Ankylosing Spondylitis: The Functional Approach

The Spine That Fuses

There is a particular cruelty to ankylosing spondylitis. It attacks the spine — the central column of the body, the axis around which all movement organizes. It begins with inflammation at the sacroiliac joints, where the spine meets the pelvis, and progresses upward through the lumbar, thoracic, and cervical vertebrae. Over years and decades, if unchecked, it can fuse the entire spine into a single rigid column — the “bamboo spine” visible on X-ray, where vertebrae merge into one continuous bone.

AS is the prototypical axial spondyloarthritis: inflammation at the entheses (where tendons and ligaments insert into bone), at the sacroiliac joints, at the spinal facet joints, and at the vertebral margins where the annulus fibrosus meets the vertebral body. It also reaches beyond the spine — to peripheral joints, the eyes (acute anterior uveitis in up to 40%), the gut (subclinical inflammation in up to 60%), and rarely the heart (aortitis, conduction abnormalities).

It affects roughly 0.5-1% of the population, predominantly young men (3:1 male-to-female ratio, though this gap is narrowing with improved diagnosis in women), with typical onset between ages 17 and 35. The genetic association is among the strongest in all of medicine: over 90% of AS patients carry HLA-B27, though only 5-20% of HLA-B27-positive individuals develop the disease. Something beyond genetics must pull the trigger.

Functional medicine searches for those triggers — and finds them, remarkably, in the gut.

Pathophysiology: Enthesitis and the IL-23/IL-17 Axis

The primary site of disease in AS is the enthesis — the fibrocartilaginous zone where tendons, ligaments, and joint capsules attach to bone. This is fundamentally different from rheumatoid arthritis (which targets the synovium) and explains the unique imaging findings, clinical presentation, and therapeutic responses of AS.

Entheses are mechanically stressed sites. Microtrauma at these sites exposes matrix proteins to immune surveillance. In HLA-B27-positive individuals, this normal micro-damage triggers an abnormal immune response:

1. IL-23-producing myeloid cells accumulate at the entheses.
2. IL-23 activates resident entheseal T cells (many of which are innate-like lymphocytes rather than conventional T cells) to produce IL-17.
3. IL-17 drives dual pathology:
   • Bone erosion at the enthesis (through RANKL-mediated osteoclast activation).
   • Pathological new bone formation (syndesmophytes, ankylosis) through osteoblast stimulation — the paradoxical hallmark of AS where destruction and construction occur simultaneously.
4. TNF-alpha amplifies inflammation and recruits additional immune cells.

The result: chronic inflammation that progressively restricts spinal mobility through both pain/spasm (reversible) and structural fusion (irreversible).

The HLA-B27 Mystery

HLA-B27 is the strongest genetic risk factor, but the mechanism by which it causes disease remains debated. Three leading hypotheses:

• Arthritogenic peptide theory: HLA-B27 presents specific self-peptides (possibly from cartilage or entheseal proteins) to CD8+ T cells, triggering autoimmune attack.
• Misfolding hypothesis: HLA-B27 molecules are prone to misfolding in the endoplasmic reticulum, triggering an unfolded protein response that activates IL-23 production.
• Molecular mimicry: HLA-B27 shares structural features with microbial antigens — most notably from Klebsiella pneumoniae — leading to cross-reactive immune responses.

All three may contribute. The molecular mimicry hypothesis has the most direct implications for functional intervention.

Diagnostic Testing

• HLA-B27 — Positive in >90% of AS. A negative result makes AS unlikely but does not exclude it (HLA-B27-negative spondyloarthritis exists).
• CRP and ESR — Elevated in 40-60% of active AS. Normal inflammatory markers do not exclude active disease.
• MRI of sacroiliac joints — The gold standard for early detection. Shows bone marrow edema (active sacroiliitis) before any structural damage is visible on X-ray. This is the test that catches AS years earlier than conventional X-ray.
• X-ray of pelvis and spine — Shows structural changes: sacroiliac sclerosis, joint space narrowing, syndesmophytes, bamboo spine. These are late findings indicating irreversible damage. The goal is to intervene before X-ray changes appear.
• BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) — Patient-reported outcome questionnaire measuring fatigue, spinal pain, joint pain/swelling, enthesitis, and morning stiffness severity/duration. Score 0-10; >/= 4 indicates active disease.
• BASFI (Bath Ankylosing Spondylitis Functional Index) — Functional assessment.
• Chest expansion measurement — Reduced (<5 cm) in costovertebral involvement.

Functional additions: comprehensive stool analysis (particularly for Klebsiella), intestinal permeability markers, vitamin D, HPA axis assessment, comprehensive metabolic panel.

Conventional Treatment

NSAIDs: Surprisingly Disease-Modifying

Unlike in most rheumatic diseases, NSAIDs in AS appear to be disease-modifying, not just symptomatic. Wanders’ 2005 study showed that continuous NSAID use (celecoxib) significantly reduced radiographic spinal progression over 2 years compared to on-demand use. The hypothesis: prostaglandin-mediated inflammation directly drives new bone formation, and continuous NSAID suppression prevents this.

This makes NSAIDs first-line therapy in AS — taken continuously rather than as-needed.

Biologics

• TNF inhibitors — Adalimumab, etanercept, infliximab, golimumab, certolizumab. Highly effective for pain, stiffness, and inflammation. Reduce MRI inflammation. Whether they prevent structural progression long-term remains debated.
• IL-17 inhibitors — Secukinumab, ixekizumab. Effective for AS. Contraindicated in active IBD.

Other Agents

• Sulfasalazine — Effective only for peripheral joint involvement, not axial disease.
• Methotrexate — Not effective for axial AS.
• Corticosteroids — Local injection for enthesitis or peripheral joints. Systemic steroids generally avoided (less effective than in RA, rebound risk).

The Klebsiella Hypothesis: Molecular Mimicry in the Gut

Professor Alan Ebringer’s decades-long research at King’s College London produced one of the most provocative hypotheses in AS: that Klebsiella pneumoniae in the gut drives AS through molecular mimicry with HLA-B27.

The evidence chain:

1. HLA-B27 shares amino acid sequences with enzymes produced by Klebsiella pneumoniae (nitrogenase, pullulanase).
2. Anti-Klebsiella antibodies are elevated in AS patients compared to healthy HLA-B27 carriers and controls.
3. AS disease activity correlates with elevated anti-Klebsiella IgA levels (indicating mucosal immune response to the bacterium).
4. Klebsiella colonization of the gut is increased in AS patients.
5. Klebsiella thrives on starch — dietary starch provides substrate for Klebsiella proliferation.

Ebringer’s 1996 proposal: A low-starch diet would reduce Klebsiella populations, reduce anti-Klebsiella antibody production, reduce cross-reactive immune activation against HLA-B27, and reduce AS disease activity.

This hypothesis has not been validated through large randomized controlled trials, but multiple case series and patient-reported outcomes support it. The biological plausibility is strong, and the intervention (dietary starch reduction) carries no risk.

Diet: Starving the Fire

The Low-Starch/No-Starch Diet

The London AS Diet (developed through the AS community and informed by Ebringer’s research) involves elimination or severe restriction of dietary starch. Appelboom’s 2017 case series documented symptomatic improvement in AS patients following this approach.

Starch sources to reduce or eliminate: bread, pasta, rice, potatoes, corn, cereals, baked goods, legumes (contain both starch and resistant starch).

Replace with: non-starchy vegetables (leafy greens, cruciferous, zucchini, bell peppers, tomatoes, cucumber, asparagus, mushrooms), proteins (meat, fish, eggs, poultry), healthy fats (olive oil, avocado, coconut oil, nuts, seeds), fruits (moderate amounts — lower starch than grains).

The iodine test can be used at home to identify starchy foods: a drop of iodine solution on food turns blue-black in the presence of starch.

This is essentially a modified paleo/low-carb approach and overlaps significantly with anti-inflammatory and Mediterranean eating patterns.

Anti-Inflammatory Principles

Regardless of starch restriction:

• Abundant omega-3 sources: wild salmon, sardines, mackerel, herring, supplemental fish oil.
• Anti-inflammatory spices: turmeric, ginger, rosemary, oregano.
• Colorful vegetables and fruits: polyphenols, antioxidants.
• Eliminate processed foods, refined sugar, industrial seed oils.
• Moderate alcohol or eliminate entirely (increases gut permeability).

Intermittent Fasting

Time-restricted eating (16:8 or 18:6 patterns) reduces inflammatory markers, improves insulin sensitivity, and may reduce Klebsiella substrate availability. Fasting periods naturally reduce starch intake and promote autophagy.

The Supplement Protocol

Omega-3 Fatty Acids: 3-4 g EPA/DHA daily

Sundstrom’s 2006 study showed a trend toward improvement in AS disease activity with omega-3 supplementation. Omega-3s reduce TNF-alpha, IL-17, and other inflammatory cytokines driving entheseal inflammation. EPA competes with arachidonic acid for cyclooxygenase enzymes, and the specialized pro-resolving mediators (resolvins, protectins, maresins) actively resolve inflammation rather than merely suppressing it.

Curcumin: 1,000-2,000 mg daily

Curcumin inhibits NF-kB (the master switch for inflammatory gene expression), reduces TNF-alpha and IL-17, and has documented efficacy in multiple inflammatory arthritides. Bioavailable forms essential: Meriva, BCM-95, liposomal, or combined with piperine. Some patients apply curcumin paste topically to the sacroiliac area for local anti-inflammatory effect.

Boswellia serrata: 300-400 mg three times daily

Boswellic acids (specifically AKBA — acetyl-11-keto-beta-boswellic acid) inhibit 5-lipoxygenase, reducing leukotriene synthesis. Anti-inflammatory and analgesic effects complement curcumin through a different mechanism. Look for standardized extracts containing >/= 30% AKBA.

Vitamin D: 5,000-10,000 IU daily

Vitamin D deficiency is highly prevalent in AS — estimates range from 50-80% of patients. Deficiency correlates with disease activity, structural damage progression, and bone density loss (AS patients face paradoxical osteoporosis despite new bone formation at entheses). Vitamin D modulates the IL-23/IL-17 axis, supports Treg function, and is critical for bone metabolism. Target 60-80 ng/mL.

Probiotics: 50-100 billion CFU daily

If Klebsiella overgrowth drives immune activation in AS, then restoring a healthy microbiome is directly therapeutic. Multi-strain probiotics emphasizing Lactobacillus and Bifidobacterium species compete with Klebsiella for ecological niches. Saccharomyces boulardii has specific anti-Klebsiella properties. Prebiotic fiber (not starch-based — use vegetable fiber, psyllium, acacia, partially hydrolyzed guar gum) supports commensal bacteria.

Vitamin K2 (MK-7): 200 mcg daily

Vitamin K2 directs calcium to bones and teeth while keeping it out of soft tissues and arterial walls. In AS, where bone metabolism is dramatically dysregulated (erosion at entheses, pathological new bone formation, paradoxical osteoporosis), vitamin K2 supports appropriate bone mineralization. It activates osteocalcin (which deposits calcium in bone) and matrix Gla protein (which prevents vascular calcification). Combined with vitamin D and adequate calcium, K2 optimizes the bone metabolism that AS disrupts.

Additional Support

• Magnesium 400-600 mg daily — Muscle relaxation, sleep support, anti-inflammatory. Critical for the muscle spasm that accompanies spinal inflammation.
• Zinc 30 mg daily — Immune modulation, gut barrier support.
• NAC 1,200-2,400 mg daily — Glutathione support, anti-inflammatory, gut permeability reduction.

Exercise: The Most Important Intervention

If you remember one thing from this article, let it be this: exercise is the single most important intervention in ankylosing spondylitis. More important than any supplement. Arguably as important as any medication. No drug, biologic, or diet can substitute for daily movement in AS.

The spine fuses in the position it is held. If the spine is allowed to stiffen into a flexed (stooped) posture — the natural tendency as pain drives guarding and forward positioning — the fusion will lock that posture permanently. Daily extension exercises literally shape what position the spine fuses into.

Daily Stretching and Mobility (non-negotiable)

• Spinal extension: Prone press-ups (cobra pose), corner chest stretches, foam roller thoracic extension. Hold 30 seconds, repeat 3-5 times. Do these multiple times daily.
• Rotation: Seated trunk rotation, supine windshield wipers, standing rotation stretches.
• Lateral flexion: Side bends, lateral stretching.
• Cervical range of motion: Chin tucks (critical — prevents forward head posture), rotation, lateral flexion. Do 10 repetitions hourly if cervical spine is involved.
• Chest expansion: Deep breathing exercises with arms overhead. Maintains rib cage mobility and vital capacity.
• Hip flexor stretching: The psoas tightens in AS, contributing to stooped posture. Half-kneeling hip flexor stretch, 2 minutes per side daily.

Swimming

The single best exercise modality for AS. Water supports the spine while providing resistance for strengthening. Backstroke is particularly valuable (promotes spinal extension). Water temperature should be warm (83-88 degrees F) to reduce stiffness.

Yoga

Gentle to moderate yoga is excellent for AS — combines flexibility, strength, balance, and breath work. Extension-focused postures (cobra, upward dog, bridge, camel) are therapeutic. Avoid extreme flexion postures early in the morning when stiffness is maximum.

Posture Awareness

• Sleep posture: Firm mattress (not soft). Sleep on the back with a thin pillow (or no pillow — to prevent cervical flexion). A pillow under the knees should be avoided (promotes hip flexion contracture). If sleeping on the side, a pillow between the knees maintains alignment.
• Work posture: Ergonomic assessment. Standing desk or sit-stand alternation. Monitor at eye level to prevent cervical flexion.
• Driving: Lumbar support, headrest adjusted for contact with the back of the head, mirrors adjusted for current range of motion (as a benchmark for monitoring).
• Wall posture checks: Stand with heels, buttocks, shoulders, and head against a wall. If the head cannot touch without extending the neck, cervical fusion or flexion posture has begun. Check monthly.

Physiotherapy

A physiotherapist experienced in AS is invaluable. Group exercise programs specifically for AS (offered by national AS societies) improve adherence and outcomes. Regular reassessment of range of motion, BASMI (Bath Ankylosing Spondylitis Metrology Index), and exercise prescription refinement.

Sleep and Morning Stiffness

Morning stiffness lasting 30+ minutes is a hallmark of AS. It reflects the overnight accumulation of inflammatory mediators in immobile spinal structures.

Management strategies:

• Morning hot shower or bath — 15-20 minutes. Heat reduces muscle spasm and improves mobility. Some patients keep a heating pad by the bed.
• Gentle morning stretching — Before getting out of bed: supine pelvic tilts, knee-to-chest, gentle rotation. Then standing: spinal extension, lateral flexion, rotation.
• Evening NSAID or timed-release formulation — Taking the NSAID at bedtime provides anti-inflammatory coverage during the overnight hours when inflammation accumulates.
• Mattress selection — Medium-firm. Not too soft (spinal alignment loss) or too hard (pressure point pain). Memory foam or latex with good support.
• Pillow positioning — Thin pillow (or cervical roll) that supports the cervical lordosis without flexing the neck forward. The goal is neutral spine alignment.
• Sleep timing — 7-9 hours. Adequate sleep allows inflammatory resolution. Growth hormone released during deep sleep supports tissue repair.

Uveitis Prevention: Protecting the Eyes

Acute anterior uveitis (iritis) occurs in up to 40% of AS patients — a painful, red eye with photophobia and blurred vision caused by immune-mediated inflammation of the iris and ciliary body. It is a medical urgency requiring prompt ophthalmologic treatment (topical steroids, cycloplegics) to prevent synechiae and vision loss.

Functional prevention strategies:

• Omega-3 fatty acids — Anti-inflammatory effects on ocular tissue.
• Curcumin — Small studies suggest benefit in anterior uveitis, with anti-inflammatory effects comparable to corticosteroids in some patients (Lal 1999).
• Vitamin D optimization — Immune modulation reduces uveitis flare frequency.
• Stress management — Stress is a common uveitis trigger. HPA axis support, vagal toning, adequate sleep.
• Gut health — The gut-eye axis parallels the gut-joint axis. Microbiome restoration and permeability repair may reduce ocular inflammation.
• Prompt treatment — At the first sign of eye redness, pain, or photophobia, see an ophthalmologist the same day. Delayed treatment increases the risk of complications.

The Integrated Protocol

1. Daily exercise — Extension stretching, mobility, swimming, yoga. Non-negotiable. This shapes your future spine.
2. Low-starch/anti-inflammatory diet — Reduce Klebsiella substrate, reduce inflammation.
3. Continuous NSAIDs — First-line, disease-modifying per Wanders 2005.
4. Biologics (TNF or IL-17 inhibitors) for inadequate NSAID response.
5. Omega-3 3-4 g EPA/DHA daily.
6. Curcumin 1,000-2,000 mg daily (bioavailable form).
7. Boswellia 300-400 mg three times daily.
8. Vitamin D 5,000-10,000 IU daily — target 60-80 ng/mL.
9. Vitamin K2 (MK-7) 200 mcg daily.
10. Probiotics 50-100 billion CFU daily.
11. Gut restoration — Stool testing, Klebsiella assessment, permeability repair.
12. Posture program — Firm mattress, thin pillow, ergonomic workstation, wall checks.
13. Morning stiffness management — Hot shower, gentle stretching, evening NSAID.
14. Uveitis prevention — Omega-3, curcumin, vitamin D, stress management.
15. Monitor: CRP, ESR, BASDAI, spinal mobility measurements, MRI if clinically indicated.

Ankylosing spondylitis is a disease that crystallizes the relationship between discipline and freedom. The spine wants to fuse. Inflammation wants to calcify. Gravity wants to pull you forward. Every day, the disease moves toward rigidity. And every day, through movement, stretching, extension, and conscious postural awareness, you push back. Not once. Not as a heroic effort. But as a daily practice — as routine as brushing your teeth, as fundamental as breathing.

The patients who maintain their mobility in AS are not those with the mildest disease. They are those with the most consistent practice.

If the spine fuses in the position it is held, what position are you choosing to hold yours in today?