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

Background: 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. Objectives: 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. Methods: Weighted mean differences for total, heme, and nonheme iron absorption (%) and serum ferritin (mu g/L) were obtained from pooled analysis of the highest daily calcium intake compared to the lowest daily calcium intake. Results: 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). Conclusions: 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.

Automated summary

The intake of calcium has a negative effect on iron absorption, but its impact on iron status is mixed. Further research is needed to establish recommendations for pregnant women on iron and calcium supplementation, as current studies are insufficient.