1.
The Role of Iron in Brain Development: A Systematic Review.
McCann, S, Perapoch Amadó, M, Moore, SE
Nutrients. 2020;12(7)
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Iron deficiency is the most common vitamin or mineral deficiency worldwide and is particularly common among pregnant women, infants and young children due to high iron demands during periods of rapid growth. Iron plays an important role in the development of the brain, and animal studies suggest that getting enough iron in pregnancy and early childhood is particularly important. The aims of this systematic review were to (i) investigate the relationship between iron status and brain development and (ii) assess whether this relationship differs according to age or type of development (‘domain’). The researchers looked for studies on iron deficiency or iron supplementation in pregnancy and up to 4 years of age. 26 observational studies and 28 intervention studies were included in the review. There was no clear relationship between iron status and developmental outcomes across any of the ages or domains included. Many of the studies were of low quality and there was a wide variation in study design, along with a lack of research on pregnancy and early infancy. The researchers concluded that evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
Abstract
One-third of children falter in cognitive development by pre-school age. Iron plays an important role in many neurodevelopmental processes, and animal studies suggest that iron sufficiency in pregnancy and infancy is particularly important for neurodevelopment. However, it is not clear whether iron deficiency directly impacts developmental outcomes, and, if so, whether impact differs by timing of exposure or developmental domain. We searched four databases for studies on iron deficiency or iron supplementation in pregnancy, or at 0-6 months, 6-24 months, or 2-4 years of age. All studies included neurodevelopmental assessments in infants or children up to 4 years old. We then qualitatively synthesized the literature. There was no clear relationship between iron status and developmental outcomes across any of the time windows or domains included. We identified a large quantity of low-quality studies, significant heterogeneity in study design and a lack of research focused on pregnancy and early infancy. In summary, despite good mechanistic evidence for the role of iron in brain development, evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
2.
High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.
Smith, EM, Jones, JL, Han, JE, Alvarez, JA, Sloan, JH, Konrad, RJ, Zughaier, SM, Martin, GS, Ziegler, TR, Tangpricha, V
JPEN. Journal of parenteral and enteral nutrition. 2018;42(1):87-94
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Anaemia is common in critically ill patients and is associated with increased mortality and potentially an extended need for a ventilator. Treatment for anaemia can be invasive and carries a level of risk; therefore further studies on complementary therapies are warranted. Vitamin D has the potential to decrease anaemia through decreasing the production of the iron-regulatory hormone hepcidin. The study aimed to test whether high dose vitamin D would affect haemoglobin concentrations in critically ill patients. In this pilot double-blind randomised control trial, 30 critically ill patients were assigned 250,000 IU vitamin D, 500,000 IU vitamin D or placebo split over 5 doses in 5 days. Blood was taken weekly for up to four weeks and analysed for vitamin D and hepcidin concentrations. Vitamin D concentrations increased significantly in both groups that received vitamin D, compared to no change in the placebo group. Compared to placebo, haemaglobin concentrations significantly increased by 8% in the group receiving 500,000 IU vitamin D but not in the lower dose group. After one week, hepcidin concentrations were significantly decreased in the 500,000 IU vitamin D group, however this was not sustained and no differences between either group and placebo were observed at the end of the study. This did not translate into a reduction in anaemia in either group at any point throughout the study. Extremely high dose vitamin D supplementation was shown to significantly increase circulating vitamin D concentrations and acutely reduce hepcidin. Although anaemia was not affected, clinicians could use this study as an example of safe usage of high dose vitamin D in critically ill patients to improve haemaglobin concentrations, which could reduce the need for invasive treatments, reduce hospital stay duration and treatment costs.
Abstract
BACKGROUND Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. MATERIALS AND METHODS Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. RESULTS At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. CONCLUSION In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.
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Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD.
Lee, T, Clavel, T, Smirnov, K, Schmidt, A, Lagkouvardos, I, Walker, A, Lucio, M, Michalke, B, Schmitt-Kopplin, P, Fedorak, R, et al
Gut. 2017;66(5):863-871
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Iron deficiency is common in patients with Inflammatory Bowel Disease (IBD) and the standard management is with oral iron replacement therapy. However, this is thought to worsen IBD symptoms, as free iron in the gut can alter the composition of the resident gut bacteria and may contribute to inflammation. This open-labelled clinical trial compared oral iron replacement to intravenous iron replacement in subjects with Crohn’s disease (CD), Ulcerative Colitis and iron-deficient, non-inflamed subjects. The data collected included microbiome sequencing, metabolic profiling, serum iron and inflammation markers. Whilst both interventions alleviated deficiency, the intravenous iron replacement was slightly more effective at raising ferritin levels. The results showed that iron replacement therapy shifted the microbiome diversity and composition depending on free iron availability in the gut. A reduced microbiome diversity already distinguishes IBD from healthy subjects and a further decline in abundance following iron replacement therapy was particularly noticeable with oral iron supplementation and in Crohn's Disease subjects. However, over the short course of three months, this was not linked to disease severity in this study. This study affirms the importance of assessing for iron deficiency in IBD clients whilst supporting IV iron replacement being a favourable alternative to oral supplementation for individuals with unstable microbiota.
Abstract
OBJECTIVE Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). DESIGN The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. RESULTS Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. CONCLUSIONS Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. TRIAL REGISTRATION NUMBER clinicaltrial.gov (NCT01067547).
4.
[Abnormal effect of nitrosation inhibitors in human gastric juice].
Ermilov, VB, Shendrikova, IA, Volkov, DP, Stefanenko, IuF, Chernomordikov, VG
Voprosy onkologii. 1986;32(10):58-64
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Growth faltering in infancy establishes a trajectory for lifelong health of the individual and population. Stunted growth is due to the combined effect inadequate diet (malnutrition) and infection that affects the gut mucosal lining, with increased nutrient loss due to maldigestion and malabsorption, and increased nutritional requirements due to inflammation. Intestinal integrity in infants has been improved through supplementation with vitamin A and Zinc. Iron deficiency anemia may impair intestinal integrity. This study investigates the effects of complementary fortified food on gut integrity and systemic inflammation among Zambian infants age 6-18months. Infants of 6 months +/- 2 weeks old were randomised to either 50g/day richly fortified porridge mix or 50g basal porridge mix fortified with micronutrient levels planned for maize fortification in Zambia. At 18 months, the richly fortified porridge group had a significantly higher mean lactulose to mannitol ratio than the basal-fortified group, indicating they had significantly higher intestinal permeability. This effect was not modified by child’s sex, maternal HIV status, concurrent breast-feeding or baseline anaemia. The biological significance of this increase in intestinal permeability is questionable, however further research is warranted to understand the effect of iron supplementation on gut permeability in infants with normal iron status. In conclusion, a richly fortified complementary/replacement food did not benefit and may have worsened intestinal permeability. Further investigation into local interactions of key micronutrients with gut integrity, particularly in micronutrient-replete infants is needed.
Abstract
The paper discusses the effect of vitamins C and E and Plantaglucide on nitroso compounds yield in the course of nitrosation of amines in human gastric juice. The study group included 56 subjects. The above drugs capable of inhibiting in vitro nitrosation produced an anomalous effect in gastric juice of some subjects, i.e. potentiated nitroso compounds yield in nitrosation of amines by sodium nitrite. The said action of vitamins C and E was apparent in dimethylamine and amidopyrine nitrosation but it was not in morpholine nitrosation. Sharply increased levels in nitroso compounds were observed in some mice fed precursors of nitroso compounds in combination with vitamin C and Plantaglucide. These data point to an anomalous effect of the drugs on the body.