The effect of a low-nickel diet and nickel sensitization ongastroesophageal reflux disease: A pilot study Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This prospective pilot study investigated the therapeutic potential of a Low‑Nickel diet (LNiD) in patients with refractory gastroesophageal reflux disease (GERD) and explored whether epicutaneous patch testing for nickel (Ni) could predict dietary responsiveness. The researchers sought to determine whether dietary nickel contributes to GERD pathophysiology and whether identifying nickel sensitivity via patch testing can inform clinical decision-making.
Who was studied?
Twenty adult patients with a confirmed diagnosis of GERD were enrolled at a single site in West Virginia. All had persistent GERD symptoms despite at least three months of proton pump inhibitor (PPI) therapy and a GERD-HRQL score ≥30 at baseline. Patch testing was conducted using nickel sulfate and three additional common allergens (cobalt chloride, balsam of Peru, and cinnamic aldehyde), but patients were blinded to their patch test results until the end of the study. All participants adhered to a standardized low-nickel diet for eight weeks. GERD symptom severity was evaluated pre- and post-intervention using the validated GERD Health-Related Quality of Life (GERD-HRQL) questionnaire, which assesses heartburn, regurgitation, and overall symptom burden.
What were the most important findings?
Nineteen out of twenty participants (95%) reported substantial improvement in GERD symptoms after following the low-nickel diet. Mean total GERD-HRQL scores dropped by 27.05 points, while mean heartburn and regurgitation scores declined by 11.45 and 10.85 points, respectively—all statistically significant reductions (p <0.001). Improvements were consistent across participants, regardless of nickel patch test results. Although 3 participants (15%) tested positive for nickel sensitivity, their symptom improvement was only modestly different from those who tested negative. Importantly, the magnitude of symptom reduction was not significantly correlated with patch test status. Nearly half of participants (45%) reported being satisfied with their GERD symptoms post-intervention, a notable shift from the 95% dissatisfaction rate at baseline.
While the study did not measure microbiome parameters directly, the data suggest nickel may act as a dietary irritant that exacerbates esophageal inflammation independently of overt allergic sensitization. This opens the possibility that dietary nickel contributes to barrier disruption or mucosal immune activation along the upper gastrointestinal tract—mechanisms well-documented in nickel-induced contact mucositis and consistent with microbial shifts observed in conditions like irritable bowel syndrome IBS and H. pylori infection, both of which have been responsive to nickel restriction.
What are the greatest implications of this study?
This study establishes that a low-nickel diet may be a powerful non-pharmacologic intervention for GERD, even in patients unresponsive to standard therapy. The data challenge the assumption that only patients with demonstrable nickel allergy benefit from nickel restriction, suggesting that dietary nickel may provoke inflammation through mechanisms not captured by skin-based patch testing. This has important clinical implications: patch test–guided exclusion diets may miss a substantial subset of patients who stand to benefit from nickel reduction. The findings justify broader consideration of dietary nickel as a contributing factor in GERD and potentially other inflammatory gastrointestinal conditions. Importantly, the intervention had excellent adherence and tolerability, supporting its viability in routine care. Future randomized, controlled trials with larger sample sizes and microbial/metallomic profiling are warranted to validate these findings and explore underlying mechanisms.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.