Manganese

Biological Roles#

Non-Enzymatic Antioxidant Role#

Beyond enzyme cofactors, manganese(II) (Mn2+) forms low-molecular-weight complexes with metabolites (phosphate, carboxylates, amino acids, peptides) that scavenge superoxide non-enzymatically.

In Borrelia burgdorferi—a pathogen that has eliminated iron from its biology entirely—MnSOD at the cell surface handles extracellular superoxide while cytoplasmic manganese-metabolite complexes (H-manganese) handle intracellular superoxide.^{[12]Londono 2025 — EPR Spectroscopy Reveals Antioxidant Manganese Defenses in the Lyme Disease Pathogen Borrelia burgdorferiAndres F Londono, Ajay Sharma, Venkatesan Kathiresan et al. · 2025Open reference 12 ↓}

The ratio of enzyme-bound manganese (L-manganese) to metabolite-bound manganese (H-manganese) predicts radiation resistance across all domains of life: Deinococcus radiodurans has >90% H-manganese while E. coli has only ~10%, explaining their vastly different radiation tolerance.^{[12]Londono 2025 — EPR Spectroscopy Reveals Antioxidant Manganese Defenses in the Lyme Disease Pathogen Borrelia burgdorferiAndres F Londono, Ajay Sharma, Venkatesan Kathiresan et al. · 2025Open reference 12 ↓}

Dietary and Environmental Sources#

Genetic Determinants of Exposure#

The Crohn's disease-associated SNP rs13107325 in SLC39A8 (ZIP8) alters manganese (Mn) handling at the colonic mucosal-luminal interface. Homozygous A391T mice exhibit higher manganese in bulk colon tissue with reduced luminal manganese availability, altering the metal environment accessible to gut microbes.^{[17]ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and InflammationYang JC, Zhao M, Chernikova D et al. · 2024Open reference 17 ↓}

This demonstrates that host genetics can reshape microbial metal access independently of dietary exposure.

Microbiome Interactions#

Metals as Selective Pressures on Gut Microbiota#

manganese (Mn) exposure reshapes gut microbial communities with sex-specific effects.^{[18]Influence of Toxic Metal Exposure on the Gut Microbiota (Review)Federica Giambo, Sebastiano Italia, Michele Teodoro et al. · 2021Open reference 18 ↓}

Fecal microbiota transplant (FMT) can alleviate manganese-induced neurotoxicity in rats, demonstrating that manganese's neurological effects are partly mediated through the gut-brain axis.^{[19]Toxic and Essential Metals: Metabolic Interactions with the Gut Microbiota and Health ImplicationsQinheng Zhu, Boyan Chen, Fu Zhang et al. · 2024Open reference 19 ↓[18]Influence of Toxic Metal Exposure on the Gut Microbiota (Review)Federica Giambo, Sebastiano Italia, Michele Teodoro et al. · 2021Open reference 18 ↓}

In the infant gut, manganese drives specific taxonomic selection: serum manganese was identified as a key contributor to Burkholderia-Caballeronia-Paraburkholderia abundance (posterior inclusion probability = 0.535), and synergistic manganese-copper (Cu) interactions shaped Clostridium sensu stricto abundance.^{[20]Yan 2025 — Association Between Infants' Serum Levels of 26 Metals and Gut Microbiota: A Hospital-Based Cross-Sectional Study in ChinaXing Yan, Jun Qiu, Ruiwen Huang et al. · 2025Open reference 20 ↓}

Prenatal manganese exposure (measured in maternal hair) was associated with increased Bifidobacterium relative abundance in 3-month-old infants.^{[21]Xiong 2025 — Prenatal Exposure to Trace Elements Impacts Mother-Infant Gut Microbiome, Metabolome and Resistome During the First Year of LifeShimao Xiong, Bing Xie, Naiyi Yin et al. · 2025Open reference 21 ↓}

The ZIP8 A391T Crohn's risk variant, which reduces luminal manganese availability, resulted in decreased Lactobacillus abundance in mice—consistent with Lactobacillus species being manganese-dependent organisms that rely on manganese rather than iron for their antioxidant strategy.^{[17]ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and InflammationYang JC, Zhao M, Chernikova D et al. · 2024Open reference 17 ↓}

Bacterial Mn Acquisition Systems#

Pathogenic bacteria have evolved multiple manganese (Mn) import systems to ensure supply of this critical cofactor:

Bacteria also require manganese export to avoid toxicity. MntE (CDF pump) and MgtA (P-type ATPase) export excess manganese in streptococci; loss of MntE renders S. pneumoniae hypersensitive to manganese (growth abolished at 700 uM).^{[24]Opoku 2024 — Calcium Rescues Streptococcus pneumoniae D39 delta-mntE Manganese-Sensitive Growth PhenotypeReuben Opoku, Edgar Carrasco, Nicholas R De Lay et al. · 2024Open reference 24 ↓}

In E. coli, MntP is the primary manganese efflux pump, regulated by both the MntR metalloregulator and a yybP-ykoY manganese-sensing riboswitch in its 5'-UTR.^{[25]Prakash 2024 — Rho and Riboswitch-Dependent Regulations of mntP Gene Expression Evade Manganese and Membrane ToxicitiesAnand Prakash, Arunima Kalita, Kanika Bhardwaj et al. · 2024Open reference 25 ↓}

Mn-Sensing Riboswitches#

Bacteria sense manganese (Mn) through the yybP-ykoY riboswitch family—the largest metal-sensing riboswitch family known, with over 1,000 unique representatives across bacterial phyla.^{[26]Stephen 2025 — Structurally Distinct Manganese-Sensing Riboswitch Aptamers Regulate Different Expression Platform ArchitecturesChristine Stephen, Danea E Palmer, Clarisa Bautista et al. · 2025Open reference 26 ↓}

These RNA-based sensors detect the labile manganese(II) pool co-transcriptionally—metal ion sampling begins before the riboswitch RNA is fully synthesized.^{[26]Stephen 2025 — Structurally Distinct Manganese-Sensing Riboswitch Aptamers Regulate Different Expression Platform ArchitecturesChristine Stephen, Danea E Palmer, Clarisa Bautista et al. · 2025Open reference 26 ↓}

The E. coli alx riboswitch uniquely integrates two orthogonal signals—manganese(II) concentration and pH—through a single RNA element.

At alkaline pH (where manganese toxicity is greatest because manganese(II) oxidizes to DNA-cleaving manganese(IV)), the riboswitch becomes 1,000-fold more sensitive to manganese(II), enabling response to physiologically relevant fluctuations specifically when export is most needed.^{[27]Palmer 2026 — pH-Dependent Allosteric Remodeling of a Bacterial Riboswitch Couples Alkaline Activation to Metal SensingDanea Palmer, Adrien Chauvier, Tomas F D Silva et al. · 2026Open reference 27 ↓}

Mn-Dependent Virulence in Key Pathogens#

Staphylococcus aureus requires manganese (Mn) for SodA/SodM superoxide dismutase activity and oxidative stress defense against host immune attack.^{[8]Metal Ion Acquisition in Staphylococcus aureus: Overcoming Nutritional ImmunityJames E. Cassat, Eric P. Skaar · 2012Open reference 8 ↓} Under host calprotectin-mediated manganese starvation, the small RNA RsaC activates a "manganese-sparing response"—suppressing the manganese-hungry SodA to redistribute scarce manganese to other essential enzymes.

RsaC is required for virulence in both subcutaneous and systemic mouse infection models.^{[9]McFarlane 2025 — A Manganese-Sparing Response Balances Competing Cellular Demands to Enable Staphylococcus aureus InfectionRiley A McFarlane, Jana N Radin, Rafat Mazgaj et al. · 2025Open reference 9 ↓}

RsaC joins a growing family of metal-responsive sRNAs: RyhB (iron (Fe)-sparing in E. coli), s-SodF (nickel (Ni)-SOD suppression in Streptomyces), and NikS (nickel-responsive in H. pylori).^{[9]McFarlane 2025 — A Manganese-Sparing Response Balances Competing Cellular Demands to Enable Staphylococcus aureus InfectionRiley A McFarlane, Jana N Radin, Rafat Mazgaj et al. · 2025Open reference 9 ↓}

Streptococcus pneumoniae depends on PsaA as its sole high-affinity manganese importer. Zinc competitively inhibits manganese uptake through PsaA with an EC50 of 30.2 uM zinc (Zn) at 1 uM manganese.

When manganese import is blocked, pneumococcal SOD loads with iron instead—a classic mis-metallation event that renders the enzyme inactive against superoxide, leaving the bacterium vulnerable to oxidative killing by host phagocytes.^{[22]Eijkelkamp et al. 2014 — Extracellular Zinc Competitively Inhibits Manganese Uptake in Streptococcus pneumoniaeBart A. Eijkelkamp, Jacqueline R. Morey, Stephanie L. Neville et al. · 2014Open reference 22 ↓}

The zinc:manganese ratio, not the absolute concentration of either metal, determines bacterial vulnerability.^{[22]Eijkelkamp et al. 2014 — Extracellular Zinc Competitively Inhibits Manganese Uptake in Streptococcus pneumoniaeBart A. Eijkelkamp, Jacqueline R. Morey, Stephanie L. Neville et al. · 2014Open reference 22 ↓}

Group B Streptococcus (S. agalactiae) is a manganese-centric organism that relies on manganese for SOD activity and oxidative stress defense; host manganese restriction via calprotectin is a potent anti-GBS strategy.^{[28]Goh 2024 — An Opportunistic Pathogen Under Stress: How Group B Streptococcus Responds to Cytotoxic Reactive Species and Conditions of Metal Ion Imbalance to SurviveKelvin G K Goh, Devika Desai, Ruby Thapa et al. · 2024Open reference 28 ↓}

Excess zinc(II) in phagosomes displaces manganese(II) from SodA and other manganese-dependent enzymes, compounding the damage.^{[28]Goh 2024 — An Opportunistic Pathogen Under Stress: How Group B Streptococcus Responds to Cytotoxic Reactive Species and Conditions of Metal Ion Imbalance to SurviveKelvin G K Goh, Devika Desai, Ruby Thapa et al. · 2024Open reference 28 ↓}

Borrelia burgdorferi has taken the most extreme approach: eliminating iron entirely from its biology.

With no iron-dependent enzymes, B. burgdorferi avoids Fenton chemistry and circumvents host nutritional immunity targeting iron—but at the cost of absolute dependence on manganese for its antioxidant defense.^{[12]Londono 2025 — EPR Spectroscopy Reveals Antioxidant Manganese Defenses in the Lyme Disease Pathogen Borrelia burgdorferiAndres F Londono, Ajay Sharma, Venkatesan Kathiresan et al. · 2025Open reference 12 ↓}

Mis-Metallation: When Manganese is the Wrong Metal#

Mn Excess Mis-Metalates Iron Sensors#

Elevated manganese (Mn) occupies the iron (Fe)-sensing Fur (ferric uptake regulator) protein, causing iron import genes to remain repressed even when iron is needed.

Unincorporated intracellular iron then generates toxic hydroxyl radicals via Fenton chemistry—a non-obvious cascade linking manganese excess to oxidative stress through iron dysregulation rather than direct manganese toxicity.^{[1]Martin & Waters 2022 — Manganese Homeostasis, Stress, and Pathogenesis in BacteriaJulia E. Martin, Lauren S. Waters · 2022Open reference 1 ↓}

This Fur mis-metallation has been demonstrated in both pathogenic bacteria and cyanobacteria: in Synechocystis, excess manganese produces a transcriptome that partly resembles iron limitation even though iron levels are unchanged, because manganese-bound Fur erroneously signals iron sufficiency.^{[30]Reis 2024 — Study of Excess Manganese Stress Response Highlights the Central Role of Manganese Exporter Mnx for Holding Manganese Homeostasis in Synechocystis sp. PCC 6803Mara Reis, Sanja Zenker, Prisca Viehoever et al. · 2024Open reference 30 ↓}

Cells respond to manganese-driven mis-metallation by upregulating ribosomes, proteases, and chaperones—investing in protein quality control to replace mis-metalated proteins with correctly metalated copies.^{[30]Reis 2024 — Study of Excess Manganese Stress Response Highlights the Central Role of Manganese Exporter Mnx for Holding Manganese Homeostasis in Synechocystis sp. PCC 6803Mara Reis, Sanja Zenker, Prisca Viehoever et al. · 2024Open reference 30 ↓}

Mn Toxicity from Excess#

Uncontrolled manganese (Mn) accumulation is itself toxic. In S. pneumoniae lacking the MntE efflux transporter, excess manganese (300-700 uM) impairs growth, increases capsule production, and reduces biofilm formation.^{[24]Opoku 2024 — Calcium Rescues Streptococcus pneumoniae D39 delta-mntE Manganese-Sensitive Growth PhenotypeReuben Opoku, Edgar Carrasco, Nicholas R De Lay et al. · 2024Open reference 24 ↓}

In E. coli, the MntP efflux pump is essential; its regulation by a manganese-sensing riboswitch and Rho-dependent transcription termination prevents both manganese accumulation (too little MntP) and membrane protein toxicity (too much MntP).^{[25]Prakash 2024 — Rho and Riboswitch-Dependent Regulations of mntP Gene Expression Evade Manganese and Membrane ToxicitiesAnand Prakash, Arunima Kalita, Kanika Bhardwaj et al. · 2024Open reference 25 ↓}

At elevated pH, manganese(II) oxidizes to manganese(IV), which cleaves RNA and DNA, and manganese(II) hydroxide increases reactive oxygen species generation.^{[27]Palmer 2026 — pH-Dependent Allosteric Remodeling of a Bacterial Riboswitch Couples Alkaline Activation to Metal SensingDanea Palmer, Adrien Chauvier, Tomas F D Silva et al. · 2026Open reference 27 ↓}

In metabolite-depleted cells, excess free manganese(II) that cannot form protective metabolite complexes becomes directly cytotoxic through off-target binding—a form of self-poisoning observed in stationary-phase B. burgdorferi.^{[12]Londono 2025 — EPR Spectroscopy Reveals Antioxidant Manganese Defenses in the Lyme Disease Pathogen Borrelia burgdorferiAndres F Londono, Ajay Sharma, Venkatesan Kathiresan et al. · 2025Open reference 12 ↓}

Conditions Associated#

Parkinsonism and Neurotoxicity#

manganese (Mn) neurotoxicity is the most thoroughly documented health effect. Dose-dependent parkinsonism in welders shows an annual UPDRS3 increase of 0.24 points per mg manganese/m3-year of cumulative exposure (p<0.001); a worker with 20 years of welding would show nearly a 7-point increase.^{[16]Dose-Dependent Progression of Parkinsonism in Manganese-Exposed WeldersBrad A. Racette, Susan Searles Nielsen, Susan R. Criswell et al. · 2017Open reference 16 ↓}

The phenotype predominantly affects upper limb bradykinesia, rigidity, and impaired speech/facial expression.^{[16]Dose-Dependent Progression of Parkinsonism in Manganese-Exposed WeldersBrad A. Racette, Susan Searles Nielsen, Susan R. Criswell et al. · 2017Open reference 16 ↓} Workers whose baseline examination was within 5 years of first manganese exposure showed dramatically higher progression (4.45 vs 0.23 UPDRS3/year), suggesting an early vulnerability window.^{[16]Dose-Dependent Progression of Parkinsonism in Manganese-Exposed WeldersBrad A. Racette, Susan Searles Nielsen, Susan R. Criswell et al. · 2017Open reference 16 ↓}

FCAW in confined spaces showed a 6.7-fold higher progression rate than non-confined FCAW.^{[16]Dose-Dependent Progression of Parkinsonism in Manganese-Exposed WeldersBrad A. Racette, Susan Searles Nielsen, Susan R. Criswell et al. · 2017Open reference 16 ↓}

manganese accumulates preferentially in the globus pallidus and striatum of the basal ganglia, unlike most toxic metals that target cortical regions.^{[34]Common and Trace Metals in Alzheimer's and Parkinson's DiseasesDoroszkiewicz J, Farhan JA, Mroczko J et al. · 2023Open reference 34 ↓}

Mechanism involves oxidative stress in dopaminergic neurons through mitochondrial accumulation, electron transport chain disruption, and ROS generation via Fenton-like chemistry.^{[34]Common and Trace Metals in Alzheimer's and Parkinson's DiseasesDoroszkiewicz J, Farhan JA, Mroczko J et al. · 2023Open reference 34 ↓}

In the metal-driven PD framework, manganese acts alongside iron and nickel to reshape gut microbial communities, with downstream Neuroinflammation converging on dopaminergic neuron vulnerability.^{[35]Microbial Metallomics and Parkinson's Disease: A Unified Metal-Driven Framework Linking Ferroptosis, Dysbiosis, and alpha-Synuclein PathologyKaren Pendergrass · 2025Open reference 35 ↓}

Alzheimer's Disease#

manganese (Mn) impairs autophagy at low concentrations; Drp1 inhibition is protective against manganese-induced autophagic impairment.^{[36]Associations of Environmental Exposure to Arsenic, Manganese, Lead, and Cadmium with Alzheimer's Disease: A Review of Recent Evidence from Mechanistic StudiesGiasuddin Ahmed, Md. Shiblur Rahaman, Enrique Perez et al. · 2025Open reference 36 ↓} Acute manganese exposure increases cortical GLAST expression and seizure susceptibility in APP/PSEN1 mice.^{[36]Associations of Environmental Exposure to Arsenic, Manganese, Lead, and Cadmium with Alzheimer's Disease: A Review of Recent Evidence from Mechanistic StudiesGiasuddin Ahmed, Md. Shiblur Rahaman, Enrique Perez et al. · 2025Open reference 36 ↓}

manganese primarily affects the basal ganglia (parkinsonism) rather than cortical regions (AD), distinguishing its neurodegeneration pattern from lead or mercury.^{[37]Heavy Metals Exposure and Alzheimer's Disease and Related DementiasBakulski KM, Seo YA, Hickman RC et al. · 2020Open reference 37 ↓} manganese alterations in brain tissue of dementia patients connect to SOD2 cofactor function and mitochondrial antioxidant defense.^{[38]Scholefield et al. 2024 — Brain Metallomic Signatures Distinguish DLB from AD and PDDMelissa Scholefield, Stephanie J. Church, Jingshu Xu et al. · 2024Open reference 38 ↓}

Inflammatory Bowel Disease#

Plasma manganese (Mn) was significantly lower in ulcerative colitis patients (1.4 ug/L) compared to healthy controls (2.4 ug/L, p=0.041).^{[39]Clinical and inflammatory biomarkers of inflammatory bowel diseases are linked to plasma trace elements and toxic metals; new insights into an old conceptAmerikanou C, Karavoltsos S, Gioxari A et al. · 2022Open reference 39 ↓}

The ZIP8 A391T Crohn's disease risk variant reduces luminal manganese availability in the colon, reshaping the microbiome—with age-dependent microbiome shifts (R2 increasing from 3% at 2 months to 9% at 12 months) and spontaneous Metal-Driven Inflammation developing by 10 months.^{[17]ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and InflammationYang JC, Zhao M, Chernikova D et al. · 2024Open reference 17 ↓}

Lactobacillus depletion in ZIP8 mutant mice is consistent with the manganese-dependent antioxidant biology of lactic acid bacteria.^{[17]ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and InflammationYang JC, Zhao M, Chernikova D et al. · 2024Open reference 17 ↓}

Breast Cancer#

A meta-analysis of 36 case-control studies (n=4,151) found serum manganese (Mn) significantly lower in breast cancer patients (SMD: -2.95, 95% CI: -4.26 to -1.64, Asian studies).^{[40]Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-AnalysisLiu L, Chen J, Liu C et al. · 2022Open reference 40 ↓}

manganese depletion disrupts MnSOD antioxidant function, converging with the copper (Cu) elevation and zinc (Zn) depletion also observed in the same meta-analysis.^{[40]Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-AnalysisLiu L, Chen J, Liu C et al. · 2022Open reference 40 ↓}

PCOS and Reproductive Health#

Serum manganese (Mn) was significantly lower in both obese and non-obese PCOS patients compared to controls (0.086 vs 0.225 ug/dl), possibly reflecting impaired MnSOD antioxidant capacity.^{[41]A Comparative Study of Blood Levels of Manganese, Some Macroelements and Heavy Metals in Obese and Non-Obese Polycystic Ovary Syndrome PatientsSarah H. Mhaibes, Mohammed A. Taher, Ala H. Badr · 2017Open reference 41 ↓}

A more recent Slovenian case-control study (n=70) found no significant manganese differences, though this study prioritized copper (Cu) and molybdenum (Mo) findings.^{[42]Smovršnik 2025 — Association of Trace Elements with Polycystic Ovary Syndrome in Women — A Case-Control StudyTinkara Smovršnik, Bojana Pinter, Milena Horvat et al. · 2025Open reference 42 ↓}

Thyroid Function#

Elevated manganese (Mn) levels found in autoimmune hypothyroidism; manganese affects deiodinase (DIO) activity and T4 to T3 conversion.^{[43]Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases — A Literature ReviewBrylinski L, Kostelecka K, Wolinski F et al. · 2025Open reference 43 ↓} Higher blood manganese observed in thyroid cancer patients.^{[43]Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases — A Literature ReviewBrylinski L, Kostelecka K, Wolinski F et al. · 2025Open reference 43 ↓}

Cancer#

Serum manganese (Mn) decreased in prostate cancer patients (0.001 vs 0.0024 ug/ml, p<0.005), potentially impairing MnSOD-mediated mitochondrial antioxidant defense.^{[44]Serum Levels of Selenium, Zinc, Copper, Manganese, and Iron in Prostate Cancer PatientsSaleh A. K. Saleh, Heba M. Adly, Altaf A. Abdelkhaliq et al. · 2020Open reference 44 ↓}

manganese elevated 1.26-fold in lung cancer serum; aluminum (Al)/manganese ratios serve as potential LC biomarkers (AUC close to 1).^{[45]Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary DiseaseBelen Callejon-Leblic, Saida Sanchez Espirilla, Carolina Gotera-Rivera et al. · 2023Open reference 45 ↓} In COPD-to-LC transition, manganese showed dramatically altered profiles (0.41-fold decrease), suggesting progressive manganese dyshomeostasis.^{[45]Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary DiseaseBelen Callejon-Leblic, Saida Sanchez Espirilla, Carolina Gotera-Rivera et al. · 2023Open reference 45 ↓}

Renal Injury#

In a longitudinal study (n=384, 4 repeated measurements), urinary manganese (Mn) was associated with renal biomarkers including UACR (beta=2.60), though with complex dose-response relationships at high levels.^{[46]Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidenceYin G, Zhao S, Zhao M et al. · 2024Open reference 46 ↓}

Perinatal Exposure#

One longitudinal cohort found a positive association between 3rd trimester blood manganese (Mn) and continuous EPDS (depression) scores (beta=0.13, 95% CI: 0.04-0.21).^{[47]Exposure to environmental chemicals and perinatal psychopathologyJacobson MH, Ghassabian A, Gore AC et al. · 2022Open reference 47 ↓} manganese treatment (50-300 uM) induces cytochrome C release, caspase activation, and protein aggregation in dopaminergic neurons.^{[48]Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseasesChin-Chan M, Navarro-Yepes J, Quintanilla-Vega B · 2015Open reference 48 ↓}

A meta-analysis of prenatal metal exposure and ASD found no consistent association for manganese specifically, though other metals (cadmium) showed significant effects.^{[49]Dou 2024 — Exposure to Heavy Metals in Utero and Autism Spectrum Disorder at Age 3: A Meta-Analysis of Two Longitudinal CohortsJohn F. Dou, Rebecca J. Schmidt, Heather E. Volk et al. · 2024Open reference 49 ↓}

Cross-Condition Pattern: Mn Depletion#

A notable cross-condition pattern emerges from the evidence: manganese (Mn) depletion appears in breast cancer,^{[40]Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-AnalysisLiu L, Chen J, Liu C et al. · 2022Open reference 40 ↓} ulcerative colitis,^{[39]Clinical and inflammatory biomarkers of inflammatory bowel diseases are linked to plasma trace elements and toxic metals; new insights into an old conceptAmerikanou C, Karavoltsos S, Gioxari A et al. · 2022Open reference 39 ↓} PCOS,^{[41]A Comparative Study of Blood Levels of Manganese, Some Macroelements and Heavy Metals in Obese and Non-Obese Polycystic Ovary Syndrome PatientsSarah H. Mhaibes, Mohammed A. Taher, Ala H. Badr · 2017Open reference 41 ↓} and prostate cancer.^{[44]Serum Levels of Selenium, Zinc, Copper, Manganese, and Iron in Prostate Cancer PatientsSaleh A. K. Saleh, Heba M. Adly, Altaf A. Abdelkhaliq et al. · 2020Open reference 44 ↓}

In each case, manganese depletion is accompanied by impaired MnSOD function and oxidative stress—suggesting a shared vulnerability axis where reduced manganese-dependent antioxidant capacity contributes to disease progression.

Interactions with Other Metals#