Female rats consuming an iron and omega-3 fatty acid deficient diet preconception require combined iron and omega-3 fatty acid supplementation for the prevention of bone impairments in offspring.

We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42-45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.

Higher n-3 polyunsaturated fatty acid status during early pregnancy is associated with lower risk for depression at 12 months postpartum: The NuPED study.

Perinatal depression can negatively affect the health of the mother and her offspring. N-3 polyunsaturated fatty acids (PUFA) may play a role in the aetiology of depression. Therefore, we investigated the association of n-3 PUFA status during early pregnancy with perinatal depression among women living in urban Johannesburg, South Africa. For this prospective analysis, we analysed red blood cell (RBC) total phospholipid fatty acid (FA) composition (% of total FA) of 242 pregnant women at <18 weeks' gestation. We used the Edinburgh Postnatal Depression Scale (EPDS) to identify women at risk for depression (EPDS score ≥9) at <18, 22 and 36 weeks' gestation, and at 6 and 12 months postpartum. RBC EPA status was negatively (ß=-0.22, p<0.05), and the AA/EPA ratio positively (ß=0.24, p<0.05) associated with EPDS scores at 12 months postpartum. Higher RBC DHA and n-3 index were further associated with lower odds (OR=0.56 [95% CI: 0.32-0.91]; OR=0.63 [95% CI: 0.39-0.94]), while higher n-6/n-3 PUFA and AA/EPA ratios early in pregnancy were associated with higher odds for depression at 12 months postpartum ((OR=2.34 [95% CI: 1.12-4.97]; OR=1.02 [95% CI: 1.00-1.05]). Our results suggest that women with a higher RBC n-3 PUFA status during early pregnancy may be at lower risk for depression at 12 months postpartum.

Moving Complementary Feeding Forward: Report on a Workshop of the Federation of International Societies for Pediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN) and the World Health Organization Regional Office for Europe.

The WHO Regional Office for Europe and the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition held a joint workshop, "Moving Complementary Feeding Forward" at the sixth World Congress Pediatric Gastroenterology, Hepatology, and Nutrition in 2021. Here we summarize workshop presentations and discussions. The workshop covered health implications of complementary feeding (CF) including allergies, challenges to meet dietary needs during the CF period, quality of commercial complementary foods (CFD) and respective marketing practices, national CF guidelines in Europe, a nutrient profiling system for CFD, and global policy perspectives on the standards and regulation of marketing for CFD. Adequate CF practices are of critical importance for short and long-term child health, prevention of nutrient deficiencies, normal growth and development, and reducing the risk of allergies. The workshop identified the need to improve feeding practices, harmonize evidence-based information and develop guidance jointly with various stakeholders, improve the composition and marketing practices of commercial CFD and their transparent labeling based on nutrient profiling. Renewed efforts for collaboration between scientists, public health experts, pediatric associations, national governments, and the WHO are necessary for advancing progress.

The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.

OBJECTIVES: We developed a natural polyphenol supplement that strongly chelates iron in vitro and assessed its effect on non-heme iron absorption in patients with hereditary hemochromatosis (HH). METHODS: We performed in vitro iron digestion experiments to determine iron precipitation by 12 polyphenol-rich dietary sources, and formulated a polyphenol supplement (PPS) containing black tea powder, cocoa powder and grape juice extract. In a multi-center, single-blind, placebo-controlled cross-over study, we assessed the effect of the PPS on iron absorption from an extrinsically labelled test meal and test drink in patients (n = 14) with HH homozygous for the p.C282Y variant in the HFE gene. We measured fractional iron absorption (FIA) as stable iron isotope incorporation into erythrocytes. RESULTS: Black tea powder, cocoa powder and grape juice extract most effectively precipitated iron in vitro. A PPS mixture of these three extracts precipitated ~ 80% of iron when 2 g was added to a 500 g iron solution containing 20 µg Fe/g. In the iron absorption study, the PPS reduced FIA by ~ 40%: FIA from the meal consumed with the PPS was lower (3.01% (1.60, 5.64)) than with placebo (5.21% (3.92, 6.92)) (p = 0.026)), and FIA from the test drink with the PPS was lower (10.3% (7.29 14.6)) than with placebo (16.9% (12.8 22.2)) (p = 0.002). CONCLUSION: Our results indicate that when taken with meals, this natural PPS can decrease dietary iron absorption, and might thereby reduce body iron accumulation and the frequency of phlebotomy in patients with HH. TRIAL REGISTRY: clinicaltrials.gov (registration date: 9.6.2019, NCT03990181).

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

The effect of oral iron supplementation on the gut microbiota, gut inflammation, and iron status in iron-depleted South African school-age children with virally suppressed HIV and without HIV.

PURPOSE: Both HIV and oral iron interventions may alter gut microbiota composition and increase gut inflammation. We determined the effect of oral iron supplementation on gut microbiota composition, gut inflammation, and iron status in iron-depleted South Africa school-aged children living with HIV (HIV+) but virally suppressed on antiretroviral therapy and children without HIV (HIV-ve). METHODS: In this before-after intervention study with case-control comparisons, we provided 55 mg elemental iron from ferrous sulphate, once daily for 3 months, to 33 virally suppressed (< 50 HIV RNA copies/mL) HIV+ and 31 HIV-ve children. At baseline and endpoint, we assessed microbial composition of faecal samples (16S rRNA sequencing), and markers of gut inflammation (faecal calprotectin), anaemia (haemoglobin) and iron status (plasma ferritin, soluble transferrin receptor). This study was nested within a larger trial registered at clinicaltrials.gov as NCT03572010. RESULTS: HIV+ (11.3y SD ± 1.8, 46% male) and HIV-ve (11.1y SD ± 1.7, 52% male) groups did not significantly differ in age or sex ratio. Following iron supplementation, improvements were observed in haemoglobin (HIV+ : 118 to 124 g/L, P = 0.003; HIV-ve: 120 to 124 g/L, P = 0.003), plasma ferritin (HIV+ : 15 to 34 µg/L, P < 0.001; HIV-ve: 18 to 37 µg/L, P < 0.001), and soluble transferrin receptor (HIV+ : 7.1 to 5.9 mg/L, P < 0.001; HIV-ve: 6.6 to 5.7 mg/L, P < 0.001), with no significant change in the relative abundance of any genera, alpha diversity of the gut microbiota (HIV+ : P = 0.37; HIV-ve: P = 0.77), or faecal calprotectin (HIV+ : P = 0.42; HIV-ve: P = 0.80). CONCLUSION: Our findings suggest that oral iron supplementation can significantly improve haemoglobin and iron status without increasing pathogenic gut microbial taxa or gut inflammation in iron-depleted virally suppressed HIV+ and HIV-ve school-age children.

Barriers and facilitators of micronutrient supplementation among non-pregnant women of reproductive age in Johannesburg, South Africa.

The prevalence of anaemia among South African women of reproductive age (WRA) remains high at 39%. Multiple micronutrient supplementation (MMS) may be an effective strategy in the prevention and management of anaemia. Our aim was to understand facilitators and barriers to preconception MMS adherence and to explore perceptions and beliefs of MMS in the prevention and treatment of anaemia among non-pregnant WRA. This qualitative study was embedded in a preconception MMS intervention trial of WRA and was conducted in two phases. Phase one assessed the barriers and facilitators of MMS adherence. Individual interviews were conducted with the community health workers (n = 7) administering MMS, and with non-pregnant WRA (n = 25) participating in the trial. Phase two included four focus groups with participating WRA (n = 26), which further explored participants' perceptions and beliefs of MMS provision and adherence, and strategies to improve adherence. The reported facilitators to supplementation were family support, interaction with the community health workers, easy access to MMS, and experienced benefits of MMS. Barriers to preconception supplementation included the lack of family support, the link of supplements to antenatal care, and the perceived lack of benefits of MMS. Participants reported negative associations of supplements with medication, individual and societal stigma around medication and challenges around the supplementation schedule. For successful preconception MMS interventions, young women, their families, and communities need to be convinced of the value of supplementation. Public health interventions utilising preconception supplementation will require specialised training for health care providers, targeted counselling materials and community household support.

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

Efficacy of novel small-quantity lipid-based nutrient supplements in improving long-chain polyunsaturated fatty acid status of South African infants: a randomised controlled trial.

BACKGROUND/OBJECTIVES: The objective of this study was to investigate the efficacy of small-quantity lipid-based nutrient supplements (SQ-LNS) containing essential fatty acids (EFAs) with or without long-chain polyunsaturated fatty acids (LCPUFAs) in improving LCPUFA status in South African infants fed complementary food. SUBJECTS/METHODS: Six-month-old infants (n = 750) were randomised to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNSs contained micronutrients and EFAs. SQ-LNS-plus additionally contained the LCPUFAs arachidonic acid (AA) and docosahexaenoic acid (DHA), lysine, phytase and other nutrients. Plasma total phospholipid FA composition (% of total FAs) was measured at baseline (n = 353) and at 12 months (n = 293). RESULTS: At baseline, geometric mean (95% CI) plasma DHA and AA were 4.1 (4.0-4.3) and 11.5 (11.2-11.8)% respectively, with significantly higher plasma DHA and AA in breastfed than non-breastfed infants. Infants receiving the SQ-LNS-plus had significantly higher plasma DHA (4.52 (4.3-4.9)) at 12 months than the controls (3.8 (3.6-4.0)), with a higher effect size in infants who no longer received breast milk (ß = 1.148 (95% CI = 0.597, 1.699)) than in infants who were still breastfeeding (ß = 0.544 (95% CI = 0.179, 0.909)). There was no effect of either of the two SQ-LNSs on plasma AA. Consequently, infants receiving the SQ-LNS-plus had a significantly lower plasma n-6 to n-3 PUFA ratio at 12 months than control infants did. CONCLUSIONS: Our study suggests that the provision of SQ-LNS-plus is efficacious in improving plasma DHA status. Particularly, infants who are no longer breastfed may benefit most from LCPUFA-enriched SQ-LNS.

Maternal iron-deficiency is associated with premature birth and higher birth weight despite routine antenatal iron supplementation in an urban South African setting: The NuPED prospective study.

BACKGROUND: Recent studies are suggesting a U-shaped relationship between antenatal iron exposure and birth outcomes. Little is known about the iron status and associated birth outcomes of pregnant women in South Africa. Our aim was to assess iron status at early, mid- and late pregnancy, and to determine associations with gestational age and birth weight in women in Johannesburg, South Africa. METHODS: In this prospective study of 250 pregnant women, we measured haemoglobin, biomarkers of iron status and inflammation at <18, 22 and 36 weeks of gestation, plus birth weight and gestational age at delivery. Associations of anaemia and iron status with birth outcomes were determined using regression models adjusted for confounders. RESULTS: At enrolment, the prevalence of anaemia, iron depletion (ID) and iron deficiency erythropoiesis (IDE) was 29%, 15% and 15%, respectively, and increased significantly with pregnancy progression. Anaemia and ID at 22 weeks, as well as IDE at 36 weeks were associated with higher birth weight (ß = 135.4; 95% CI: 4.8, 266.1 and ß = 205.4; 95% CI: 45.6, 365.1 and ß = 178.0; 95% CI: 47.3, 308.7, respectively). Women in the lowest ferritin quartile at 22 weeks gave birth to babies weighing 312 g (95% CI: 94.8, 528.8) more than those in the highest quartile. In contrast, IDE at 22 weeks was associated with a higher risk for premature birth (OR: 3.57, 95% CI: 1.24, 10.34) and women in lower haemoglobin quartiles at <18 weeks had a shorter gestation by 7 days (ß = -6.9, 95% CI: -13.3, -0.6) compared to those in the highest quartile. CONCLUSION: Anaemia, ID and IDE prevalence increased during pregnancy despite routine iron supplementation. ID and anaemia at mid-pregnancy were associated with higher birth weight, while IDE was associated with premature birth. These results suggest that current antenatal screening and supplementation practices in South Africa need to be revisited.

Interventions to prevent iron deficiency during the first 1000 days in low-income and middle-income countries: recent advances and challenges.

PURPOSE OF REVIEW: Iron deficiency remains highly prevalent in women and young children in low-income and middle-income countries. To prevent the potentially life-long consequences of iron deficiency when occurring during early life, the WHO recommends iron supplementation of pregnant women and young children. However, increasing evidence of limited efficacy and risk of current iron intervention strategies are cause of concern. This review aims to highlight recent advances and challenges of established and novel intervention strategies for the prevention of iron deficiency during the first 1000 days in low-income and middle-income countries. RECENT FINDINGS: Recent meta-analyses and trials challenged the WHO's current recommendation to provide iron-folic acid rather than multiple micronutrient supplements during routine antenatal care. Furthermore, several studies explored optimal windows for iron supplementation, such as prior to conception. Studies are demonstrating that infectious and noninfectious inflammation is compromising the efficacy of iron interventions in vulnerable groups. Therefore, strategies addressing iron deficiency should focus on targeting infection and inflammation while simultaneously providing additional iron. Furthermore, both iron deficiency and iron supplementation may promote an unfavourable gut microbiota. Recent trials in infants indicate that the provision of a prebiotic together with iron may alleviate the adverse effects of iron on the gut microbiome and gut inflammation, and may even enhance iron absorption. SUMMARY: Recent studies highlight the need for and potential of novel intervention strategies that increase the efficacy and limit the potential harm of universal iron supplementation.

Associations of plasma total phospholipid fatty acid patterns with feeding practices, growth, and psychomotor development in 6-month-old South African infants.

The objective of this study was to assess plasma fatty acid (FA) patterns of 6-month-old South African infants and to determine their association with feeding practices, growth, and psychomotor development. Plasma total phospholipid FA composition (% of total FAs) of 6-month-old infants (n = 353) from a peri-urban township was analysed, and principal component and factor analysis were performed to identify plasma FA patterns. Feeding practices, anthropometric measurements, and psychomotor development scores were determined. Four major plasma phospholipid FA patterns were identified: A plant-based C18 FA, a high n-6 long-chain polyunsaturated fatty acids (LCPUFA), a C16:1 and long-chain saturated fatty acid (SFA), and a high n-3 and low n-6 LCPUFA pattern. Formula feeding was associated with higher, whereas breastfeeding was associated with lower scores for the plant-based C18 FA and C16:1 and long-chain SFA patterns. On the other hand, breastfeeding, the consumption of cow's milk, and the consumption of semisolid foods were associated with higher scores, whereas formula feeding was associated with lower scores for the high n-6 LCPUFA pattern. Breastfeeding and the consumption of semisolids were also associated with higher high n-3 and low n-6 LCPUFA pattern scores. The C16:1 and long-chain SFA and high n-3 and low n-6 LCPUFA patterns were positively associated with psychomotor development scores. In 6-month-old South African infants, we identified distinct plasma FA patterns that presumably represent the FA quality of their diet and that are associated with psychomotor development. Our results suggest that breast milk is an important source of n-6 LCPUFAs and formula-fed infants may be at risk of inadequate LCPUFA intake.

How will South Africa's mandatory salt reduction policy affect its salt iodisation programme? A cross-sectional analysis from the WHO-SAGE Wave 2 Salt & Tobacco study.

OBJECTIVE: The WHO's global targets for non-communicable disease reduction recommend consumption of<5 g salt/day. In 2016, South Africa was the first country to legislate maximum salt levels in processed foods. South Africa's salt iodisation fortification programme has successfully addressed iodine deficiency but information is dated. Simultaneous monitoring of sodium reduction and iodine status is required to ensure compatibility of the two public health interventions. DESIGN/SETTING/PARTICIPANTS: A nested cohort design within WHO's 2015 Study on global AGEing and adult health (n=2887) including individuals from households across South Africa. Randomly selected adults (n=875) provided 24-hour and spot urine samples for sodium and iodine concentration analysis (the primary and secondary outcome measures, respectively). Median 24-hour urinary iodine excretion (UIE) and spot urinary iodine concentrations (UIC) were compared by salt intakes of <5g/day, 5-9g/dayand >9 g/day. RESULTS: Median daily sodium excretion was equivalent to 6.3 g salt/day (range 1-43 g/day); 35% had urinary sodium excretion values within the desirable range (<5 g salt/day), 37% had high values (5-9 g salt/day) and 28% had very high values (>9 g salt/day). Median UIC was 130 µg/L (IQR=58-202), indicating population iodine sufficiency (≥100 µg/L). Both UIC and UIE differed across salt intake categories (p<0.001) and were positively correlated with estimated salt intake (r=0.166 and 0.552, respectively; both p<0.001). Participants with salt intakes of <5 g/day were not meeting the Estimated Average Requirement for iodine intake (95 µg/day). CONCLUSIONS: In a nationally representative sample of South African adults, the association between indicators of population iodine status (UIC and UIE) and salt intake, estimated using 24-hour urinary sodium excretion, indicate that low salt intakes may compromise adequacy of iodine intakes in a country with mandatory iodisation of table salt. The iodine status of populations undergoing salt reduction strategies needs to be closely monitored to prevent re-emergence of iodine deficiency.

Type of dietary fat intakes in relation to all-cause and cause-specific mortality in US adults: an iso-energetic substitution analysis from the American National Health and Nutrition Examination Survey linked to the US mortality registry.

Accumulating evidence indicates that saturated fat intake is related to mortality risk increase, whereas unsaturated fat intake is associated with reduced mortality risk. The aim of the present study was to estimate the mortality risk reduction related to a dietary change from saturated fat to mono- or polyunsaturated fat intake. The American National Health and Nutrition Examination Surveys conducted between 1999 and 2010 were linked to the 2011 national US death registry resulting in an observational prospective mortality study. Proportional hazards Cox models were used to evaluate the association between saturated, monounsaturated and polyunsaturated fat with all-cause and cause-specific mortality. Substitution analysis was conducted to estimate an iso-energetic substitution of 10 % of the energy from dietary fat intake applied to the substitution of saturated fat with an equal amount of energy from monounsaturated or polyunsaturated fat. The highest tertile intakes of saturated fat resulted in an increased risk (12 %) of all-cause and specific-cause mortality, whereas the highest tertile intakes of polyunsaturated fat resulted in a reduced risk (7 %) of all-cause and specific-cause mortality when compared with the corresponding lowest tertile. Iso-energetic substitution revealed that a substitution of 10 % of energy (from total fat) from saturated fat to an equal amount of energy from monounsaturated or polyunsaturated fat resulted in a significant reduction of the mortality risk ranging from 4 to 8 %. Iso-energetic substitution of saturated fat with monounsaturated and polyunsaturated fat reduced all-cause and specific-cause mortality in US adults.

Sensitivity of fatty acid desaturation and elongation to plasma zinc concentration: a randomised controlled trial in Beninese children.

Zn status may affect fatty acid (FA) metabolism because it acts as a cofactor in FA desaturase and elongase enzymes. Zn supplementation affects the FA desaturases of Zn-deficient rats, but whether this occurs in humans is unclear. We evaluated the associations between baseline plasma Zn (PZn) concentration and plasma total phospholipid FA composition, as well as the effect of daily consumption of Zn-fortified water on FA status in Beninese children. A 20-week, double-blind randomised controlled trial was conducted in 186 school age children. The children were randomly assigned to receive a daily portion of Zn-fortified, filtered water delivering on average 2·8 mg Zn/d or non-fortified filtered water. Plasma total phospholipid FA composition was determined using capillary GLC and PZn concentrations by atomic absorption spectrometry. At baseline, PZn correlated positively with dihomo-γ-linolenic acid (DGLA, r 0·182; P=0·024) and the DGLA:linoleic acid (LA) ratio (r 0·293; P<0·000), and negatively with LA (r -0·211; P=0·009) and the arachidonic acid:DGLA ratio (r -0·170; P=0·036). With the intervention, Zn fortification increased nervonic acid (B: 0·109; 95 % CI 0·001, 0·218) in all children (n 186) and more so in children who were Zn-deficient (n 60) at baseline (B: 0·230; 95 % CI 0·023, 0·488). In conclusion, in this study, Zn-fortified filtered water prevented the reduction of nervonic acid composition in the plasma total phospholipids of children, and this effect was stronger in Zn-deficient children. Thus, Zn status may play an important role in FA desaturation and/or elongation.

Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron.

Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from ß-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

Iodine status and associations with feeding practices and psychomotor milestone development in six-month-old South African infants.

Iodine is important for normal growth and psychomotor development. While infants below 6 months of age receive iodine from breast milk or fortified infant formula, the introduction of complementary foods poses a serious risk for deteriorating iodine status. This cross-sectional analysis assessed the iodine status of six-month-old South African infants and explored its associations with feeding practices and psychomotor milestone development. Iodine concentrations were measured in infant (n = 386) and maternal (n = 371) urine (urinary iodine concentration [UIC]), and in breast milk (n = 257 [breast milk iodine concentrations]). Feeding practices and psychomotor milestone development were assessed in all infants. The median (25th-75th percentile) UIC in infants was 345 (213-596) µg/L and was significantly lower in stunted (302 [195-504] µg/L) than non-stunted (366 [225-641] µg/L) infants. Only 6.7% of infants were deficient. Maternal UIC (128 [81-216] µg/L; rs  = 0.218, p < 0.001) and breast milk iodine concentrations (170 [110-270] µg/kg; rs  = 0.447, p < 0.0001) were associated with infant UIC. Most infants (72%) were breastfed and tended to have higher UIC than non-breastfed infants (p = 0.074). Almost all infants (95%) consumed semi-solid or solid foods, with commercial infant cereals (60%) and jarred infant foods (20%) being the most common solid foods first introduced. Infants who reported to consume commercial infant cereals ≥4 days weekly had significantly higher UIC (372 [225-637] µg/L) than those reported to consume commercial infant cereals seldom or never (308 [200-517] µg/L; p = 0.023). No associations between infant UIC and psychomotor developmental scores were observed. Our results suggest that iodine intake in the studied six-month-old infants was adequate. Iodine in breast milk and commercial infant cereals potentially contributed to this adequate intake.

Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.

BACKGROUND: Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES: Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. DESIGN: In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO4, 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na2EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. RESULTS: The adjusted geometric mean BPb concentration at baseline was 4.3 µg/dL (95% CI: 4.2, 4.3 µg/dL), and at endpoint these values were 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for FeSO4, 2.9 µg/dL (95% CI: 2.7, 3.0 µg/dL) for NaFeEDTA, 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for EDTA, and 3.7 µg/dL (95% CI: 3.5, 3.9 µg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. CONCLUSIONS: Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.

A dose-response crossover iodine balance study to determine iodine requirements in early infancy.

BACKGROUND: Optimal iodine intake during infancy is critical for brain development, but no estimated average requirement (EAR) is available for this age group. OBJECTIVE: We measured daily iodine intake, excretion, and retention over a range of iodine intakes in early infancy to determine the minimum daily intake required to achieve iodine balance. DESIGN: In a dose-response crossover study, we randomly assigned healthy infants (n = 11; mean ± SD age 13 ± 3 wk) to sequentially consume over 33 d 3 infant formula milks (IFMs) containing 10.5, 19.3, and 38.5 µg I/100 kcal, respectively. Each IFM was consumed for 11 d, consisting of a 6-d run-in period followed by a 4-d balance period and 1 run-out day. RESULTS: Iodine intake (mean ± SD: 54.6 ± 8.1, 142.3 ± 23.1, and 268.4 ± 32.6 µg/d), excretion (55.9 ± 8.6, 121.9 ± 21.7, and 228.7 ± 39.3 µg/d), and retention (-1.6 ± 8.3, 20.6 ± 21.6, and 39.8 ± 34.3 µg/d) differed among the low, middle, and high iodine IFM groups (P < 0.001 for all). There was a linear relation between daily iodine intake and both daily iodine excretion and daily iodine retention. Zero balance (iodine intake = iodine excretion, iodine retention = 0 µg/d) was achieved at a daily iodine intake of 70 µg (95% CI: 60, 80 µg). CONCLUSION: Our data indicate the iodine requirement in 2- to 5-mo-old infants is 70 µg/d. Adding an allowance for accumulation of thyroidal iodine stores would produce an EAR of 72 µg and a recommended dietary allowance of 80 µg. This trial was registered at clinicaltrials.gov as NCT02045784.