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The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men
Jacob K Kresovich1,2, Catherine M Bulka3, Brian T Joyce4,3
1Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. kresovich@northwestern.edu.
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.
Insights
Higher dietary manganese intake, an essential nutrient, is linked to increased inflammatory biomarkers like interleukins (IL-1β, IL-6, IL-8). This study also found manganese affects DNA methylation in inflammation-related genes.
Area of Science:
- Nutritional Science
- Molecular Biology
- Immunology
Background:
- Manganese is an essential trace element vital for numerous physiological functions.
- Emerging evidence suggests a potential role for manganese in modulating inflammatory responses.
- Understanding the relationship between dietary manganese and inflammation is crucial for public health.
Purpose of the Study:
- To investigate the association between estimated dietary manganese intake and circulating inflammatory biomarkers.
- To explore the impact of dietary manganese on the DNA methylation patterns of genes involved in inflammation.
- To determine if manganese intake above nutritional adequacy influences inflammatory pathways.
Main Methods:
- Analysis of 1023 repeated measures of dietary manganese intake and inflammatory biomarkers from 633 participants in the Normative Aging Study.
- Utilized mixed-effect linear regression models to assess associations, adjusting for relevant covariates.
- Examined DNA methylation changes in genes related to inflammatory biomarker production, including NKAP and NKAPP1.
Main Results:
- Positive linear trends were observed between higher estimated dietary manganese intake and increased concentrations of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8).
- Specifically, the highest quartile of manganese intake showed significantly greater IL-1β, IL-6, and IL-8 levels compared to the lowest quartile.
- Higher manganese intake was associated with altered DNA methylation in inflammatory genes, including NKAP and NKAPP1, suggesting a molecular mechanism linking manganese to inflammation.
Conclusions:
- Estimated dietary manganese intake, particularly at levels slightly exceeding nutritional adequacy, is associated with elevated circulating inflammatory biomarkers.
- Dietary manganese influences the epigenetic regulation of genes involved in inflammatory processes.
- These findings highlight a potential link between manganese consumption and chronic inflammation, warranting further investigation.
