scholarly journals Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota

2021 ◽  
Vol 12 (2) ◽  
pp. 491-502
Author(s):  
Sarah R. Bloor ◽  
Rudolph Schutte ◽  
Anthony R. Hobson

Iron deficiency anaemia (IDA) is a worldwide healthcare problem affecting approximately 25% of the global population. The most common IDA treatment is oral iron supplementation, which has been associated with gastrointestinal (GI) side effects such as constipation and bloating. These can result in treatment non-adherence and the persistence of IDA. Intravenous iron does not cause GI side effects, which may be due to the lack of exposure to the intestinal lumen. Luminal iron can cause changes to the gut microbiota, aiding the promotion of pathogenic species and decreasing beneficial protective species. Iron is vital for methanogenic archaea, which rely on iron for growth and metabolism. Increased intestinal methane has been associated with slowing of intestinal transit, constipation, and bloating. Here we explore the literature to understand a potential link between iron and methanogenesis as a novel way to understand the mechanism of oral iron supplementation induced GI side effects.

Author(s):  
Suvarna Rai

Background: A large number of antenatal women have difficulty consuming oral iron due to its well-known side effects. A simple alternative for it needs to be found. Aim and objective was to study the efficacy of parenteral iron prophylaxis as an alternative for antenatal women who are not able to consume oral iron.Methods: A prospective case control study was conducted at a tertiary care centre in Hyderabad city, India from March 2016- March 2017. 73 non-anemic antenatal women between 14-24 weeks who were not taking oral iron supplementation were identified. 39 of them were willing for parenteral iron supplementation were included in Cases group and 34 who were not taking iron supplementation in any form were controls. Cases were administered three doses of IV Iron sucrose 200mg in 100 ml normal saline between 24-28 weeks, 28 – 32 weeks and 35-37 weeks Hemoglobin was checked again at 32weeks, 36 weeks, just prior to and on 3rd day post-delivery. Data obtained was analyzed using SPSS software.Results: 67% of antenatal women discontinued oral iron due to its gastric side effects. No bias took place during selection of cases and controls. 7.69% of the ‘cases group’ developed anemia despite parenteral prophylaxis. All of them were diagnosed as mild anemia. 70.59% of the ‘controls group’ developed anemia eventually of which 8 were mild, 13 were moderate, 3 were severe and none were very severe. Mostly women became anemic after delivery. About 59% of antenatal women in cases group had no adverse effects with Iron Sucrose Injections, 8 of them had itching or rash and 9 of them complained of brownish discoloration of urine.11 of them had pain at the infusion site and only 1 of them had fever on administering parenteral therapy. None of these were severe enough to cause discontinuation of parenteral iron administration. No statistically significant difference could be found in maternal and perinatal morbidity and mortality between the two groups. The mean cost of parenteral iron prophylaxis was Rs. 1650.Conclusions: Women who do not take oral Iron supplementation in pregnancy are more prone to develop anemia subsequently. The commonest cause of non-compliance to oral iron is gastric intolerance. 3 doses of Intravenous Iron Sucrose 200mg prevents anemia in antenatal women who do not take oral iron supplementation. Hence, it can now be considered a convenient option for them.


2019 ◽  
Author(s):  
Awad Mahalhal ◽  
Michael D. Burkitt ◽  
Carrie A. Duckworth ◽  
Georgina L. Hold ◽  
Barry J. Campbell ◽  
...  

AbstractPatients taking oral iron supplementation often suffer from gastrointestinal side effects. We have previously shown that acute alterations in oral iron exacerbate dextran sodium sulphate (DSS) induced colitis and are associated with dysbiosis. As patients take iron supplementation for long periods, we asked whether this too would influence colitis and the microbiome. We assessed the impact of long-term changes in dietary iron, by feeding chow containing 100ppm, 200ppm and 400ppm (reflecting a deficient, normal or supplemented diet, respectively) for up to 9 weeks to female wild-type C57BL/6 (WT) mice in presence or absence of chronic colitis, or acute colitis induced after 8 weeks, induced by DSS. Assessment was made based on (i) clinical and histological severity of colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of16SrRNA. In mice with long term changes to their dietary iron, reduced iron intake (100ppm iron diet) was associated with increased weight loss and histology scoring in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a clear change in the faecal microbiome in the 100 and 400ppm iron DSS-treated groups and in controls consuming the 400ppm iron diet. Proteobacteria levels increased significantly at day-63 compared to baseline and Bacteroidetes levels decreased in the 400ppm iron DSS group at day-63 compared to baseline; mirroring our previously published work in acute colitis. Long term dietary iron alterations clearly affects gut microbiota signatures but do not appear to exacerbate chronic colitis. However, acute colitis is exacerbated by changes in dietary iron. More work is needed to understand the impact of iron supplementation of the pathologenesis of IBD and rise that possiblity that the change in the microbiome, in patients with colitis, is a consequence of the increase in luminal iron and not simply the presence of colitis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jane L. Tarry-Adkins ◽  
Susan E. Ozanne ◽  
Catherine E. Aiken

AbstractWe systematically assessed the impact of metformin treatment on maternal pregnancy outcomes. PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov and Cochrane databases were systematically searched (inception-1st February 2021). Randomised controlled trials reporting pregnancy outcomes in women randomised to metformin versus any other treatment for any indication were included. Outcomes included gestational weight gain (GWG), pre-eclampsia, gestational hypertension, preterm birth, gestational age at delivery, caesarean section, gestational diabetes, glycaemic control, and gastrointestinal side-effects. Two independent reviewers conducted screening, with a third available to evaluate disagreements. Risk-of-bias and GRADE assessments were conducted using Cochrane Risk-of-Bias and GRADE-pro software. Thirty-five studies (n = 8033 pregnancies) met eligibility criteria. GWG was lower in pregnancies randomised to metformin versus other treatments (1.57 kg ± 0.60 kg; I2 = 86%, p < 0.0001), as was likelihood of pre-eclampsia (OR 0.69, 95% CI 0.50–0.95; I2 = 55%, p = 0.02). The risk of gastrointestinal side-effects was greater in metformin-exposed versus other treatment groups (OR 2.43, 95% CI 1.53–3.84; I2 = 76%, p = 0.0002). The risk of other maternal outcomes assessed was not significantly different between metformin-exposed versus other treatment groups. Metformin for any indication during pregnancy is associated with lower GWG and a modest reduced risk of pre-eclampsia, but increased gastrointestinal side-effects compared to other treatments.


1998 ◽  
Vol 9 (4) ◽  
pp. 664-668 ◽  
Author(s):  
N Ahsan

In the treatment of anemia of chronic renal failure, the most common cause of recombinant human erythropoietin (rhEPO) resistance is iron deficiency. In peritoneal dialysis (PD) patients, oral iron therapy is an accepted and convenient method of iron supplementation. The effectiveness of oral iron, however, is limited by many factors, including gastrointestinal side effects and poor gastric absorption. This study prospectively compared the efficacy of single intravenous infusion of total dose iron (ITDI group) given in an outpatient setting with oral iron (oral group) for the treatment of anemia in PD patients. Twenty-five adult stable PD patients with baseline hematocrit 25 to 35% were entered into the study. Thirteen patients with serum transferrin saturation (TSAT) < 25% received ITDI, and 12 patients with TSAT between 25 and 35% received oral iron. One patient in the oral group received emergent blood transfusion and was excluded from analysis. Hematocrit and iron indices were measured at monthly intervals. Doses of rhEPO were adjusted monthly to maintain target hematocrit at 35%. At the end of the study (6 mo), despite similar baseline mean hematocrit (31.0 +/- 0.9 versus 33.0 +/- 1.0%), comparable mean baseline weekly rhEPO dose (7886 +/- 1449 versus 6370 +/- 1553 U/wk), and significantly lower level of mean TSAT (11.3 +/- 3.5 versus 30.1 +/- 3.5%; P < 0.05), the ITDI group when compared with the oral group had significantly higher mean hematocrit (36.0 +/- 1.0 versus 31.4 +/- 1.1%; P < 0.05) and TSAT (33.7 +/- 3.7 versus 22.6 +/- 4.0%; P < 0.05) values. In addition, the final mean dose of weekly rhEPO was significantly lower in the ITDI group (4799 +/- 981 versus 9998 +/- 1027 U/wk; P < 0.05). No patient in the ITDI group developed an adverse reaction to intravenous iron. It is concluded that ITDI represents a more efficacious method of iron supplementation in PD patients receiving rhEPO. Moreover, ITDI is safe and well tolerated and can be administered in an outpatient setting.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Thibault Cuisiniere ◽  
Annie Calvé ◽  
Gabriela Fragoso ◽  
Manon Oliero ◽  
Roy Hajjar ◽  
...  

Abstract Background Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. Results Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylum-dominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. Conclusions Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3819
Author(s):  
Carlos Poveda ◽  
Dora I. A. Pereira ◽  
Marie C. Lewis ◽  
Gemma E. Walton

Ferrous iron supplementation has been reported to adversely alter the gut microbiota in infants. To date, the impact of iron on the adult microbiota is limited, particularly at low supplementary concentrations. The aim of this research was to explore the impact of low-level iron supplementation on the gut microbiota of healthy and Irritable Bowel Syndrome (IBS) volunteers. Anaerobic, pH-controlled in vitro batch cultures were inoculated with faeces from healthy or IBS donors along with iron (ferrous sulphate, nanoparticulate iron and pea ferritin (50 μmol−1 iron)). The microbiota were explored by fluorescence in situ hybridisation coupled with flow cytometry. Furthermore, metabolite production was assessed by gas chromatography. IBS volunteers had different starting microbial profiles to healthy controls. The sources of iron did not negatively impact the microbial population, with results of pea ferritin supplementation being similar to nanoparticulate iron, whilst ferrous sulphate led to enhanced Bacteroides spp. The metabolite data suggested no shift to potentially negative proteolysis. The results indicate that low doses of iron from the three sources were not detrimental to the gut microbiota. This is the first time that pea ferritin fermentation has been tested and indicates that low dose supplementation of iron is unlikely to be detrimental to the gut microbiota.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amanda Bries ◽  
Chong Wang ◽  
Brian Wels ◽  
Isaac Agbemafle ◽  
Olivia Meier ◽  
...  

Abstract Objectives Iron deficiency anemia (IDA) is a widespread nutritional deficiency. Iron supplementation with ferrous sulfate (FeSO4) is the most common strategy to treat IDA; however, the compliance with daily FeSO4 administration is poor, due to contraindicating side effects. Previously, we have reported that A. oryzae (Ultimine®; ULT) is a novel iron source. Therefore, the objective of this study was to determine the biochemical assessment, non-transferrin bound iron (NTBI) and commonly related gastrointestinal side effects to assess the safety of A. oryzae compared to FeSO4. Methods Female participants (n = 16) with serum ferritin concentrations 40 µg/L were randomized to a double-blind, 9-wk cross-over study with a 3-wk placebo washout period between treatments. Oral iron supplements (65 mg Fe), FeSO4 and ULT were administered for 21 consecutive days for each subject. Side effect questionnaires were collected 3d/wk over the 9-wk study period. Side effects and biochemical markers (nausea, heartburn, abdominal pain, fatigue, headache, diarrhea, constipation, oxidative stress and liver and kidney function) from iron supplementation were evaluated, along with serum iron, % transferrin saturation (TS) and NBTI 8 h curves. Results Serum iron, TS, and NTBI were all markedly higher with FeSO4 at each time-point from 2–8 hours (P < 0.001) compared to ULT, whereas NTBI was undetected. Among treatments, FeSO4 resulted in higher inflammation, though not statistically significant. Compliance based on returned pills was higher with ULT (97.3%) than placebo and FeSO4 (95.2% and 93.2%, respectively). Subjects taking FeSO4 reported abdominal discomfort 2% more than ULT, which was not significantly different. FeSO4 caused marginally higher incidence of combined nauseation, constipation and diarrhea when subjects were taking FeSO4 (P < 0.07). Iron status was maintained similarly by both oral iron supplements. Oxidative stress, inflammation, kidney and liver function markers were not elevated with ULT supplementation, suggesting safety of its consumption. Conclusions Better compliance and less gastrointestinal related side effects were reported with ULT compared to FeSO4, while maintaining normal iron status. Our data suggests ULT is a safe oral iron supplement for treatment of IDA. Funding Sources Cura Global Health, Inc.


Transfusion ◽  
1998 ◽  
Vol 38 (8) ◽  
pp. 764-770 ◽  
Author(s):  
SM Kasper ◽  
H Lazansky ◽  
C Stark ◽  
M Klimek ◽  
R Laubinger ◽  
...  

2018 ◽  
Author(s):  
Yolanda Guillén ◽  
Marc Noguera-Julian ◽  
Javier Rivera ◽  
Maria Casadellà ◽  
Muntsa Rocafort ◽  
...  

AbstractThe impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the host’s genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.


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