Heme Iron Intake Research Articles

Associations Between Iron Homeostasis and Pancreatic Enzymes After an Attack of Pancreatitis.

Dysregulation of iron homeostasis and exocrine pancreatic dysfunction are linked but remain undefined in individuals with a history of pancreatitis. The objective is to investigate the relationship between iron homeostasis and pancreatic enzymes in individuals after a pancreatitis attack. This was a cross-sectional study of adults with a history of pancreatitis. Markers of iron metabolism (hepcidin and ferritin) and pancreatic enzymes (pancreatic amylase, pancreatic lipase, and chymotrypsin) were measured in venous blood. Habitual dietary iron intake data (total, heme, and nonheme iron) were collected. Multivariable linear regression analyses were performed while considering covariates. One hundred and one participants were studied at a median of 18 months after their last pancreatitis attack. Hepcidin was significantly associated with pancreatic amylase (β coefficient, -6.68; 95% confidence interval, -12.88 to -0.48; P = 0.035) and heme iron intake (β coefficient, 0.34; 95% confidence interval, 0.08 to 0.60; P = 0.012) in the adjusted model. Hepcidin was not significantly associated with pancreatic lipase or chymotrypsin. Ferritin was not significantly associated with pancreatic enzymes and dietary iron intake. An iron homeostasis-exocrine pancreas crosstalk exists in individuals after an attack of pancreatitis. The role of iron homeostasis in pancreatitis warrants high-quality purposely-designed studies.

Dietary Iron Intake and New-Onset Hypertension: A Nationwide Cohort Study from China.

The relationship of dietary iron intake with the risk of hypertension remains uncertain. We aimed to investigate the prospective association between dietary iron intake and new-onset hypertension among Chinese adults. A nationwide cohort study. Using data from seven rounds of the China Health and Nutrition Survey (CHNS) from 1997 to 2015. A total of 12,245 participants without hypertension at baseline were included in this study. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household weighing inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by physician or currently under antihypertensive treatment during the follow-up. During a median follow-up of 6.1 years, 4,304 (35.1%) participants developed hypertension. Overall, there was a U-shaped association between dietary total iron intake and new-onset hypertension (P for nonlinearity <0.001), with the lowest risk observed at 18.2-<22.1 mg/day (quintile 2-3). Similarly, a U-shaped association between dietary nonheme iron intake and new-onset hypertension was found (P for nonlinearity <0.001), with the lowest risk at 17.4-<21.3 mg/day (quintile 2-3). However, the association between dietary heme iron intake and new-onset hypertension followed a L-shape (P for nonlinearity <0.001), and a significantly lower risk of new-onset hypertension was found in participants with quintile 2-5 of dietary heme iron intake (adjusted HR, 0.75; 95% CI: 0.68, 0.82), compared with those in quintile 1 (<0.25 mg/day). The association between dietary iron and new-onset hypertension was nonlinear in Chinese adults, following a U-shape for total or nonheme iron intake, and a L-shape for heme iron intake.

Maternal heme-enriched diet promotes a gut pro-oxidative status associated with microbiota alteration, gut leakiness and glucose intolerance in mice offspring

Maternal environment, including nutrition and microbiota, plays a critical role in determining offspring's risk of chronic diseases such as diabetes later in life. Heme iron requirement is amplified during pregnancy and lactation, while excessive dietary heme iron intake, compared to non-heme iron, has shown to trigger acute oxidative stress in the gut resulting from reactive aldehyde formation in conjunction with microbiota reshape. Given the immaturity of the antioxidant defense system in early life, we investigated the extent to which a maternal diet enriched with heme iron may have a lasting impact on gut homeostasis and glucose metabolism in 60-day-old C3H/HeN mice offspring.As hypothesized, the form of iron added to the maternal diet differentially governed the offspring's microbiota establishment despite identical fecal iron status in the offspring. Importantly, despite female offspring was unaffected, oxidative stress markers were however higher in the gut of male offspring from heme enriched-fed mothers, and were accompanied by increases in fecal lipocalin-2, intestinal para-cellular permeability and TNF-α expression. In addition, male mice displayed blood glucose intolerance resulting from impaired insulin secretion following oral glucose challenge. Using an integrated approach including an aldehydomic analysis, this male-specific phenotype was further characterized and revealed close covariations between unidentified putative reactive aldehydes and bacterial communities belonging to Bacteroidales and Lachnospirales orders.Our work highlights how the form of dietary iron in the maternal diet can dictate the oxidative status in gut offspring in a sex-dependent manner, and how a gut microbiota-driven oxidative challenge in early life can be associated with gut barrier defects and glucose metabolism disorders that may be predictive of diabetes development.

Changes in Dietary Total and Nonheme Iron Intake Is Associated With Incident Frailty in Older Men: The Concord Health and Aging in Men Project.

Nutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty. Cross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression. Incidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile -2.61-0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]). Maintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men.

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

We aimed to assess the long-term association of total, heme, non-heme, and supplemental iron intake and risk of type 2 diabetes (T2D). 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. 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 1mg/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). 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. The protocol of this systematic review was registered at PROSPERO (registration number: CRD42021226835).

Correlation Between High Serum Ferritin Level and Gestational Diabetes: A Systematic Review.

Gestational diabetes mellitus (GDM) is a growing pregnancy-related health problem all over the world. It has been noticed that women with high serum ferritin levels have a strong relationship with GDM by increased insulin resistance and increased insulin secretion from the pancreas resulting in pancreatic beta-cell exhaustion. Heme iron is also responsible for increasing the body's iron store and hence causing oxidative injury to pancreatic cells.In this systematic review, we researched the association between high serum ferritin levels and GDM. Three databases were consulted for articles related to GDM and high ferritin. These include Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, and PubMed Central (PMC). Additional articles were retrieved from the institutional database. After filtering, 10 articles were finally selected, and quality was checked using the Joanna Briggs Institute (JBI) Critical Appraisal quality check tool. Serum iron biomarkers including ferritin, iron, and soluble transferrin receptor (sTfR) were measured.Our systematic review indicates that high maternal serum ferritin has a significant role in the development of GDM. We have also noticed the importance of sTfR and serum hepcidin as biomarkers to monitor high ferritin levels. Our study also observed a positive relationship between high heme iron intake and gestational diabetes mellitus. Therefore, more research is required to understand this relationship to identify populations at risk.

Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study.

Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case-control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants. Out of the 828 participants (median age: 58.7years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7µg/L and 35.2% in males, respectively, and 77µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight. Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.

HUBUNGAN ASUPAN BESI HEME DAN NON-HEME KADAR FERRITIN PADA CALON PENGANTIN PEREMPUAN DI KOTA PADANG

Women of childbearing age are prone to anemia, especially iron-deficiency anemia. The outcome might be seen in the high maternal mortality rate in the Padang city (16 cases. Serum ferritin can be used as an initial indicator to determine iron deficiency. A decrease in serum ferritin levels can be influenced by iron intake. This study aimed to determine the relationship between heme and non-heme iron intake with ferritin serum concentration in women’s bride candidates in Padang City. This analytical study with a cross-sectional design involved 30 bride candidates, 20-30 years old. Iron intake were collected using the Semi-Quantitative Food Frequency Questionnaire (SQ-FFQ), and serum ferritin levels were measured using the Enhanced ChemiLuminescence Immuno Assay (ECLIA) method. Data were analyzed using the Pearson correlation coefficient test. The results showed the mean of heme and non-heme iron intake was 2.76 ± 0.90 mg/day and 3.83 ± 0.97 mg/day, respectively, and the mean of serum ferritin levels was 46.27 ± 27.61 ng/ml. The test showed no significant correlation between heme (r=0.094, p=0.622) and non-heme iron (r=-0.179, p=0.345) intake with serum ferritin levels. This study concludes that there is no relationship between heme and non-heme iron intake with serum ferritin levels on bride candidates in Padang City. Therefore, to prevent the incidence of anemia during pregnancy, it is highly recommended for the brides to increase their iron intake from both animal and vegetable sources.

Analysis of Environmental Determinants of Heme and Nonheme Iron Intake in a National Sample of Polish Adolescents.

Intake of sufficient amounts of iron by adolescents is a matter of great concern. Therefore, it is crucial to determine the factors that may influence iron intake in this specific population. The present study aimed to analyze the environmental determinants of the intake of heme and nonheme iron in a national homogenous sample of Polish adolescents. Adolescents (aged 15–20 years) were randomly chosen from all the regions of Poland by performing a sampling of secondary schools (random quota sampling). The total iron intake, as well as the intake of heme iron, nonheme iron, animal iron, plant iron, and iron from various food products, was assessed among 1385 female respondents and 1025 male respondents using the validated IRON Intake Calculation—Food Frequency Questionnaire (IRONIC-FFQ). The intake was compared between the subgroups stratified by meat intake in the region, gross domestic product (GDP) in the region, and size of the city (rural vs. urban environment). It was observed that meat intake in the region did not influence the intake of total iron, as well as the intake of heme iron, nonheme iron, animal iron, plant iron, and iron from various food products (p > 0.05). However, GDP and the size of the city were determined as the most influencing factors, as they were associated with iron intake in both female and male adolescents, with the most prominent differences between the subgroups found in the case of females. Female adolescents from high-GDP regions had significantly higher intake of heme iron (p = 0.0047) and animal iron (p = 0.0029), and lower intake of nonheme iron compared to those from low-GDP regions (p = 0.0342). The total iron intake was higher among female adolescents who were from medium cities than those from big cities (p = 0.0350), but significantly higher animal iron intake (p = 0.0404) and plant iron intake (p = 0.0385) were observed among females from villages and small towns compared to females from other groups. Based on the results, it may be concluded that size of the city and the economic status of the region are the most important environmental determinants of iron intake in adolescents and, hence, they should be taken into account while developing educational programs, especially for the female adolescent population.

Chronic intestinal inflammation drives colorectal tumor formation triggered by dietary heme iron in vivo

The consumption of red meat is associated with an increased risk for colorectal cancer (CRC). Multiple lines of evidence suggest that heme iron as abundant constituent of red meat is responsible for its carcinogenic potential. However, the underlying mechanisms are not fully understood and particularly the role of intestinal inflammation has not been investigated. To address this important issue, we analyzed the impact of heme iron (0.25 µmol/g diet) on the intestinal microbiota, gut inflammation and colorectal tumor formation in mice. An iron-balanced diet with ferric citrate (0.25 µmol/g diet) was used as reference. 16S rRNA sequencing revealed that dietary heme reduced α-diversity and caused a persistent intestinal dysbiosis, with a continuous increase in gram-negative Proteobacteria. This was linked to chronic gut inflammation and hyperproliferation of the intestinal epithelium as attested by mini-endoscopy, histopathology and immunohistochemistry. Dietary heme triggered the infiltration of myeloid cells into colorectal mucosa with an increased level of COX-2 positive cells. Furthermore, flow cytometry-based phenotyping demonstrated an increased number of T cells and B cells in the lamina propria following heme intake, while γδ-T cells were reduced in the intraepithelial compartment. Dietary heme iron catalyzed formation of fecal N-nitroso compounds and was genotoxic in intestinal epithelial cells, yet suppressed intestinal apoptosis as evidenced by confocal microscopy and western blot analysis. Finally, a chemically induced CRC mouse model showed persistent intestinal dysbiosis, chronic gut inflammation and increased colorectal tumorigenesis following heme iron intake. Altogether, this study unveiled intestinal inflammation as important driver in heme iron-associated colorectal carcinogenesis.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Electronic structure and reactivity of heme bound insulin

Insulin resistance as well as insulin deficiency are said to be principal to the development of type 2 diabetes mellitus (T2Dm). Heme has also been suggested to play an important role in the disease etiology since many of the heme deficiency symptoms constitute the common pathological features of T2Dm. Besides, iron overload, higher heme iron intake and transfusion requiring diseases are associated with a higher risk of T2Dm development. In this study the interaction between these two key components i.e. heme and insulin has been studied spectroscopically under different conditions which include the effect of excess peptide as well as increasing pH. The resultant heme-insulin complexes in their reduced state are found to produce very little partially reduced oxygen species (PROS) on getting oxidized by molecular oxygen. The interaction between insulin and previously reported T2Dm relevant heme-amylin complex were also examined using absorption and resonance Raman spectroscopy. The corresponding data suggest that insulin sequesters heme from heme-amylin to form the much less cytotoxic heme-insulin.

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03–5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4–5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6–27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

Association between Habitual Dietary Iron Intake and Glucose Metabolism in Individuals after Acute Pancreatitis.

Dietary intake of iron is known to be associated with impaired glucose metabolism. However, its involvement in derangements of glucose metabolism after acute pancreatitis (AP) is not completely understood. The aim was to investigate the association between dietary iron intake and markers of glucose metabolism in individuals after an attack of AP. Fasting blood samples were collected to analyse markers of glucose metabolism (fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)). The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of dietary iron (total, haem, and non-haem). Multivariable linear regression analyses were conducted and six statistical models were built to adjust for covariates. A total of 109 individuals after AP were studied in a cross-sectional fashion. Total iron (β (95% confidence interval) = −0.19 (−0.35, −0.05); p = 0.01 in the most adjusted model) and non-haem iron (β (95% confidence interval) = −0.19 (−0.33, −0.04); p = 0.03 in the most adjusted model) were significantly associated with FPG, consistently in all adjusted model. Total iron and non-haem iron did not have consistent significant associations with HbA1c. Dietary haem iron intake was not associated with either FPG or HbA1c. Habitual intake of dietary iron is inversely associated with FPG in individuals after an attack of AP and may be involved in the pathogenesis of new-onset diabetes after pancreatitis. Prospective longitudinal studies are now warranted to unveil the specific mechanism underlying the involvement of dietary iron.

Factors Associated with Anemia among Selected Women of Reproductive Age in Tondo, Manila, Philippines

Background. Anemia is the most common medical disorder throughout a woman’s life. Given that anemia during reproductive years impacts future gestational and perinatal health, then any factors possibly associated with the disorder should be studied and ultimately addressed.&#x0D; Objective. This study aimed to determine anemia prevalence and its associated factors (socio-demographic,lifestyle, knowledge, dietary and biochemical) among a select group of women of reproductive age (WRA) living in Tondo, Manila.&#x0D; Methods. This is an analytic cross-sectional study that utilized interviewer-assisted questionnaire and bloodextraction to collect data from 166 WRA (18-40 years).&#x0D; Results. Anemia prevalence among the study participants was found to be 9.0%. In terms of associated factors,being anemic was found to be more likely if the WRA has these factors: higher parity, graduated from college;unemployed; living in a low-income household; took iron supplements, and; have low knowledge on iron. On the other hand, increase in age, increase intake of heme iron and non-heme iron food sources, and an increase in blood ferritin concentration were factors that made anemia less likely among WRA.&#x0D; Conclusion. Examining these factors provides insight into the multicausal nature of anemia. Thus, preventionand control programs should focus on the contribution and interrelatedness of these factors to address anemia.

Anxiety is a potential effect modifier of the association between red and processed meat consumption and cancer risk: findings from the NutriNet-Santé cohort.

Red and processed meats are recognized by the International Agency for Research on Cancer as probably carcinogenic and carcinogenic to humans, respectively. Heme iron has been proposed as a central factor responsible for this effect. Furthermore, anxiety affects the intestinal barrier function by increasing intestinal permeability. The objective of this work was to assess how anxiety modifies the association between red and processed meat consumption and cancer risk in the NutriNet-Santé prospective cohort (2009-2019). Using multi-adjusted Cox models in a sample of 101,269 subjects, we studied the associations between the consumption of red and processed meat, the amount of heme iron coming from these meats and overall, colorectal, prostate, and breast cancer risks, overall and separately among participants with and without anxiety. An increase in red and processed meat consumption was associated with an increased risk of developing colorectal cancer in the total population (HR for an increase of 50g/day = 1.18 (1.01-1.37), p = 0.03). After stratification on anxiety, the HR 50g/day was 1.42 (1.03-1.94, p = 0.03) in anxious participants and 1.12 (0.94-1.33, p = 0.20) in other participants. Similar trends were observed for overall cancer risk. Analyses conducted with heme iron also provided similar results. Our results strengthen the existing body of evidence supporting that red and processed meat consumption and heme iron intake are associated with an increased risk of overall and more specifically colorectal cancer, and suggest that anxiety modifies these associations, with an increased risk in anxious participants.

Sociodemographic factors associated with low intake of bioavailable iron in preschoolers: National Health and Nutrition Survey 2012, Mexico

BackgroundChildren < 5 years of age are at risk of developing an iron deficiency due to a low intake of bioavailable iron (FeBio). Few studies have estimated dietary FeBio in children at a national level in relation to sociodemographic characteristics. This study aimed to estimate FeBio intake and its association with sociodemographic factors among Mexican children aged 12–59 months.MethodsA cross-sectional study was carried out. Information on serum ferritin and diet was obtained from a national survey and representative sample of 1012 Mexican children aged 12–59 months. We used a 24-h recall to estimate total iron, heme and non-heme iron, vitamin C, phytates, calcium, and meat intake. We calculated FeBio intake using an algorithm. Differences in FeBio intake were analyzed by area of residence (rural/urban), country region (north, center, south), and socioeconomic status (SES), using linear regression models by age subgroups (12–23 and 24–59 months) and total population, while adjusting for study design.ResultsTotal iron intake was 9.2 ± 6.7 mg/d. The estimated average of total FeBio fluctuated between 0.74–0.81 mg/d, with a bioavailability of 9.15–12.03% of total iron. Children aged 12–23 months residing in rural areas consumed less FeBio than those in urban areas (β = − 0.276) (p < 0.05). Children aged 24–59 months with high SES consumed more FeBio (β = 0.158 mg/d) than those of a low SES (p < 0.05).ConclusionsFeBio is low in Mexican preschoolers. Being from a rural area and having low SES were negatively associated with FeBio intake. These results can benefit interventions seeking to improve iron status.

Dietary Iron Intake and Incident Type 2 Diabetes in Chinese Middle-Aged and Elderly Population: A Prospective Cohort Study

Abstract Objectives Excessive dietary iron intake may lead to iron overload and further induce pancreatic islet damage to increase risk of diabetes, which has a higher prevalence in middle-aged and elderly population. We aimed to explore the association between dietary iron intake and incident type 2 diabetes (T2D) in Chinese middle-aged and elderly population. Methods This study was based on the Guangzhou Nutrition and Health Study (GNHS), an on-going, community-based prospective cohort study that recruited participants aged 40–75 years from 2008. All participants were followed up every three years. 2765 participants free of diabetes were included in data analysis. Dietary iron intake was obtained by a validated food-frequency questionnaire at baseline. T2D was ascertained by self-reported diabetes medications, fasting glucose ≥7.0 mmol/L or glycosylated hemoglobin ≥6.5%. Cox proportional hazards models were used to estimate HRs and 95% CIs. Results We ascertained 209 incident diabetes cases during 13,634 person-years of observation. The mean ± SD intakes of dietary total iron, heme iron and nonheme iron among all participants were 20.40 ± 2.73 mg/d, 1.26 ± 0.62 mg/d and 19.14 ± 2.66 mg/d, respectively. The multivariate-adjusted HR and 95% CI for T2D for the highest quartile of heme iron intake compared with the lowest quartile was 2.11 (95% CI: 1.14–3.89, P-trend = 0.014). However, the association between total iron intake or a nonheme iron intake with T2D risk was no significant difference. The adjusted HR for T2D risk was 1.79 (95% CI:1.05–3.08, P-trend = 0.037) for heme iron intake from red meat, while no association was found for heme iron intake from poultry or fish. Conclusions Greater intake of heme iron, especially heme iron from red meat, was associated with higher risk of incident T2D in Chinese middle-aged and elderly population, while intakes of total iron and nonheme were not related to diabetes. Controlling heme iron intake, especially red meat intake, may be a target to prevent T2D in middle-aged and elderly population. Funding Sources The National Science Foundation of China; the National Science Foundation of Guangdong Province, China.

Dietary iron intake and risk of death due to cardiovascular diseases: A systematic review and dose-response meta-analysis of prospective cohort studies.

Many studies have investigated the association between dietary iron intake and death due to cardiovascular disease (CVD), but the results were inconsistent. We performed a dose-response meta- analysis to quantitatively assess the risk of CVD mortality with dietary intake of iron (total iron, heme iron, and non-heme iron). PubMed and Embase databases were searched for articles published up to February 21, 2019. Prospective cohort studies were included if reporting relative risks (RRs) and 95% confidence intervals (CIs) for risk of CVD mortality associated with dietary iron intake. Restricted cubic splines were used to model the dose-response association. We included eight articles (19 studies including 720,427 participants [46,045 deaths due to CVD]) in the meta-analysis. When comparing the highest versus lowest level of dietary heme iron intake, the pooled RR for CVD mortality was 1.19 (95% CI, 1.01-1.39). With a 1-mg/day increase in dietary heme iron intake, the pooled RR for death due to CVD, stroke, coronary heart disease, and myocardial infarction were 1.25 (95% CI, 1.17-1.33), 1.17 (1.04-1.32), 1.25 (0.70-2.22), and 1.17 (0.55-2.50) respectively. The association between dietary iron intake and CVD mortality was linear (pnonlinearity> 0.05). Higher dietary intake of heme iron was associated with a greater risk of CVD mortality. Reducing consumption of heme iron may help to prevent premature death due to CVD.

Dietary Nonheme, Heme, and Total Iron Intake and the Risk of Diabetes in Adults: Results From the China Health and Nutrition Survey.

Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population. We included 17,026 adults (8,346 men and 8,680 women) who were part of the China Health and Nutrition Survey (1991-2015) prospective cohort. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. Diabetes cases were identified through a questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. A total of 547 men and 577 women developed diabetes during 202,138 person-years of follow-up. For men, the adjusted HRs (95% CIs) for quintiles of nonheme iron intake were 1.00, 0.77 (0.58-1.02), 0.72 (0.54-0.97), 0.63 (0.46-0.85), and 0.87 (0.64-1.19) (P-nonlinearity = 0.0015). The corresponding HRs (95% CIs) for women were 1.00, 0.63 (0.48-0.84), 0.57 (0.43-0.76), 0.58 (0.43-0.77), and 0.67 (0.49-0.91) (P-nonlinearity < 0.0001). The dose-response curves for the association between nonheme iron and total iron intake and diabetes followed a reverse J shape in men and an L shape in women. No significant associations were observed between heme iron intake and diabetes risk. Total iron and nonheme iron intake was associated with diabetes risk, following a reverse J-shaped curve in men and an L-shaped curve in women. Sufficient intake of nonheme or total iron might be protective against diabetes, while excessive iron intake might increase the risk of diabetes among men.