Elevated levels of whole blood nickel in a group of Sri Lankan women with endometriosis: a case control study Original paper
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Endometriosis
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
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Metals
Metals
Heavy metals play a significant and multifaceted role in the pathogenicity of microbial species.
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Karen Pendergrass
Read MoreKaren 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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Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
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 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.
What was studied?
This study investigated blood nickel and endometriosis by examining whether circulating levels of three metalloestrogens—nickel, cadmium, and lead—were associated with the presence of endometriosis in reproductive-age Sri Lankan women. The researchers aimed to determine whether elevated concentrations of these metals in whole blood might reflect an exposure pattern contributing to the accumulation of metals previously detected in ectopic endometrial tissue. Using highly sensitive analytic techniques, including Total Reflection X-ray Fluorescence and graphite furnace atomic absorption spectroscopy, the study quantified blood metal concentrations and evaluated their statistical relationship to surgically confirmed endometriosis. This work expands on prior findings showing these metals embedded in endometriotic lesions and attempts to clarify whether systemic metal burden may play a mechanistic or exposure-related role.
Who was studied?
The study enrolled 100 women of reproductive age undergoing laparoscopy or laparotomy at a major Sri Lankan hospital. Fifty women with visually confirmed endometriosis formed the case group, and fifty age-matched women without endometriosis served as controls. None were current smokers, minimising confounding from tobacco-related cadmium exposure. Both groups were similar in age and BMI, and indications for surgery among controls included dysmenorrhea, chronic pelvic pain, subfertility, or ovarian masses. All participants provided preoperative venous blood samples, which were processed under tightly controlled laboratory conditions with rigorous quality assurance to ensure high-precision trace metal measurement.
Most important findings
The key discovery was a significantly elevated geometric mean whole blood nickel concentration in women with endometriosis compared with controls. Nickel levels in cases averaged 2.6 μg/L, more than triple the 0.8 μg/L observed in controls. Cadmium and lead levels did not differ significantly, although cases showed slightly lower cadmium and slightly higher lead concentrations. Notably, blood nickel levels reported here fell within ranges considered nontoxic in general populations, yet the consistent elevation in cases suggests biologically relevant exposure or altered handling of nickel in affected women. Nickel’s known ability to activate estrogen receptors in vitro underscores its potential role as a metalloestrogen influencing ectopic tissue survival.
| Metal | Cases (μg/L) | Controls (μg/L) | Statistical Significance |
|---|---|---|---|
| Nickel | 2.6 | 0.8 | Significant (P=0.016) |
| Cadmium | 0.7 | 0.8 | Not significant |
| Lead | 11.0 | 6.9 | Not significant |
| Interpretation | Elevated in endometriosis | Baseline levels | Nickel shows clear association |
Key implications
These findings suggest that nickel exposure or retention may be associated with endometriosis, potentially through estrogen receptor activation or other endocrine-disrupting mechanisms. Although causality cannot be established from this study, the elevated systemic nickel burden aligns with the presence of nickel in ectopic lesions and contributes to the hypothesis that environmental metals may influence disease development. Future work should explore exposure sources, dose–response relationships, and mechanistic pathways linking trace metals to estrogen-dependent inflammatory disease.
Citation
Silva N, Senanayake H, Waduge V. Elevated levels of whole blood nickel in a group of Sri Lankan women with endometriosis: a case control study. BMC Research Notes. 2013;6:13. 1756-0500-6-13
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.