Vitamin A (Night Vision)

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was abou

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP. OBJECTIVES: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2020, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and OpenGrey. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 February 2020. SELECTION CRITERIA: We included randomized controlled trials that enrolled participants of any age diagnosed with any degree of severity or type of RP, and evaluated the effectiveness of vitamin A, fish oils (DHA), or both compared to placebo, vitamins (other than vitamin A), or no therapy, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials. DATA COLLECTION AND ANALYSIS: We prespecified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one-year follow-up, and mean change in visual acuity, at five-year follow-up. Two review authors independently extracted data and evaluated risk of bias for all included trials. We also

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the stu

OBJECTIVE: To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. DESIGN: Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. RESULTS: 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). CONCLUSIONS: Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other so

BACKGROUND: Zinc deficiency may result in abnormal dark adaptation or night blindness, a symptom primarily of vitamin A deficiency. During a placebo-controlled trial in Nepal, weekly vitamin A supplementation of women reduced but failed to eliminate the incidence of night blindness during pregnancy, suggesting a role for zinc. OBJECTIVE: The study examined the efficacy of daily zinc supplementation in restoring night vision of pregnant women who developed night blindness while routinely receiving either vitamin A, beta-carotene, or placebo in a field trial. DESIGN: Women (n = 202) who reported to be night blind during pregnancy were randomly assigned in a double-blind manner, stratified on vitamin A, beta-carotene, or placebo receipt, to receive 25 mg Zn or placebo daily for 3 wk. Thus, the 6 groups studied were as follows: beta-carotene + zinc, beta-carotene alone, vitamin A + zinc, vitamin A alone (vitamin A + placebo), zinc alone (zinc + placebo), and placebo (2 placebos: one for the vitamin A or beta-carotene study and one for the zinc study). Women underwent a clinic-based assessment that included pupillary threshold testing and phlebotomy before and after supplementation. Supplement use and daily history of night blindness were obtained at home twice every week. RESULTS: Zinc treatment increased serum zinc concentrations, but alone (zinc alone group), failed to restore night vision or to improve dark adaptation. However, women in the vitamin A + zinc group who had baseline serum zinc concentrations <9.9 micromol/L were 4 times more likely to have their night vision restored (95% CI: 1.1, 17.3) than were women in the placebo group and tended to have a small improvement in pupillary threshold scores (by 0.21 log candela/m2; P = 0.09). CONCLUSION: These data suggest that zinc potentiated the effect of vitamin A in restoring night vision among night-blind pregnant women with low initial serum zinc concentrations.

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP. OBJECTIVES: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2013. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating the effectiveness of vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials. DATA COLLECTION AND ANALYSIS: We pre-specified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one year; as well as mean change in visual acuity at five-year follow-up. Two authors independently evaluated risk of

While previous meta-analyses have established a link between vitamin A supplementation and outcomes in children with pneumonia, the efficacy and safety of different dosing regimens remain unclear. Existing evidence is predominantly based on single-dose trials, creating a critical knowledge gap. We systematically searched PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and VIP databases from their inception to December 2025. Study searches were independently carried out in December 2025 by two reviewers. Two researchers used the Cochrane risk of bias tool to independently assess the quality of the included studies. Data analysis was conducted through the "netmeta" package in R software (version 4.3.3). Twenty-five trials involving 3116 patients were included. Network meta-analysis revealed that medium-dose vitamin A supplementation was most effective in reducing the duration of fever and cough. Low-to-medium doses were consistently associated with better clinical outcomes than high-dose regimens. However, evidence regarding safety outcomes remained limited and inconclusive. CONCLUSION: Low-to-medium dose vitamin A supplementation appears superior to high-dose regimens for alleviating clinical symptoms in children with pneumonia. However, the evidence is limited by high heterogeneity, indirect comparisons between dose groups, and poor reporting of adverse events. Future trials should prioritize direct dose-comparisons and rigorous safety monitoring to refine dosing guidelines. WHAT IS KNOWN: • Pneumonia poses a significant threat to the health and lives of children. Vitamin A supplementation plays an adjuvant role in the treatment of pneumonia in children. • There are currently divergent conclusions in the research regarding the optimal dosage of vitamin A, particularly with regard to the safety of high-dose supplementation and the effectiveness of low-dose supplementation. WHAT IS NEW: • This study revealed that medium-to-low-dose vitamin A supplementation appears to be more effective than high-dose therapy in alleviating the primary symptoms of childhood pneumonia. • This study also suggests that children in developed regions

BACKGROUND: Vitamin A (VA) deficiency impairs immune function. STUDY DESIGN: A randomized, placebo-controlled intervention trial, stratified by sex and birthweight median (BWM), was conducted in 306 infants in Dhaka, Bangladesh to evaluate the effect of 50,000 IU VA given within 48 h of birth on responses to Bacillus Calmette Guérin (BCG), oral polio virus (OPV), Tetanus Toxoid (TT) and Hepatitis B virus (HBV) vaccines. METHODS: VA, BCG and OPV were administered within 48 h of birth. OPV was again administered at 6, 10 and 14 w with TT and HBV. Vaccine-specific responses included delayed-type hypersensitivity (DTH) at 15 w for BCG and antibody responses at 15 w (ex vivo PBMC secretion) and 2 y for OPV (IgA, IgG), TT (IgG) and HBV (IgG). T-cell proliferation and cytokine production (IFN-γ, IL-2, -4, -5, -10, -13 and -17A) in response to vaccine antigens and a polyclonal stimulus (staphylococcus enterotoxin B [SEB]) were measured at 6 w, 15 w and 2 y. Statistical analysis determined main effects of the intervention, and interactions with sex and birthweight. RESULTS: VA increased the DTH response in infants above the BWM but did not affect antibody responses to vaccines. The CD4 T-cell stimulation index (SI) was reduced by VA for BCG (6 w) and SEB (overall). VA increased TT- and HBV-specific IL-2 and IL-5 at 15 w and increased SEB-stimulated IL-5 in girls but decreased IL-5 in boys at 15 w. VA increased BCG-specific IL-13 and SEB-stimulated IL-5 in girls. VA decreased TT-specific and SEB-stimulated IL-17 in boys and decreased IL-10 in response to BCG, HBV (below BWM only) and SEB at 15 w. CONCLUSIONS: Neonatal VA modestly improved the DTH response to BCG but had no effect on antibody responses to OPV, TT and HBV. VA affected CD4 T-cell function, at times in a sex-specific manner. TRIAL REGISTRY: This trial is registered at Clinical. TRIALS: gov. Registry numbers are NCT015839720 and NCT02027610. Published by Elsevier Ltd.

BACKGROUND: Vitamin D interacts with vitamin A through receptor heterodimerization. This post hoc analysis of the AMATERASU randomized clinical trial (RCT) of vitamin D3 supplementation examined whether serum vitamin A levels modify the association of vitamin D with relapse or death in patients with digestive tract cancer. METHODS: The primary outcome was relapse or death. Relapse-free survival (RFS) was evaluated using Nelson-Aalen cumulative hazard functions and Cox proportional hazards models. Serum vitamin A levels were categorized stepwise using clinical reference ranges and quantile cutoffs (halves, tertiles, quartiles, quintiles, and deciles), with post hoc grouping of the most coherent quantiles for analysis. RESULTS: Among 363 patients (mean age, 66 years; 67.8% male), serum vitamin A ranged from 0.15 to 4.30 μmol/L [median (IQR), 1.38 (1.05-1.74)] and correlated positively with 25-hydroxyvitamin D (ρ = 0.31; P < 0.0001). Patients in the lowest decile had higher relapse or death risk [HR, 2.05; 95% confidence interval (CI), 1.10-3.84; P = 0.03] than those in deciles 2 to 10. In the middle range (deciles 6-8), 5-year RFS was greater with vitamin D versus placebo (81.4% vs. 54.9%; HR, 0.31; 95% CI, 0.14-0.69; P = 0.004), with no effect in lower (deciles 1-5) or higher (deciles 9-10) ranges (Pinteraction = 0.008). CONCLUSIONS: Vitamin D supplementation may reduce relapse and death among patients with middle-to-upper range of serum vitamin A levels. IMPACT: These exploratory findings provide the first RCT evidence that serum vitamin A levels modify the effect of vitamin D supplementation on relapse or death among patients with digestive tract cancer. ©2026 American Association for Cancer Research.

PURPOSE: The aim of the MultiVeg study, a double-blind, randomised controlled trial (RCT), was to investigate the nutritional status of healthy vegans following 4 months of multinutrient supplementation. METHODS: A double-blind, RCT was conducted with 72 vegan adults (19-57 years) in Germany. Data on anthropometric parameters, dietary nutrient intake, and nutritional status were collected. The nutritional status of the participants was assessed at baseline and after 4 months. The results were compared between groups using ANCOVA. The results for vitamins and choline are presented here. RESULTS: After adjustment for baseline values, age, sex, and multiple testing, no significant between-group differences in biomarker concentration changes from baseline to 4 months were observed for vitamin A, retinol-binding protein, transthyretin, beta-carotene, methylmalonic acid, homocysteine, choline, total osteocalcin, carboxylated and undercarboxylated osteocalcin, and folate. In contrast, significant between-group differences in changes were observed for flavin adenine dinucleotide (FAD), serum vitamin B12, holotranscobalamin, and the combined vitamin B12 status indicator (cB12) after adjustment. CONCLUSION: A multinutrient supplement containing 82 µg of vitamin B12 per day significantly positively affected vitamin B12 blood biomarkers in healthy vegans. REGISTRATION: This study was registered in the German Clinical Trials Register (DRKS00028151). © 2025. The Author(s).

OBJECTIVE: We assessed the effectiveness of weekly iron and semestrial high-dose vitamin A supplementation on hemoglobin (Hb) concentration, and iron and vitamin A status of schoolchildren in rural Ethiopia. METHOD: Using a 2 × 2 factorial design, 504 schoolchildren aged 7-10 years were randomly assigned to one of the four arms: control placebo; high-dose vitamin A; iron; or iron and high-dose vitamin A. Semestrial 200,000 IU vitamin A and weekly 42 mg of iron supplement were provided for 11 months. At baseline and at endline, Hb and serum concentrations of ferritin (sF), soluble transferrin receptor (sTfR), and retinol-binding protein (RBP) were measured. Serum indicators were adjusted for inflammation indicators, while Hb was adjusted for village altitude. Total body iron was calculated from sTfR and sF concentrations using an established formula. RESULT: At baseline, prevalence of anemia (Hb < 11.0 g/dL), iron deficiency (sTfR > 8.3 mg/L or sF < 15 μg/L), iron-deficiency anemia, and vitamin A deficiency (RBP < 0.7 μmol/L) were 27.8%, 21.7%, 6.3% and 12.2%, respectively. Both iron and vitamin A supplementation had no significant effect on Hb, sTfR, and RBP concentrations. Supplementing iron weekly significantly increased sF (6.86 μg/L, 95%CI: 1.67, 12.05) and total body iron (0.45 mg/Kg, 95%CI: 0.17, 0.74), while semestrial vitamin A supplementation had no significant effect on both sF and total body iron. CONCLUSION: Intermittent iron and vitamin A supplementation had no significant detectable effects on Hb, sTfR, and RBP concentrations of schoolchildren. Weekly iron supplementation improved sF concentrations. These findings suggest that providing iron and vitamin A supplements to populations where the extent of the deficiencies is not a major public health problem may not be beneficial. © 2025. The Author(s), under exclusive licence to Springer Nature Limited.

Emerging evidence suggests a bidirectional relationship between vitamin A deficiency (VAD) and gut microbiota, with implications to host health. This double-blind randomised controlled trial (NCT03256123) aims to investigate the effects of 6-month red palm olein (RPO)-enriched biscuit supplementation on gut microbiota of 328 vitamin A-deficient primary schoolchildren (aged 8-12 years) in rural Malaysia, randomised to receive either RPO-enriched biscuits (experimental group, n = 145) or palm olein (PO)-enriched biscuits (control group, n = 183). Stool samples are collected at baseline, 3-month and 6-month of supplementation, and analysed using 16S rRNA gene sequencing. The primary outcome is the changes in gut microbiota composition, while secondary outcomes include alteration in gut microbiota diversity, correlations with blood biomarkers, and microbial network structure. Compared to the control group, the experimental group shows significant reductions in alpha diversity indices (e.g., observed ASVs and chao1, P < 0.001), and increased abundance of potentially beneficial gut bacteria, such as Anaerostipes, UCG-010 and Lachnospiraceae_NK4A136_group (Padj < 0.05), which also positively correlate with improvements in alpha-carotene, beta-carotene, alpha-tocopherol, packed cell volume, and mean corpuscular volume (Padj < 0.05). Microbial network analysis reveals that the experimental group exhibits a more cohesive and stable network, evidenced by higher average degree and clustering coefficient values, and lower average path lengths (P < 0.001). Our findings shed light on the potential of RPO-enriched biscuit supplementation in modulating gut microbiota in vitamin A-deficient children by enhancing microbial network cohesiveness and enriching potentially beneficial bacterial taxa which are linked to enhanced micronutrient and haematological outcomes. These findings lay a valuable foundation and expand the existing evidence base for understanding the relationship between provitamin A carotenoids and gut microbiota. © 2025. The Author(s).

BACKGROUND: A few studies examined behavioral difficulties among children in low-income countries or the influence of early life nutrition interventions. OBJECTIVES: We examined the effect of micronutrient supplementation done as part of 2 randomized trials during pregnancy or in early preschool age on behavioral outcomes among school-aged children in rural Nepal. METHODS: Children between 7 and 9 y of age were enrolled in a cohort follow-up study in which the Conners Rating Scale-Revised was administered to their parents and teachers. These children were offspring of participants in a cluster-randomized trial during pregnancy receiving daily iron-folic acid, iron-folic acid + zinc, or multiple micronutrients, compared with a control (all groups received vitamin A). These children between 12 and 35 mo of age also received daily placebo, iron-folic acid, zinc alone, or iron-folic acid + zinc in a separate randomized trial. Factor analysis identified 2 attention-deficit hyperactivity disorder-related behaviors for parent scores (hyperactivity/oppositional and inattention) and 2 for teacher scores (hyperactivity and inattention). Using mixed-effects linear regression analysis, we analyzed the effect of early life supplementation on these behavioral domains in school children (n = 1255). RESULTS: Exposure to prenatal iron-folic acid resulted in lower oppositionality/hyperactivity and inattention scores in children assessed via parental ratings in both unadjusted and adjusted analyses. Iron-folic acid with zinc reversed the positive effect seen with iron-folic acid. Multiple micronutrient supplementation resulted in a lower oppositionality and/or hyperactivity score, using parent and teacher ratings in the adjusted analysis. All 3 supplement groups in the preschool trial reduced child inattention when assessed by parents. Based on teacher ratings, groups that had received iron-folic acid alone or with zinc during preschool had reduced scores of hyperactivity in both unadjusted and adjusted analyses. CONCLUSIONS: Our study shows potential benefit of early life exposure to micronutrient supplementation for child-related behavior outcomes in a South Asian setting where

BACKGROUND: Globally, over half of women of reproductive age are affected by at least one micronutrient deficiency, often exacerbated during pregnancy and lactation, contributing to adverse maternal and child health outcomes. This systematic review and meta-analysis synthesized impact of vitamin supplementation on maternal, infant and lactational nutritional status in low- and middle-income countries. METHODS: MEDLINE, EMBASE, CENTRAL, and WHO library databases were searched. Eligible studies included randomized controlled trials of micronutrient supplementation in healthy pregnant/lactating women, assessing maternal/infant micronutrient status or milk composition. Random-effects meta-analysis was performed for outcomes with ≥2 studies, and evidence quality was evaluated using GRADE. RESULTS: Eighty-seven papers (76 trials, including 65 for meta-analysis) were included. Maternal vitamin B-12 supplementation during pregnancy increased serum cobalamin concentrations (standard mean difference [SMD] 0.39; 95% CI 0.11, 0.68; P=0.01) and reduced deficiency (OR 0.43; 95% CI 0.19, 0.95; P=0.04), with improved B-12 concentrations in milk, especially when administered postpartum (SMD 0.33; 95% CI 0.02, 0.63; P=0.04), but had no consistent effect on infant or cord serum cobalamin concentrations. Vitamin A supplementation during pregnancy or postpartum improved maternal serum concentrations (SMD 0.60; 95% CI 0.13, 1.08; P<0.001) and reduced deficiency at thresholds ≤0.7 μmol/L (OR 0.55; 95% CI 0.43, 0.71; P<0.001); however, its effects on infant and cord serum levels were negligible. Postpartum vitamin A supplementation improved milk vitamin A concentrations (SMD 0.53; 95% CI 0.19, 0.86; P<0.001), particularly with single high-dose regimens. Supplementation with vitamin D during pregnancy increased maternal serum vitamin D concentrations (SMD 1.68; 95% CI 0.99, 2.37; P<0.001), reduced deficiency at thresholds ≤50 nmol/L (OR 0.30; 95% CI 0.14, 0.64; P<0.001) and increased vitamin D concentrations in infant and cord serum. CONCLUSIONS: Micronutrient supplementation during pregnancy and lactation improved maternal nutritional status but showed inconsistent effects on infant nu

BACKGROUND: Nutrition is vital for preterm infant development. Vitamins play key roles as cofactors and gene regulators for metabolic and immune functions and are common added components of preterm infant nutrition. However, information on how vitamins impact in-hospital and neurodevelopmental outcomes is sparse. We aimed to determine the effect of fat- and water-soluble vitamin supplementation on clinical outcomes during neonatal care and later neurodevelopment of very preterm (≤32 weeks' gestation) and very low birth weight (≤1500 g) infants. METHODS AND FINDINGS: 4 databases and 3 clinical trial registries were systematically searched for randomised controlled trials (RCTs). Two reviewers independently extracted data and assessed quality using the Cochrane Risk of Bias tool. Meta-analyses were conducted using a random-effect model for each vitamin subgroup. Data are presented as risk ratios [95% confidence intervals]. Of 4074 references identified, 43 studies were included in the review. Only 2 reported neurodevelopment at 2 years, and only 4 were studies of water-soluble vitamins (vitamin C, 3 studies; B12 and folate, 1 study). Survival free from neurodisability was not affected by supplementation of vitamin A (0.89 [0.74-1.08], n = 538, very low certainty of evidence) or vitamin D (0.76 [0.46-1.27], n = 78, very low certainty of evidence). The incidence of bronchopulmonary dysplasia was decreased by vitamins D (0.58 [0.41-0.83]) and C (0.59 [0.37-0.93]), very low certainty of evidence), retinopathy of prematurity was decreased by vitamins A (0.77 [0.61-0.98]) and E (0.10 [0.01-0.80]), very low to low certainty of evidence) and intraventricular haemorrhage was decreased by vitamin E (0.70 [0.52-0.92], moderate certainty of evidence). Culture-proven sepsis was decreased by vitamin A (0.88 [0.77-0.99], moderate certainty of evidence). CONCLUSIONS: There are few and inconclusive data on the effect of vitamin supplementation in preterm infants on later neurodevelopment. Evidence for shorter-term outcomes is mostly of low certainty. Together with substantial heterogeneity in trial design, it therefore is difficult to recommend a specific supplementation regimen.

PURPOSE: Despite the increased size of the Asian American population and reported differences in nutrient metabolism according to ancestry, diets of East Asian descendants (EA) in the U.S. have not been directly compared with adults of Northern European descent (NE). We compared the diet quality and food and nutrient intake between EA and NE residing in similar geographic locations. METHODS: Dietary intake was evaluated in a cohort of 487 adult males and pre-menopausal, non-pregnant females of genetically confirmed EA (n = 251) and NE (n = 253) ancestry. Participants were aged 18-50 y, non-smokers, and without obesity or other chronic diseases. The Healthy Eating Index (HEI), food group intakes, nutrient intakes, and supplement use was assessed by a food frequency questionnaire (DHQIII) and a single 24-h recall (ASA24). Intakes were compared between ancestries by Student's t-test or Mann-Whitney U test. RESULTS: East Asian adults had similar total HEI scores compared to NE (P = 0.09). However, higher intakes of dark-green vegetables, meat, seafood, vitamin A, vitamin K, and heme iron (all P < 0.05) were found in adults of EA compared to NE ancestry. Compared to EA, NE consumed significantly more fruit, whole grains, dairy, nuts and seeds, coffee, alcohol, fat and added sugar (all P < 0.05). CONCLUSIONS: Diet quality was similar, but food and nutrient intakes differed, between EA and NE residing in close geographical proximity within the U.S. Whether dietary intake differences are associated with differences in health outcomes between these ancestral groups must be determined. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/study/NCT04198545 . © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: In Pakistan, maternal micronutrient deficiencies are highly prevalent, and stunting affects 43% of infants by 6-mo postpartum. Human milk composition for some micronutrients can be negatively affected by suboptimal maternal nutrition; however, it is unknown whether this affects infant growth. OBJECTIVES: We aimed to determine whether mothers receiving multiple micronutrient supplements (MMSs) compared with standard of care had 1) greater concentrations of iodine, vitamins A, E, and B12, and folate in their milk at 3-mo postpartum; and 2) improved growth of their offspring. Associations between milk micronutrients and infant growth were also explored. METHODS: This substudy was nested within a district-based, cluster-randomized, controlled trial (MaPPS Trial; 25,477 females) with the primary aim of evaluating whether maternal MMS (preconception: twice-weekly, pregnancy and postpartum: daily, to 6-mo postpartum) compared with the standard of care (preconception: no intervention; pregnancy and postpartum: daily iron and folic acid supplementation, to 6-mo postpartum) in rural Pakistan improved infant birthweight. Substudy mother-infant dyads (n = 186) were recruited if infants were term-born and predominantly or exclusively breastfed. Milk micronutrient concentrations were compared to reference values derived from mother's milk [mother's milk adequacy estimates (MAEs)]. RESULTS: MMS increased milk iodine and vitamin A concentrations, but not vitamins B12 or E, nor folate. Importantly, few milk sample micronutrients in either arm were above existing MAEs. MMS compared to standard of care did not improve infant growth. Independent of allocation, having all 5 milk micronutrients below MAEs was associated with decreased infant length-for-age z-score (β: -0.39, 95% CI: -0.73, -0.04; P = 0.03). CONCLUSIONS: In a population with maternal micronutrient deficiencies, providing maternal MMS was not associated with milk micronutrient concentrations above MAEs; however, infants born to mothers with milk below MAEs for all investigated micronutrients appeared to experience poorer growth. Further research is needed to understand longer-term implications, if any. CLIN

Background: Coronary artery disease (CAD) is a common heart disease characterized by plaque buildup in the coronary arteries. Saffron, which is rich in active compounds, has strong antioxidant properties that help reduce free radicals and plasma malondialdehyde (MDA) levels. This study aimed to evaluate the effects of crocetin supplementation on antioxidant and inflammatory markers, as well as serum leptin levels, in CAD patients. Methods: In this double-blind, placebo-controlled trial conducted in Ahvaz, Iran, 50 clinically diagnosed CAD patients, including men and women aged 40-65, were randomly assigned to two parallel groups to receive either one tablet of 10 mg crocetin (n = 25) or one placebo (n = 25) daily for eight weeks. The primary outcome was high-sensitivity C-reactive protein (hs-CRP) levels, and the secondary outcomes included the activities of superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA) levels, the atherogenic index of plasma (AIP), leptin levels, anthropometric measurements, and body composition. Both groups followed similar dietary and exercise regimens. Results: We found no significant differences between the intervention and placebo groups regarding C-reactive protein (CRP) levels, as indicated by ANCOVA (P = 0.695). Similarly, ANCOVA results for leptin (P = 0.854), superoxide dismutase (SOD) (P = 0.520), malondialdehyde (MDA) (P = 0.178), and the atherogenic index of plasma (AIP) (P = 0.409) also did not show significant differences. However, a significant result was observed for catalase (CAT) (P = 0.008). The comparison of mean differences within the intervention and placebo groups showed clinical improvements for several measurements. Importantly, hs-CRP levels were -119.62 in the intervention group compared to -156.91 in the placebo group. Other mean differences included SOD (41.72 vs. -7.33), MDA (-0.99 vs. -0.16), AIP (-0.13 vs. 0.04), leptin (-1.86 vs. -0.09), systolic blood pressure (SBP) (-0.25 vs. 0.13), and diastolic blood pressure (DBP) (-0.24 vs. -0.01). Conclusions: Crocetin supplementation significantly improved inflammation, oxidative stress status, and leptin levels in CAD patients. Although further s

Previous studies have shown that high-dose vitamin supplements can improve vaccine-induced immune responses and pathogen protection in the context of vitamin deficiencies. To further elucidate the influence of vitamin supplements on immune responses toward pediatric vaccines, we performed a randomized controlled clinical trial (PCVIT) of 20 healthy children 1-4 years of age in Memphis, Tennessee. Study participants received a booster vaccine for pneumococcus and a primary vaccine for hepatitis A virus with or without a high-dose, oral, liquid supplement of 10,000 IU retinyl palmitate. We found that the children enrolled in PCVIT had higher baseline vitamin levels than previously described older children and adults living in Memphis. Only one child in PCVIT had a serum retinol level of less than 0.3 µg/mL. The children frequently consumed milk and baby foods that were likely vitamin-fortified, providing an explanation for the relatively high vitamin levels. Most children in PCVIT responded well to pneumococcus and hepatitis A vaccines by pathogen-specific antibody upregulation. The one child with a serum retinol level below 0.3 µg/mL did not receive a vitamin supplement and exhibited the lowest fold-change in antibody responses toward pneumococcal serotypes. A correlation matrix encompassing demographics, vitamin levels, vaccine-induced immune responses, C-reactive protein, and total serum immunoglobulin isotypes, including IgG2 and IgA, identified variables associated with vaccination outcomes. Perhaps because children were predominantly retinol-sufficient at baseline, the high-dose vitamin A supplement exhibited no benefit to vaccine-induced immune responses. In fact, when vitamin supplemented and vitamin unsupplemented groups were compared among participants with the highest baseline retinol levels, there was a trend toward weaker vaccine-induced immune responses in the vitamin supplemented group. Results encourage the performance of larger clinical studies before high-dose vitamin supplements are recommended for populations that are otherwise vitamin-replete.

OBJECTIVE: This study aimed to investigate the effectiveness of carotenoid-rich red palm olein (RPO) in treating or preventing xerophthalmia among Malaysian rural primary schoolchildren with confirmed vitamin A deficiency (VAD) (plasma retinol <0.70 µmol/L) and marginal vitamin A status (plasma retinol 0.70 to <1.05 µmol/L). METHODS: A double-blinded, cluster randomized controlled trial was conducted on 504 schoolchildren aged 8-12 years from ten rural primary schools in Malaysia. The selected schools were randomly assigned into two groups: the experimental group (n = 249) received RPO-enriched biscuits (326.3 µg retinol equivalents/day), while the control group (n = 255) received palm olein (PO)-enriched biscuits for 6 months (4 days/week). Chi-square test and mixed effects logistic regression model were applied to examine the effects of supplementation on the resolution or prevention of xerophthalmia. RESULTS: After 6-month supplementation, a higher resolution rate of xerophthalmia (31.2%) was observed in the experimental group compared to the control group (24.1%), but this difference lacked statistical significance (p = 0.11). Nevertheless, the experimental group showed a significantly higher prevention rate of xerophthalmia (81.8%) or conjunctival xerosis (82.5%) than the control group (56.5% or 57.6%, respectively) after 6-month supplementation (p < 0.001). Moreover, schoolchildren in the experimental group were 4.8 times less likely to develop xerophthalmia compared to the control group. CONCLUSION: A 6-month supplementation of RPO-enriched biscuits demonstrated potential benefits in preventing xerophthalmia or conjunctival xerosis among vitamin A-deficient primary schoolchildren in rural areas of Malaysia. Therefore, RPO may offer a promising preventive solution to xerophthalmia for populations at a high risk of developing VAD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123). © 2025. The Author(s), under exclusive licence to Springer Nature Limited.

BACKGROUND & AIMS: Sickle cell disease (SCD), a neglected chronic genetic blood disorder that severely impacts the pediatric population, often leading to premature death, is associated with compromised nutritional status. This study aimed to evaluate the effect of nutritional supplementation in SCD-related complications. METHODS: A systematic review with searches in PubMed, Scopus and Web of Science was performed. Randomized controlled trials (RCT) assessing diet or supplements as complementary therapy for children and adolescents with SCD were included (PROSPERO:CRD42024532369). The data for outcomes of interest (efficacy, safety) were pooled by means of pairwise and network meta-analyses with ranking (p-score) analysis. The results were presented as odds ratio or mean differences with 95 % confidence intervals (NMAstudio2.0). RESULTS: Twenty RCTs were included (2002-2023) (n = 2058), analyzing 9 dietary supplements on different regimens. All patients were in use of hydroxyurea as active treatment. Supplementation with fatty acids (n = 3 studies) and l-arginine (n = 4) presented higher efficacy and safety, significantly improving pain intensity, vaso-occlusive crises (VOC) and inflammation when compared to usual care/placebo (p < 0.05). Vitamin D3 (n = 6) at different dosages may reduce respiratory complications and length of hospital stay, yet further studies are needed to confirm its significant effects. Evidence is limited and of poor quality regarding the effects of add-on vitamin A (n = 2), magnesium sulfate (n = 2) and zinc (n = 4) for this population. CONCLUSIONS: The complementary use of certain supplements (fatty acids, l-arginine, vitamin D3) can enhance the management of VOC and improve patients' physiological functions. These supplements are often affordable and can contribute towards the reduction of opioid use and shorten patients' hospital stays - especially in low/middle-income countries where resources are scarce. Although further studies are needed to refine these findings (e.g., appropriate doses/regimens), practical guidelines and decision-makers may benefit from updated evidence.