Seth M. Armah

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.

Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana.

BACKGROUND Lysine affects diarrhea and anxiety via effects on serotonin receptors, enhanced intestinal repair, and sodium chloride-dependent opioid peptide transport. OBJECTIVE The objective was to investigate the effects of lysine supplementation on morbidity, growth, and anxiety in children and adults of peri-urban areas of Accra, Ghana. DESIGN In a double-blind randomized trial, the effect of lysine supplementation (1 g lysine/d) compared with that of placebo was examined in 2 groups of men, women, and children (n = 271). Primary outcomes included diarrheal and respiratory morbidity, growth, and anxiety and complement C3, C-reactive protein, serum cortisol, transferrin, and ferritin values. Independent-sample t tests, odds ratios, generalized estimating equations, 4-parameter sinusoid regression, and generalized linear models were used. RESULTS Thirty percent of men, 50% of women, and 15% of children were at risk of lysine inadequacy. Supplementation in children reduced diarrheal episodes [19 lysine, 35 placebo; odds ratio (OR): 0.52; 95% CI: 0.29, 0.92; P = 0.046] and the total number of days ill (21 lysine, 47 placebo; OR: 0.44; 95% CI: 0.26, 0.74; P = 0.034). Mean days ill per child per week (0.058 ± 0.039 lysine, 0.132 ± 0.063 placebo; P = 0.017) were negatively associated with weight gain with control for baseline weight and study group (P = 0.04). Men had fewer coryza episodes (23 lysine, 39 placebo; OR: 0.60; 95% CI: 0.36, 1.01; P = 0.05), total number of days ill (lysine: 130; placebo: 266; OR: 0.51; 95% CI: 0.28, 0.93; P = 0.03), and mean days ill per person per week (lysine: 0.21 ± 0.23; placebo: 0.41 ± 0.35; P = 0.04). Serum ferritin (P = 0.045) and C-reactive protein (P = 0.018) decreased in lysine-supplemented women but increased in placebo-supplemented women. CONCLUSION Lysine supplementation reduced diarrheal morbidity in children and respiratory morbidity in men in Ghana.

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.

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.

Influence of diet and supplements on iron status after gastric bypass surgery

BACKGROUND Iron deficiency is common after Roux-en-Y gastric bypass (RYGB) surgery, but there is no consensus on the optimal diet quality and quantity for restoring and preserving iron status. OBJECTIVES The authors explored the impact of dietary and supplemental sources of iron and absorptive factors on iron status. SETTING Academic, United States. METHODS In a cross-sectional cohort of individuals who underwent RYGB, nutrient intakes from food and supplements were measured using 3-day food records. Blood biomarkers of iron status, including concentrations of ferritin, total iron binding capacity, serum transferrin receptor (sTfR), and the sTfR:ferritin ratio, were assessed by a reference laboratory; iron deficiency was defined as having at least 2 abnormal measures. Associations between iron status biomarkers and dietary predictors were determined using regression analysis. RESULTS Of the 36 participants, 97% were female, the mean age was 45 years (95% confidence interval, 41-48 years), and body mass index was 32 (30-35) kg/m(2). Iron deficiency was found in 42% of participants. Dietary intake of heme iron, found in meats, was favorably associated with 3 iron status biomarkers (ferritin, β = .366; sTfR:ferritin ratio, β = -.459; and total iron binding capacity, β = -18.26; all P<.05), independent of obesity-induced inflammation. Intake of vitamin C from food contributed to iron status (ferritin, β = .010 and sTfR:ferritin ratio, β = -.011; P<.05). Use of supplementary non-heme iron, at doses recommended for prophylaxis (45 mg/d), was positively associated with serum ferritin (β = .964; P = .029). CONCLUSIONS For patients who have undergone RYGB, consuming high, but realistic amounts of heme iron in meat, vitamin C from food, and adherence to recommended iron supplements can prevent iron deficiency.

Fractional Zinc Absorption for Men, Women, and Adolescents Is Overestimated in the Current Dietary Reference Intakes

BACKGROUND The fractional zinc absorption values used in the current Dietary Reference Intakes (DRIs) for zinc were based on data from published studies. However, the inhibitory effect of phytate was underestimated because of the low phytate content of the diets in the studies used. OBJECTIVE The objective of this study was to estimate the fractional absorption of dietary zinc from the US diet by using 2 published algorithms. METHODS Nutrient intake data were obtained from the NHANES 2009-2010 and the corresponding Food Patterns Equivalents Database. Data were analyzed with the use of R software by taking into account the complex survey design. The International Zinc Nutrition Consultative Group (IZiNCG; Brown et al. Food Nutr Bull 2004;25:S99-203) and Miller et al. (Br J Nutr 2013;109:695-700) models were used to estimate zinc absorption. RESULTS Geometric means (95% CIs) of zinc absorption for all subjects were 30.1% (29.9%, 30.2%) or 31.3% (30.9%, 31.6%) with the use of the IZiNCG model and Miller et al. model, respectively. For men, women, and adolescents, absorption values obtained in this study with the use of the 2 models were 27.2%, 31.4%, and 30.1%, respectively, for the IZiNCG model and 28.0%, 33.0%, and 31.6%, respectively, for the Miller et al. model, compared with the 41%, 48%, and 40%, respectively, used in the current DRIs. For preadolescents, estimated absorption values (31.1% and 32.8% for the IZiNCG model and Miller et al. model, respectively) compare well with the conservative estimate of 30% used in the DRIs. When the new estimates of zinc absorption were applied to the current DRI values for men and women, the results suggest that the Estimated Average Requirement (EAR) and RDA for these groups need to be increased by nearly one-half of the current values in order to meet their requirements for absorbed zinc. CONCLUSIONS These data suggest that zinc absorption is overestimated for men, women, and adolescents in the current DRI. Upward adjustments of the DRI for these groups are recommended.

Associations between Diet Behaviors and Measures of Glycemia, in Clinical Setting, in Obese Adolescents

OBJECTIVE To determine the influence of dietary behaviors, assessed in a clinical setting, on measures of glycemia in overweight and obese adolescents. STUDY DESIGN The study is a retrospective, cross-sectional chart review. Eligible participants were overweight youth (N = 146, age 9-21 years) who attended the Youth Diabetes Prevention Clinic in Indianapolis, IN. Glycemic status was assessed during a 2-hour oral glucose tolerance test (OGTT). In the Bright Futures Questionnaire, a recommended clinical tool for assessing unhealthy behaviors in youth, nutrition-specific questions were modified to quantify dietary habits. Associations between dietary habits and measures of glycemia were determined using multiple linear regression models. Skewed data are presented as geometric means and 95% confidence intervals. RESULTS Of the 146 adolescents who were assessed [60% girls, age 13.7 years (13.3, 14.0), BMI 33.9 kg/m(2) (33.3, 34.5)], 40% were diagnosed with prediabetes. Higher intake of dessert foods was associated with increased glucose levels at 2 hours following the OGTT (β = 0.23, p = 0.004), and higher intake of packaged snack foods was associated with elevated levels of hemoglobin A1c (β = 0.04, p = 0.04), independent of adiposity. CONCLUSIONS In obese youth, high intakes of dessert and packaged snack items were associated with elevated concentrations of glucose at 2 hours following the OGTT and hemoglobin A1c. Findings demonstrate the usefulness of a modified Bright Futures Questionnaire, used in a clinical setting, for identifying dietary behaviors associated with hyperglycemia in obese adolescents. ClinicalTrials.gov registration number: NCT02535169.

Impact of Iron-enriched Aspergillus oryzae on Iron Bioavailability, Safety and Gut Microbiota in Rats

Iron deficiency is a leading global nutritional problem. Ferrous sulfate (FeSO4) is the most common iron source used for supplementation. Because of many side effects associated with its consumption, it is important to identify new forms of iron. The objectives of this study were to assess the bioavailability of iron-enriched Aspergillus oryzae, Aspiron (ASP), evaluate the toxicity of high-dose iron supplementation with ASP, and determine the ASP impact on gut microbiota in rats. In this study, we investigated iron bioavailability using the hemoglobin repletion test. Aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen levels were determined to evaluate the effect on liver and kidney functions. Protein carbonyls were measured to assess oxidative damage to proteins. Fecal samples at the end of the 14 day repletion period were used for 16S rRNA sequencing for gut microbiota analysis. The slope ratio method using a common intercept linear regression model was used to compare the bioavailability of ASP to FeSO4. Iron repletion increased hemoglobin concentrations with both ASP and FeSO4 treatments compared to the control group, except in the lowest ASP group. The slope ratio indicated that relative iron bioavailability of ASP was 60% of that of FeSO4 when hemoglobin change was compared to iron in the diet. Similar results were obtained when absolute iron intake was compared on the basis of food consumption. In comparison to the control, protein carbonyl concentrations were significantly ( p < 0.05) higher in the FeSO4 group but not with the ASP group. Supplementation with both sources of iron reduced the Enterobacteriaceae population in the gut microbiota of the rats. A higher relative abundance of bacteria from the phylum Verrucomicrobia was also observed with the highest dose of ASP. Iron-enriched A. oryzae with 60% relative bioavailability of FeSO4 did not show any signs of adverse effects after 14 days of iron supplementation. Future human studies are needed to understand the ASP detailed effect on gut microbiota.

Iron Absorption from Iron-enriched Aspergillus oryzae is Similar to Ferrous Sulfate in Healthy Female Subjects

Abstract Background Iron deficiency anemia (IDA) remains a global health issue, affecting mainly children and adolescent and pregnant women. Because of problems associated with current iron compounds used in both supplementation and fortification areas, there is an emerging interest in new natural iron sources to combat IDA. Objective The objective of this study was to compare the iron absorption of iron-enriched Aspergillus oryzae [Aspiron (ASP)] with FeSO4 in humans. Methods Iron absorption was assessed using stable isotope and serum iron response methods after oral intake of iron by healthy women in 2 separate studies. In the first study, ASP was intrinsically labelled with 58Fe into a dry form containing 8% iron. Subjects (n = 16, 18–35 y) were randomly assigned to consume liquid semipurified meals labelled with 2 stable iron isotopes, 57FeSO4 (10 mg) and ASP containing 2 mg 58Fe and 8 mg natural abundance iron, in 2 visits. Isotope enrichment was measured 2 wk after the last meal was eaten. In the second study, 17 subjects were randomly assigned to consume a test meal with 3 iron supplements during 3 separate visits: FeSO4, 10 mg Fe, and ASP in 2 iron doses, 10 mg and 20 mg. Changes in serum iron were measured at regular intervals for 4 h after supplementation. Results The first study showed that the difference in iron absorption from FeSO4 and ASP was not significant (17.18% ± 14.2% compared to 15.14% ± 12.3%; P = 0.07). The results of the second study suggested that the iron from ASP was released slowly compared to FeSO4 and the area under the curve did not reflect the absorption of ASP iron, but rather the rate of iron release. Conclusions Iron-enriched A. oryzae has high relative bioavailability and may cause lower iron surges into the blood compared to FeSO4.

Negative Effect of Camu-Camu (Myrciaria dubia) Despite High Vitamin C Content on Iron Bioavailability, Using a Caco-2 Cell Model

Abstract It is well known that vitamin C is an important enhancer of nonheme iron bioavailability due to its high reducing capacity. Camu-camu, a fruit that grows in the jungle of Peru, contains high amount of vitamin C (2,780 mg per 100 g). In this study, we investigated the effect of camu-camu on nonheme iron bioavailability from two different meals (rice with lentils and wheat flour porridge) using an in vitro Caco-2 cell model. These two meals were treated with three different camu-camu juice concentrations (C0 = 0 g, C1 = typical consumption, and C2 = 3X typical consumption). The results showed that camu-camu reduced rather than enhanced nonheme iron bioavailability. The inhibiting trend was significant (p<0.0001) in the wheat flour porridge (from 124 to 91 and 35 μg ferritin/μg protein, for C0, C1 and C2, respectively). With the rice with lentils, there was no significant effect of camu-camu due to the high polyphenols and phytate contents of the meal. Relative bioavailability values obtained showed significant decrease with increasing camu-camu juice concentration for both meals. As expected, the ascorbic acid added to the meals at a concentration equivalent to that present in C2, had no effect on bioavailability with rice meal but increased significantly with wheat flour meal. The findings of this study suggest that camu-camu, in the traditional way of preparation, may significantly reduce nonheme iron bioavailability because of its high polyphenol content which overrides the beneficial effect of its high ascorbic acid content