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PurposeWe aimed to assess the long-term association of total, heme, non-heme, and supplemental iron intake and risk of type 2 diabetes (T2D).MethodsPubMed, 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.ResultsEleven 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).ConclusionsIn 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 numberThe protocol of this systematic review was registered at PROSPERO (registration number: CRD42021226835).

Duodenal biopsies are considered a suitable source of enterocytes for studies of dietary iron absorption. However, the expression level of molecules involved in iron absorption may vary along the length of duodenum. We aimed to determine whether the expression of molecules involved in the absorption of heme and non‐heme iron differs depending on the location in the duodenum. Analysis was performed with samples of duodenal biopsies from 10 individuals with normal iron metabolism. Samples were collected at the following locations: (a) immediately post‐bulbar, (b) 1–2 cm below the papilla of Vater and (c) in the distal duodenum. The gene expression was analyzed at the mRNA and protein level using real‐time PCR and Western blot analysis. At the mRNA level, significantly different expression of HCP1, DMT1, ferroportin and Zip8 was found at individual positions of duodenum. Position‐dependent expression of other molecules, especially of FLVCR1, HMOX1 and HMOX2 was also detected but with no statistical significances. At the protein level, we observed statistically significantly decreasing expression of transporters HCP1, FLVCR1, DMT1, ferroportin, Zip14 and Zip8 with advancing positions of duodenum. Our results are consistent with a gradient of diminishing iron absorption along the duodenum for both heme and non‐heme iron.

Adequate dietary iron (Fe) intake is crucial for preventing Fe-deficient anemia, a recognized global public health concern which is important in Armenia. This study aimed to analyze the intake of Fe, both heme (from animal tissues) and non-heme (more prevalent, but less efficiently absorbed), as well as the Fe dietary sources, among adults in a representative national sample in Armenia. The study was conducted on 1400 individuals aged 18–80 and above, who were enrolled from all regions of Armenia. The Fe intake was assessed through a 24 h dietary recall survey, while Fe occurrence was determined through atomic absorption spectrophotometry (AAS). The results showed a high proportion of adults with a Fe intake lower than the average requirements set by EFSA (65%, 80% and 85% of males, total females and females at fertile age, respectively). Main Fe sources were bread, fruits and vegetables; heme Fe accounted only for <5% of total Fe intake. Compared to males, females had a lower intake of all forms of Fe (p < 0.05). Significant differences were observed in the intake of different forms of Fe between regions (p < 0.05), while the age-group 36–55 years had higher intakes of total Fe. Our data call for comprehensive nutritional security strategies in order to reduce iron deficiency in Armenia, that represents a public health concern.

The final stage of Fe deficiency is Fe deficiency anaemia, with repercussions for human health, especially in children under 5 years of age. Studies conducted in Brazilian public daycare centres show high prevalence of anaemia. The present study aims to evaluate the availability of Fe in the meals of the Municipal Centers of Early Childhood Education in Maceió. The experimental design comprises selection of algorithms, menu evaluation, calculation of the estimates, comparison between the estimates obtained and the recommendations, and analysis of correlation between meal constituents, and of the concordance between the absorbable Fe estimates. Four algorithms were selected and a monthly menu consisting of 22 d. The correlation analysis showed a moderate positive correlation to animal tissue (AT) v. non-heme iron (r = 0·42; P = 0·04), and negative to AT v. Ca (r = −0·54; P = 0·09) and Ca v. phytates (r = −0·46, P = 0·03). Estimates of absorbable Fe ranged from 0·23 to 0·44 mg/d. The amount of Fe available, unlike the total amount of Fe offered, does not meet the nutritional recommendations on most school days. The Bland–Altman analysis indicated that the Monsen and Balinfty and Rickard et al. showed greater agreement. The results confirm the need to adopt strategies to increase the availability of Fe in school meals.

Classic characteristics are poor predictors of the risk of thromboembolism. Thus, better markers for the carotid atheroma plaque formation and symptom causing are needed. Our objective was to study by microarray analysis gene expression of genes involved in homeostasis of iron and heme in carotid atheroma plaque from the same patient. mRNA gene expression was measured by an Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 68 specimens of endarteriectomy from 34 patients. Two genes involved in iron-heme homeostasis, CD163 and heme oxygenase (HO-1), were analysed in 34 plaques. CD163 (2.18, p = 1.45E−08) and HO-1 (fold-change 2.67, p = 2.07E−09) mRNAs were induced. We suggest that atheroma plaques show a more pronounced induction of CD163 and HO-1. Although further evidence is needed, our results support previous data. To our knowledge, this is the first report comparing gene expression between intact arterial tissue and carotid plaque using microarray analysis.

Iron intake and heme/non-heme iron proportions are crucial for iron deficiency anemia prevention. Women of childbearing age are indicated by World Health Organization as the primary target group, but maintaining iron balance is particularly challenging for adolescents. The aim of the presented study was to analyze heme and non-heme iron intake and dietary sources in adolescent menstruating females in a national Polish sample. The study was conducted in a representative sample of adolescents (aged 15–20) who were recruited from all regions of Poland based on secondary school sampling (random quota sampling), with 1385 female adolescents being included in the sample. The iron intake was assessed using the previously validated IRONIC-FFQ (IRON Intake Calculation–Food Frequency Questionnaire). The intakes of iron, heme iron, non-heme iron, and iron from food product groups were assessed and compared with those of male adolescents (n = 1025) who were recruited from the same schools, as well as between sub-groups stratified by age, body mass index, anemia history, following vegetarian diet, applying iron supplementation and school type. Compared with male individuals, females were characterized by a lower intake of all forms of iron. It was stated that non-heme iron intake was highest in younger ones, overweight ones, vegetarian ones, and comprehensive school students. Female adolescents with anemia history were characterized by similar iron intake as others. For the target group, there is inadequate nutritional education and a necessity to broaden the knowledge about specific sources of iron.

PurposeWe assessed the association of total meat, processed, and unprocessed red meat and iron intake with the risk of developing gestational diabetes mellitus (GDM) in pregnant women.MethodsWe conducted a prospective study among 3298 disease-free Spanish women participants of the SUN cohort who reported at least one pregnancy between December 1999 and March 2012. Meat consumption and iron intake were assessed at baseline through a validated, 136-item semi-quantitative, food frequency questionnaire. We categorized total, red, and processed meat consumption and iron intake into quartiles. Logistic regression models were used to adjust for potential confounders.ResultsWe identified 172 incident cases of GDM. In the fully adjusted analysis, total meat consumption was significantly associated with a higher risk of GDM [OR = 1.67 (95% CI 1.06–2.63, p-trend 0.010)] for the highest versus the lowest quartile of consumption. The observed associations were particularly strong for red meat consumption [OR = 2.37 (95% CI 1.49–3.78, p-trend < 0.001)] and processed meat consumption [OR = 2.01 (95% CI 1.26–3.21, p-trend 0.003)]. Heme iron intake was also directly associated with GDM [OR = 2.21 (95% CI 1.37–3.58, p-trend 0.003)], although the association was attenuated and lost its statistical significance when we adjusted for red meat consumption [OR = 1.57 (95% CI 0.91–2.70, p-trend 0.213)]. No association was observed for non-heme and total iron intake, including supplements.ConclusionsOur overall findings suggest that higher pre-pregnancy consumption of total meat, especially red and processed meat, and heme iron intake, are significantly associated with an increased GDM risk in a Mediterranean cohort of university graduates.

The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women. Case-control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk. A case-control study of women at three major hospitals in Guangzhou, China. From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited. In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer. Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

Iron is essential for numerous physiological processes, including oxygen transport, energy metabolism, and immune function. This study evaluated the efficacy and safety of three iron formulations combining heme and non-heme iron, comparing them with existing market products and the original form of iron. The formulations tested were GlobiFer® Forte, a combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter referred to as nutraceutical product 1); GlobiFer®, a combination of heme and non-heme iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product 2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier model, all three formulations significantly increased tight junction protein expression and TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed that all three iron formulations had higher absorption rates than controls. Nutraceutical product 1 showed the highest absorption, associated with increased expression of the iron transporters such as the primary non-heme iron transporter, DMT1, and the leading apical heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found to be the most effective, based on percentage. Overall, combining heme and non-heme iron improved intestinal absorption and supported iron metabolism, with Nutraceutical Product 1 proving the most promising in terms of efficacy and safety. These results support the development of optimised dual-source iron supplements to improve bioavailability and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in clinical use.

Phenylobacterium immobile strain E is a soil bacterium with a striking metabolism relying on xenobiotics, such as the herbicide pyrazon, as sole carbon source instead of more bioavailable molecules. Pyrazon is a heterocyclic aromatic compound of environmental concern and its biodegradation pathway has only been reported in P. immobile. The multicomponent pyrazon oxygenase (PPO), a Rieske non-heme iron oxygenase, incorporates molecular oxygen at the 2,3 position of the pyrazon phenyl moiety as first step of degradation, generating a cis-dihydrodiendiol. The aim of this work was to identify the genes encoding for each one of the PPO components and enable their functional assembly in Escherichia coli. P. immobile strain E genome sequencing revealed genes encoding for RO components, such as ferredoxin-, reductase-, α- and β-subunits of an oxygenase. Though, P. immobile E displays three prominent differences with respect to the ROs currently characterized: (1) an operon-like organization for PPO is absent, (2) all the elements are randomly scattered in its DNA, (3) not only one, but 19 different α-subunits are encoded in its genome. Herein, we report the identification of the PPO components involved in pyrazon cis-dihydroxylation in P. immobile, its appropriate assembly, and its functional reconstitution in E. coli. Our results contributes with the essential missing pieces to complete the overall elucidation of the PPO from P. immobile.Key points• Phenylobacterium immobile E DSM 1986 harbors the only described pyrazon oxygenase (PPO).• We elucidated the genes encoding for all PPO components.• Heterologous expression of PPO enabled pyrazon dihydroxylation in E. coli JW5510.