Too Much Too Little: Clarifying the Relationship Between Maternal Iodine Intake and Neurodevelopmental Outcomes.

BACKGROUND: In 2009, the Australian government mandated the fortification of bread salt with iodine. In 2010, pregnant and lactating women were also advised to take an iodine-containing supplement. Our assessment of this policy in an iodine-sufficient population showed that children whose mothers were in the highest and lowest quartiles of iodine intake performed more poorly on early childhood tests of cognition and language than those in the second quartile. However, we did not quantify the iodine intake associated with optimal neurodevelopment. OBJECTIVES: The aim was to establish the iodine intake range in pregnancy associated with optimal child neurodevelopment. METHODS: A prospective cohort study of pregnant women and their young children (n = 699). Iodine intake was assessed by a validated food frequency questionnaire at 16 and 28 wk of gestation. Child neurodevelopment at 18 mo of age was measured using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). The relationship between average iodine intake during pregnancy and child neurodevelopment was assessed using linear regression with fractional polynomials and adjustment for confounders. RESULTS: Mean (SD) iodine intake was similar at study entry and 28 wk, 308 (120) µg/d, with 82% of women taking iodine supplements at study entry. The relationship between iodine intake during pregnancy and Bayley-III cognitive and language scores was curvilinear (P = 0.001 and P = 0.004, respectively), with the lowest Bayley-III scores observed at lower and higher iodine intakes. The inflection point that drove the association between lower iodine intake in pregnancy and poorer child neurodevelopment scores was around 185 µg/d; for the higher pregnancy iodine intakes, language and cognitive scores were negatively affected from ∼350 µg/d to 370 µg/d, respectively. Higher iodine intakes were being driven by supplement use. CONCLUSIONS: Targeted, not blanket, iodine supplementation may be needed for pregnant women with low-iodine intake from food.

The Effect of Iron Supplements on the Gut Microbiome of Females of Reproductive Age: A Randomized Controlled Trial.

BACKGROUND: Iron deficiency is the most common nutritional deficiency worldwide, particularly for young children and females of reproductive age. Although oral iron supplements are routinely recommended and generally considered safe, iron supplementation has been shown to alter the fecal microbiota in low-income countries. Little is known about the effect of iron supplementation on the fecal microbiota in high-income settings. OBJECTIVES: To assess the effect of oral iron supplementation compared with placebo on the gut microbiome in nonpregnant females of reproductive age in a high-income country. METHODS: A 21-d prospective parallel design double-blind, randomized control trial conducted in South Australia, Australia. Females (18-45 y) were randomly assigned to either iron (65.7 mg ferrous fumarate) or placebo. Fecal samples were collected prior to commencing supplements and after 21 d of supplementation. The primary outcome was microbiota ß-diversity (paired-sample weighted unique fraction metric dissimilarity) between treatment and placebo groups after 21 d of supplementation. Exploratory outcomes included changes in the relative abundance of bacterial taxa. RESULTS: Of 82 females randomly assigned, 80 completed the trial. There was no significant difference between the groups for weighted unique fraction metric dissimilarity (mean difference: 0.003; 95% confidence interval: -0.007, 0.014; P = 0.52) or relative abundance of common bacterial taxa or Escherichia-Shigella (q > 0.05). CONCLUSIONS: Iron supplementation did not affect the microbiome of nonpregnant females of reproductive age in Australia. This trial was registered at clinicaltrials.gov as NCT05033483.

Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Iron-Fortified Foods Are Needed To Meet the Estimated Average Requirement for Iron in Australian Infants Aged 6 to 12 Months.

BACKGROUND: Meeting iron intake recommendations is challenging for infants 6-12 mo, especially breastfed infants. Three-quarters of Australian infants 6-12 mo have iron intakes below the estimated average requirement (7 mg), placing them at risk of iron deficiency. After 6 mo, breastmilk is no longer sufficient to meet the increased demand for iron, and iron-rich complementary foods are recommended. Iron-fortified foods may be a means of improving iron intake in infants, particularly those that are breastfed. OBJECTIVES: The aims of the study were as follows: 1) to examine the effect of milk-type and fortified foods on iron intake and the prevalence of inadequacy in infants 6-12 mo; 2) to model the effect of fixed amounts of iron-fortified infant cereal (IFIC) at 6 levels of iron fortification on total iron intake and the prevalence of inadequacy; and 3) to assess the effect IFIC on the intake of other nutrients in the diet. DESIGN: Secondary analysis of cross-sectional dietary intake data of infants 6-12 mo (n = 286) participating in the Australian Feeding Infants and Toddlers Study (OzFITS) 2021. RESULTS: Median (interquartile range) iron intake was 8.9 (7.5, 10.3); 6.3 (4.5, 8.2); and 2.7 (1.5, 4.4) mg/d in formula-fed, combination-fed, and breastfed infants, respectively. The corresponding prevalence of inadequacy was 19%, 67%, and 96%. Infants who consumed fortified foods had higher median iron intakes than those who did not, 6.2 compared with 1.9 mg/d. Dietary modeling showed that consuming 18 g (300 kJ) of IFIC, fortified at 35 mg/100 g dry weight, reduces the prevalence of inadequacy for iron from 75% to 5% for all infants. CONCLUSIONS: Iron intakes are low in Australian infants, especially for breastfed infants in the second half of infancy. Modeling shows that 300 kJ of IFIC, the current manufacturer-recommended serving, fortified at 35 mg/100 g dry weight, added to infant diets would be an effective means to reduce the prevalence of inadequacy for iron.

Restricting diet for perceived health benefit: A mixed-methods exploration of peripartum food taboos in rural Cambodia.

Food taboos encompass food restrictions practiced by a group that go beyond individual preferences. During pregnancy and lactation, food taboos may contribute to inadequate nutrition and poor maternal and infant health. Restriction of specific fish, meat, fruits and vegetables is common among peripartum women in many Southeast Asian countries, but data from Cambodia are lacking. In this mixed-methods study, 335 Cambodian mothers were asked open-ended questions regarding dietary behaviours during pregnancy and up to 24 weeks postpartum. Descriptive statistics and content analysis were used to characterize food taboos and multiple logistic regression analyses were conducted to identify predictors of this practice. Participants were 18-44 years of age, all of Khmer ethnicity and 31% were primiparous. Sixty-six per cent of women followed food taboos during the first 2 weeks postpartum, whereas ~20% of women restricted foods during other peripartum periods. Pregnancy taboos were often beneficial, including avoidance of sugar-sweetened beverages, coffee and alcohol. Conversely, postpartum avoidances typically included nutrient-dense foods such as fish, raw vegetables and chicken. Food taboos were generally followed to support maternal and child health. No significant predictors of food taboos during pregnancy were identified. Postpartum, each additional live birth a woman had reduced her odds of following food taboos by 24% (odds ratio [95% confidence interval]: 0.76 [0.61-0.95]). Specific food taboo practices and rationales varied greatly between women, suggesting that food taboos are shaped less by a strict belief system within the Khmer culture and more by individual or household understandings of food and health during pregnancy and postpartum.

Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women.

BACKGROUND: The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. OBJECTIVES: In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. METHODS: Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18-45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. RESULTS: Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 µg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). CONCLUSIONS: Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.

Maternal Late-Pregnancy Serum Unmetabolized Folic Acid Concentrations Are Not Associated with Infant Allergic Disease: A Prospective Cohort Study.

BACKGROUND: The increase in childhood allergic disease in recent decades has coincided with increased folic acid intakes during pregnancy. Circulating unmetabolized folic acid (UMFA) has been proposed as a biomarker of excessive folic acid intake. OBJECTIVE: We aimed to determine if late-pregnancy serum UMFA and total folate concentrations were associated with allergic disease risk in the offspring at 1 y of age in a population at high risk of allergy. METHODS: The cohort consisted of 561 mother-infant pairs from Western Australia. To be eligible the infant had to have a first-degree relative (mother, father, or sibling) with a history of medically diagnosed allergic disease. Maternal venous blood was collected between 36 and 40 wk of gestation. Serum UMFA was measured by LC-tandem MS. Serum total folate was determined using a microbiological method with chloramphenicol-resistant Lactobacillus rhamnosus as the test organism, and was collected between 36 and 40 wk of gestation. UMFA concentrations were measured by tandem MS using stable isotope dilution; folate concentrations were determined using the microbiological method with standardized kits. Infant allergic disease outcomes of medically diagnosed eczema, steroid-treated eczema, atopic eczema, IgE-mediated food allergy, allergen sensitization, and medically diagnosed wheeze were assessed at 1 y of age. RESULTS: Median (IQR) concentrations for UMFA and serum folate were 1.6 (0.6-4.7) and 53.2 (32.6-74.5) nmol/L, respectively. Of the infants, 34.6% had medically diagnosed eczema, 26.4% allergen sensitization, and 14.9% had an IgE-mediated food allergy. In both adjusted and unadjusted models there was little evidence of association between UMFA or serum folate and any of the infant allergy outcomes. CONCLUSIONS: In this cohort of children at high risk of allergic disease there was no association between maternal UMFA or serum folate concentrations measured in late pregnancy and allergic disease outcomes at 1 y of age.

Effect of a functional fibre supplement on glycemic control when added to a year-long medically supervised weight management program in adults with type 2 diabetes.

PURPOSE: Soluble fibre beneficially affects metabolism but whether it can augment the reductions in glycemia induced through intensive weight management has not been extensively studied. Our objective was to examine the adjunct effect of the soluble viscous fibre PGX® on glycemic control in adults with type 2 diabetes (T2D) enrolled in a year-long medically supervised weight management program. METHODS: In a placebo-controlled, double-blind study, 290 adults with overweight/obesity and T2D were randomized to receive PGX (15-20 g/day) or isocaloric placebo (rice flour, 6.4-8.6 g/day) as an adjunct to intensive weight management for 52 weeks. The primary outcome was change in glycemic control (HbA1c). Other outcome measures included weight loss, blood lipids, blood pressure, cytokines and fecal microbiota. RESULTS: Compared to baseline HbA1c in PGX (7.2 ± 1.1%) and placebo (7.0 ± 0.9%) groups, there was a significant reduction at 16 and 26 weeks, however, only PGX showed a significant absolute reduction of 0.23% at 52 weeks; there were no between-group differences in HbA1c. At 52 weeks, only PGX significantly decreased body weight compared to baseline and reduced waist circumference at all time points. Compared to baseline, only PGX showed a significant reduction in LDL cholesterol at 16 and 26 weeks. PGX significantly increased the relative abundance of Collinsella, Parabacteroides and Roseburia. CONCLUSION: Adding PGX to a weight management program for individuals with T2D provides a sustained reduction in HbA1c compared to placebo. Improvements in other metabolic outcomes suggest that PGX may be a promising adjunct to weight loss programs in patients with T2D. CLINICAL TRIAL: This trial was registered at ClinicalTrials.gov as NCT01644201.

The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age.

BACKGROUND: Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common. OBJECTIVE: We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia. METHODS: Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences. RESULTS: Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n = 53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n = 475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P < 0.001). CONCLUSIONS: Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375.

Are the nutrient and textural properties of Australian commercial infant and toddler foods consistent with infant feeding advice?

Infant feeding guidelines worldwide recommend first foods to be Fe rich with no added sugars and that nutrient-poor discretionary foods are to be avoided. Feeding guidelines also recommend exposing infants to a variety of foods and flavours with increasingly complex textures. Here, we compare nutritional and textural properties of commercial infant and toddler foods available in Australia with established infant feeding guidelines. Nutrition information and ingredient lists were obtained from food labels, manufacturer and/or retailer websites. In total, 414 foods were identified, comprising mostly mixed main dishes, fruit and vegetable first foods and snacks. Most products were poor sources of Fe, and 80 % of first foods were fruit-based. Half of all products were purées in squeeze pouches, and one-third of all products were discretionary foods. The nutritional content of many products was inconsistent with guidelines, being low in Fe, sweet, smooth in consistency or classified as discretionary. Reformulation of products is warranted to improve Fe content, particularly in mixed main dishes, expand the range of vegetable-only foods and textural variety. Greater regulatory oversight may be needed to better inform parents and caregivers. Frequent consumption of commercial baby foods low in Fe may increase the risk of Fe deficiency. Excessive consumption of purées via squeeze pouches may also have implications for overweight and obesity risk.

Suboptimal Biochemical Riboflavin Status Is Associated with Lower Hemoglobin and Higher Rates of Anemia in a Sample of Canadian and Malaysian Women of Reproductive Age.

BACKGROUND: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood. OBJECTIVES: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia. METHODS: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia. RESULTS: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P < 0.001). This relation remained significant (P = 0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40. CONCLUSIONS: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.

Maternal folic acid supplementation with vitamin B12 deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet.

Epidemiologic studies have reported relationships between maternal high folate and/or low B12 status during pregnancy and greater adiposity and insulin resistance in children. The goal of this study was to determine the effects of maternal folic acid supplementation (10 mg/kg diet), with (50 µg/kg diet) and without B12, on adult female offspring adiposity and glucose homeostasis. Female C57BL/6J mice were fed 1 of 3 diets from weaning and throughout breeding, pregnancy, and lactation: control (2 mg/kg diet folic acid, 50 µg/kg diet B12), supplemental folic acid with no B12 (SFA-B12), or supplemental folic acid with adequate B12 (SFA+B12). Female offspring were weaned onto the control diet or a Western diet (45% energy fat, 2 mg/kg diet folic acid, 50 µg/kg diet B12) for 35 wk. After weaning, control diet-fed offspring with SFA-B12 dams had fasting hyperglycemia, glucose intolerance, lower ß cell mass, and greater islet hepatocyte nuclear factor 1 homeobox α and nuclear receptor subfamily 1 group H member 3 mRNA than did offspring from control dams. In Western diet-fed offspring, those with SFA-B12 dams had lower fasting blood glucose and plasma insulin concentrations, and were smaller than control offspring. Our findings suggest that maternal folic acid supplementation with B12 deficiency during pregnancy/lactation programs the metabolic health of adult female offspring but is dependent on offspring diet.-Henderson, A. M., Tai, D. C., Aleliunas, R. E., Aljaadi, A. M., Glier, M. B., Xu, E. E., Miller, J. W., Verchere, C. B., Green, T. J., Devlin, A. M. Maternal folic acid supplementation with vitamin B12 deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet.

Lactating Canadian Women Consuming 1000 µg Folic Acid Daily Have High Circulating Serum Folic Acid Above a Threshold Concentration of Serum Total Folate.

Background: Consumption of high-dose folic acid supplements is common throughout pregnancy and lactation in several countries, including Canada, Brazil, and the United States, and may lead to high levels of circulating unmetabolized folic acid. Objective: The objective of the study was to characterize serum and whole-blood folate forms in Canadian lactating women regularly consuming a daily high-dose folic acid supplement. Methods: One-hundred and seventeen Canadian lactating women aged between 18 and 42 y, with a geometric mean ± SD prepregnancy body mass index (kg/m2) of 23.1 ± 1.2, were enrolled in a vitamin D supplementation trial between 13 and 22 wk of gestation. As part of the trial, the women received a daily multivitamin containing 1000 µg folic acid throughout pregnancy and lactation until 8 wk postpartum. At 8 wk postpartum, serum folate forms, including folic acid and RBC total folate, were determined from nonfasted blood samples. Differences in median folate vitamer concentrations among quintiles of serum total folate status were assessed by the Wald test and quantile regression methods. A breakpoint in the relation between serum folic acid and serum total folate was modeled with the use of the segmented package in R. Results: Median serum total folate concentration among participants was 79.3 nmol/L (5th-95th percentile 30.7-186 nmol/L) and median RBC folate concentration was 2790 nmol/L (5th-95th percentile 1330-4850 nmol/L). There was a breakpoint in the relation between serum total folate and serum folic acid at 78.5 nmol/L (95% CI: 67.9, 89.1 nmol/L), below which serum folic acid was not associated with serum total folate, and above which serum folic acid increased 0.78 nmol/L (95% CI: 0.70, 0.86 nmol/L; P < 0.001) for each 1 nmol/L increase in serum total folate. Conclusions: These data demonstrate the potential for high serum folic acid concentrations proportional to overall folate concentrations in lactating women with serum total folate >80 nmol/L taking high-dose supplemental folic acid. This study was registered at clinicaltrials.gov as NCT01112891.

l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women.

Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative. Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy. Methods: In a 12-wk, randomized, placebo-controlled intervention trial, healthy Malaysian women (n = 142, aged 20-45 y) were randomly assigned to receive 1 of the following supplements daily: 1 mg (2.27 µmol) folic acid, 1.13 mg (2.27 µmol) l-5-MTHF, or a placebo. The primary outcomes were plasma and RBC folate and vitamin B-12 concentrations. Secondary outcomes included plasma total homocysteine, total cysteine, methionine, betaine, and choline concentrations and monocyte long interspersed nuclear element-1 (LINE-1) methylation. Results: The folic acid and l-5-MTHF groups had higher (P < 0.001) RBC folate (mean ± SD: 1498 ± 580 and 1951 ± 496 nmol/L, respectively) and plasma folate [median (25th, 75th percentiles): 40.1 nmol/L (24.9, 52.7 nmol/L) and 52.0 nmol/L (42.7, 73.1 nmol/L), respectively] concentrations compared with RBC folate (958 ± 345 nmol/L) and plasma folate [12.6 nmol/L (8.80, 17.0 nmol/L)] concentrations in the placebo group at 12 wk. The l-5-MTHF group had higher RBC folate (1951 ± 496 nmol/L; P = 0.003) and plasma folate [52.0 nmol/L (42.7, 73.1 nmol/L); P = 0.023] at 12 wk than did the folic acid group [RBC folate, 1498 ± 580 nmol/L; plasma folate, 40.1 nmol/L (24.9, 52.7 nmol/L)]. The folic acid and l-5-MTHF groups had 17% and 15%, respectively, lower (P < 0.001) plasma total homocysteine concentrations than did the placebo group at 12 wk; there were no differences between the folic acid and l-5-MTHF groups. No differences in plasma vitamin B-12, total cysteine, methionine, betaine, and choline and monocyte LINE-1 methylation were observed. Conclusion: These findings suggest differential effects of l-5-MTHF compared with folic acid supplementation on blood folate concentrations but no differences on plasma total homocysteine lowering in Malaysian women. This trial was registered at clinicaltrials.gov as NCT01584050.

Effect of enhanced homestead food production and aquaculture on dietary intakes of women and children in rural Cambodia: A cluster randomized controlled trial.

The Cambodian diet is low in nutrient-dense animal-source foods. Enhanced homestead food production (EHFP) and aquaculture, which increase availability of nutrient-dense foods, are promising interventions to improve dietary intake. This study examined the effect of EHFP with or without aquaculture on dietary intake and prevalence of inadequate intake of select nutrients among women and children living in rural Cambodia, compared to controls. In a registered, cluster randomized controlled trial in Prey Veng, Cambodia, 10 households in each of 90 villages (n = 900) were randomized by village to receive EHFP, EHFP plus aquaculture, or control. After 22-month intervention, 24-hr dietary recalls (24HRs) were collected from mothers aged 18-50 years (n = 429) and their children aged 6 months-7 years (n = 421), reported by their mothers. Usual intake distributions (generated using 24HRs and repeat 24HRs on a subsample) were used to estimate prevalence of inadequate intake. Compared to controls, women in the EHFP group had significantly higher zinc (+1.0 mg/d) and Vitamin A (+139 retinol activity equivalents/d) intakes, and women in the EHFP plus aquaculture group had significantly higher iron (+2.7 mg/d), Vitamin A (+191 retinol activity equivalents/d), and riboflavin (+0.17 mg/d) intakes. Women in the EHFP plus aquaculture group also had significantly lower prevalence of inadequate iron (-7%, at 10% bioavailability), Vitamin A (-19%), and riboflavin (-17%) intakes, compared to controls. No significant differences in intakes or nutrient adequacy were observed among children or between EHFP and EHFP plus aquaculture groups. The biological importance of the small differences in nutrient intakes among women remains to be established.

Household Consumption of Thiamin-Fortified Fish Sauce Increases Erythrocyte Thiamin Concentrations among Rural Cambodian Women and Their Children Younger Than 5 Years of Age: A Randomized Controlled Efficacy Trial.

OBJECTIVES: To assess whether ad libitum consumption of thiamin-fortified fish sauce over 6 months yields higher erythrocyte thiamin diphosphate concentrations (eTDP) among women of childbearing age and their children aged 12-59 months compared with control sauce containing no thiamin. STUDY DESIGN: In this double-blind, randomized controlled efficacy trial, 276 nonpregnant, nonlactating women (18-45 years of age) and their families in Prey Veng, Cambodia, were randomized to receive 1 of 3 fish sauce formulations: low thiamin concentration (low, 2 g/L), high thiamin concentration (high, 8 g/L), or a control (no thiamin) fish sauce. Baseline (t = 0) and endline (t = 6 months) eTDP were measured with the use of high-performance liquid chromatography with a fluorescence detector. RESULTS: Fish sauce consumption did not differ between treatment groups (P = .19). In intent-to-treat analysis, women's baseline-adjusted endline eTDP (mean; 95% CI) was higher among women in the low (259; 245-274 nmol/L) and high (257; 237-276 nmol/L) groups compared with control (184; 169-198 nmol/L; P < .001); low and high groups did not differ (P = .83). Similarly, children's baseline-adjusted eTDP was higher in the low (259; 246-271 nmol/L) and high (257; 243-270 nmol/L) groups compared with control (213; 202-224 nmol/L; P < .001). CONCLUSION: Fortified fish sauce appears to be an efficacious means of improving biochemical thiamin status in nonpregnant, nonlactating women and their children (1-5 years of age) living in rural Cambodia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02221063.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa.Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children.Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and α-thalassemia deletions.Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes.Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

Folic Acid Supplementation of Female Mice, with or without Vitamin B-12, before and during Pregnancy and Lactation Programs Adiposity and Vascular Health in Adult Male Offspring.

BACKGROUND: The developmental origins of health and disease theory suggest that disturbances in the fetal and early postnatal environment contribute to chronic adulthood diseases, such as type 2 diabetes and cardiovascular disease. Greater adiposity and insulin resistance have been reported in children of women with high erythrocyte folate but poor vitamin B-12 status during pregnancy. The mechanisms underlying this relation are not known. OBJECTIVE: The objective of this study was to investigate the effects of maternal supplemental folic acid, with or without vitamin B-12, on adiposity, glucose homeostasis, and vascular health in adult male offspring mice. METHODS: Female C57BL/6J mice were fed a control diet (M-CON, 2 mg folic acid/kg, 50 µg vitamin B-12/kg) or a folic acid-supplemented diet with [10 mg folic acid/kg, 50 µg vitamin B-12/kg (SFA+B12)] or without [10 mg folic acid/kg, no vitamin B-12 (SFA-B12)] vitamin B-12 for 6 wk before mating and during pregnancy and lactation. The offspring were weaned onto a control diet (16% energy from fat) or a western diet (45% energy from fat) until 23 wk of age. The effects of maternal diet on adiposity, vascular function, and glucose tolerance were assessed in 6 groups of adult male offspring: control diet-fed M-CON, SFA+B12, and SFA-B12 and western diet-fed M-CON, SFA+B12, and SFA-B12. RESULTS: Control and western diet-fed SFA-B12 and SFA+B12 offspring had smaller visceral and subcutaneous adipose tissue than M-CON offspring (P < 0.05). Control SFA-B12 and SFA+B12 offspring had lower serum total adiponectin and vitamin B-12 concentrations and lower NADPH oxidase 2 expression in aorta compared with M-CON offspring (P < 0.05). These effects were not observed in western diet-fed offspring. CONCLUSIONS: Folic acid supplementation of female mice before and during pregnancy and lactation, with or without dietary vitamin B-12, affects adult male offspring adiposity, vascular function, and one-carbon metabolism in those fed a control diet but not a western diet.

Vitamin D supplementation is associated with higher serum 25OHD in Asian and White infants living in Vancouver, Canada.

To prevent rickets, the Health Canada and the American Academy of Pediatrics recommend that breastfed infants receive a daily vitamin D supplement of 10 µg d(-1) . Compliance with this recommendation is variable and its effect on infant vitamin D status is unclear. We measured serum 25-hydroxyvitamin D (25OHD) in Asian immigrant (n=28) and White (n=37) mothers and their infants aged 2-4 months living in Vancouver (49°N). Mothers completed health and demographic questionnaires. All subjects were term infants who were primarily breastfed. Analysis of variance, χ(2) , multiple regression and logistic regression analysis were performed as appropriate. Mean 25OHD of the infants was 31 (95% confidence interval 28-34) ng mL(-1) . Only two infants had a 25OHD concentration indicative of deficiency, <10 ng mL(-1) . Of the infants, 14% (n=9) and 49% (n=32) were vitamin D insufficient based on two commonly used cut-offs of 20 and 30 ng mL(-1) , respectively. Fifty-eight (89%) infants had been given a vitamin D supplement. Mean 25OHD was 9.4 ng mL(-1) higher in infants consuming ≥10 µg d(-1) of vitamin D from supplements vs. those consuming less (P=0.003). Mother's 25OHD, season, skin colour or ethnicity (Asian vs. White) did not influence infant 25OHD. The infants in our study, most of whom received vitamin D supplements, were generally protected against low 25OHD. The study was limited by sample size and the nature of the cross-sectional study design.