Ethnic Differences in Iron Status

Abstract

Iron is unique among all minerals in that humans have no regulatable excretory pathway to eliminate excess iron after it is absorbed. Iron deficiency anemia occurs when absorbed iron is not sufficient to meet body iron demands, whereas iron overload and subsequent deposition of iron in key organs occur when absorbed iron exceeds body iron demands. Over time, iron accumulation in the body can increase risk of chronic diseases, including cirrhosis, diabetes, and heart failure. To date, only ∼30% of the interindividual variability in iron absorption can be captured by iron status biomarkers or iron regulatory hormones. Much of the regulation of iron absorption may be under genetic control, but these pathways have yet to be fully elucidated. Genome-wide and candidate gene association studies have identified several genetic variants that are associated with variations in iron status, but the majority of these data were generated in European populations. The purpose of this review is to summarize genetic variants that have been associated with alterations in iron status and to highlight the influence of ethnicity on the risk of iron deficiency or overload. Using extant data in the literature, linear mixed-effects models were constructed to explore ethnic differences in iron status biomarkers. This approach found that East Asians had significantly higher concentrations of iron status indicators (serum ferritin, transferrin saturation, and hemoglobin) than Europeans, African Americans, or South Asians. African Americans exhibited significantly lower hemoglobin concentrations compared with other ethnic groups. Further studies of the genetic basis for ethnic differences in iron metabolism and on how it affects disease susceptibility among different ethnic groups are needed to inform population-specific recommendations and personalized nutrition interventions for iron-related disorders.

Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

“…Multiple studies showed a higher prevalence of ID in Indians compared to other Southeast Asian and European populations [ 17 , 20 , 90 , 91 , 92 ], which potentially can be explained by dietary habits since vegetarianism and drinking tea is very common among the Indian population [ 93 ]. Besides containing mainly non-haeme iron, a plant-based diet is full of phytates and polyphenols, which are known potent inhibitors of non-haeme iron absorption, making vegetarians more prone to develop ID [ 87 , 94 , 95 ]. In a study of 226 HFrEF patients from the Himachal Pradesh heart failure registry, it was found that HF patients that consume a vegetarian diet were 2.5 times more likely to have ID (odds ratio 2.5 (95% confidence interval 1.4–4.6)) [ 96 ].…”

“…Increasing iron intake orally in HF patients using Forceval (mix of micronutrients including 12 mg of iron) for 12 months did not significantly increase serum ferritin or serum iron [ 94 ]. Furthermore, in the IRONOUT-HF study, it was found that taking oral iron polysaccharide tablets (150 mg twice daily) for 16 weeks did not improve functional capacity and quality of life in patients with HFrEF in spite of the minimal improvement in iron stores [ 95 ]. It is worth noting that the cumulative amount of oral iron received within the study period exceeds the recommended dosage intravenously to correct ID by more than 15 times [ 8 , 95 ].…”

“…Furthermore, in the IRONOUT-HF study, it was found that taking oral iron polysaccharide tablets (150 mg twice daily) for 16 weeks did not improve functional capacity and quality of life in patients with HFrEF in spite of the minimal improvement in iron stores [ 95 ]. It is worth noting that the cumulative amount of oral iron received within the study period exceeds the recommended dosage intravenously to correct ID by more than 15 times [ 8 , 95 ]. Knowing that the main source of iron used by the body is endogenously obtained as a result of scavenging iron from senescent erythrocytes by macrophages [ 67 ], these results may implicate mechanisms other than insufficient dietary iron intake alone as a cause of ID in HF.…”

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications

“…The development of new and more effective iron formulations is also related to the increased and more selective requirements for more specific iron formulations by an increasing number of patients in addition to IDA, with other categories of anaemia not related to increased body iron requirements, such as pregnant women or vegetarian populations ( Table 2 ) [ 52 ]. Many of these other categories of anaemic patients have a different pathophysiology and tolerance to iron formulations by comparison to IDA patients ( Table 2 ) [ 13 , 67 , 68 ].…”

“…One major category involving millions of patients are those suffering from the anaemia of chronic disease or anaemia of inflammation, including patients with inflammatory, infectious and neoplastic diseases, such as different cancer types and inflammatory bowel disease. In most of the anaemia of chronic disease cases, sufficient iron is stored in the body, but compartmentalised in the reticuloendothelial system and cannot become readily available to the haematopoietic tissues for the production of sufficient amounts of haemoglobin [ 67 , 68 ].…”