Dietary iron intake and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective cohort studies.

PURPOSE: We aimed to assess the long-term association of total, heme, non-heme, and supplemental iron intake and risk of type 2 diabetes (T2D). METHODS: PubMed, Scopus, and Web of Science were searched to October 2021. Two researchers extracted data in duplicate and rated the certainty in the estimates using the GRADE approach. Random-effects models were applied to estimate the relative risks (RRs) and 95% CIs. Dose-response associations were modeled by a one-stage weighted mixed-effects meta-analysis. RESULTS: Eleven prospective cohort studies 323,788 participants and 28,837 incident cases of T2D were included. High versus low category meta-analysis indicated that higher heme iron intake was associated with a 20% higher risk of T2D (95% CI 1.07, 1.35; I2 = 77%, n = 11; GRADE = moderate). Dose-response analysis indicated a positive monotonic association, wherein each 1 mg/day increment in heme iron intake was related to a 16% higher risk (95% CI 1.03, 1.30). No significant relationship was detected between dietary intakes of total, non-heme, and supplemental iron and risk of T2D (GRADE = very low). CONCLUSIONS: In summary, higher heme iron intake was associated with a higher risk of T2D. Our results are in line with existing evidence indicating that adopting a Western-style dietary pattern, rich in dietary sources of heme iron, was associated with a higher risk of T2D. REGISTRY AND REGISTRY NUMBER: The protocol of this systematic review was registered at PROSPERO (registration number: CRD42021226835).

The Chemical Forms of Iron in Commercial Prenatal Supplements Are Not Always the Same as Those Tested in Clinical Trials.

In the US, 70% of pregnant women use an iron-containing prenatal supplement product; however, only 2.6% of pregnant women have iron-deficiency anemia and 16.3% are iron deficient. Yet, published data on the amounts and chemical forms of iron used in formulating these products are not available, although they are known to affect bioavailability. This information is especially important in comparing commercially available products with those that were tested in clinical trials. Our examination of nonprescription and prescription iron-containing prenatal supplement products in NIH's Dietary Supplement Label Database (DSLD) and DailyMed found the labeled amount of elemental iron ranged between 9 and 60 mg/serving in 148 nonprescription supplements and between 4.5 and 106 mg/serving in 101 prescription supplements. Ferrous fumarate was the preferred chemical form used in these products. In contrast, ferrous sulfate was the preferred chemical form of iron reported in the clinical trials summarized in a 2015 Cochrane Systematic review assessing the effects of daily oral iron supplements for pregnant women. Ferrous sulfate was not found on any prenatal supplement product label in the DSLD or DailyMed. The chemical forms of products on the market and those tested in clinical trials are dissimilar, and we believe this may have clinical implications. The findings raise several questions. Do outcomes in clinical trials correlate with the benefits and risks that might adhere to iron supplements with different iron formulations? Should the differences in chemical forms, their bioavailability, and safety profiles, be considered in greater depth when evaluating the effect of the various formulations on maternal iron nutriture? Should new clinical trials for pregnant and lactating women in the US use a form of iron not found in prenatal supplements sold in the US or should a more common form be used?

Reduction of costs for anemia-management drugs associated with the use of ferric citrate.

BACKGROUND: Ferric citrate is a novel phosphate binder which has the potential to reduce usage of erythropoietin-stimulating agents (ESAs) and intravenous (IV) iron used for anemia management during hemodialysis (HD) among patients with end-stage renal disease (ESRD). Currently, the potential health care cost savings on a national scale due to the use of ferric citrate in ESRD are undetermined. METHODS: Per-patient-per-year costs of ESAs (Epogen(®) and Aranesp(®) [Amgen Inc., CA, USA]) and IV iron (Venofer(®) [American Regent, Inc., NY, USA] and Ferrlecit(®) [Sanofi US, Bridgewater, NJ, USA]) were based on RED BOOK™ (Truven Health Analytics New York, NY, USA) costs combined with the Centers for Medicare and Medicaid Services (CMS) base rate and actual usage in 2011 for the four drugs. The annual number of outpatients undergoing HD in the US was based on frequencies reported by the USRDS (United States Renal Data System). Monte Carlo uncertainty analysis was performed to determine total annual costs and cost reduction based on ferric citrate usage. RESULTS: Total annual cost of ESAs and IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming CMS base rate value was 5.127 (3.664-6.260) billion USD. For actual utilization in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780-4.930) billion USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%, then total cost would be reduced by 21.2% to 4.038 (2.868-4.914) billion USD for the CMS base rate, and by 21.8% to 3.111 (2.148-3.845) billion USD, based on 2011 actual utilization. CONCLUSION: It is likely that US health care costs for anemia-management drugs associated with ESRD among HD patients can be reduced by using ferric citrate as a phosphate binder.