Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease Original paper

What was studied?

This study examined how a low-nickel diet influences persistent gastrointestinal and extraintestinal symptoms in celiac patients who remain symptomatic despite full serologic and histologic remission on a gluten-free diet. Because a gluten-free diet often increases dietary nickel exposure—especially from foods like corn—the investigators explored whether nickel allergic contact mucositis (ACM) contributes to symptom relapse in patients who would otherwise be considered to have non-responsive celiac disease. Nickel sensitivity was evaluated using an oral mucosa patch test, and symptom changes were assessed through a modified Gastrointestinal Symptom Rating Scale.

Who was studied?

A total of 102 adults with celiac disease adhering to a strict gluten-free diet for at least 12 months were screened. After excluding individuals with lactose intolerance, Helicobacter pylori infection, inflammatory bowel disease, cancer, or insufficient symptom severity, 20 women aged 23–65 completed the study. All participants were in confirmed serologic and histologic remission yet reported relapsing gastrointestinal or systemic symptoms. Each underwent nickel oral mucosa patch testing and subsequently followed a low-nickel diet for three months in addition to their gluten-free diet.

Most important findings

The study revealed consistent nickel sensitivity among the final cohort: all 20 participants exhibited positive findings on the oral mucosa patch test, indicating nickel ACM. Symptomatic patterns showed three distinct phases. Symptoms initially improved with gluten withdrawal but then recurred during prolonged gluten-free eating, suggesting increasing dietary nickel load from nickel-rich gluten-free staples. After initiation of the low-nickel regimen, patients experienced marked improvement across both gastrointestinal and systemic symptoms. The trend was evident in symptom trajectory graphs, where nickel-related symptoms such as bloating, loose stools, dermatitis, headache, and fatigue demonstrated a clear rise during prolonged gluten-free eating and an equally clear drop after nickel restriction. Table 1 summarizes symptom directionality, showing more than 80% of symptoms improving after the diet change.

Key implications

This study highlights nickel ACM as an underrecognized contributor to persistent symptoms in celiac patients on long-term gluten-free diets. Since many gluten-free foods are naturally high in nickel, dietary nickel exposure becomes a potential trigger for IBS-like and systemic manifestations. The findings support incorporating nickel sensitivity evaluation into the workup for non-responsive celiac disease once gluten exposure and villous damage are excluded. Clinically, a structured low-nickel diet may reduce symptoms substantially and prevent misclassification of nickel sensitivity as refractory celiac disease or unexplained IBS-like relapse. The work also underscores broader dietary-microbial interactions: nickel-sensitive mucosal inflammation likely alters microbial ecology, contributing to symptom generation and emphasizing the relevance of nickel-associated microbial signatures in clinical microbiome frameworks.

Citation

Borghini R, De Amicis N, Bella A, Greco N, Donato G, Picarelli A. Beneficial effects of a low-nickel diet on relapsing IBS-like and extraintestinal symptoms of celiac patients during a proper gluten-free diet: Nickel allergic contact mucositis in suspected non-responsive celiac disease. Nutrients. 2020;12(8):2277. nutrients-12-02277