An evaluation of EDTA compounds for iron fortification of cereal-based foods

Fe absorption was measured in adult human subjects consuming different cereal foods fortified with radiolabelled FeSO4, ferrous fumarate or NaFeEDTA, or with radiolabelled FeSO4 or ferric pyrophosphate in combination with different concentrations of Na2EDTA. Mean Fe absorption from wheat, wheat–soyabean and quinoa (Chenopodium quinoa) infant cereals fortified with FeSO4 or ferrous fumarate ranged from 0·6 to 2·2 %. For each infant cereal, mean Fe absorption from ferrous fumarate was similar to that from FeSO4 (absorption ratio 0·91–1·28). Mean Fe absorption from FeSO4-fortified bread rolls was 1·0 % when made from high-extraction wheat flour and 5·7 % when made from low-extraction wheat flour. Fe absorption from infant cereals and bread rolls fortified with NaFeEDTA was 1·9–3·9 times greater than when the same product was fortified with FeSO4. Both high phytate content and consumption of tea decreased Fe absorption from the NaFeEDTA-fortified rolls. When Na2EDTA up to a 1:1 molar ratio (EDTA:Fe) was added to FeSO4-fortified wheat cereal and wheat–soyabean cereal mean Fe absorption from the wheat cereal increased from 1·0 % to a maximum of 5·7 % at a molar ratio of 0·67:1, and from the wheat–soyabean cereal from 0·7 % to a maximum of 2·9 % at a molar ratio of 1:1. Adding Na2EDTA to ferric pyrophosphate-fortified wheat cereal did not significantly increase absorption (P\u3e0·05). We conclude that Fe absorption is higher from cereal foods fortified with NaFeEDTA than when fortified with FeSO4 or ferrous fumarate, and that Na2EDTA can be added to cereal foods to enhance absorption of soluble Fe-fortification compounds such as FeSO4

Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P\u3c0.0001) upregulated ferroportin 1 expression and significantly (P\u3c0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P\u3c0.05) and DNA fragmentation by 29% (P=0.086) and increased cell viability by 22% (P\u3c0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P\u3c0.05) and intracellular iron by 28% (P\u3c0.01), indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1

Green Tea Consumption Reduces Oxidative Stress in Parkinson’s Disease Patients

Oxidative stress is one of the underlying causes of Parkinson’s disease (PD). Because of its antioxidant effect, we hypothesize that green tea consumption (3 cups daily for 3 months) would improve antioxidant status and reduces oxidative damage in Parkinson’s disease. Fifteen subjects who were within the first five years of PD, on stable PD medication, and not regular green tea consumers were recruited. Iron status, oxidative stress and PD status were evaluated before and after 3 months of green tea consumption. Hemoglobin, serum iron, iron saturation and ferritin concentrations were used to assess iron status. Antioxidant enzymes including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured to determine antioxidant status. Lipid peroxidation and protein carbonyls were measured as oxidative damage markers. There were no changes in total motor scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), PDQ-39 total scores and various iron status markers after 3 months. Catalase (p \u3c 0.05) and SOD activities (p \u3c 0.005) were increased significantly indicating an improvement of antioxidant status. Both lipid peroxidation and protein carbonyls decreased by ~52% (p \u3c 0.01) with green tea consumption, indicating less oxidative stress. In conclusion, 3 cups of green tea consumption for 3 months can improve antioxidant status and reduce oxidative damage in PD patients. Further studies are needed to determine if these changes result in slowing the disease progression

Effect of maternal cigarette smoking on newborn iron stores

Background: Maternal smoking has been known to have a negative impact on the well being of the developing fetus. Prenatal smoking has been associated with premature births, low birth weight and with certain birth defects. Small research studies have also found a negative correlation between maternal smoking and neonatal body iron. Objectives: To study and compare the relationship between maternal and infants’ body iron in smokers and non-smokers in a large matched-pair cohort. Methods: This was a prospective cohort study involving 144 mothers – 72 smokers and 72 non-smokers and their respective infants. Samples were obtained from maternal and infants’ cord blood at delivery for Serum transferrin receptor (sTfR) and ferritin levels. Serum TfR and ferritin were measured by RAMCO ELISA and RIA assays. Total Body Iron (TBI) was calculated using the sTfR/ferritin ratio in a previously described formula by Cook et al. Results: Women who smoked had lower sTfR, higher ferritin and higher body iron compared to nonsmoking women. In contrast to their respective mothers, we found a small, but statistically significant negative correlation between smoking and infants’ total body iron. The number of packs per day smoked was also negatively correlated with infants’ ferritin and total body iron. Lower birth weight was noted in babies of smokers compared to nonsmokers (mean /- SD=3270 +/-475 vs. 3393 g +/- 475 g, p=0.03). Conclusion: Women who smoked during pregnancy had higher iron stores but their newborn infants had lower iron stores than those of non-smoking mothers. The more packs per day (PPD) and more days smoked during pregnancy led to lower total body iron of the babies. There may be a negative dose-dependent response between fetal smoke exposure and infant iron stores

Fermentation and Lactic Acid Addition Enhance Iron Bioavailability of Maize

Maize is one of the most important cereal crops for human consumption, yet it is of concern due to its low iron bioavailability. The objective of this study was to determine the effects of processing on iron bioavailability in common maize products and elucidate better processing techniques for enhancing iron bioavailability. Maize products were processed to represent different processing techniques: heating (porridge), fermentation (ogi), nixtamalization (tortillas), and decortication (arepas). Iron and phytate contents were evaluated. Iron bioavailability was assessed using the Caco-2 cell model. Phytate content of maize products was significantly reduced by decortication (25.6%, p ) 0.003) and nixtamalization (15%, p ) 0.03), and iron content was reduced by decortication (29.1%, p ) 0.002). The relative bioavailability (RBA, compared to 100% bioavailability of porridge with FeSO4) of ogi was significantly higher than that of other products when fortified with FeSO4 (p \u3c 0.001) or reduced iron (p \u3c 0.001). Addition of lactic acid (6 mg/g of maize) significantly increased iron solubility and increased bioavailability by about 2-fold (p \u3c 0.01), especially in tortillas. The consumer panel results showed that lactic acid addition does not significantly affect the organoleptic characteristics of tortillas and arepas (p ) 0.166 and 0.831, respectively). The results suggest that fermentation, or the addition of small amounts of lactic acid to unfermented maize products, may significantly improve iron bioavailability. Lactic acid addition may be more feasible than the addition of highly bioavailable but expensive fortificants. This approach may be a novel means to increase the iron bioavailability of maize products to reduce the incidence of iron deficiency anemia

Mapping of iron and zinc quantitative trait loci in soybean for association to iron deficiency chlorosis resistance

Iron deficiency chlorosis (IDC) in soybean results in yield losses or in extreme cases death. Breeding for resistance has shown limited success with no cultivar having complete resistance. Mineral content of the soybean could be an indicator of the ability of the plant to withstand the effects of IDC. Iron (Fe) and zinc (Zn) concentration was examined in soybean seed and leaves. SSR, RFLP, and BARCSOYSSR markers were used to construct a linkage map used for mapping of Fe and Zn concentrations. The QTL analysis for the combined data identified one major QTL for seed Fe accumulation on chromosome 20 that explained 21.5% of the variation. This QTL was in the marker interval pa_515-1-Satt239, with marker pa_515-1 previously being used to map an Fe-efficiency QTL. This provides the first evidence of a potential genetic link between Fe-efficiency and Fe accumulation in the soybean seed

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.)), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70 %, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90 %. Inhibition by black tea was 79-94 %, peppermint tea 84 %, pennyroyal 73 %, cocoa 71 %, vervain 59 %, lime flower 52 % and camomile 47 %. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and cocoa can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutritio

EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly () increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, ) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased () TH+ cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels

Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; P < .001) and 30 μmol/L IP6 pretreatment decreased it by 38% (P < .05). Similarly, a 63% protection (P < .001) against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in caspase-3 activity (P < .001) and a 42% increase in DNA fragmentation (P < .05) with 6-OHDA treatment were decreased by 41% (P < .01) and 27% (P < .05), respectively, with 30 μmol/L IP6. Together, our data suggest that IP6 protects against 6-OHDA-induced cell apoptosis in both normal and iron-excess conditions, and IP6 may offer neuroprotection in PD