Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was studied?
This original study examined how whole-blood concentrations of selenium (Se), manganese (Mn), and chromium (Cr) relate to erythrocyte health indices, red blood cell (RBC) count, hemoglobin, and hematocrit using nationally representative NHANES 2015–2016 and 2017–2020 data. The analysis further distinguished effects of deficiency versus elevation via subpopulation exclusions and probed mechanisms by relating Mn to RBC volume, RBC hemoglobin, red cell distribution width, serum iron, transferrin saturation, transferrin receptor, and recent anemia treatment. Findings emphasized that chromium showed consistent inverse associations with all erythrocyte metrics; selenium showed small but consistent positive associations; and manganese displayed a mixed pattern, higher RBC counts but lower hemoglobin and hematocrit when Mn was clinically elevated, suggesting a microcytic profile. These data have immediate relevance for HTMC heavy metal certification by clarifying threshold-sensitive risks from Cr and Mn and potential protective roles of Se.
Who was studied?
The study included 23,844 US adults interviewed in NHANES, with 14,088 providing laboratory measures for hematology and trace minerals. Chromium was measured only in participants aged 40 years and older, limiting generalizability for younger adults. Weighted demographics approximated the US population, with an even sex distribution, a mean age of 48 years, and the majority being non-Hispanic white; most participants were non-smokers and had at least a high school education. Clinically, nearly 90% had elevated Se within the authors’ reference range, Mn was mostly normal with a minority elevated, and no participants had clinically elevated Cr; most were Cr-deficient by the study’s laboratory definition. These distributions enabled analyses of normal-range variability and Mn elevations, but constrained inference on high Cr exposures. The population breadth enhances the applicability of results to consumer-facing certification programs like HTMC heavy metal certification by reflecting typical US dietary exposures.
Most important findings
| Critical point | Details |
|---|---|
| Higher whole-blood Cr was inversely associated with RBC count, hemoglobin, and hematocrit in unadjusted and adjusted models; OE models confirmed monotonic negative partial dependence up to ~4 µg/L; no participants had clinically elevated Cr, so harms were detected within low-normal range. | Higher whole-blood Cr was inversely associated with RBC count, hemoglobin, and hematocrit in unadjusted and adjusted models; OE models confirmed monotonic negative partial dependence up to ~4 µg/L; no participants had clinically elevated Cr, so harms were detected within–low-normal range. |
| Selenium consistently protective | Se showed small positive associations with RBC count, hemoglobin, and hematocrit; effects persisted after excluding Se-deficient or elevated subjects, suggesting benefit across typical exposures, plausibly via selenoprotein antioxidant function. |
| Manganese raises RBC count but may drive microcytosis when elevated | Mn positively associated with RBC count overall, yet in models including Mn-elevated subjects, Mn was inversely associated with hemoglobin and hematocrit; excluding elevated Mn flipped these to positive, indicating threshold behavior. |
| Evidence consistent with impaired iron handling under high Mn | Elevated Mn associated with lower RBC volume, lower RBC hemoglobin, higher RDW, lower serum iron, lower transferrin saturation (controlling for Fe), and higher odds of recent anemia treatment—features consistent with microcytic anemia possibly via DMT1 competition. |
| Confounding and robustness | Associations remained after adjusting for demographics, socioeconomic factors, and smoking; robust standard errors used; OE models (test R² up to ~0.45) corroborated nonlinearity and directionality. |
| Key limitations for regulation | Cr measured only in ≥40-year-olds; no clinically elevated Cr; few Se/Mn deficiencies; some values below LOD imputed; OE unweighted—interpret population effects cautiously. |
Key implications
For HTMC heavy metal certification, primary regulatory impacts include recognizing chromium as a risk even within normal ranges and manganese as a risk at elevated levels that can induce microcytic patterns; certification requirements should set conservative Cr limits and flag Mn elevations while acknowledging selenium’s protective associations without endorsing excess. Industry applications span ingredient screening and supplier QA for grains, vegetables, and supplements. Research gaps include age-specific chromium effects and causal Mn thresholds. Practical recommendations prioritize batch-level Cr testing, Mn caps aligned to anemia risk, and context-aware Se evaluation.
Citation
Costa AM, Sias RJ, Fuchs SC. Effect of Whole Blood Dietary Mineral Concentrations on Erythrocytes: Selenium, Manganese, and Chromium: NHANES Data. Nutrients. 2024;16(21):3653. doi:10.3390/nu16213653
