Multiple Sclerosis: The Functional Medicine Approach

The Wires Lose Their Insulation

Imagine your nervous system as an electrical network. Every nerve fiber is a wire, and every wire is wrapped in myelin — a fatty insulation sheath that allows electrical signals to travel fast and clean. In multiple sclerosis, the immune system strips this insulation away. Signals slow, stutter, and fail. The result depends on where the damage occurs: vision blurs, limbs weaken, balance falters, bladder control fails, cognition fogs, fatigue crushes.

MS is a disease of neuroinflammation and demyelination — an autoimmune attack on the central nervous system. It affects approximately 2.8 million people worldwide, strikes women three times more often than men, and typically appears between ages 20 and 40. It is the leading cause of non-traumatic neurological disability in young adults.

The conventional model has produced impressive disease-modifying therapies that reduce relapse rates and slow progression. But conventional medicine has little to say about why the immune system attacks myelin in the first place, or what environmental factors can be modified to change the disease trajectory. Functional medicine fills that gap with an approach that is both evidence-based and profoundly hopeful.

Disease Patterns and Pathophysiology

Types of MS

• Relapsing-Remitting MS (RRMS) — 85% of initial diagnoses. Distinct attacks (relapses) followed by partial or complete recovery (remissions). Inflammatory lesions on MRI.
• Secondary Progressive MS (SPMS) — Develops in many RRMS patients over time. Gradual neurological decline between relapses, eventually without clear relapses.
• Primary Progressive MS (PPMS) — 10-15% of diagnoses. Steady neurological decline from onset without distinct relapses. Less inflammatory, more neurodegenerative.

Immunological Mechanism

MS is driven primarily by Th1 and Th17 immune cells that cross the blood-brain barrier (BBB). In a healthy brain, the BBB tightly controls what enters the central nervous system. In MS, the BBB becomes permeable — allowing autoreactive T cells, B cells, and inflammatory mediators to enter the CNS.

Once inside, these immune cells recognize myelin antigens (myelin basic protein, myelin oligodendrocyte glycoprotein, proteolipid protein) and mount an inflammatory attack. Macrophages strip myelin from axons. Oligodendrocytes (the cells that produce myelin) are damaged. Over time, the axons themselves degenerate — the transition from relapsing-inflammatory to progressive-neurodegenerative disease.

Diagnostic Testing

• MRI — The cornerstone. Shows white matter lesions (plaques) in characteristic locations: periventricular, juxtacortical, infratentorial, spinal cord. Gadolinium-enhancing lesions indicate active inflammation.
• Cerebrospinal fluid (CSF) — Oligoclonal bands (present in >90% of MS) indicate intrathecal antibody production. Elevated IgG index.
• Evoked potentials — Visual, somatosensory, brainstem auditory. Detect subclinical demyelination.
• Vitamin D level — Should be checked in every patient.
• EBV serology — Anti-EBNA, anti-VCA antibodies.

The EBV Connection: The Strongest Environmental Link

In January 2022, Bjornevik and colleagues published a landmark study in Science that transformed our understanding of MS causation. Following 10 million US military personnel over 20 years, they demonstrated that EBV infection increased the risk of MS 32-fold. Among MS patients, EBV seropositivity was near-universal. Seroconversion from EBV-negative to EBV-positive preceded MS onset but not the other way around.

This is not merely an association. The magnitude of risk (32-fold) and the temporal relationship (infection precedes disease) make EBV the strongest single risk factor ever identified for MS. The mechanisms likely include molecular mimicry between EBV proteins and myelin antigens, EBV-infected B cells in the CNS producing pathogenic antibodies, and chronic immune activation.

This discovery has spurred development of EBV-targeted therapies, including anti-CD20 B cell depletion (ocrelizumab, which targets EBV-harboring B cells and is highly effective in MS) and EBV vaccine candidates.

Functional implications: supporting immune surveillance against EBV (vitamin D, zinc, selenium, lysine, medicinal mushrooms), monitoring EBV reactivation markers (EBV early antigen antibodies), and reducing the immune dysregulation that allows EBV to drive disease.

Conventional Disease-Modifying Therapies

Modern DMTs have transformed RRMS outcomes:

• Interferons (interferon beta-1a, beta-1b) — Moderate efficacy, injectable. First-generation DMTs.
• Glatiramer acetate — Myelin decoy peptide. Moderate efficacy, injectable.
• Natalizumab — Anti-alpha4-integrin antibody. Highly effective. Blocks immune cell migration across BBB. Risk of PML (progressive multifocal leukoencephalopathy) with JC virus.
• Ocrelizumab — Anti-CD20 B cell depletion. Highly effective in RRMS and the first therapy approved for PPMS.
• Fingolimod — Sphingosine-1-phosphate receptor modulator. Traps lymphocytes in lymph nodes. Oral, effective.
• Others — Dimethyl fumarate, teriflunomide, cladribine, siponimod, ofatumumab.

These therapies reduce relapses by 30-70% depending on the agent. They are important. They are also incomplete without addressing the environmental and nutritional factors that modulate disease activity.

Vitamin D: The Most Important Single Nutrient

The vitamin D-MS relationship is one of the most robust in all of autoimmune medicine.

Munger’s 2004 study of nurses found that women supplementing with 400 IU of vitamin D daily had a 40% reduction in MS risk — and that was with a dose now considered inadequate. MS prevalence increases with latitude (less sun exposure), is higher in people born in spring (lowest vitamin D at birth), and improves with migration to sunnier climates during childhood.

Mechanistically, vitamin D suppresses Th17 differentiation, promotes regulatory T cells, supports BBB integrity, and enhances myelin repair by oligodendrocytes. It is neuroprotective at a fundamental level.

Optimal levels: 60-80 ng/mL. Most MS patients are profoundly deficient at diagnosis (commonly 10-20 ng/mL). Standard supplementation: 5,000-10,000 IU daily with monitoring.

The Coimbra Protocol

Dr. Cicero Coimbra’s high-dose vitamin D protocol for autoimmune diseases uses 40,000-100,000 IU daily — supraphysiological doses that suppress the autoimmune response through vitamin D receptor activation. This requires:

• Strict calcium restriction — Low-calcium diet, no dairy, 2.5 liters of water daily.
• Regular monitoring — Serum calcium, PTH, 24-hour urine calcium, creatinine, bone density.
• Medical supervision — Hypercalcemia and renal calcification are real risks.

The protocol is controversial within mainstream medicine but has documented responses — including stabilization and even improvement in progressive MS patients. It should only be pursued under the supervision of a Coimbra-trained practitioner with rigorous laboratory monitoring. This is not DIY supplementation.

The Wahls Protocol: Food as Medicine for the Brain

Dr. Terry Wahls’ story is one of the most compelling in functional medicine. Diagnosed with RRMS that progressed to secondary progressive, she declined to the point of being wheelchair-bound and dependent. Through intensive nutritional and lifestyle intervention, she went from wheelchair to bicycle — a transformation documented on video and in her published research.

The Wahls Protocol centers on 9 cups of vegetables and fruits daily:

• 3 cups of deeply colored (berries, beets, carrots — rich in antioxidants).
• 3 cups of sulfur-rich (broccoli, cabbage, cauliflower, onions, garlic, mushrooms — support detoxification and glutathione).
• 3 cups of greens (kale, spinach, chard — rich in minerals, folate, vitamins K and C).

Plus: grass-fed meat and organ meats (rich in B12, CoQ10, D), wild-caught fish (omega-3, DHA), seaweed (iodine, minerals), fermented foods (probiotics), and elimination of gluten, dairy, and eggs.

Wahls’ 2019 randomized controlled trial compared the Wahls Protocol to the Swank Diet (low-saturated-fat diet) in RRMS patients. Both groups showed significant reduction in fatigue (the most disabling MS symptom), with the Wahls group showing improvement in multiple additional outcomes.

The Wahls Protocol is not merely a diet. It is a mitochondrial rescue strategy — providing the substrates (B vitamins, CoQ10, sulfur, antioxidants) that damaged neurons and oligodendrocytes need to survive and repair.

The Gut-Brain Axis in MS

The gut-brain connection in MS is being confirmed with increasing precision:

• Berer’s 2011 research showed that germ-free mice (no gut bacteria) were resistant to experimental autoimmune encephalomyelitis (the animal model of MS), but colonization with gut bacteria triggered disease. The microbiome is not a bystander — it is a driver.
• MS patients show reduced Bacteroides fragilis (which produces polysaccharide A, an anti-inflammatory molecule that promotes Treg cells) and increased pro-inflammatory species.
• LPS from gut bacteria can increase BBB permeability, facilitating immune cell entry into the CNS.
• Short-chain fatty acids (butyrate, propionate) produced by gut bacteria support Treg function, BBB integrity, and oligodendrocyte maturation.

Gut interventions:

• High-fiber diet (30-40 g/day from vegetables, legumes if tolerated, prebiotic foods).
• Multi-strain probiotics emphasizing Lactobacillus and Bifidobacterium species (100 billion CFU).
• Butyrate supplementation (sodium butyrate 600-1200 mg daily) or butyrate-producing food sources (resistant starch, cooked-then-cooled potatoes).
• Fermented foods: sauerkraut, kimchi, kefir (if dairy tolerated), kombucha.
• Gluten-free trial — gluten increases zonulin and intestinal permeability, which may translate to BBB permeability.
• Test and treat SIBO, parasites, dysbiosis.

The Supplement Protocol

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

DHA is the dominant fatty acid in myelin. Supplementation supports myelin repair, reduces neuroinflammation, and improves BBB integrity. EPA provides anti-inflammatory and resolvin-generating properties. High-quality fish oil or algae-based DHA for vegetarians.

Alpha-Lipoic Acid: 1,200 mg daily

Yadav’s 2005 study showed that alpha-lipoic acid reduced MMP-9 (matrix metalloproteinase-9 — the enzyme that degrades the BBB and allows immune cells into the CNS), ICAM-1 (immune cell adhesion molecule), and T cell migration. It is both water and fat soluble, crosses the BBB, recycles glutathione and vitamins C and E, and supports mitochondrial function. R-alpha-lipoic acid is the bioactive form.

High-Dose Biotin: 300 mg daily

Tourbah’s 2016 MD1003 trial investigated high-dose pharmaceutical-grade biotin (300 mg/day — 10,000 times the recommended daily intake) in progressive MS. Results: 12.6% of treated patients showed improvement in disability versus 0% on placebo. Biotin is a cofactor for carboxylases involved in fatty acid synthesis (myelin production) and energy metabolism in demyelinated axons. This dose requires medical supervision and can interfere with laboratory tests (troponin, thyroid function, cortisol — labs must be informed).

CoQ10: 200-400 mg daily

Mitochondrial dysfunction is a major driver of neurodegeneration in progressive MS. CoQ10 supports electron transport chain function and has demonstrated anti-inflammatory effects in MS patients — reducing TNF-alpha and IL-6.

Lion’s Mane (Hericium erinaceus): 1,000-3,000 mg daily

This medicinal mushroom contains hericenones and erinacines that stimulate nerve growth factor (NGF) production — the molecule that promotes neuronal growth, myelin repair, and neuroplasticity. Animal studies show enhanced remyelination. Human trials show improved cognition. A uniquely relevant supplement for any demyelinating condition.

Additional Support

• Vitamin D 5,000-10,000 IU daily — As detailed above. Non-negotiable.
• Magnesium 400-600 mg daily — Neuroprotective, reduces spasticity and muscle cramps.
• B12 (methylcobalamin) 5,000 mcg sublingual — Critical for myelin synthesis. Deficiency mimics MS and worsens it.
• Acetyl-L-carnitine 1,500-3,000 mg daily — Neuroprotective, supports axonal energy metabolism.

Low Dose Naltrexone (LDN): 1.5-4.5 mg at bedtime

Gironi’s 2008 pilot study in primary progressive MS showed that LDN improved quality of life, mood, and fatigue. LDN modulates the immune system through endorphin rebound — increasing beta-endorphin and met-enkephalin levels, which enhance regulatory T cell function and reduce pro-inflammatory cytokine production. It is well-tolerated, inexpensive, and widely used in the MS functional medicine community.

Lifestyle: The Non-Negotiables

Exercise

Robert Motl’s extensive research program has established that exercise in MS reduces fatigue, improves walking speed and endurance, enhances cognition, and improves quality of life. Exercise may also be neuroprotective — increasing BDNF (brain-derived neurotrophic factor), supporting neuroplasticity, and reducing neuroinflammation.

• Aerobic exercise — 30 minutes, 3-5 times weekly. Walking, cycling, swimming, recumbent bike.
• Resistance training — 2-3 times weekly. Critical for maintaining strength and preventing falls.
• Balance training — Yoga, tai chi, standing exercises. Falls are a major source of injury in MS.
• Stretching — Daily. Addresses spasticity and maintains range of motion.

Adapt to current ability. Some patients swim. Some walk with a cane. Some do seated exercises. Movement matters at every level of disability.

Stress Management

Mohr’s 2004 landmark study demonstrated that stressful life events increase the risk of new MRI lesions and clinical relapses in MS. Stress triggers HPA axis activation, increases BBB permeability, and shifts immune function toward the Th1/Th17 responses that drive demyelination.

• MBSR (Mindfulness-Based Stress Reduction) — Documented reductions in fatigue, depression, and anxiety in MS.
• Vagal toning — Deep breathing, cold water face immersion, meditation, yoga.
• Psychological support — Therapy for adjustment, grief, anxiety, and depression. CBT and ACT have evidence in MS.
• Social connection — Isolation worsens outcomes. Support groups, community, purpose.

Sleep

Sleep disturbance is common in MS (pain, spasticity, nocturia, restless legs, depression, medication effects) and profoundly impacts fatigue and cognition. Sleep optimization: consistent schedule, dark/cool room, melatonin 3-5 mg, magnesium glycinate, treatment of underlying causes (nocturia management, spasticity treatment, sleep apnea screening).

Heat Management

The Uhthoff phenomenon — temporary worsening of MS symptoms with heat exposure — affects the majority of patients. Demyelinated nerves conduct more poorly at higher temperatures. Strategies: cooling vests, cool showers before activity, air-conditioned environments, cold beverages, avoiding hot tubs and saunas. Some patients find that planned cooling before exercise extends their exercise tolerance.

The Integrated Protocol

1. Conventional DMT as indicated by neurologist — these are important and evidence-based.
2. Vitamin D 5,000-10,000 IU daily — target 60-80 ng/mL. Consider Coimbra Protocol referral for progressive disease.
3. Wahls Protocol or Mediterranean diet — 9 cups vegetables, eliminate gluten, emphasize omega-3 sources.
4. Omega-3/DHA 3-4 g daily.
5. Alpha-lipoic acid 1,200 mg daily.
6. High-dose biotin 300 mg daily (progressive MS, under supervision).
7. CoQ10 200-400 mg daily.
8. Lion’s mane 1,000-3,000 mg daily.
9. LDN 1.5-4.5 mg at bedtime.
10. Gut restoration — Probiotics, butyrate, fiber, fermented foods, gluten elimination.
11. Exercise — Aerobic, resistance, balance, stretching. Adapted to ability.
12. Stress management — MBSR, vagal toning, psychological support.
13. Sleep optimization.
14. Heat management strategies.

MS is a disease that conventional medicine has learned to slow but not to stop. Functional medicine adds something essential: the understanding that the terrain of the body — its nutritional status, its microbial ecology, its inflammatory load, its toxic burden, its stress response — shapes how the immune system behaves. Change the terrain, and you change the trajectory.

Dr. Terry Wahls went from wheelchair to bicycle not by finding a new drug, but by giving her mitochondria what they needed to repair. That is the functional medicine proposition for MS — not a replacement for DMTs, but a deepening of what is possible when you treat the whole person, not just the lesions on their MRI.

If your nervous system could tell you what it needs to repair, what would it ask for?