H. pylori: Beyond Triple Therapy

The Spiral Invader

Helicobacter pylori is one of the most successful pathogens in human history. It colonizes the stomachs of roughly half the world’s population. It has co-evolved with us for at least 60,000 years. And it possesses an engineering elegance that would impress any microbiologist.

The bacterium is spiral-shaped — a corkscrew designed to burrow through the thick mucus layer protecting the gastric epithelium. Once anchored, it produces urease, an enzyme that converts urea into ammonia and carbon dioxide. The ammonia neutralizes stomach acid in its immediate vicinity, creating a pH-neutral microenvironment where the bacterium thrives. It has built itself a bunker inside a war zone.

But H. pylori is not a single entity with a single personality. Its virulence depends on which genetic weapons it carries. The two most studied virulence factors — cagA (cytotoxin-associated gene A) and vacA (vacuolating cytotoxin A) — dramatically change the clinical picture. CagA-positive strains inject the CagA protein directly into gastric epithelial cells via a type IV secretion system, disrupting cell signaling, promoting inflammation, and significantly increasing the risk of gastric ulcers and gastric cancer. VacA produces a toxin that creates vacuoles in epithelial cells, impairs immune function, and promotes bacterial persistence.

Not all H. pylori infections are equal. A cagA-positive, vacA s1/m1 strain is a different clinical threat than a cagA-negative, vacA s2/m2 strain. This matters for treatment decisions.

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Testing: Getting the Diagnosis Right

Stool Antigen Test (Preferred for Active Infection)

The monoclonal stool antigen test detects active H. pylori infection with sensitivity and specificity both exceeding 95%. It can confirm both initial infection and successful eradication. Must be performed at least 2 weeks after stopping PPIs and 4 weeks after stopping antibiotics to avoid false negatives.

Urea Breath Test

The patient swallows a capsule containing carbon-13 or carbon-14 labeled urea. If H. pylori is present, its urease enzyme cleaves the labeled urea, and the labeled carbon dioxide appears in exhaled breath within 30 minutes. Sensitivity and specificity exceed 95%. Same PPI and antibiotic washout periods apply.

Serology (IgG Antibodies)

Blood antibody testing tells you the immune system has seen H. pylori at some point. It cannot distinguish between active and past infection. After successful eradication, IgG antibodies can remain positive for years. Serology is useful for epidemiological screening but poor for clinical management. Do not use it to confirm eradication.

Endoscopic Biopsy

The gold standard when endoscopy is already indicated (alarm symptoms, ulcers, family history of gastric cancer). Allows histological examination, culture for antibiotic sensitivity, and assessment of gastric mucosal damage. Rapid urease test (CLO test) on biopsy tissue gives results in hours.

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The Antibiotic Resistance Crisis

Here is the uncomfortable truth about H. pylori treatment in the 2020s: the standard regimens are failing at alarming rates.

Classic triple therapy — a PPI plus clarithromycin plus amoxicillin for 14 days — was the backbone of H. pylori eradication for two decades. Global clarithromycin resistance now exceeds 30% in many regions (Europe, Asia, parts of the US). In some countries it reaches 50%. When resistance is present, triple therapy fails in roughly half of cases.

Metronidazole resistance runs even higher — 40-50% globally. Levofloxacin resistance is climbing. We are watching the slow-motion collapse of empiric antibiotic therapy for one of the world’s most common infections.

The Maastricht VI/Florence consensus (2022) now recommends:

• Bismuth quadruple therapy as first-line in areas with high clarithromycin resistance: PPI + bismuth subsalicylate + metronidazole + tetracycline for 14 days
• Concomitant therapy as an alternative: PPI + amoxicillin + clarithromycin + metronidazole for 14 days (the shotgun approach)
• Culture-guided therapy whenever possible after first treatment failure
• Vonoprazan-based regimens: Vonoprazan, a potassium-competitive acid blocker, provides more potent and consistent acid suppression than PPIs, improving antibiotic efficacy (Chey 2022)

Even with optimized regimens, first-line eradication rates hover around 80-90%. Second-line rates drop further. This is precisely where functional and integrative approaches earn their place — not as replacements for antibiotics when they are needed, but as adjuncts that improve eradication rates and as standalone options for patients who have failed multiple rounds or who prefer to avoid further antibiotics.

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The Functional Protocol

Mastic Gum

Mastic gum — the resin of the Pistacia lentiscus tree, cultivated primarily on the Greek island of Chios — has been used for gastric complaints in the Mediterranean for centuries. Dabos 2010 published a randomized controlled trial showing that 350mg of mastic gum three times daily for 14 days eradicated H. pylori in 30% of patients as monotherapy and produced significant symptom improvement in those not fully eradicated.

Dose: 500mg three times daily, taken on an empty stomach. Typical course: 4-8 weeks. Mastic gum has direct bactericidal activity against H. pylori and reduces mucosal inflammation. It is well-tolerated with minimal side effects.

Sulforaphane (Broccoli Sprouts)

Yanaka 2009 published a landmark study in Cancer Prevention Research: daily consumption of 70g of broccoli sprouts (standardized to sulforaphane content) for 8 weeks reduced H. pylori colonization by 40% measured by urea breath test, and significantly reduced markers of gastric inflammation and oxidative stress.

Sulforaphane — an isothiocyanate released when glucoraphanin in broccoli is processed by the enzyme myrosinase — inhibits urease, disrupts bacterial membranes, and activates Nrf2 (the master antioxidant transcription factor) in gastric epithelial cells, reducing inflammation and oxidative damage.

Dose: 30-60mg sulforaphane daily from broccoli sprout extract or whole sprouts (3-day-old sprouts contain the highest concentration). Continue for at least 8 weeks.

Lactobacillus reuteri DSM 17648 (Pylopass)

This specific strain works through a unique mechanism: it binds directly to H. pylori cells through surface adhesion molecules, causing bacterial agglutination (clumping). The clumped bacteria are swept through the GI tract and eliminated. Mehling 2013 demonstrated significant reduction in H. pylori load measured by urea breath test.

Dose: 200mg (2 x 10^10 CFU) daily. Available as Pylopass. Can be used as an adjunct to any treatment regimen.

NAC (N-Acetyl Cysteine) — Biofilm Disruption

H. pylori forms biofilms — organized communities encased in a protective extracellular matrix that antibiotics struggle to penetrate. NAC disrupts these biofilms by cleaving disulfide bonds in the matrix.

Fontes 2015 demonstrated that NAC pre-treatment significantly improved antibiotic efficacy against H. pylori biofilms in vitro. Clinically, NAC 600mg twice daily as pre-treatment (starting 5-7 days before antibiotics) and during antibiotic therapy may improve eradication rates.

Additional Agents

• Vitamin C: 500mg twice daily. Creates an acidic environment hostile to H. pylori and has direct bactericidal effects (Jarosz 1998 — reduced H. pylori infection density by 79% with 5g/day, though lower doses are more practical long-term)
• Bismuth subsalicylate: 524mg four times daily. Directly toxic to H. pylori, disrupts the bacterial cell wall, and can be used alongside natural agents
• Black seed oil (Nigella sativa): 2g/day. Salem 2010 demonstrated anti-H. pylori activity comparable to triple therapy in some patients. Contains thymoquinone, which has direct antimicrobial and anti-inflammatory properties.
• Manuka honey: UMF 10+ (equivalent to MGO 263+). Contains methylglyoxal, which has demonstrated in vitro bactericidal activity against H. pylori (Almasaudi 2017). Take 1 tablespoon on an empty stomach, 30 minutes before meals.
• Garlic: Allicin — the active compound released when garlic is crushed — has bactericidal activity against H. pylori including some antibiotic-resistant strains. Stabilized allicin extract 300-600mg daily.

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Probiotics During Eradication Treatment

When antibiotics are used — and sometimes they must be — probiotics taken concurrently improve outcomes on two fronts: they increase eradication rates and reduce antibiotic side effects.

Saccharomyces boulardii: 500mg twice daily, started 5 days before antibiotics and continued 2 weeks after. A 2015 meta-analysis (Szajewska) found S. boulardii increased H. pylori eradication rates by 11% and reduced antibiotic-associated diarrhea by 51%.

Lactobacillus rhamnosus GG: 1 x 10^10 CFU daily during and 2 weeks after antibiotic treatment. Reduces GI side effects and supports microbiome recovery.

Multi-strain probiotics: Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium lactis — taken at least 2 hours apart from antibiotics.

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Post-Eradication Gut Repair Protocol

Eradicating H. pylori is step one. Healing the damage it left behind is step two. After decades of colonization, the gastric mucosa may be inflamed, atrophied, or both. The microbiome has been disrupted first by the infection and then by the antibiotics.

Phase 1: Mucosal Repair (Weeks 1-4)

• Zinc carnosine: 75mg twice daily — heals gastric mucosa (Mahmood 2007)
• DGL: 400mg chewable, 20 minutes before meals — stimulates protective mucus
• L-glutamine: 5g twice daily — primary fuel for gut epithelial cells
• Aloe vera inner leaf juice: 2-4 oz before meals — anti-inflammatory, mucosal healing

Phase 2: Microbiome Restoration (Weeks 2-8)

• Multi-strain probiotic: High-potency (50-100 billion CFU) with Lactobacillus and Bifidobacterium diversity
• Saccharomyces boulardii: 500mg daily for 4 weeks post-antibiotics
• Prebiotic fiber: Partially hydrolyzed guar gum (PHGG) 5g/day, gradually increasing — feeds beneficial bacteria without excessive fermentation
• Fermented foods: Sauerkraut, kimchi, kefir — introduce gradually

Phase 3: Acid and Enzyme Optimization (Weeks 4-8)

• Assess HCl status with the betaine HCl challenge test (see GERD protocol)
• Digestive bitters before meals to stimulate endogenous secretion
• Digestive enzymes with meals if needed

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When to Retest

Retesting is mandatory. Symptoms alone cannot confirm eradication — asymptomatic infection is common and carries ongoing risks (ulcers, gastric cancer with cagA-positive strains, MALT lymphoma).

Timing: At least 4 weeks after completing treatment (antibiotic or herbal), and at least 2 weeks off PPIs. Stool antigen test or urea breath test — not serology.

If eradication fails:

1. Use a different regimen — do not repeat the same antibiotics
2. Request culture with antibiotic sensitivity testing if available (endoscopy)
3. Consider bismuth quadruple therapy if not already tried
4. Add or intensify herbal antimicrobials
5. Address biofilm with NAC pre-treatment
6. Ensure compliance — the most common reason for failure is incomplete adherence to 14-day regimens

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The Complexity of H. pylori

Not every H. pylori infection requires treatment. In some individuals, particularly those colonized with less virulent strains, H. pylori may play a regulatory role in gastric acid homeostasis and even immune modulation. Martin Blaser’s research at NYU has raised important questions about the consequences of universal H. pylori eradication — including increased rates of esophageal reflux, Barrett’s esophagus, and esophageal adenocarcinoma in populations where H. pylori has been eradicated.

The functional approach weighs the individual picture: virulence factors, symptom severity, family history of gastric cancer, presence of ulcers or precancerous changes, and patient preference. Treat when treatment is warranted. Support the terrain always.

What if the goal were not simply to kill a bacterium, but to restore the entire gastric ecosystem to a state where it can protect itself?