Low-Nickel Diet in Endometriosis: Symptom Relief and Nickel Mucositis Evidence Original paper

What was studied?

This open-label pilot study evaluated the prevalence of nickel-related allergic contact mucositis in women with endometriosis who reported irritable bowel syndrome (IBS)-like symptoms, and whether a low-nickel diet in endometriosis alleviates gastrointestinal, extra-intestinal, and gynecologic symptoms. Participants underwent a nickel oral mucosa patch test (omPT), then followed a three-month low-nickel diet that excluded high-nickel foods such as legumes, whole grains, cocoa, and tomatoes as summarized in Table 1 on page 4. Symptom burden was quantified with a modified Gastrointestinal Symptom Rating Scale at baseline and after the dietary intervention, and pre-post differences were analyzed with Wilcoxon signed-rank tests.

Who was studied?

Eighty-three women with imaging or laparoscopically confirmed endometriosis were screened; 51 met symptom criteria, four were excluded for celiac disease or wheat allergy, and 16 dropped out, leaving 31 women (mean age 33.5 years) who completed the protocol. Clinical characteristics and sites of disease are detailed in Table 2 on pages 7–8. Notably, 28 of 31 completers (90.3 percent) had a positive omPT and were diagnosed with nickel allergic contact mucositis, whereas 3 of 31 were omPT-negative.

Most important findings

After three months of the low-nickel diet, all 15 gastrointestinal symptoms showed statistically significant reductions in intensity, including abdominal pain, bloating, reflux, altered bowel habits, and urgency. The bar charts on page 9 (Figure 3) illustrate consistent downward shifts across domains. Extra-intestinal symptoms such as headache, fatigue, brain fog, and dermatitis also declined significantly, as did gynecologic symptoms central to endometriosis care, including dysmenorrhea, dyspareunia, and chronic pelvic pain; these trends are shown on page 10 (Figure 4). Collectively, the data suggest that nickel exposure may trigger a low-grade mucosal inflammatory state that phenocopies IBS and amplifies pelvic pain symptomatology in a substantial subset of patients with endometriosis. From a microbiome-relevant perspective, the authors frame nickel as a metalloestrogen and environmental factor that can interact with mucosal immunity and symptom generation; the IBS-like phenotype of nickel allergic contact mucositis aligns with clinical entities frequently linked to gut dysbiosis, offering a plausible interface for future microbiome signatures work even though microbial taxa were not directly assayed in this study. The high positivity rate of omPT in this endometriosis cohort, combined with the broad symptom relief on a targeted elimination diet, positions nickel sensitivity as a potential major association for inclusion in a microbiome-signatures database focused on environmental and host-mucosal interactions.

Key implications

Clinically, routine consideration of nickel sensitivity is warranted in endometriosis patients who report IBS-like symptoms or refractory pelvic pain. The omPT offers a practical diagnostic adjunct, and a supervised low-nickel diet is a reasonable, time-limited therapeutic trial when omPT is positive. For translational research, these findings motivate integration of nickel exposure assessment and nickel-responsive symptom phenotyping into microbiome studies of endometriosis. Although the trial is limited by its small sample size, single-center design, and open-label methodology with notable dietary adherence challenges, the magnitude and breadth of symptom improvement across gastrointestinal, extra-intestinal, and gynecologic domains indicate that nickel allergic contact mucositis may be a clinically meaningful, modifiable driver of symptom burden in endometriosis. Future controlled studies should incorporate objective dietary nickel exposure metrics and mucosal or fecal biomarkers to map nickel-linked inflammatory pathways to microbial community features and to identify major microbial associations that co-vary with nickel-sensitive phenotypes.

Citation

Borghini R, Porpora MG, Casale R, Marino M, Palmieri E, Greco N, Donato G, Picarelli A. Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study. Nutrients. 2020;12(2):341. doi:10.3390/nu12020341.