Calcium Intake and Iron Status in Human Studies: A Systematic Review and Dose-Response Meta-Analysis of Randomized Trials and Crossover Studies

• Published in: The Journal of nutrition 2021-05, Vol.151 (5), p.1084-1101
• Main Authors: Abioye, Ajibola Ibraheem, Okuneye, Taofik A, Odesanya, Abdul-Majeed O, Adisa, Olufunmilola, Abioye, Asanat I, Soipe, Ayorinde I, Ismail, Kamal A, Yang, JaeWon F, Fasehun, Luther-King, Omotayo, Moshood O
• Format: Article
• Language: English
• Subjects: Absorption; Anemia; Biomarkers; Calcium; Calcium - administration & dosage; Calcium - metabolism; calcium and iron interaction; calcium and preeclampsia; Clinical trials; Cross-Over Studies; Diet; Dietary supplements; Dosage; Ferritin; Ferritins - blood; Hematology; Heme; Hemoglobin; Heterogeneity; Human nutrition; Humans; Ingestion; Iron; Iron - administration & dosage; Iron - metabolism; maternal anemia; maternal nutrition; Meta-analysis; Nutrition; Nutrition research; Prenatal experience; Reviews; Statistical analysis; Systematic review
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxaa437

The interaction between dietary (and supplementary) divalent ions has been a long-standing issue in human nutrition research. Developing an optimal calcium and iron supplementation recommendation requires detailed knowledge of the potential trade-offs between: 1) the clinical effects of concurrent intake on iron absorption and hematological indices; and 2) the potentially negative effects of separated ingestion on adherence to iron and/or calcium supplements. Human clinical studies have examined the effects of calcium intake on iron status, but there are no meta-analyses or recent reviews summarizing the findings. To synthesize peer-reviewed, human, randomized, and cross-over studies on effects of calcium consumption on iron indices without age, gender, or any other restrictions. Weighted mean differences for total, heme, and nonheme iron absorption (%) and serum ferritin (μg/L) were obtained from pooled analysis of the highest daily calcium intake compared to the lowest daily calcium intake. The negative effect of calcium intake was statistically significant in short-term iron absorption studies, but the effect magnitude was low [weighted mean difference (WMD) = −5.57%; 95% CI: −7.09 to −4.04]. The effect of calcium on the iron status was mixed. The inverse dose-response association of calcium intake with the serum ferritin concentration was significant (P value = 0.0004). There was, however, no reduction in the hemoglobin concentration (WMD = 1.22g/L; 95% CI: 0.37–2.07). The existing body of studies is insufficient to make recommendations with high confidence due to heterogeneity in designs, limitations of ferritin as an iron biomarker, and a lack of intake studies in pregnant women. Prescribing separation of prenatal calcium and iron supplements in free-living individuals is unlikely to affect the anemia burden. There is a need for effectiveness trials comparing the effects of prescribing separated intake to concurrent intake, with functional endpoints as primary outcomes and adherence to each supplement as intermediate outcomes.