Iron Fortification and Inulin Supplementation in Early Infancy: Evaluating the Impact on Iron Metabolism and Trace Mineral Status in a Piglet Model.

Background: Infant formula in the United States contains abundant iron, raising health concerns about excess iron intake in early infancy. Objectives: Using a piglet model, we explored the impact of high iron fortification and prebiotic or synbiotic supplementation on iron homeostasis and trace mineral bioavailability. Methods: Twenty-four piglets were stratified and randomly assigned to treatments on postnatal day 2. Piglets were individually housed and received an iron-adequate milk diet (AI), a high-iron milk diet (HI), HI supplemented with 5% inulin (HI with a prebiotic [HIP]), or HIP with an oral gavage of Ligilactobacillus agilis YZ050, an inulin-fermenting strain, every third day (HI with synbiotic [HIS]). Milk was provided in 14 meals daily, mimicking formula feeding in infants. Fecal consistency score and body weight were recorded daily or every other day. Blood and feces were sampled weekly, and tissues collected on postnatal day 29. Data were analyzed using mixed model analysis of variance with repeated measures whenever necessary. Results: Diet did not affect growth. HI increased hemoglobin, hematocrit, and serum iron compared to AI. Despite marginal adequacy, AI upregulated iron transporter genes and maintained satisfactory iron status in most pigs. HI upregulated hepcidin gene expression in liver, caused pronounced tissue iron deposition, and markedly increased colonic and fecal iron. Inulin supplementation, regardless of L. agilis YZ050, not only attenuated hepatic iron overload but also decreased colonic and fecal iron without altering pH or the expression of iron regulatory genes. HI lowered zinc (Zn) and copper (Cu) in the duodenum and liver compared to AI, whereas HIP and HIS further decreased Zn and Cu in the liver and diminished colonic and fecal trace minerals. Conclusions: Early-infancy excessive iron fortification causes iron overload and compromises Zn and Cu absorption. Inulin decreases trace mineral absorption likely by enhancing gut peristalsis and stool frequency.

Perspectives on Iron Deficiency as a Cause of Human Disease in Global Public Health.

Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines.

Iron nanoparticles as food additives and food supplements, regulatory and legislative perspectives.

Recently, the use of nanotechnology in food has gained great interest. Iron nanoparticles with unique chemical, physical and structural properties allow their potential use mainly as iron fortifiers, colorants and antimicrobial agents. However, in the market we can find only supplements and food colorants based on iron nanoparticles. Their use in food fortification has so far been focused only on in vitro and in vivo experimental studies, since the toxicological evaluation of these studies has so far been the basis for the proposals of laws and regulations, which are still in an early stage of development. Therefore, the aim of this work was to summarize the use of the different forms of iron nanoparticles (oxides, oxyhydroxides, phosphates, pyrophosphates and sulfates) as food additives and supplements and to resume the perspectives of legislation regarding the use of these types of nanoparticles in the food industry.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Human milk-derived versus bovine milk-derived fortifier use in very low birth weight infants: growth and vitamin D status.

Background: Human milk-derived fortifier (HMDF) coupled with human milk feeding in extremely premature infants reduces the adverse outcome risks of early exposure to bovine milk ingredients but may not provide enough nutrients for adequate catch-up growth compared with bovine milk-derived fortifier (BMDF). Objective: This study aims to compare HMDF and BMDF effects on growth parameters and serum 25-hydroxy vitamin D (25OHD) levels in preterm very low birth weight (VLBW) infants during the first 8 weeks of life. Methods: We present a retrospective chart review of inpatient VLBW infants with birth weight <1,500 g and gestational age <32 completed weeks who received either their mother's milk or donor breast human milk fortified with HMDF or BMDF for the first 8 weeks. Weight, head circumference, length gain, and 25OHD level were calculated at 4 and 8 weeks of age. Results: A total of 139 VLBW infants (91 HMDF + 48 BMDF) received fortified human milk without any supplemental premature formula from birth to 4 weeks of age, of whom 44 (37 HMDF + 7 BMDF) continued until 8 weeks of age. There was no statistically significant difference in the growth parameters between the two groups at 4 and 8 weeks of age. Serum 25OHD level in the HMDF group was significantly higher compared with that in the BMDF group at 4 weeks of age despite receiving lower vitamin D supplementation. Conclusion: Similar gain in growth parameters in HMDF and BMDF groups at 4 and 8 weeks of age was observed, suggesting that HMDF provides adequate nutrients for growth in VLBW infants. A higher 25OHD level in HMDF may suggest better absorption.

Can a Fraction of Flour and Sugar Be Replaced with Fruit By-Product Extracts in a Gluten-Free and Vegan Cookie Recipe?

Certain food by-products, including not-good-for-sale apples and pomegranate peels, are rich in bioactive molecules that can be collected and reused in food formulations. Their extracts, rich in pectin and antioxidant compounds, were obtained using hydrodynamic cavitation (HC), a green, efficient, and scalable extraction technique. The extracts were chemically and physically characterized and used in gluten-free and vegan cookie formulations to replace part of the flour and sugar to study whether they can mimic the role of these ingredients. The amount of flour + sugar removed and replaced with extracts was 5% and 10% of the total. Physical (dimensions, color, hardness, moisture content, water activity), chemical (total phenolic content, DPPH radical-scavenging activity), and sensory characteristics of cookie samples were studied. Cookies supplemented with the apple extract were endowed with similar or better characteristics compared to control cookies: high spread ratio, similar color, and similar sensory characteristics. In contrast, the pomegranate peel extract enriched the cookies in antioxidant molecules but significantly changed their physical and sensory characteristics: high hardness value, different color, and a bitter and astringent taste. HC emerged as a feasible technique to enable the biofortification of consumer products at a real scale with extracts from agri-food by-products.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review.

BACKGROUND: The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. OBJECTIVE: Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm. RESULTS: The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16). CONCLUSIONS: Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.

Women in Canada are consuming above the upper intake level of folic acid but few are meeting dietary choline recommendations in the second trimester of pregnancy: data from the CHILD cohort study.

There is concern that during a low-risk pregnancy, women are consuming more than recommended (400 µg/day) supplemental folic acid and may not meet recommendations for other nutrients. The objective of this study was to determine folic acid supplement use and dietary folate intakes in the second trimester (week 18) of pregnancy in women (n = 2996) in the Canadian CHILD cohort study. Vitamin B12 and choline intakes were also assessed because they are metabolically related to folate. The majority of participants (71.6%) were consuming a daily prenatal supplement. Twenty-eight percent of women (n = 847) reported consuming a folic acid supplement and of these women, 45.3% had daily supplemental folic acid intakes above the upper intake level (UL; 1000 µg/day). Daily dietary folate intakes were (mean (SD)) 575 (235) DFE µg/day. In contrast, only 24.8% of women met the dietary choline adequate intake (AI) recommendation (AI ≥ 450 mg/day) with a mean (SD) intake of 375 (151) mg/day. Further understanding of the impact of supplemental folic acid intake above the UL and low choline intake during pregnancy requires further investigation.

Vitamin D fortification of foods - sensory, acceptability, cost, and public acceptance considerations.

In terms of vitamin D food fortification, there are a number of important considerations in relation to selection of the food vehicle and fortificant. While there has been much research focus on the ability of fortified foods to improve vitamin D status, other considerations, such as sensory properties and acceptability, cost, and public attitudes around vitamin D-fortified foods, have received less attention. Thus, the present narrative review aimed to summarize the existing knowledge around these important considerations. In summary, its findings suggest that: i) vitamin D addition to various food vehicles, at levels consistent with the supply of part or all the recommended intake, does not alter their sensory characteristics or overall acceptability; ii) overall, vitamin D fortification of foods is relatively cost-effective, despite the fact that some attitudinal studies highlighted participant concerns about the potential cost/expense of vitamin D-fortified foods; iii) evidence from various attitudinal studies suggest a high level of acceptance and/or purchase intention (i.e., extent to which customers are willing and inclined to buy) of vitamin D-fortified food products by the general public; and iv) there have been repeated calls for vitamin D public health educational/information campaigns to help educate consumers about the health risks associated with vitamin D deficiency and nutritional benefits associated with consumption of vitamin D-fortified foods. Such campaigns could positively mediate attitudes and acceptance of vitamin D-fortified foods amongst the public, and could also help address misconceptions and allay fears around vitamin D for concerned individuals. Lastly, the findings of the present review also highlight the existence of between-country differences, even within Europe, in relation to attitudes and purchase intention of vitamin D-fortified foods and the perceived appropriateness of certain food vehicles for vitamin D fortification, as well as the best mix of communication channels for a vitamin D public health educational/information campaign.

The impact of replacing milk with plant-based alternatives on iodine intake: a dietary modelling study.

PURPOSE: Cow's milk is the primary source of iodine in the UK, but consumption of plant-based milk alternatives (PBMA) is increasing and these products are often not fortified with iodine. We evaluated the impact that replacing current milk consumption with PBMA would have on iodine intake. METHODS: We used data from the National Diet and Nutrition Survey (2016-2019) for children (1.5-10 years), girls 11-18 years, and women of reproductive age (WRA). We used a dietary modelling approach with scenarios using brand-level iodine-fortification data (0, 13, 22.5, 27.4 and 45 µg/100 mL). Relative to usual diet, we calculated change in iodine intake, and the proportion with intake below the Lower Reference Nutrient Intake (LRNI) or above the upper limit. RESULTS: For all groups, replacement with PBMA, either unfortified or fortified at the lowest concentration, resulted in a meaningful decrease in iodine intake, and increased the proportion with intake < LRNI; compared to usual diet, iodine intake reduced by 58% in children 1.5-3 years (127 vs. 53 µg/day) and the proportion with intake < LRNI increased in girls (11-18 years; 20% to 48%) and WRA (13% to 33%) if an unfortified PBMA was used. Replacement of milk with PBMA fortified at 27.4 µg/100 mL had the lowest impact. CONCLUSION: Replacing milk with commercially available PBMAs has potential to reduce population iodine intake, depending on the fortification level. PBMAs fortified with ≥ 22.5 and < 45 µg iodine/100 mL would be required to minimize the impact on iodine intake. Research is needed on the impact of total dairy replacement.

Firm-Level and Public-Sector Costs Make Small-Scale Maize Flour Fortification Challenging in Uganda.

BACKGROUND: Maize flour in Uganda is milled by hundreds of enterprises, mostly small- (5-20 metric tons [MT]/day) and micro-scale (<5 MT/day) mills or firms. A mandatory maize flour fortification program exists for medium-scale mills (>20 MT/day) and policymakers are considering including smaller-scale millers. OBJECTIVE: We estimated the private and public costs of maize flour fortification at different scales and explored their implications for extending the mandatory fortification to include smaller-scale mills. METHODS: We used secondary data on the structure of the maize flour market and primary data on milling and fortification costs to estimate mill and regulatory costs at 3 scales of flour production: micro, small, and medium. RESULTS: For micro-, small-, and medium-size operations, respectively, operational costs of fortification were US$13, US$9, and US$7 per metric ton (MT) of maize flour, which represented 20%, 16%, and 16% of annual operating costs, and the ratio of fortification equipment cost to mill equipment costs was higher for micro-scale mills (2.7) than for small- (0.38) and medium-scale (0.54) maize mills. Governmental regulatory costs rise if smaller-scale mills are included due to the increased number of facility inspections. CONCLUSIONS: Fortification and regulatory costs increase as production scale decreases. Up-front capital costs of fortification would be daunting for micro- and small-scale mills. Medium-scale mills, which supply social protection programs, might be able to manage fortification costs and other challenges. Decision-makers should consider all costs and cost burdens, and the realities of enforcement capabilities before expanding fortification programs to include smaller-scale operations.

Plain language titleCosts of Small-scale Maize Flour Fortification in UgandaPlain language summaryA study of the costs of adding vitamins and minerals by small-scale maize flour millers in Uganda was undertaken to understand if it would be commercially beneficial from a business and operations perspective for them to do so, and if requiring them to do so would impose additional cost burdens on government to ensure that fortification standards were met.Why was the study done?Maize flour is consumed by the majority of Uganda's population, especially the rural poor. If the flour were fortified, it would reduce vitamin and mineral deficiencies among those at risk. The most important constraint to market-wide fortification is the presence of many small-scale mills or firms that neither have the resources nor the technology to adopt and sustain the fortification process. To date, no study has been done to calculate the costs that small-scale mills would have to face to fortify flour, or what the cost implications for government would be for including smaller-scale mills in a national fortification program, including the costs of enforcing regulations.What did the researchers do?The researchers interviewed millers of several scales of operation to collect cost information on their operations and interviewed representatives of government regulatory bodies to estimate the costs of testing maize flour to ensure compliance with regulations. Researchers estimated the cost to the mills of adding fortification to their business models, and the impacts on the government costs (eg, testing additional samples, etc.) of including smaller-scale mills in the fortification program.What did the researchers find?The researchers looked at 3 different types of mills based on their capacity to mill maize flour­micro-scale firms milled less than 5 metric tons (MT) a day, small-scale firms milled 5 to 20 MT per day, and medium-scale firms milled over 20 MT a day. For micro-, small-, and medium-size firms, respectively, fortification increased operational costs by US$13, US$9, and US$7 per MT of maize flour, which represented 20%, 16%, and 16% of annual operating costs. Similarly, governmental regulatory costs rose if smaller-scale mills were included because of the increased number of facility inspections required since the current legislation requires mandatory annual inspections.What do the findings mean?Fortification and regulatory costs increase as the scale of production by the millers decreases. If fortification by small- and micro-scale mills were made mandatory, up-front costs of fortification equipment and materials would be daunting for micro- and small-scale millers. Ugandan medium-scale millers might manage fortification costs and other challenges, but only if the social protection programs they supplied were of sufficient volume and regularity.

Global heterogeneity in folic acid fortification policies and implications for prevention of neural tube defects and stroke: a systematic review.

Background: Folic acid (pteroylmonoglutamic acid) supplements are highly effective for prevention of neural tube defects (NTD) prompting implementation of mandatory or voluntary folic acid fortification for prevention of NTDs. We used plasma folate levels in population studies by country and year to compare effects of folic acid fortification types (mandatory or voluntary folic acid fortification policies) on plasma folate levels, NTD prevalence and stroke mortality rates. Methods: We conducted systematic reviews of (i) implementation of folic acid fortification in 193 countries that were member states of the World Health Organization by country and year, and (ii) estimated population mean plasma folate levels by year and type of folic acid fortification. We identified relevant English language reports published between Jan 1, 1990 and July 31, 2023 using Google Scholar, Medline, Embase and Global Health. Eligibility criteria were observational or interventional studies with >1000 participants. Studies of pregnant women or children <15 years were excluded. Using an ecological study design, we examined the associations of folic acid fortification types with NTD prevalence (n = 108 studies) and stroke mortality rates (n = 3 countries). Findings: Among 193 countries examined up to 31 July 2023, 69 implemented mandatory folic acid fortification, 47 had voluntary fortification, but 77 had no fortification (accounting for 32%, 53% and 15% of worldwide population, respectively). Mean plasma folate levels were 36, 21 and 17 nmol/L in populations with mandatory, voluntary and no fortification, respectively (and proportions with mean folate levels >25 nmol/L were 100%, 15% and 7%, respectively). Among 75 countries with NTD prevalence, mean (95% CI) prevalence per 10,000 population were 4.19 (4.11-4.28), 7.61 (7.47-7.75) and 9.66 (9.52-9.81) with mandatory, voluntary and no folic acid fortification, respectively. However, age-standardised trends in stroke mortality rates were unaltered by the introduction of folic acid fortification. Interpretation: There is substantial heterogeneity in folic acid fortification policies worldwide where folic acid fortification are associated with 50-100% higher population mean plasma folate levels and 25-50% lower NTD prevalence compared with no fortification. Many thousand NTD pregnancies could be prevented yearly if all countries implemented mandatory folic acid fortification. Further trials of folic acid for stroke prevention are required in countries without effective folic acid fortification policies. Funding: Medical Research Council (UK) and British Heart Foundation.

Nutrients and phytochemical density in Mesembryanthemum crystallinum L. cultivated in growing media supplemented with dosages of nitrogen fertilizer.

Mesembryanthemum crystallinum L. is an annual halophyte that originated from southern Africa. However, little has been reported about factors that modulate the quantity of secondary metabolites in the plant. In this study, the twin effect of different nitrogen concentrations (0.36, 0.6, 0.8 g/L) and growing media (LECA clay, peat, vermiculite and silica sand) on plant growth, chlorophyll contents, minerals, proximate and antioxidant metabolites in hydroponically cultivated M. crystallinum was investigated. This is important to determine the dosage of N fertilizer that will optimize the bio-productivity and biosynthesis of secondary metabolites and antioxidants in M. crystallinum grown in a hydroponic system. The untreated plant (0 g/L N) was taken as the control. At the end of the experiment, optimum yields in leaf number (9.2), fresh weight (50.40 g), Ca, N, and Protein (34.04 %) were recorded in M. crystallinum grown with peat enhanced with different dosages of N-fertilizer. Likewise, chlorophyll level, dry weight, ABTS/TEAC, FRAP, ADF and NDF contents were optimized in LECA clay treated with N-fertilizer. Silica sand with 0.36 g/L dosage of nitrogen fertilizer optimized P, Mn and Zn levels, so also the moisture (9.83 % at 0.8 g/L N), fat (2.38 %, 0 g/L N) and carbohydrates (44.98 and 44.95 %). The highest ash content, Mg and Fe were recorded in the untreated vermiculite as well as polyphenols and K, at 0.6 g/L; Cu and root length (14.60 cm), at 0.8 g/L. In conclusion, different dosages of nitrogen fertilizer and growing media could enhance the growth potential, chlorophyll, phytochemicals, and nutritional properties of M. crystallinum.

Low-dose daily folic acid (400 µg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial.

BACKGROUND: Folic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. OBJECTIVE: The objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. METHODS: In this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 µg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. RESULTS: Among 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 µg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 µg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). CONCLUSIONS: Folate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption. This trial was registered at clinicaltrials.gov as NCT03421483.

Strategic food vehicles for vitamin D fortification and effects on vitamin D status: A systematic review and meta-analysis of randomised controlled trials.

There has been growing interest in the potential of vitamin D food fortification in Europe as a means of addressing low vitamin D status. The WHO-FAO suggest that choosing a suitable food vehicle and ensuring the combination of the food vehicle and the fortificant will be efficacious and effective are of key importance to a successful food fortification programme. Our key objective was to conduct a systematic review and meta-analysis to investigate the effect of various animal- and plant-based food vehicles fortified with vitamin D (as D3 or D2) on circulating 25-hydroxyvitamin D [25(OH)D] concentrations. A list of prioritised food vehicles was established and we searched PubMed, Embase, Scopus and Web of Science for randomised controlled trials (RCTs) which used these vehicles individually, and which met prespecified criteria. The searches identified 49 papers which described suitable RCTs using vitamin D-fortified bread/savoury biscuits (n = 5), orange juice (n = 5), UV-mushrooms (n = 8), cheese (n = 3), yogurt (n = 5), fluid milk (n = 13), powdered milk (n = 5), eggs (n = 2), edible oils (n = 4), or breakfast cereal (n = 1). No suitable RCTs were identified for rice, maize flour, butter, margarine or dairy spreads, plant-based milk or yogurt alternatives. Random-effects meta-analyses of each food vehicle individually indicated weighted mean differences (WMD) in 25(OH)D in the range ∼9-35 nmol/L (3-15 RCT arms, depending on vehicle), and all statistically significant (P < 0.01-0.0001), with the exception of UV-mushrooms (P = 0.06). Heterogeneity was variable (I2 =33-99%, depending on vehicle), but subgroup analysis based on vitamer and dose reduced it in some instances. Sub-group analysis on the basis of whether the food vehicles were from plant-based or animal-based origin showed no significant difference in WMD (15.2 versus 15.9 nmol/L, respectively; P = 0.48). These results support the use of various animal- and plant-based food vehicles for vitamin D fortification to improve circulating 25(OH)D concentrations in populations. This work was registered with PROSPERO as CRD42023439883.

The Effect of Iron-Fortified Lentils on Blood and Cognitive Status among Adolescent Girls in Bangladesh.

BACKGROUND: Iron deficiency is highly prevalent in South Asia, especially among women and children in Bangladesh. Declines in cognitive performance are among the many functional consequences of iron deficiency. OBJECTIVE: We tested the hypothesis that, over the course of a 4-month iron fortification trial, cognitive performance would improve, and that improvement would be related to improvements in iron status. METHODS: Participants included 359 adolescent girls attending Bangladesh Rural Advancement Committee (BRAC) clubs as a subsample of a larger double-blind, cluster-randomized community trial in which participants were assigned to one of three conditions: a condition in which no lentils were supplied (NL, n = 118, but which had the usual intake of lentils), a control (non-fortified) lentil condition (CL, n = 124), and an iron-fortified lentil condition (FL, n = 117). In the FL and CL conditions, approximately 200 g of cooked lentils were served five days per week for a total of 85 feeding days. In addition to biomarkers of iron status, five cognitive tasks were measured at baseline (BL) and endline (EL): simple reaction time task (SRT), go/no-go task (GNG), attentional network task (ANT), the Sternberg memory search Task (SMS), and a cued recognition task (CRT). RESULTS: Cognitive performance at EL was significantly better for those in the FL relative to the CL and NL conditions, with this being true for at least one variable in each task, except for the GNG. In addition, there were consistent improvements in cognitive performance for those participants whose iron status improved. Although there were overall declines in iron status from BL to EL, the declines were smallest for those in the FL condition, and iron status was significantly better for those in FL condition at EL, relative to those in the CL and NL conditions. CONCLUSIONS: the provision of iron-fortified lentils provided a protective effect on iron status in the context of declines in iron status and supported higher levels of cognitive performance for adolescent girls at-risk of developing iron deficiency.

Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions.

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.

Sensory panel results of a dried fish powder supplement among caregivers and young children in Zambia.

OBJECTIVE: To evaluate the acceptability of traditional Zambian dishes fortified with Complementary Food for Africa+Dried Fish Powder (ComFA+Fish), a locally sourced protein/micronutrient blend designed to impact nutrient deficiencies among infants and young children (IYC) and improve pregnancy and birth outcomes among women of reproductive age (WRA). DESIGN: During two sensory panels, caregivers evaluated: (1) the acceptability of four ComFA+Fish dishes for household consumption, including fortified chibwabwa fisashi, savory Kapenta chutney, fortified complementary maize porridge and fortified bean-vegetable soup and (2) whether their IYC found the fortified complementary maize porridge acceptable. SETTING: Lake Kariba, Southern Province, Zambia. PARTICIPANTS: Women of reproductive age (n 42) and their IYC aged 6-11 months (n 16) and 12-23 months (n 26) were recruited from fishing villages in Gwembe, Siavonga and Sinazongwe District. RESULTS: A majority of caregivers extremely liked/liked the: (1) fortified chibwabwa fisashi's sensory attributes (94·7 %), convenience (92·8 %) and overall acceptability (100 %); (2) savory Kapenta chutney's sensory attributes (81·8 %), convenience (92·8 %) and overall acceptability (100 %); (3) fortified complementary porridge's sensory attributes (83·5 %), convenience (90·5 %) and overall acceptability (88·1 %) and (4) fortified bean-vegetable soup's sensory attributes (66·8 %), convenience (87·5 %) and overall acceptability (87·5 %). Further, a majority of caregivers evaluated the fortified complementary porridge as highly acceptable to their IYC. CONCLUSIONS: Results suggest that ComFA+Fish is strategically well placed to fill nutritional gaps among IYC and WRA in Zambia and has the potential to be scaled across sub-Saharan Africa.