Iron-enriched Aspergillus oryzae as an alternative to iron sulphate to limit iron accumulation, growth and motility of the enteric pathogen S. Typhimurium.

Excess unabsorbed iron in the gastrointestinal tract may select for enteric pathogens and increase the incidence and severity of infectious disease. Aspergillus oryzae (Ao) is a filamentous fungus that has the ability to accumulate and store large amounts of iron, and when used as a supplement or fortificant, has similar absorption to ferrous sulphate (FeSO4) in humans. The objective of this study was to determine the effect of iron-enriched Ao (Ao iron) compared with FeSO4 on iron accumulation, growth and motility of the Gram-negative enteric pathogen, S. Typhimurium. S. Typhimurium was cultured in media containing no added iron or 1 µM elemental iron as either Ao iron or FeSO4. S. Typhimurium cultured with FeSO4 accumulated more iron than those cultured with Ao iron. Genes regulated by the iron-activated transcriptional repressor, Fur, did not differ between control and Ao iron, but decreased in S. Typhimurium cultured with FeSO4 compared with both groups. Growth of S. Typhimurium was greater when cultured with FeSO4 compared with Ao iron and control. S. Typhimurium swam faster, had greater acceleration and travelled further when cultured with FeSO4 compared with Ao iron and control; swim speed, acceleration and distance travelled did not differ between Ao iron and control. These findings provide evidence that Ao iron reduces the virulence of a common enteric pathogen in vitro. Further research is required to determine whether iron-enriched Ao is a suitable iron supplement to improve iron delivery in areas with a high infection burden.

Edible insects prevent changes to brain monoamine profiles from malnourishment in weaned rats.

Background: Childhood malnutrition can have devastating consequences on health, behavior, and cognition. Edible insects are sustainable low cost high protein and iron nutritious foods that can prevent malnutrition. However, it is unclear whether insect-based diets may help prevent changes to brain neurochemistry associated with malnutrition.Materials and Methods: Weanling male Sprague-Dawley rats were malnourished by feeding a low protein-iron diet (LPI, 5% protein and ∼2 ppm Fe) for 3 weeks or nourished by feeding a sufficient protein-iron diet (SPI, 15% protein 20 ppm FeSO4) for the duration of the study. Following 3 weeks of LPI diet, three subsets of the malnourished rats were placed on repletion diets supplemented with cricket, palm weevil larvae, or the SPI diet for 2 weeks, while the remaining rats continued the LPI diet for an additional 2 weeks. Monoamine-related neurochemicals (e.g. serotonin (5-HT), dopamine (DA), norepinephrine) and select monoamine metabolites were measured in the hypothalamus, hippocampus, striatum, and prefrontal cortex using Ultra High-Performance Liquid Chromatography.Results: Five weeks of LPI diets disrupted brain monoamines, most notable in the hypothalamus. Two weeks supplementation with cricket and palm weevil larvae diets prevented changes to measures of 5-HT and DA turnover in the hippocampus and hypothalamus. Moreover, these insect diets prevented the malnutrition-induced imbalance of 5-HT and DA metabolites in the hippocampus, striatum, and hypothalamus.Conclusion: Edible insects such as cricket and palm weevil larvae could be sustainable nutrition intervention to prevent behavioral and cognitive impairment associated abnormal brain monoamine activities that results from early life malnutrition.

Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP+-Induced Apoptosis in a Cell Culture Model of Parkinson's Disease.

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP+)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP+. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP+. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP+ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

Iron Absorption from Bouillon Fortified with Iron-Enriched Aspergillus oryzae Is Higher Than That Fortified with Ferric Pyrophosphate in Young Women.

BACKGROUND: Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes. METHODS: In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 µg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies. RESULTS: Geometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = -0.41, P = 0.014) and hepcidin (r = -0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption. CONCLUSIONS: ASP-p-fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Phytic Acid Protects from Oxidative Stress Induced by Iron-Overload and High-Fat Diets in ß2-Microglobulin Knockout Mice.

The objective of this study was to examine the protective effect of phytic acid (PA) in reducing oxidative stress in an animal model for human hereditary hemochromatosis (HH) fed high-fat diets. Sixty-four ß2 microglobulin knockout (ß2m KO) mice were randomly assigned to three treatments by feeding: control (basal), atherogenic (AT), and polyunsaturated fatty acid (PUFA) diets. One-half of the mice in each treatment group were fed 2% (wt/wt) PA. The ß2m+/+ mice (wild type (WT)) were fed a basal diet. All seven groups were fed for 10 weeks with a 50-ppm iron-containing diet (AIN-93G). Free iron and lipids were measured in serum samples. Nonheme iron, thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase concentrations were measured in the liver tissue. Nonheme iron concentration in ß2m KO mice (on the basal diet) was 20× higher (p < 0.0001) than in the WT mice. Compared to the WT mice, ß2m KO mice had a significantly higher concentration of free iron in the serum (p < 0.0001), six-fold higher hepatic TBARs (p < 0.0001), and 18% lower hepatic SOD level. When PA was added to the ß2m KO basal diet, a reduction (26 to 50%) of iron concentration was seen in the liver and heart. The addition of PA also significantly reduced TBARs in all three dietary groups of the iron-overloaded group, but most effectively in the control group. An increase in SOD concentration was seen only in the PUFA group, but serum triacylglycerol (TG) concentration was reduced in both dietary fat groups. In conclusion, our results suggest that PA protects against oxidative stress-induced by genetic iron overload alone or when fed high fat.

Epigallocatechin Gallate Protects against TNFα- or H2O2- Induced Apoptosis by Modulating Iron Related Proteins in a Cell Culture Model.

Oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson's disease (PD). Considering the entwined relationship among these factors, epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its protective effects against those factors. The objective of this study is to determine whether EGCG protects N27 dopaminergic neuronal cells from H2O2 - and TNFα- induced neurotoxicity. Seven treatments were included: control, H2O2, TNFα, FeSO4, H2O2 + EGCG, TNFα + EGCG, FeSO4 + EGCG. Cells were pretreated with 10 µM EGCG, followed by 50 µM H2O2, 30 ng/ml TNFα or 50 µM FeSO4. Neuroprotective effects of EGCG were assessed by cell viability assay, caspase-3 activity, intracellular reactive oxygen species (ROS) generation, and iron related protein expressions. Caspase-3 activity was increased to 2.8 fold (P < 0.001) and 1.5 fold (P < 0.01) with H2O2 and TNFα treatment; However, EGCG pretreatment significantly decreased the caspase activity by 50.2% (P < 0.001) and 30.1% (P < 0.05). Similarly, cell viability was reduced to 69.2% (P < 0.01) and 89% (P < 0.01) by H2O2 and TNFα, which was partially blocked by EGCG pretreatment. Also, EGCG significantly (P < 0.001) protected against H2O2- induced ROS in a time dependent manner. In addition, both H2O2 and TNFα significantly (P < 0.05) upregulated hepcidin expression and marginally reduced ferroportin (Fpn) expression unlike iron treatment alone. Collectively, our results show that EGCG protects against both TNFα- and H2O2- induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated mainly by hepcidin and partially by Fpn.

Epigallocatechin Gallate Has a Neurorescue Effect in a Mouse Model of Parkinson Disease.

Background: Parkinson disease (PD) is a neurodegenerative disorder that has been associated with many factors, including oxidative stress, inflammation, and iron accumulation. The antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG), a major polyphenol in green tea, may offer protection against PD.Objective: We sought to determine the neurorescue effects of EGCG and the role of iron in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD.Methods: We evaluated the neurorescue effect of EGCG (25 mg/kg, 7 d, oral administration) against MPTP-induced (20 mg/kg, 3 d, intraperitoneal injection) neurodegeneration in C57 male black mice. Thirty mice weighing ∼25 g were divided into 3 groups: control, MPTP, and MPTP + EGCG. The neurorescue effect of EGCG was assessed with the use of motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron-related protein expression.Results: Compared with the control group, MPTP treatment shortened the mice's latency to fall from the rotarod by 16% (P < 0.05), decreased the striatal dopamine concentration by 58% (P < 0.001) and dihydroxyphenylacetic acid by 35% (P < 0.05), and increased serum protein carbonyls by 71% (P = 0.07). However, EGCG rescued MPTP-induced neurotoxicity by increasing the rotational latency by 17% (P < 0.05) to a value similar to the control group. Striatal dopamine concentrations were 40% higher in the MPTP + EGCG group than in the MPTP group (P < 0.05), but the values were significantly lower than in the control group. Compared with the MPTP and control groups, mice in the MPTP + EGCG group had higher substantia nigra ferroportin expression (44% and 35%, respectively) (P < 0.05) but not hepcidin and divalent metal transporter 1 expression.Conclusion: Overall, our study demonstrated that EGCG regulated the iron-export protein ferroportin in substantia nigra, reduced oxidative stress, and exerted a neurorescue effect against MPTP-induced functional and neurochemical deficits in mice.

Total Iron Bioavailability from the US Diet Is Lower Than the Current Estimate.

BACKGROUND: Total (heme and nonheme) iron bioavailability from the US diet has been estimated to be 18% based on a single human absorption study. New data, however, suggest that it may be time to revisit this estimate. OBJECTIVE: We estimated total iron bioavailability from the US diet with the use of our recently reported algorithm that estimates nonheme iron absorption and a conservative value for heme iron absorption. METHODS: We used dietary intake and biomarker information from the NHANES 2001-2002, MyPyramid Equivalents Database, and Food and Nutrient Database for Dietary Studies. The survey package in R software was used to estimate means and CIs, taking into account the strata, primary sampling units, and appropriate survey weight. We implemented 2 different approaches to estimate total iron absorption. In the first approach, we included all survey participants but adjusted the geometric mean of nonheme iron absorption to 15 µg ferritin/L serum to mimic values of individuals with no iron stores; in the second approach, absorption was estimated for only nonanemic subjects with no iron stores. A total sample size of 6631 was used based on availability of dietary and iron status biomarker data and C-reactive protein concentration ≤ 6 mg/L. RESULTS: The geometric mean (95% CI) of unadjusted nonheme iron absorption for all subjects was 3.7% (3.6%, 3.8%), higher in female subjects [5.6% (5.4%, 5.7%)] than male subjects [2.6% (2.5%, 2.7%)] (P < 0.0001). Nonheme iron absorption was lower in non-Hispanic whites [3.5% (3.4%, 3.6%)] than Mexican Americans [4.5% (4.2%, 4.8%)] and non-Hispanic blacks [4.4% (4.1%, 4.7%)]. Estimated total iron absorption was 15.5% or 15.1%, depending on which approach was used to carry out the calculations. CONCLUSION: This study provides useful data for evaluating the current value of iron bioavailability from the US diet.

Regular Consumption of a High-Phytate Diet Reduces the Inhibitory Effect of Phytate on Nonheme-Iron Absorption in Women with Suboptimal Iron Stores.

BACKGROUND: High phytate (HP) consumption is a concern in developing countries because of the high prevalence of iron deficiency in these countries. OBJECTIVE: We investigated whether habitual consumption of an HP diet reduces the inhibitory effect of phytate on nonheme-iron absorption. METHODS: Thirty-two nonanemic females, 18-35 y of age, with normal body mass index but with suboptimal iron stores (serum ferritin, ≤30 µg/L), were matched for serum ferritin concentration and randomly assigned to HP and low-phytate (LP) groups, in a parallel design study. Each subject consumed HP or LP foods with at least 2 of their daily meals for 8 wk, resulting in a change in phytate intake (from 718 to 1190 mg/d in the HP group and 623 to 385 mg/d in the LP group). The serum iron response over 4 h after a test meal containing 350 mg of phytate was measured at baseline and postintervention. Ferritin, transferrin receptor, and hepcidin concentrations were measured at baseline and 8 wk. RESULTS: Twenty-eight subjects completed the study (n = 14 per group). The serum iron response to the test meal increased in the HP group at postintervention, resulting in a 41% increase in the area under the curve (AUC; P < 0.0001). However, no effect was observed in the LP group (21% decrease in AUC; P = 0.76). The postintervention serum iron response was lower (P < 0.0001) in the LP group than in the HP group after controlling for the baseline serum iron response and hepcidin concentration, reflecting in a 64% lower AUC. CONCLUSIONS: We found that habitual consumption of an HP diet can reduce the negative effect of phytate on nonheme-iron absorption among young women with suboptimal iron stores. Future studies are needed to explore possible mechanisms. This trial was registered at clinicaltrials.gov as NCT02370940.

An integrated microcredit, entrepreneurial training, and nutrition education intervention is associated with better growth among preschool-aged children in rural Ghana.

BACKGROUND: Poor diet quality is a determinant of the high prevalence rates of malnutrition in Ghana. There is little evidence on the effectiveness of a multisector intervention to improve children's diets and nutritional status. OBJECTIVE: The project tested whether participation in an entrepreneurial and nutrition education intervention with microcredit was associated with the nutritional status of children 2-5 y of age. METHODS: A quasi-experimental 16-mo intervention was conducted with microcredit loans and weekly sessions of nutrition and entrepreneurship education for 179 women with children 2-5 y of age [intervention group (IG)]. Nonparticipating women and their children from the same villages (nonparticipant, n = 142) and from similar neighboring villages (comparison, n = 287) were enrolled. Repeated measures linear regression models were used first to examine children's weight-for-age (WAZ), height-for-age (HAZ), and body mass index-for-age (BAZ) z scores at baseline and at 4 follow-up time points ∼4 mo apart. Time, intervention status, time-by-intervention interaction terms, region of residence, household wealth rank, household head occupation, number of children <5 y of age, and child sex and age were included. RESULTS: There was a significant interaction between the IG and time for BAZ (P = 0.02) with significant Bonferroni-corrected pairwise comparisons between the IG and comparison group (CG) at 8 mo (difference of 0.36 ± 0.09 z score, P < 0.0001). The WAZ group difference was significant between 4 and 16 mo (P = 0.01 for interaction) and peaked at 8-12 mo (differences of ∼0.28 z). The HAZ of children in the IG was significantly higher than that in the CG, reaching a 0.19 z difference at 16 mo (P < 0.05). When the fixed effects models were fitted in sensitivity analyses, some group anthropometric differences were of lower magnitude but remained significant. CONCLUSION: An integrated package of microcredit and education may improve nutritional outcomes of children living in poor, rural communities.

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling.

6-Hydroxydopamine (6-OHDA) is a classic neurotoxin that has been widely used in Parkinson's disease research. 6-OHDA can increase intracellular reactive oxygen species (ROS) and can cause cell damage, which can be attenuated with (-)-Epigallocatechin-3-gallate (EGCG) treatment. However, the mechanism by which EGCG alters the 6-OHDA toxicity remains unclear; In this study, we found 6-OHDA (25 µM) alone increased intracellular ROS concentration in N27 cells, which was attenuated by pretreating with EGCG (100 µM). We evaluated the intracellular oxidative damage by determining the level of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content. 6-OHDA significantly increased TBARS by 82.7% (P < .05) and protein carbonyl content by 47.8 (P < .05), compared to the control. Pretreatment of EGCG decreased TBARS and protein carbonyls by 36.4% (P < .001) and 27.7% (P < .05), respectively, compared to 6-OHDA alone treatment. Antioxidant effect was tested with E2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and peroxisome-proliferator activator receptor γ (PPARγ) expression. 6-OHDA increased Nrf2 expression by 69.6% (P < .001), HO-1 by 173.3% (P < .001), and PPARγ by 122.7% (P < .001), compared with untreatment. EGCG pretreatment stabilized these alterations induced by 6-OHDA. Our results suggested that the neurotoxicity of 6-OHDA in N27 cells was associated with ROS pathway, whereas pretreatment of EGCG suppressed the ROS generation and deactivated the Nrf2/HO-1 and PPARγ expression.

Corrigendum: Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial - the safe iron study.

[This corrects the article DOI: 10.3389/fnut.2023.1230061.].

A complete diet-based algorithm for predicting nonheme iron absorption in adults.

Many algorithms have been developed in the past few decades to estimate nonheme iron absorption from the diet based on single meal absorption studies. Yet single meal studies exaggerate the effect of diet and other factors on absorption. Here, we propose a new algorithm based on complete diets for estimating nonheme iron absorption. We used data from 4 complete diet studies each with 12-14 participants for a total of 53 individuals (19 men and 34 women) aged 19-38 y. In each study, each participant was observed during three 1-wk periods during which they consumed different diets. The diets were typical, high, or low in meat, tea, calcium, or vitamin C. The total sample size was 159 (53 × 3) observations. We used multiple linear regression to quantify the effect of different factors on iron absorption. Serum ferritin was the most important factor in explaining differences in nonheme iron absorption, whereas the effect of dietary factors was small. When our algorithm was validated with single meal and complete diet data, the respective R(2) values were 0.57 (P < 0.001) and 0.84 (P < 0.0001). The results also suggest that between-person variations explain a large proportion of the differences in nonheme iron absorption. The algorithm based on complete diets we propose is useful for predicting nonheme iron absorption from the diets of different populations.

Echinacea sanguinea and Echinacea pallida extracts stimulate glucuronidation and basolateral transfer of Bauer alkamides 8 and 10 and ketone 24 and inhibit P-glycoprotein transporter in Caco-2 cells.

The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator. We hypothesized that Bauer alkamides 8, 10, and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit the P-glycoprotein transporter in Caco-2 human intestinal epithelial cells. Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix. Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11. Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts. Bauer alkamides 8, 10, and 11 (175-230 µM) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~ 90 µM total alkamides) and E. pallida (5 mg/mL, containing 285 µM total alkamides) decreased the efflux of the P-glycoprotein transporter probe calcein-AM from Caco-2 cells. These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits. Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics, which are substrates for the P-glycoprotein transporter.

Iron Deficiency and Iron Deficiency Anemia in Women with and without Obesity: NHANES 2001-2006.

Obesity has been linked to numerous health and nutritional problems, including impaired iron metabolism, a common cause of anemia. We aimed to determine the prevalence of anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among women aged 20-49 years based on body mass index (BMI) status. We used measures of iron status and body mass index from the 2001-2006 National Health and Nutrition Examination Survey (NHANES). Mean serum ferritin, erythrocyte protoporphyrin, and soluble transferrin receptor were higher, while those of serum iron, percent transferrin saturation, and mean cell volume (MCV) were lower in women with obesity than those with normal weight (all p < 0.016). ID based on the ferritin model was 12.5 ± 1.0% vs. 22.9 ± 1.6% (p < 0.001); 9.0 ± 0.9% vs. 20.0 ± 1.3% (p < 0.001) based on the MCV model; and 8.1 ± 1.0% vs. 10.5 ± 1.2% (p > 0.05) based on the BII model for women with normal weight and women with obesity, respectively. Anemia prevalence was 5.5 ± 0.8% (normal) vs. 9.3 ± 1.0% (obese) (p = 0.005). The IDA estimates based on the ferritin and MCV models were similar but higher than that from the BII model (p < 0.001). Generally, the prevalence rates of ID and anemia (and IDA) were higher for women with obesity, but the method used to define deficiency mattered. The choice of iron indices is important for estimating ID and IDA in populations with obesity.

Combined Effect of Maternal Obesity and Diabetes on Excessive Fetal Growth: Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 2012-2015.

Introduction: Obesity and dysregulation in glucose metabolism are risk factors for excessive fetal growth, but their combined effects are not often examined in a single study. Methods: Data from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System Phase 7 (2012-2015) were used. Logistic regression was used to investigate the association between maternal prepregnancy BMI and pre-existing diabetes/gestational diabetes on the odds of delivering a large-for-gestational-age infant or an infant with macrosomia. Results: Complete data for 128,199 singleton births were used. The proportions of large-for-gestational-age infants and infants with macrosomia increased with the degree of obesity (p<0.001) and were higher in women with diabetes than in those without (p<0.001). Compared with the AOR among normal-weight women, the AOR of delivering large-for-gestational-age infants and infants with macrosomia among women with morbid obesity (BMI≥40) were 2.82 (p<0.001) and 2.67 (p<0.001), respectively. Compared with the AOR among nondiabetic women, the AOR of delivering a large-for-gestational-age infant was 1.88 (p<0.001) among those with pre-existing diabetes and 1.49 (p<0.001) among those with gestational diabetes. Except for the underweight group, women with pre-existing diabetes were nearly twice as likely to deliver a large-for-gestational-age infant as those with similar BMI without diabetes. Women with morbid obesity and gestational diabetes were twice as likely to have a large-for-gestational-age infant and an infant with macrosomia as nondiabetic women with normal BMI. Conclusions: We have shown that when maternal obesity and diabetes, particularly pre-existing diabetes, occur together, the risk of delivering large-for-gestational-age and macrosomia increases significantly. Our findings call for public health attention to address maternal obesity and diabetes to minimize suboptimal fetal growth.

Effects of green tea polyphenols on inflammation and iron status.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocatechin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were fed an iron-deficient diet for 2 weeks and then randomly divided into four groups (n 8 each): positive controls, negative controls, lipopolysaccharide (LPS, 0⋅5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet) for 3 additional weeks. The study involved testing two control groups, both treated with saline. One group (positive control) was fed a regular diet containing standard iron, while the negative control was fed an iron-deficient diet. Additionally, two treatment groups were tested. The first group was given LPS, while the second group was administered LPS and fed an EGCG diet. Iron status, hepcidin, C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (P = 0⋅02) and the LPS + EGCG (P = 0⋅01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative control (P < 0⋅001) but not with both LPS groups. SAA concentrations were significantly lower in the LPS + EGCG group compared to LPS alone group. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial - the safe iron study.

Introduction: The safety of novel forms of iron in healthy, iron-replete adults as might occur if used in population-based iron supplementation programs was examined. We tested the hypotheses that supplementation with nanoparticulate iron hydroxide adipate tartrate (IHAT), an iron-enriched Aspergillus oryzae product (ASP), or ferrous sulphate heptahydrate (FS) are safe as indicated by erythrocyte susceptibility to malarial infection, bacterial proliferation, and gut inflammation. Responses to FS administered daily or weekly, and with or without other micronutrients were compared. Methods: Two phases of randomized, double-blinded trials were conducted in Boston, MA. Phase I randomized 160 volunteers to six treatments: placebo, IHAT, ASP, FS, and FS plus a micronutrient powder (MNP) administrated daily at 60 mg Fe/day; and FS administered as a single weekly dose of 420 mg Fe. Phase II randomized 86 volunteers to IHAT, ASP, or FS administered at 120 mg Fe/day. Completing these phases were 151 and 77 participants, respectively. The study was powered to detect effects on primary endpoints: susceptibility of participant erythrocytes to infection by Plasmodium falciparum, the proliferation potential of selected pathogenic bacteria in sera, and markers of gut inflammation. Secondary endpoints for which the study was not powered included indicators of iron status and gastrointestinal symptoms. Results: Supplementation with any form of iron did not affect any primary endpoint. In Phase I, the frequency of gastrointestinal symptoms associated with FS was unaffected by dosing with MNP or weekly administration; but participants taking IHAT more frequently reported abdominal pain (27%, p < 0.008) and nausea (4%, p = 0.009) than those taking FS, while those taking ASP more frequently reported nausea (8%, p = 0.009). Surprisingly, only 9% of participants taking IHAT at 120 mg Fe/day (Phase II) reported abdominal pain and no other group reported that symptom. Discussion: With respect to the primary endpoints, few differences were found when comparing these forms of iron, indicating that 28 days of 60 or 120 mg/day of IHAT, ASP, or FS may be safe for healthy, iron-replete adults. With respect to other endpoints, subjects receiving IHAT more frequently reported abdominal pain and nausea, suggesting the need for further study. Clinical Trial Registration: ClinicalTrials.gov, NCT03212677; registered: 11 July 2017.

Inflammatory Markers and Hepcidin are Elevated but Serum Iron is Lower in Obese Women of Reproductive Age.

Limited evidence suggests that serum iron and hepcidin concentrations are dysregulated in obesity and inflammation. The objective of the present study was to compare C-reactive protein, interleukin-6, circulating levels of hepcidin, serum lipids, and iron status in obese vs. normal-weight women of childbearing age. Healthy women aged 18-30 years were recruited for the study (n = 47: 25 obese and 22 normal weight). Fasting blood samples were obtained to measure serum lipids (total cholesterol, HDL, LDL cholesterol, triglycerides, non-HDL cholesterol), complete blood count, serum iron, total iron-binding capacity, transferrin saturation, serum ferritin, hepcidin, C-reactive protein, and interleukin-6. Obese women had significantly higher mean serum C-reactive protein (p < 0.001), interleukin-6 (p < 0.001), hepcidin (p = 0.024), triglycerides (p < 0.001) and total cholesterol/HDL ratio (p < 0.001) but lower HDL (p = 0.001) and serum iron/hepcidin ratio (p = 0.011) compared with normal-weight women. BMI correlated positively with inflammatory markers, triglycerides, LDL and total cholesterol/HDL ratio, and negatively with HDL and serum iron/hepcidin ratio. Serum iron correlated negatively with ferritin in the obese group (p = 0.030) but positively in normal weight women (p = 0.002). BMI and ferritin were the only predictors of serum iron/hepcidin ratio accounting for 23% of the variation among subjects. Studies are needed to examine anti-inflammatory dietary approaches that can improve iron biomarkers in obese women.

Cytotoxicity assessment of Aflatoxin B1 after high voltage atmospheric cold plasma treatment.

Aflatoxin B1 (AFB1) is a secondary metabolite produced by Aspergillus flavus and A. parasiticus, and is a known carcinogen in humans and animals. High voltage atmospheric cold plasma (HVACP) technology has already shown promise to decontaminate AFB1 in food and feed. This study aimed to investigate the cytotoxicity of AFB1 after HVACP treatment. AFB1 (100 µM) was treated at 85 kV with HVACP for 0, 2, 5, 10, and 20 min. HepG2 cells were exposed to HVACP-treated AFB1 for 72 h and assessed for cell viability, caspase-3 activity, DNA fragmentation, and protein carbonyls for each treatment time. Cell viability, caspase-3 activity, DNA fragmentation levels, and protein carbonyls contents of HepG2 cells exposed to HVACP-treated AFB1 after 20 min was not significantly different compared to non-exposed HepG2 cells (P > 0.05). However, their contents were significantly higher in non-exposed cells compared to the other HVACP treatment times (P < 0.01). Twenty minutes of HVACP treatment for AFB1 significantly reduced AFB1 cytotoxicity and oxidative damage and showed potential as a safe aflatoxin decontamination technology.