Hematology, Iron & Nutrient Panel - References

Hematology, Iron & Nutrient Panel — Literature Dossier

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Landmark Peer-Reviewed Studies

1. Harris et al. (2021) — Blood Omega-3 Fatty Acids and All-Cause Mortality (FORCE Consortium)

• Citation: Harris, W. S., Tintle, N. L., Imamura, F., Qian, F., Korat, A. V. A., Marklund, M., … & Fatty Acids and Outcomes Research Consortium (FORCE). (2021). Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nature Communications, 12(1), 2329.
• Identifiers: DOI: 10.1038/s41467-021-22370-2 (DOI · SciDB · Scholar) | PMID: 33888689 (PubMed · Europe PMC) | PMCID: PMC8062567 (PMC Full Text)
• Study Design & Cohort: Harmonized individual-level pooled analysis of 17 prospective cohorts ($N=42,466$ individuals followed for median 16 years; $15,720$ deaths).
• Quantitative Findings & Diagnostic Thresholds:
  • Comparing Top Quintile (corresponding to Omega-3 Index $\ge 7.6–8.0\%$) vs. Bottom Quintile ($<4.0\%$):
    • All-cause mortality: $\text{HR }0.83$ ($95\%\text{ CI }0.79–0.88$, $p<0.00001$) (17% lower risk across all cohorts; up to 34% in Framingham erythrocyte subset).
    • Cardiovascular mortality: $\text{HR }0.79$ ($95\%\text{ CI }0.73–0.86$).
    • Cancer mortality: $\text{HR }0.87$ ($95\%\text{ CI }0.80–0.95$).

2. Patel et al. (2009) — Red Blood Cell Distribution Width (RDW) and Mortality Risk

• Citation: Patel, K. V., Ferrucci, L., Ershler, W. B., Longo, D. L., & Guralnik, J. M. (2009). Red blood cell distribution width and the risk of death in middle-aged and older adults. Archives of Internal Medicine, 169(5), 515–523.
• Identifiers: DOI: 10.1001/archinternmed.2009.11 (DOI · SciDB · Scholar) | PMID: 19273783 (PubMed · Europe PMC) | PMCID: PMC2762781 (PMC Full Text)
• Study Design & Cohort: Prospective nationally representative cohort from NHANES III ($N=8,175$ adults aged $\ge 45$ followed for up to 12 years).
• Quantitative Findings & Diagnostic Thresholds:
  • Every 1% increment in RDW conferred an adjusted all-cause mortality $\text{HR of }1.22$ ($95\%\text{ CI }1.15–1.29$, $p<0.001$).
  • Compared to Quintile 1 ($\text{RDW}<12.6\%$), Quintile 5 ($\text{RDW}>14.0\%$) had a multivariable-adjusted all-cause mortality $\text{HR of }2.00$ ($95\%\text{ CI }1.60–2.50$), even when restricted to non-anemic individuals with normal iron, folate, and B12.

3. Stoffel et al. (2017) — Alternate-Day vs. Consecutive-Day Oral Iron Absorption Kinetics

• Citation: Stoffel, N. U., Cercamondi, C. I., Brittenham, G., Zeder, C., Geurts-Moespot, A. J., Swinkels, D. W., … & Zimmermann, M. B. (2017). Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. The Lancet Haematology, 4(11), e524–e533.
• Identifiers: DOI: 10.1016/S2352-3026(17)30182-5 (DOI · SciDB · Scholar) | PMID: 29032957 (PubMed · Europe PMC)
• Study Design & Cohort: Two randomized controlled trials using stable iron isotopes (${}^{54}\text{Fe}{,}^{57}\text{Fe}{,}^{58}\text{Fe}$) in iron-depleted women ($\text{serum ferritin }\le 25\mu \text{g/L}$, $N=60$).
• Quantitative Findings & Diagnostic Thresholds:
  • Alternate-day dosing resulted in 34% higher fractional iron absorption ($21.8\%$ vs. $16.3\%$, $p=0.0013$) and significantly higher cumulative iron incorporation than consecutive-day dosing, because oral iron elevates serum hepcidin for 24 hours ($p=0.0031$) before returning to baseline at 48 hours.

4. Garland et al. (2014) — Meta-Analysis of Serum 25-Hydroxyvitamin D and All-Cause Mortality

• Citation: Garland, C. F., Kim, J. J., Mohr, S. B., Gorham, E. D., Grant, W. B., Giovannucci, E. L., … &anel, L. (2014). Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. American Journal of Public Health, 104(8), e43–e50.
• Identifiers: DOI: 10.2105/AJPH.2014.302034 (DOI · SciDB · Scholar) | PMID: 24922127 (PubMed · Europe PMC) | PMCID: PMC4103214 (PMC Full Text)
• Study Design & Cohort: Pooled meta-analysis of 32 prospective cohort studies ($N=566,583$ participants across 14 countries with mean 9.0-year follow-up).
• Quantitative Findings & Diagnostic Thresholds:
  • Compared to optimal 25-OH Vitamin D ($>40–50\text{ ng/mL}$), individuals with levels $<10\text{ ng/mL}$ had an adjusted all-cause mortality $\text{HR of }1.90$ ($95\%\text{ CI }1.66–2.17$), and the mortality hazard curve flattened optimally above $36–50\text{ ng/mL}$ ($90–125\text{ nmol/L}$).