Lyme Disease & Tick-Borne Infections: The Functional Approach

The Most Controversial Diagnosis in Medicine

No condition splits the medical establishment like chronic Lyme disease. The CDC and IDSA maintain that Lyme is straightforward — a deer tick bite, a bull’s-eye rash, 2-4 weeks of doxycycline, case closed. ILADS (International Lyme and Associated Diseases Society) counters that persistent infection exists, that standard testing misses half of cases, and that many patients remain severely ill after short-course antibiotics.

Functional medicine occupies the bridge. The infection matters. But the terrain matters more. A tick can bite two people — one recovers in weeks, the other descends into years of debilitating illness. The difference is not the spirochete. It is the soil it lands in: the immune system’s resilience, the gut’s integrity, the toxic burden, the stress load, the nutrient status. Address both the bug and the terrain, or you address neither fully.

Borrelia Burgdorferi: A Shape-Shifting Survivor

Borrelia burgdorferi is a spirochete — a corkscrew-shaped bacterium with extraordinary survival mechanisms. Understanding its biology explains why single-antibiotic courses fail:

Form 1 — Active spirochete: The motile, replicating form. Vulnerable to cell-wall-targeting antibiotics (doxycycline, amoxicillin, ceftriaxone). This is what standard treatment kills.

Form 2 — Cyst/round body (persister): When threatened by antibiotics, immune attack, or unfavorable conditions, Borrelia retracts into a spherical cyst form. Metabolically dormant. Invisible to the immune system. Resistant to standard antibiotics. Can revert to active form when conditions improve. Targeted by: tinidazole, metronidazole, hydroxychloroquine.

Form 3 — Biofilm colony: Borrelia forms biofilm communities — aggregates of bacteria encased in a polysaccharide matrix that antibiotics and immune cells cannot penetrate. Eva Sapi’s 2015 research at the University of New Haven showed that stevia whole-leaf extract was more effective at disrupting Borrelia biofilms than doxycycline. Targeted by: biofilm-disrupting agents (NAC, serrapeptase, stevia, lumbrokinase).

Effective treatment must hit all three forms simultaneously. This is why the standard 2-week doxycycline monotherapy leaves so many patients relapsing.

Co-Infections: Often Worse Than Lyme Itself

Ticks are not single-pathogen vectors. A single Ixodes tick can carry Borrelia plus multiple co-infections. In endemic areas, co-infection rates range from 10-50%. Co-infections often drive the most severe symptoms and must be identified and treated specifically.

Babesia (Babesia microti, B. duncani)

A malaria-like intracellular parasite that infects red blood cells. Classic symptoms: drenching night sweats, air hunger (sighing respirations — the hallmark), severe headaches, temperature dysregulation, vivid nightmares, hemolytic anemia. Standard Lyme treatment does nothing for Babesia — it requires antiparasitic therapy.

Pharmaceutical: Atovaquone 750mg 2x/day + azithromycin 250-500mg/day. Alternative: Mepron + Zithromax for 3-6 months. Duration must extend 2 months beyond symptom resolution.

Herbal: Cryptolepis sanguinolenta tincture 1 tsp 3x/day (Zhang 2020 study showed in vitro efficacy against Babesia), Artemisia annua (sweet wormwood), Sida acuta.

Bartonella (B. henselae, B. quintana)

The “rage microbe.” Symptoms unlike any other infection: ice-pick headaches (sharp, stabbing, migratory), shin pain (tibial periostitis), anxiety or rage disproportionate to circumstance, stretch mark-like striae (especially in unusual locations — arms, back, inner thighs in non-weight-change patients), lymphadenopathy, sore soles of feet, eye floaters, subcutaneous nodules.

Pharmaceutical: Rifampin 300mg 2x/day + azithromycin 250mg/day, or rifampin + doxycycline. Treatment courses are long — 4-6+ months.

Herbal: Houttuynia cordata tincture, Japanese knotweed (higher doses), Sida acuta, cryptolepis.

Ehrlichia and Anaplasma

Intracellular bacteria that infect white blood cells. Present with flu-like illness, WBC dropping below normal range, elevated liver enzymes (AST/ALT). Can be life-threatening if untreated. Responds to doxycycline — this is one case where standard treatment is correct.

Mycoplasma (M. pneumoniae, M. fermentans)

Cell-wall-deficient bacteria that attach to cell membranes and evade immune detection. Joint pain, fatigue, cognitive impairment, respiratory symptoms. Often found as co-infection in Lyme but also acquired independently. Treatment: azithromycin or doxycycline, extended courses. Herbal: berberine, garlic, oregano.

Rickettsia

Spotted fever group — rash (often petechial), fever, headache. Less chronic than other co-infections but can be acute and dangerous. Responds to doxycycline.

The Testing Controversy

This is where the medical war is fought. Understanding the limitations of standard testing is clinically essential.

Standard Two-Tier Testing (CDC)

Step 1: ELISA screen. If positive or equivocal, proceed to Step 2: Western Blot (IgM and IgG). The ELISA misses an estimated 50%+ of early Lyme cases because it takes 4-6 weeks for antibodies to develop. If you test in the first month, you will likely get a false negative. The Western Blot under CDC criteria only reports 5 IgG bands and 2 IgM bands — designed for epidemiological surveillance, not clinical diagnosis.

Better Testing Options

• IGeneX Western Blot: Reports all bands, including Lyme-specific bands 23, 31, 34, 39, and 83-93 kDa that the CDC criteria exclude. Band 31 (OspA) and Band 34 (OspB) are so specific to Borrelia that they were removed from CDC criteria specifically because they were used in vaccine development — a surveillance decision, not a clinical one.
• iSpot Lyme: T-cell-based assay measuring cellular immune response to Borrelia. Detects active infection (not just past exposure). Higher sensitivity in early disease.
• Armin Labs (Germany): EliSpot assay for Borrelia, Babesia, Bartonella, Ehrlichia, Chlamydia pneumoniae, Yersinia. Gold standard in European Lyme practice.
• Vibrant Wellness Tickborne 2.0: Comprehensive panel covering multiple species and co-infections on a single draw.

Co-infection-specific testing:

• Babesia: Babesia FISH (fluorescent in situ hybridization — detects RNA in red blood cells), Giemsa smear, Babesia IFA
• Bartonella: Galaxy Diagnostics ePCR (enrichment PCR — incubates blood sample to amplify low-level bacteremia), Bartonella IFA, FISH

The clinical bottom line: Lyme is a clinical diagnosis supported by laboratory testing. It is NOT a laboratory diagnosis. If the history, exposure, symptoms, and clinical presentation are consistent, treat empirically regardless of test results. No test has 100% sensitivity. Waiting for a positive test while the patient deteriorates is malpractice of a different kind.

Stephen Buhner Herbal Protocol

Stephen Harrod Buhner’s “Healing Lyme” (2005, revised 2015) laid the foundation for evidence-based herbal treatment of Lyme disease. His protocols are built on ethnobotanical research, in vitro studies, and clinical observation.

Core Protocol for Borrelia

• Japanese knotweed (Polygonum cuspidatum / Reynoutria japonica): 500mg standardized extract 3-4x/day. The cornerstone herb. Contains resveratrol and emodin. Anti-spirochetal, potently anti-inflammatory (inhibits NF-kB), crosses the blood-brain barrier (critical for neurological Lyme), protects endothelium, modulates cytokine cascade. Start low and increase — can provoke significant Herxheimer reactions.
• Andrographis paniculata: 400mg standardized extract (>10% andrographolides) 3x/day. Immune modulator — enhances NK cell and CD8+ T-cell function while dampening autoimmune-type inflammatory responses. Anti-spirochetal. Protects the heart (Lyme carditis). Caution: can cause GI upset; avoid in pregnancy.
• Cat’s claw (Uncaria tomentosa): 500mg 3x/day. Must be TOA-free (tetracyclic oxindole alkaloid-free) — TOAs block the immune-enhancing effects of pentacyclic oxindole alkaloids. Immune enhancement, anti-inflammatory, modulates NF-kB. Samento brand is the most studied TOA-free source.

Co-Infection Herbs

For Babesia:

• Cryptolepis sanguinolenta tincture: 1 tsp 3x/day. West African antimalarial herb. Zhang et al. (2020) showed potent in vitro activity against Babesia. The most important herbal for this parasite.
• Artemisia annua (sweet wormwood): Source of artemisinin. 500mg 3x/day. Pulse 2 weeks on, 1 week off (to prevent resistance — learned from malaria treatment).
• Sida acuta: 1 tsp tincture 3x/day. Broad-spectrum antimicrobial.

For Bartonella:

• Houttuynia cordata tincture: 1 tsp 3x/day. Anti-Bartonella activity in vitro.
• Japanese knotweed at higher doses (increases to 4x/day)
• Sida acuta: same as above — works across multiple co-infections

Biofilm Disruption

Without breaking biofilms, antimicrobials (pharmaceutical or herbal) cannot reach sequestered organisms:

• Stevia leaf extract (whole leaf, not refined stevia sweetener): Eva Sapi’s 2015 University of New Haven study showed stevia was the only agent that significantly reduced all three forms of Borrelia — including biofilm colonies. More effective than doxycycline, cefoperazone, and daptomycin at eradicating biofilms.
• NAC: 600mg 2x/day. Disrupts biofilm matrix, replenishes glutathione.
• Serrapeptase: 120,000 SPU on empty stomach. Proteolytic enzyme that degrades biofilm protein structure.
• Lumbrokinase: Fibrinolytic enzyme. 20mg 2x/day on empty stomach. Breaks down fibrin in biofilm matrix.

Pharmaceutical Protocol (ILADS-Aligned)

For practitioners using pharmaceutical antimicrobials, ILADS guidelines recommend combination therapy targeting all three Borrelia forms:

Cell-wall form: Doxycycline 200mg 2x/day (or amoxicillin 500mg 3x/day, or ceftriaxone 2g IV daily for neurological/cardiac Lyme)

Cyst form (pulsed): Tinidazole 500mg 2x/day, pulsed 2 weeks on / 2 weeks off. Alternative: Hydroxychloroquine 200mg 2x/day (continuous — also alkalinizes intracellular compartments where Borrelia hides). Metronidazole 500mg 2x/day is an option but less well-tolerated.

Biofilm disruption: Added as above (NAC, serrapeptase, stevia)

Minimum duration: 4-6 weeks, but clinical practice often requires 4-6 months or longer based on symptom response. Rotate antibiotics every 4-6 weeks to prevent resistance. Monitor liver function, CBC, and symptoms.

Terrain Support: The Functional Medicine Contribution

This is where functional medicine transforms Lyme treatment from a war of attrition into a strategic restoration:

Gut Protection During Antimicrobials

Antibiotics devastate the microbiome. Without gut support, treatment becomes a trade — killing the infection while destroying the terrain:

• Saccharomyces boulardii: 500mg 2x/day (yeast-based probiotic resistant to antibiotics, prevents C. difficile)
• Spore-based probiotics (MegaSporeBiotic or equivalent): Bacillus clausii, B. subtilis, B. coagulans — survive antibiotics, restore diversity
• Butyrate: 600mg 2x/day — short-chain fatty acid that feeds colonocytes, maintains gut barrier
• Prebiotic fiber: Partially hydrolyzed guar gum (PHGG) 5g/day — feeds beneficial bacteria

Herxheimer Reaction Management

When Borrelia die, they release endotoxins (outer surface proteins, lipoproteins) that provoke an inflammatory storm — the Jarisch-Herxheimer reaction. Symptoms flare dramatically: fever, chills, muscle pain, cognitive fog, headache. This is expected but must be managed:

• Binders: Activated charcoal 500mg, bentonite clay, chlorella — take 2 hours away from medications and food. Bind endotoxins in the gut for elimination.
• Glutathione: Liposomal 500-1000mg/day. Master detox molecule, neutralizes reactive oxygen species.
• Infrared sauna: 20-30 min sessions. Mobilizes toxins through sweat.
• Epsom salt baths: 2 cups magnesium sulfate in hot bath for 20 min. Transdermal magnesium absorption, sulfate supports phase II detoxification.
• Hydration: 3+ liters of filtered water daily. The simplest and most forgotten detox intervention.
• Lymphatic support: Dry brushing, rebounding (mini trampoline), manual lymphatic drainage massage.

Immune Modulation

The immune system in chronic Lyme is both suppressed (can’t clear the infection) and overactivated (autoimmune-type inflammation). It needs modulation, not simple “boosting”:

• Vitamin D: 5000 IU/day, target 60-80 ng/mL. Essential for antimicrobial peptide production (cathelicidin, defensins).
• Vitamin C: 3-5g/day divided doses (or IV 25-50g weekly for severe cases). Direct antimicrobial activity, immune cell fuel.
• Zinc: 30mg/day. Supports NK cell and T-cell function.
• Medicinal mushrooms: Reishi (Ganoderma lucidum) 1g 2x/day — immune modulation, anti-inflammatory; Cordyceps 1g 2x/day — mitochondrial support, oxygen utilization; Turkey Tail (Trametes versicolor) 1g 2x/day — beta-glucans enhance NK cell activity.
• LDN (low-dose naltrexone): 1.5-4.5mg at bedtime. Upregulates endogenous opioids and modulates immune function. Widely used in Lyme-literate practice.

Brain Support (Neuro-Lyme)

When Borrelia crosses the blood-brain barrier, cognitive impairment, headaches, cranial neuropathies, and psychiatric symptoms can dominate:

• Lion’s mane (Hericium erinaceus): 1-2g/day. Stimulates nerve growth factor (NGF) production. Supports remyelination and cognitive recovery.
• Citicoline: 500mg 2x/day. Phospholipid precursor that supports neuronal membrane repair.
• Phosphatidylserine: 300mg/day. Membrane phospholipid, supports cortisol regulation and cognitive function.
• NAC: 1200mg/day. Crosses BBB, reduces neuroinflammation, replenishes brain glutathione.
• Magnesium L-threonate: 2g/day. The only magnesium form proven to cross the BBB (MIT research). Supports synaptic plasticity and memory.

Adrenal Support

Chronic Lyme decimates the HPA axis. Cortisol output drops, DHEA plummets, the stress response fails:

• Ashwagandha KSM-66: 300-600mg/day
• Rhodiola rosea: 200-400mg/day
• Adrenal glandulars (for severe depletion)
• Vitamin C: 1g 3x/day (adrenals are the highest vitamin C consumers in the body)
• Pantothenic acid (B5): 500mg 2x/day

Markers of Progress

Healing from Lyme is measured in months and years, not weeks. Track these markers:

• Symptom tracking: Daily symptom log with severity scores. Trends matter more than individual days.
• CD57 (NK cell subset): Characteristically low in chronic Lyme (often <60). Rising CD57 correlates with clinical improvement and treatment response. Not diagnostic, but useful for monitoring.
• C6 peptide antibody: Specific marker of active Borrelia infection. Declining titers suggest treatment is working.
• Inflammatory markers: hs-CRP, cytokines trending downward.
• Functional capacity: Increasing activity tolerance, improving cognitive function, returning to baseline activities.

The Practitioner’s Compass

Chronic Lyme treatment is a marathon, not a sprint. The functional medicine approach — addressing infection, terrain, gut, detox, immune modulation, and neurological support simultaneously — produces outcomes that neither antibiotics alone nor herbs alone can match. The tick delivered the spark. Whether that spark becomes a wildfire depends entirely on the forest it landed in.