Background: Selenium (Se), Manganese (Mn), and Chromium (Cr) are dietary minerals ingested from specific grains, vegetables, and animal meats. Prior research showed that these minerals affect animal erythrocyte health but have unknown effects on human red blood cells (RBCs) and hematology. This study evaluated the effects of these dietary minerals on RBC count, hematocrit, and hemoglobin. Methods: We conducted a cross-sectional analysis of 23,844 American participants from the 2015–2016 and 2017–2020 National Health and Nutrition Examination Survey. We evaluated sex, age, ethnicity, education, income, and smoking status as covariates. Linear regression analyses were conducted to evaluate the effect of Cr, Se, and Mn on RBC count, hematocrit, and hemoglobin levels. We employed subpopulation-exclusion regressions further to explore the distinct effects of mineral elevation and deficiency. Additional analyses were performed to examine the relationship between Mn and RBC hemoglobin, RBC distribution width, transferrin receptor concentrations, transferrin saturation, and serum iron levels to support the interpretation of our findings. Optimizable ensemble machine learning models were used to corroborate regression results. Results: Adjusting for covariates, Cr was inversely associated with RBC count (Exp(b) = 0.954), hemoglobin (Exp(b) = 0.868), and hematocrit (Exp(b) = 0.668). Conversely, Se was positively associated with RBC count (Exp(b) = 1.003), hemoglobin (Exp(b) = 1.012), and hematocrit (Exp(b) = 1.032). Mn was positively associated with RBC count (Exp(b) = 1.020) but inversely associated with hemoglobin (Exp(b) = 0.945) and hematocrit (Exp(b) = 0.891). Conclusions: Cr was harmful to RBC health in all subpopulations, whereas Se was protective. Mn appears to contribute to the development of microcytic anemia, but only in subjects with clinically elevated Mn levels. Thus, excessive consumption of foods and supplements rich in Cr and Mn may harm human erythrocyte health and hematology.
