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The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men

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Abstract

Manganese is an essential nutrient that may play a role in the production of inflammatory biomarkers. We examined associations between estimated dietary manganese intake from food/beverages and supplements with circulating biomarkers of inflammation. We further explored whether estimated dietary manganese intake affects DNA methylation of selected genes involved in the production of these biomarkers. We analyzed 1023 repeated measures of estimated dietary manganese intakes and circulating blood inflammatory biomarkers from 633 participants in the Normative Aging Study. Using mixed-effect linear regression models adjusted for covariates, we observed positive linear trends between estimated dietary manganese intakes and three circulating interleukin proteins. Relative to the lowest quartile of estimated intake, concentrations of IL-1β were 46% greater (95% CI − 5, 126), IL-6 52% greater (95% CI − 9, 156). and IL-8 32% greater (95% CI 2, 71) in the highest quartiles of estimated intake. Estimated dietary manganese intake was additionally associated with changes in DNA methylation of inflammatory biomarker-producing genes. Higher estimated intake was associated with higher methylation of NF-κβ member activator NKAP (Q4 vs Q1: β = 3.32, 95% CI − 0.6, 7.3). When stratified by regulatory function, higher manganese intake was associated with higher gene body methylation of NF-κβ member activators NKAP (Q4 vs Q1: β = 10.10, 95% CI − 0.8, 21) and NKAPP1 (Q4 vs Q1: β = 8.14, 95% CI 1.1, 15). While needed at trace amounts for various physiologic functions, our results suggest estimated dietary intakes of manganese at levels slightly above nutritional adequacy contribute to inflammatory biomarker production.

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Abbreviations

BMI:

Body mass index

CIs:

Confidence intervals

CRP:

C-reactive protein

FDR:

False discovery rate

FFQ:

Food Frequency Questionnaire

ICAM:

Intercellular adhesion molecule 1

IL:

Interleukin

Mn:

Manganese

NAS:

Normative aging study

NFKB1:

Nuclear factor kappa B subunit 1

NFKB2:

Nuclear factor kappa B subunit 2

RELA:

Nuclear factor kappa B P65 subunit

NF-κβ:

Nuclear factor kappa-light-chain-enhancer of Active B Cells

NFKBIA:

NF-κβ inhibitor alpha

NFKBIB:

NF-κβ inhibitor beta

NKRF:

NF-κβ Repressing factor

NKIRAS1:

NF-κβ inhibitor interacting Ras-Like 1

NKIRAS2:

NF-κβ inhibitor interacting Ras Like 2

NKAP:

NF-κβ activating protein

NKAPL:

NF-κβ activating protein like

NKAPP1:

NF-κβ activating protein pseudogene 1

REL:

Proto-oncogene c-REL

RELB:

RELB proto-oncogene NF-κβ subunit

UL:

Tolerable upper intake level

TNF-α:

Tumor necrosis factor alpha

TNFR:

Tumor necrosis factor receptor, superfamily member 1B

VCAM-1:

Vascular cell adhesion protein 1

VEGF:

Vascular endothelial growth factor

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Funding

The Epidemiology Research and Information Center of US Department of Veterans Affairs (NIEHS R01-ES015172) support the Normative Aging Study. L. Hou received additional support from the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund. A. Baccarelli and J. Schwartz received additional support from the National Institute of Environmental Health Sciences (NIEHS R01-ES021733, NIEHS R01-ES015172, and NIEHS P30-ES00002). J. Kresovich received additional support from the National Cancer Institute Cancer Education and Career Development Program (NIH R25 CA057699).

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Contributions

JKK, EAH, and LH designed the study. PSV, JS, and AAB supervised study operations. JKK performed the statistical analysis. JKK and CMB drafted the manuscript. BTJ, AAB, EAH, and LH provided critical revisions to the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jacob K. Kresovich.

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The authors declare that they have no conflicts of interest.

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Supplemental Figure 1

Flow diagram of participant inclusion. (PNG 28 kb)

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Kresovich, J.K., Bulka, C.M., Joyce, B.T. et al. The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men. Biol Trace Elem Res 183, 49–57 (2018). https://doi.org/10.1007/s12011-017-1127-7

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  • DOI: https://doi.org/10.1007/s12011-017-1127-7

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