significant improvement in pain, morning stiffness, ESR, CRP, and joint tenderness — improvements sustained at one year.

This study demonstrates something important: diet is not a minor adjunct in RA. It can produce measurable, lasting changes in disease activity.

Elimination Diet

A structured elimination of common inflammatory foods (gluten, dairy, corn, soy, eggs, nightshades, sugar, alcohol, processed foods) for 30 days, followed by systematic one-at-a-time reintroduction every 3 days, allows identification of individual triggers. This is one of the most powerful tools in functional medicine for RA.

The Supplement Protocol

Omega-3 Fatty Acids: 3-6 g EPA/DHA daily

Goldberg’s 2007 meta-analysis of 17 randomized controlled trials confirmed that fish oil supplementation in RA reduces joint pain intensity, morning stiffness duration, number of painful joints, and NSAID use. The minimum effective dose appears to be around 3 g/day of combined EPA/DHA. Higher doses (up to 6 g) may provide additional benefit.

EPA competes with arachidonic acid for the COX and LOX enzyme systems, shifting eicosanoid production from pro-inflammatory (PGE2, LTB4) to anti-inflammatory (PGE3, LTB5, resolvins, protectins).

Curcumin: 1,000-1,500 mg daily

Chandran’s 2012 randomized controlled trial compared curcumin 500 mg to diclofenac sodium 50 mg in active RA. Curcumin produced equivalent improvement in DAS28 (Disease Activity Score) and was actually superior in reducing tender and swollen joint counts — without the gastrointestinal side effects of the NSAID. Use bioavailable forms: Meriva (phytosome), BCM-95, or liposomal curcumin.

Boswellia serrata: 300 mg three times daily

Boswellic acids (particularly AKBA) inhibit 5-lipoxygenase, reducing leukotriene synthesis. Anti-inflammatory and analgesic effects have been documented in multiple inflammatory conditions. Well-tolerated, works synergistically with curcumin.

Vitamin D: 5,000-10,000 IU daily (target 60-80 ng/mL)

Vitamin D deficiency is nearly universal in RA and inversely correlated with disease activity. Vitamin D modulates Th17/Treg balance, and supplementation has been shown to reduce flare frequency.

Probiotics

Vaghef-Mehrabani’s 2014 study showed that Lactobacillus casei supplementation in RA patients for 8 weeks significantly reduced disease activity (DAS28), CRP, and tender/swollen joint counts. Multi-strain probiotics containing Lactobacillus and Bifidobacterium species are recommended at 50-100 billion CFU daily.

GLA (Gamma-Linolenic Acid): 1,400-2,800 mg daily

Found in borage oil, evening primrose oil, and black currant seed oil. GLA is converted to DGLA, which competes with arachidonic acid and produces anti-inflammatory PGE1. Multiple trials show reduced morning stiffness, joint tenderness, and NSAID requirements. Borage oil provides the highest concentration of GLA.

Additional Support

• Zinc 30 mg daily — Anti-inflammatory, immune modulation, frequently depleted by methotrexate.
• Selenium 200 mcg daily — Antioxidant, immune regulation.
• B vitamins (methylated) — Essential if on methotrexate. Methylfolate, B12, B6.
• Magnesium 400 mg daily — Anti-inflammatory, muscle relaxation, bone health.

Dental Health: A Therapeutic Priority

Given the P. gingivalis-citrullination-RA axis:

1. Comprehensive periodontal evaluation — Deep pocket probing, X-rays, microbiological testing if available.
2. Aggressive periodontal treatment — Scaling and root planing, antimicrobial therapy as indicated.
3. Daily oral hygiene optimization — Electric toothbrush, interdental cleaning, antimicrobial rinse (chlorhexidine short-term, or natural alternatives like CoQ10 and tea tree oil long-term).
4. Regular dental maintenance — Every 3-4 months during active RA, not the standard 6 months.
5. Oral microbiome support — Oral probiotics (S. salivarius K12, M18), xylitol, oil pulling with coconut oil.

Exercise: Moving Through the Fire

Exercise in RA is essential, not optional. It preserves joint function, maintains bone density, reduces fatigue, improves mood, and does not increase joint damage when properly prescribed.

• Pool-based exercise — Warm water (92-96 degrees F) reduces pain and stiffness while providing resistance. Aquatic therapy is first-line exercise prescription for RA.
• Range of motion — Daily gentle stretching of all affected joints to prevent contractures.
• Strengthening — Resistance training to support joints and prevent muscle wasting. Start light, progress gradually.
• Cardiovascular — Walking, cycling, swimming. RA patients have elevated cardiovascular risk; exercise mitigates this.
• Yoga and tai chi — Combine flexibility, strength, balance, and stress reduction. Multiple trials show benefit in RA.
• Avoid high-impact activities during flares. Modify, do not stop.

The Integrated Protocol

1. Conventional DMARD therapy as indicated — methotrexate with folate co-supplementation as cornerstone.
2. Comprehensive dental evaluation and periodontal treatment.
3. Diet: Mediterranean or elimination diet; consider vegetarian trial. Remove identified triggers.
4. Omega-3 3-6 g EPA/DHA daily.
5. Curcumin 1,000-1,500 mg daily (bioavailable form).
6. Boswellia 300 mg three times daily.
7. Vitamin D 5,000-10,000 IU daily — target 60-80 ng/mL.
8. Probiotics 50-100 billion CFU daily (Lactobacillus casei emphasized).
9. GLA 1,400-2,800 mg daily (borage oil or evening primrose).
10. Gut healing — Address permeability, SIBO, dysbiosis.
11. Exercise — Pool-based, ROM, strengthening, walking.
12. Stress management — HPA axis support, vagal toning, sleep optimization.
13. Monitor: CRP, ESR, anti-CCP, DAS28, vitamin D, inflammatory markers every 3-4 months.

Rheumatoid arthritis is a disease that bridges the visible and invisible. The swollen joints are visible. The gut permeability, the oral bacteria, the food sensitivities, the stress — these are invisible but no less real. Functional medicine makes the invisible visible and treats the whole system rather than just the joints that cry out loudest.

If the fire starts in the gut and the mouth, what happens when you address the source rather than just dousing the flames?