Novel Iron-Whey Protein Microspheres Protect Gut Epithelial Cells from Iron-Related Oxidative Stress and Damage and Improve Iron Absorption in Fasting Adults

2017 ◽  
Vol 138 (4) ◽  
pp. 223-232 ◽  
Author(s):  
Jun Wang ◽  
Gabor Radics ◽  
Michael Whelehan ◽  
Aoibhe OʼDriscoll ◽  
Anne Marie Healy ◽  
...  

Background: Iron food fortification and oral iron formulations are frequently limited by poor absorption, resulting in the widespread use of high-dose oral iron, which is poorly tolerated. Methods: We evaluated novel iron-denatured whey protein (Iron-WP) microspheres on reactive oxygen species (ROS) and viability in gut epithelial (HT29) cells. We compared iron absorption from Iron-WP versus equimolar-dose (25 mg elemental iron) ferrous sulphate (FeSO4) in a prospective, randomised, cross-over study in fasting volunteers (n = 21 per group) dependent on relative iron depletion (a ferritin level ≤/>30 ng/mL). Results: Iron-WP caused less ROS generation and better HT29 cell viability than equimolar FeSO4. Iron-WP also showed better absorption with a maximal 149 ± 39% increase in serum iron compared to 65 ± 14% for FeSO4 (p = 0.01). The response to both treatments was dependent on relative iron depletion, and multi-variable analysis showed that better absorption with Iron-WP was independent of baseline serum iron, ferritin, transferrin saturation, and haemoglobin in the overall group and in the sub-cohort with relative iron depletion at baseline (p < 0.01). Conclusions: Novel Iron-WP microspheres may protect gut epithelial cells and improve the absorption of iron versus FeSO4. Further evaluation of this approach to food fortification and supplementation with iron is warranted.

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2300
Author(s):  
Helena Tiekou Lorinczova ◽  
Gulshanara Begum ◽  
Derek Renshaw ◽  
Mohammed Gulrez Zariwala

Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurcTM; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, p < 0.0001) with statistically significant intra-group increases after 180 min (p < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group (* p < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans.


2000 ◽  
Vol 20 (6) ◽  
pp. 662-666 ◽  
Author(s):  
Bahar Bastani ◽  
Shah Islam ◽  
Nasser Boroujerdi

Objective Oral iron is poorly absorbed in chronic dialysis patients. We tested the hypothesis that a superpharmacologic dose of iron sulfate (260 mg elemental iron) administered on an empty stomach results in significant iron absorption in these patients. Design A prospective open controlled trial. Setting Outpatient department of a university hospital. Patients Nine stable chronic peritoneal dialysis (PD) patients and seven normal control subjects. Method All subjects ingested a single dose of 4 tablets of iron sulfate (260 mg elemental iron total) in the morning while fasting. Outcome Measures Serum iron concentrations at baseline, and at 2 and 4 hours after the oral dose were compared between the two groups. Results The control group showed a significant rise in mean [± standard error (SE)] serum iron concentration, from a baseline value of 76.5 ± 7 μg/dL to 191 ± 10.5 μg/dL at 2 hours and to 190 ± 24 μg/dL at 4 hours. This result represents a percentage rise of 164% ± 32% at 2 hours and 152% ± 28.5% at 4 hours. In the PD patients, a significant rise in serum iron concentration was also seen, from a baseline value of 64 ± 8 μg/dL to 130 ± 3 μg/dL at 2 hours and 111 ± 18 μg/dL at 4 hours. This result represents a percentage rise of 105% ± 29% at 2 hours and 77% ± 23.5% at 4 hours. However, the absolute change in serum iron concentration in PD patients at 2 and 4 hours was approximately equal to 50% of the change in control subjects at those time points. None of the PD patients experienced gastrointestinal side effects; 4 control subjects experienced mild side effects. Conclusion Despite impaired oral iron absorption in chronic dialysis patients, a large pharmacologic dose given orally can result in significant iron absorption and may prove to be a more efficient means of oral iron supplementation therapy in these patients.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 887 ◽  
Author(s):  
Laura Giancotti ◽  
Valentina Talarico ◽  
Giuseppe Antonio Mazza ◽  
Santina Marrazzo ◽  
Pietro Gangemi ◽  
...  

Background: Celiac disease (CD) is an immunologically-mediated disorder characterized by duodenal mucosa villi atrophy. Iron absorption is usually reduced in celiac patients making every kind of oral iron treatment unhelpful because of malasorption. Feralgine™ is a new product that has been demonstrated to be more bioavailable. As such, the aim of our study was to evaluate the absorption of Feralgine™ in adult patients with CD. Methods: Twenty-six adults affected by Iron Deficiency Anemia (IDA), of which 14 were also affected by CD and 12 were not affected by CD, were enrolled. An oral iron absorption test (OIAT) was performed in each patient by administrating Feralgine™, and serum iron was evaluated at baseline (T0) and after 2 h (T1) from the oral iron ingestion. Results: The OIAT was well tolerated in all patients, and, surprisingly, an equivalent statistically significant improvement in serum iron occurred in the two groups of patients (IDA plus CD: T0 = 28.21 µg/dL vs. T1 = 94.14 µg/dL p = 0.004 and IDA without CD: T0 = 34.91 µg/dL vs. T1 = 118.83 µg/dL, p = 0.0003). Conclusions: These results demonstrated the high absorption of Feralgine™ in celiac patients, confirming our previous data obtained with Ferrous Bysglicinate in children with CD.


Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Simone Buerkli ◽  
Sung-Nan Pei ◽  
Shu-Chen Hsiao ◽  
Chien-Te Lee ◽  
Christophe Zeder ◽  
...  

Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days. Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, in the TT variant serum iron and transferrin saturation were lower (P=0.001; P


2019 ◽  
Vol 57 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Indrajeet Singh Banjare ◽  
Kamal Gandhi ◽  
Khushbu Sao ◽  
Rajan Sharma

Poor absorption of iron from food and oral iron formulations results in extensive use of high-dose oral iron, which is not tolerated. Disposal of whey, a byproduct of the cheese industry, causes environmental pollution. Whey proteins have the ability to bind significant amount of iron, thereby reducing its chemical reactivity and incompatibility with other components in foods. To make iron compatible with food, it was complexed with whey protein concentrate (WPC). After complexation, centrifugation and ultrafiltration techniques were utilised to eliminate the insoluble and free iron from the solution. To enable the availability of whey protein concentrate–iron (WPC–Fe) complex in the powder form, spray drying technique was used. Optimized spray drying conditions used for the preparation were: inlet temperature 180 °C, flow rate 2.66 mL/min and solution of total solids 15 %. The complex was observed to be stable under different processing conditions. The in vitro bioaccessibility (iron uptake) of the bound iron from the WPC–Fe complex was significantly higher (p<0.05) than that from iron(II) sulphate under simulated gastrointestinal conditions. WPC–Fe complex with improved iron bioaccessibility could safely substitute iron fortificants in different functional food preparations.


2006 ◽  
Vol 63 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Mirjana Lausevic ◽  
Natasa Jovanovic ◽  
Svetlana Ignjatovic ◽  
Gordana Grujic-Adanja ◽  
Biljana Stojimirovic

Background/Aim. Iron supplementation plays a crucial role in peritoneal dialysis (PD) patients. Oral iron substitution is more convenient than intravenous therapy in PD patients, but impaired absorption and adverse effects may be limiting factors for oral treatment. The aim of this study was to compare the absorption and side effects of high doses ferrous sulphate and ferrous gluconate in PD patients. Methods. Blood samples were taken from 29 PD patients at baseline, as well as 2, 4 and 8 hours after oral intake of 4 ferrous sulphate tablets (containing 105 mg elemental iron per tablet). The test was repeated using 8 ferrous gluconate drinkable ampoules (containing 50 mg elemental iron per ampoule). Results. The maximal increase in serum iron level during the test with iron sulphate was 113.51?103.37% versus the initial values of 183.87?37.38% during the ferrous gluconate test. The maximal values of serum iron after the intake of ferrous sulphate were 26.23?9.95 ?mol/l versus 30.97?8.65 ?mol/l after the intake of ferrous gluconate. There was a statistically significant difference between these two groups. Six patients showed an increase in serum iron of more than 300% after a high ferrous gluconate dose, while in 15 of the patients serum iron increased between 100% and 300%, and in 8 of the patients serum iron levels increased by less than 100%. Side effects occurred more frequently after the intake of ferrous sulphate than ferrous gluconate. Conclusion. High doses of oral iron were well absorbed and tolerated in PD patients. Ferrous gluconate was better absorbed and tolerated than ferrous sulphate, thus we recommend it for oral iron supplementation in PD patients.


2000 ◽  
Vol 20 (6) ◽  
pp. 667-673 ◽  
Author(s):  
Elisabeth Dittrich ◽  
Heidi Puttinger ◽  
Barbara Schneider ◽  
Walter H. Hörl ◽  
Marianne Haag–Weber ◽  
...  

Objective Iron supplementation plays a major role in erythropoietin-treated end-stage renal disease patients. For peritoneal dialysis (PD) patients, oral iron substitution is more convenient than intravenous therapy. However, disturbed iron absorption and adverse effects may be limiting factors for oral treatment. Nevertheless, we compared the response to a high-dose and low-dose oral iron absorption test between PD patients and healthy control subjects. Patients and Interventions In 34 PD patients and 15 healthy control subjects, blood samples were taken at baseline as well as 2, 4, and 8 hours after oral intake of 4 tablets iron sulfate (105 mg elemental iron per tablet). In a subgroup of 6 PD patients and 6 control subjects, the oral iron absorption test was repeated using 1 tablet iron sulfate. Results There was no significant difference in the increase in serum iron during the test between the two groups. As known for healthy subjects, iron absorption was significantly better in PD patients with absolute iron deficiency compared to those with functional iron deficiency. Iron-repleted PD patients showed the lowest iron absorption, indicating that a high dose of oral iron did not overwhelm the ability of the bowel tract to reject unneeded iron. Increasing the oral iron dose from 1 to 4 tablets was followed by a better response in a small subgroup of PD patients compared to control subjects. Side effects such as nausea and vomiting occurred more frequently during high-dose oral iron in control subjects than in PD patients (20% vs 8.8%). Conclusion High-dose oral iron is well absorbed in iron-depleted PD patients. This kind of oral iron therapy should be considered in some subgroups of PD patients with iron deficiency, particularly in those patients with poor vascularization of arm veins or intolerance to intravenous iron preparations.


2021 ◽  
Author(s):  
John Gilmer ◽  
Fiona Ryan ◽  
Anna Seoighe ◽  
Cristin Ryan ◽  
Maria Jose Santos-Martinez ◽  
...  

Background Intolerance to oral iron is thought to result in poor adherence and persistence of nutritional deficit amongst women of childbearing age, however few studies have evaluated oral iron intolerance, iron deficiency and anaemia in this setting. Iron-whey protein microspheres (IWP) could help. Methods We documented self-reported oral iron gastrointestinal intolerance, ferritin and haemoglobin levels in a screening study of women of childbearing age. Following a washout period of 16 days, we randomised 59 of these women with iron deficiency, stratified according to the presence of anaemia, to three doses of IWP: (14mg daily, 25mg daily and 50mg daily). We excluded those with established gastrointestinal disease, potential allergy to whey protein and severe anaemia. The primary endpoint was persistence and adherence (>80% based on pill-counts). Secondary endpoints included changes in self-reported oral iron gastrointestinal intolerance, gastro-intestinal symptom rating scale (GSRS), serum iron, serum ferritin, transferrin saturation and haemoglobin levels. Results A total of 128 (62.7%) of the participants had low iron stores (ferritin <30 μg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin <12 μg/L) and 33 (16.2%) had iron deficiency anaemia. Amongst 59 women who participated in the prospective study, 48 (81.4%) were classified as adherent/persistent with therapy using IWP compared to 12 (20.3%) taking the prior oral iron P<0.0001. These patients also showed significantly fewer reports of gastrointestinal intolerance with IWP (0.59 ± 0.91) and lower GSRS scores (6.2 ± 7.5) compared to the previous oral iron product (3.98 ± 2.22, and 15.6 ± 9.7 respectively, both P<0.0001). There were no differences in adherence, self-reported adverse GI effects and GSRS between the dose groups during the study. Serum iron levels increased across the whole cohort from 11.3 ± 7.4 μmol/L to 20.5 ± 11.0 μmol/L (P<0.0001), transferrin saturation levels increased from 18.4 ± 13.3 % to 33.6 ± 17.6 % (P<0.0001) and median ferritin levels overall increased from 8.00 [IQR 6.00;13.0] to 15.5 [IQR 9.00;24.2] μg/L at 12 weeks (P=0.0002). Haemoglobin levels increased from 11.36 g/dL (95%CI 10.95 to 11.77) to 12.40 g/dL (95%CI 12.03 to 12.76, P=0.0007) in patients with anaemia and were normalised in most patients taking 50mg IWP daily. Conclusions Low iron, iron deficiency and anaemia are common in women of childbearing age with a history of intolerance to oral iron. Patients with low iron (ferritin < 30 μg/L) and moderate to severe iron deficiency (ferritin <12 μg/L) have similar impairment of energy. IWP can improve self-reported oral iron adherence and tolerability as well as iron stores, haemoglobin and tiredness in these women.


2010 ◽  
Vol 105 (8) ◽  
pp. 1245-1250 ◽  
Author(s):  
Michael B. Zimmermann ◽  
Ralf Biebinger ◽  
Ines Egli ◽  
Christophe Zeder ◽  
Richard F. Hurrell

Fe absorption from water-soluble forms of Fe is inversely proportional to Fe status in humans. Whether this is true for poorly soluble Fe compounds is uncertain. Our objectives were therefore (1) to compare the up-regulation of Fe absorption at low Fe status from ferrous sulphate (FS) and ferric pyrophosphate (FPP) and (2) to compare the efficacy of FS with FPP in a fortification trial to increase body Fe stores in Fe-deficient childrenv. Fe-sufficient children. Using stable isotopes in test meals in young women (n49) selected for low and high Fe status, we compared the absorption of FPP with FS. We analysed data from previous efficacy trials in children (n258) to determine whether Fe status at baseline predicted response to FSv. FPP as salt fortificants. Plasma ferritin was a strong negative predictor of Fe bioavailability from FS (P < 0·0001) but not from FPP. In the efficacy trials, body Fe at baseline was a negative predictor of the change in body Fe for both FPP and FS, but the effect was significantly greater with FS (P < 0·01). Because Fe deficiency up-regulates Fe absorption from FS but not from FPP, food fortification with FS may have relatively greater impact in Fe-deficient children. Thus, more soluble Fe compounds not only demonstrate better overall absorption and can be used at lower fortification levels, but they also have the added advantage that, because their absorption is up-regulated in Fe deficiency, they innately ‘target’ Fe-deficient individuals in a population.


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