Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Family Medicine, General Hospital, Odan, Lagos, Nigeria.
J Nutr. 2021 May 11;151(5):1084-1101. 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.
饮食（和补充）二价离子的相互作用一直是人类营养研究中的一个长期问题。制定最佳的钙和铁补充建议需要详细了解以下方面的潜在权衡：1）同时摄入对铁吸收和血液学指标的临床影响；2）分开摄入对铁和/或钙补充剂的依从性的潜在负面影响。人体临床研究已经研究了钙摄入量对铁状态的影响，但没有荟萃分析或最近的综述总结这些发现。
综合评估同行评议的、人体的、随机的、交叉对照研究，以确定钙摄入量对铁指标的影响，不考虑年龄、性别或任何其他限制。
通过对最高日钙摄入量与最低日钙摄入量进行汇总分析，得出总铁、血红素铁和非血红素铁吸收率（%）和血清铁蛋白（μg/L）的加权均数差异。
钙摄入量对短期铁吸收研究有统计学意义，但影响幅度较小[加权均数差异（WMD）=-5.57%；95%CI：-7.09 至-4.04]。钙对铁状态的影响是混合的。钙摄入量与血清铁蛋白浓度呈负相关，这种相关性具有统计学意义（P 值=0.0004）。但血红蛋白浓度没有降低（WMD=1.22g/L；95%CI：0.37-2.07）。
由于设计的异质性、铁蛋白作为铁生物标志物的局限性以及缺乏孕妇摄入量研究，现有的研究不足以做出高可信度的推荐。在自由生活的个体中，分开开处产前钙和铁补充剂不太可能影响贫血负担。需要进行比较分别开处和同时开处补充剂效果的有效性试验，以功能终点作为主要结局，以对每种补充剂的依从性作为中间结局。
