비타민A (야간 시력)

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

1. Cochrane Database Syst Rev. 2022 Mar 16;3(3):CD008524. doi: 10.1002/14651858.CD008524.pub4. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Imdad A(1), Mayo-Wilson E(2), Haykal MR(3), Regan A(3), Sidhu J(3), Smith A(4), Bhutt

Vitamin A and fish oils for preventing the progression of retinitis pigmentosa.

2. Cochrane Database Syst Rev. 2020 Jun 18;6(6):CD008428. doi: 10.1002/14651858.CD008428.pub3. Vitamin A and fish oils for preventing the progression of retinitis pigmentosa. Schwartz SG(1), Wang X(2), Chavis P(3), Kuriyan AE(4), Abariga SA(5). Author information: (1)Bascom Palmer Eye Institute,

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

3. Cochrane Database Syst Rev. 2017 Mar 11;3(3):CD008524. doi: 10.1002/14651858.CD008524.pub3. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Imdad A(1), Mayo-Wilson E(2), Herzer K(3), Bhutta ZA(4). Author information: (1)Depar

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis.

4. BMJ. 2011 Aug 25;343:d5094. doi: 10.1136/bmj.d5094. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. Mayo-Wilson E(1), Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Author information: (1)Centre for Evidence-Based

Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women.

5. Am J Clin Nutr. 2001 Jun;73(6):1045-51. doi: 10.1093/ajcn/73.6.1045. Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women. Christian P(1), Khatry SK, Yamini S, Stallings R, LeClerq SC, Shrestha SR, Pradhan EK, West KP Jr. Author i

Vitamin A and fish oils for retinitis pigmentosa.

6. Cochrane Database Syst Rev. 2013 Dec 19;2013(12):CD008428. doi: 10.1002/14651858.CD008428.pub2. Vitamin A and fish oils for retinitis pigmentosa. Rayapudi S(1), Schwartz SG, Wang X, Chavis P. Author information: (1)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,

Different doses of vitamin A supplementation as adjuvant treatment for pneumonia in children: a network meta-analysis of randomized controlled trials.

1. Eur J Pediatr. 2026 Apr 20;185(5):283. doi: 10.1007/s00431-026-06947-x. Different doses of vitamin A supplementation as adjuvant treatment for pneumonia in children: a network meta-analysis of randomized controlled trials. Zhou CJ(1), Su ZC(1), Li S(1), Jin Y(1), Chen HC(1), Li ZJ(1), Tian YH(1), Lin YD(1), Yan TM(1), Wu FY(1), Liu ZC(1), Liu YD(1), Zhang W(1), Lei XY(1), Li MD(1)(2), Yang J(1), Mao YN(3), Zhu CR(4). Author information: (1)Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, 610041, China. (2)The Second Affiliated Hospital of Kunming Medical University, Kunming, China. (3)School of Public Health, North Sichuan Medical College, Nanchong, 637000, China. (4)Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, 610041, China. cairong.zhu@hotmail.com. 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 have higher baseline serum retinol levels, which may diminish the marginal benefits of high-dose supplementation and may even predispose them to its immunosuppressive effects. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. DOI: 10.1007/s00431-026-06947-x PMID: 42008030 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval: This network meta-analysis was conducted in accordance with the Declaration of Helsinki. Given that the study utilized only published and publicly available data from previously conducted randomized controlled trials, ethical approval and informed consent were waived by the Institutional Review Board. Competing interests: The authors declare no competing interests.

Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy.

2. Vaccine. 2026 Apr 30;80:128551. doi: 10.1016/j.vaccine.2026.128551. Epub 2026 Apr 4. Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy. Stephensen CB(1), Huda MN(2), Alam MJ(3), Khanam A(3), Afsar MNA(3), Raqib R(3), Qadri F(3), Peerson JM(4), Ahmad SM(3). Author information: (1)USDA Western Human Nutrition Research Center at University of California, Davis, CA 95616, USA; Nutrition Department, University of California, Davis, CA 95616, USA. Electronic address: Charles.Stephensen@usda.gov. (2)USDA Western Human Nutrition Research Center at University of California, Davis, CA 95616, USA; Nutrition Department, University of California, Davis, CA 95616, USA; Infectious Diseases Division, icddr,b, Mohakhali, Dhaka 1212, Bangladesh. (3)Infectious Diseases Division, icddr,b, Mohakhali, Dhaka 1212, Bangladesh. (4)USDA Western Human Nutrition Research Center at University of California, Davis, CA 95616, USA. 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. DOI: 10.1016/j.vaccine.2026.128551 PMID: 41936264 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Effect Modification by Serum Vitamin A Levels on the Association between Vitamin D and Relapse or Death in Patients with Digestive Tract Cancer.

3. Cancer Epidemiol Biomarkers Prev. 2026 Mar 2;35(3):429-437. doi: 10.1158/1055-9965.EPI-25-1427. Effect Modification by Serum Vitamin A Levels on the Association between Vitamin D and Relapse or Death in Patients with Digestive Tract Cancer. Kohmura T(1)(2), Ohdaira H(3), Suzuki Y(3), Urashima M(1). Author information: (1)Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan. (2)Department of Gastroenterological Surgery, International University of Health and Welfare Atami Hospital, Shizuoka, Japan. (3)Department of Surgery, International University of Health and Welfare Hospital, Tochigi, Japan. 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. DOI: 10.1158/1055-9965.EPI-25-1427 PMID: 41524587 [Indexed for MEDLINE]

Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial.

4. Eur J Nutr. 2025 Dec 19;65(1):9. doi: 10.1007/s00394-025-03814-7. Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial. Zerback T(1), Koeder C(2)(3), Weder S(1), Sputtek A(4), Eckert GP(5), Keller M(1). Author information: (1)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. (2)Institute for Prevention and Cancer Epidemiology (IPE), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110, Freiburg im Breisgau, Germany. christiankoeder@gmail.com. (3)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. christiankoeder@gmail.com. (4)MVZ Medical Laboratory Bremen GmbH, 28359, Bremen, Germany. (5)Institute of Nutritional Sciences, Justus-Liebig University, 35392, Giessen, Germany. 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). DOI: 10.1007/s00394-025-03814-7 PMCID: PMC12717231 PMID: 41417236 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: T.Z., S.W., C.K., A.S., and G.P.E. declare no conflict of interest. M.K. is the managing director of the Research Institute of Plant-Based Nutrition (IFPE) which received funding from Watson Nutrition for conducting the study. Ethical approval: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethics committee of the Faculty of Medicine of the University of Giessen (57/22). Consent to participate: Written consent was obtained from all subjects involved in the study.

Effectiveness of intermittent iron and high-dose vitamin A supplementation on hemoglobin, iron and vitamin A status of schoolchildren in southern Ethiopia: a randomized placebo controlled trial.

5. Eur J Clin Nutr. 2026 Feb;80(2):177-188. doi: 10.1038/s41430-025-01678-y. Epub 2025 Nov 25. Effectiveness of intermittent iron and high-dose vitamin A supplementation on hemoglobin, iron and vitamin A status of schoolchildren in southern Ethiopia: a randomized placebo controlled trial. Gutema BT(1), Sorrie MB(2)(3), Belayneh SB(4), Tariku EZ(2)(3), Boynito WG(2)(3), Zewdie TH(5), Yohanes T(4), De Henauw S(3), Levecke B(6), Abbeddou S(3). Author information: (1)School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia. befikadutariku2@gmail.com. (2)School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia. (3)Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. (4)Department of Medical laboratory, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia. (5)School of Medicine, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia. (6)Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. 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. DOI: 10.1038/s41430-025-01678-y PMID: 41291212 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: The authors declare no competing interests. Ethics approval: The study was conducted in accordance with the Declaration of Helsinki, and all procedures were approved by the Commission on Medical Ethics of Ghent University Hospital, Ghent, Belgium (EC/2019/1289) and by the National Research Ethics Review Committee of the Ministry of Science and Higher Education, Ethiopia (P.S.M/14.1/505/20). The study is registered on clinicaltrials.gov with the reference number NCT04137354 ( https://clinicaltrials.gov/study/NCT04137354 ). Letters of permission were written for district administrations, district health and education offices, kebele leaders, and school directors. Following contact with school directors, a sensitization workshop was organized for directors, teachers, and parents. Informed written consent for the children’s participation was obtained from their parents, and assent was obtained from the children.

Red palm olein biscuit supplementation modulates gut microbiota in vitamin A deficient rural Malaysian schoolchildren: a randomised controlled trial.

6. Nat Commun. 2025 Oct 22;16(1):9341. doi: 10.1038/s41467-025-64395-x. Red palm olein biscuit supplementation modulates gut microbiota in vitamin A deficient rural Malaysian schoolchildren: a randomised controlled trial. Tan PY(1)(2), Loganathan R(3), Lee SC(2)(4), Mohd Johari SN(2), Teng KT(1), Selvaduray KR(1), Lim YA(5). Author information: (1)Product Development and Advisory Services Division, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia. (2)Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia. (3)Product Development and Advisory Services Division, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia. radhika@mpob.gov.my. (4)Type 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (5)Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia. limailian@um.edu.my. 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). DOI: 10.1038/s41467-025-64395-x PMCID: PMC12546649 PMID: 41125622 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: P.Y.T, R.L. and K.R.S. are employees of the Malaysian Palm Oil Board, which received and managed the RMK-11 (Eleventh Malaysia Plan) Grant-PD219/16 (public funding) and conducted the study. K.T.T. was formerly employed by the Malaysian Palm Oil Board when the study was conducted. The funder was not involved in the study design, collection, analysis and interpretation of data, the writing of the article, or the decision to submit it for publication. Other authors declare no competing interests.

Prenatal and preschool micronutrient supplementation and behavioral outcomes in school-aged children in Nepal-a cohort study.

7. Am J Clin Nutr. 2025 Dec;122(6):1788-1796. doi: 10.1016/j.ajcnut.2025.10.006. Epub 2025 Oct 13. Prenatal and preschool micronutrient supplementation and behavioral outcomes in school-aged children in Nepal-a cohort study. Christian P(1), Zavala E(2), Hurley KM(2), Khatry SK(3), LeClerq SC(3), Fune Wu LS(2), Tielsch JM(4), Katz J(2), Murray-Kolb LE(5). Author information: (1)Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States. Electronic address: pchrist1@jhu.edu. (2)Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States. (3)Nepal Nutrition Intervention Project, Sarlahi, Nepal. (4)Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington DC, United States. (5)Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN, United States. 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 inadequate diets and nutrition deficiencies exist. Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.ajcnut.2025.10.006 PMCID: PMC12710460 PMID: 41092983 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest PC served as associate editor for the American Journal of Clinical Nutrition. All other authors report no conflicts of interest.

Effects of vitamin and multiple micronutrient supplementation for pregnant and/or lactating women on maternal and infant nutritional status in low- and middle-income countries: a systematic review and meta-analysis.

8. Adv Nutr. 2025 Dec;16(12):100487. doi: 10.1016/j.advnut.2025.100487. Epub 2025 Aug 5. Effects of vitamin and multiple micronutrient supplementation for pregnant and/or lactating women on maternal and infant nutritional status in low- and middle-income countries: a systematic review and meta-analysis. Shinde S(1), Yelverton CA(2), Yussuf M(3), Nurhussien L(2), Wang D(4), Fawzi WW(5). Author information: (1)Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America; Center for Inquiry into Mental Health, Pune, India. Electronic address: sshinde@hsph.harvard.edu. (2)Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America. (3)Africa Academy for Public Health, Dar Salaam, Tanzania. (4)Department of Global and Community Health, College of Public Health, George Mason University, Fairfax, Virginia, United States of America. (5)Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America. 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 nutritional status, highlighting the need for further research. PROSPERO REGISTRATION ID: CRD42022308715; https://tinyurl.com/y33cxekr. Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.advnut.2025.100487 PMCID: PMC12766057 PMID: 40752545 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest The authors have no competing interests to declare.

The effect of vitamin supplementation on neurodevelopmental and clinical outcomes in very low birth weight and very preterm infants: A systematic review and meta-analysis.

9. PLoS One. 2025 Jul 9;20(7):e0327628. doi: 10.1371/journal.pone.0327628. eCollection 2025. The effect of vitamin supplementation on neurodevelopmental and clinical outcomes in very low birth weight and very preterm infants: A systematic review and meta-analysis. Bronnert A(1), Bloomfield PM(1), Páramo LD(1), Lin L(1), Bloomfield FH(1), Cormack BE(2). Author information: (1)The Liggins Institute, Auckland, New Zealand. (2)Starship Child Health, Auckland, New Zealand. 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. Registry and Registry Number: This systematic review was prospectively registered on PROSPERO, ID CRD42023418552, available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418552. Copyright: © 2025 Bronnert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.1371/journal.pone.0327628 PMCID: PMC12240376 PMID: 40632831 [Indexed for MEDLINE] Conflict of interest statement: I have read the journal's policy and the authors of this manuscript have the following competing interests: BEC reports a relationship with Nestle Nutrition Institute and Nutricia Danone Australia Pty that includes board membership and speaking and lecture fees. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Dietary intake in East Asian and Northern European participants from the FeGenes study.

10. Eur J Nutr. 2025 Jun 5;64(5):205. doi: 10.1007/s00394-025-03730-w. Dietary intake in East Asian and Northern European participants from the FeGenes study. Park CY(1), Barad A(2), Xu Y(2), Bender E(2), Thomas AK(2), Haller CM(2), Gu Z(2), Pressman EK(3), O'Brien KO(4). Author information: (1)Department of Food and Nutrition, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea. parkcy@jnu.ac.kr. (2)Division of Nutritional Sciences, Cornell University, 230 Savage Hall, Ithaca, NY, 14850, USA. (3)Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, USA. (4)Division of Nutritional Sciences, Cornell University, 230 Savage Hall, Ithaca, NY, 14850, USA. koo4@cornell.edu. 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. DOI: 10.1007/s00394-025-03730-w PMCID: PMC12345378 PMID: 40471375 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Competing interests: On behalf of all authors, the corresponding authors state that there is no conflict of interest. Ethics approval: This study was approved by the Institutional Review Boards of Cornell University and the University of Rochester (IRB numbers: Cornell: IRB0008754 (1904008754); University of Rochester: 00005119) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave their informed consent prior to their inclusion in the study.

Maternal multiple micronutrient supplementation in rural Pakistan increased some milk micronutrient concentrations, but not infant growth, at three-months postpartum: a randomized controlled trial substudy.

11. Am J Clin Nutr. 2025 Jul;122(1):174-184. doi: 10.1016/j.ajcnut.2025.05.019. Epub 2025 May 21. Maternal multiple micronutrient supplementation in rural Pakistan increased some milk micronutrient concentrations, but not infant growth, at three-months postpartum: a randomized controlled trial substudy. Baxter JB(1), Wasan Y(2), Daniel AI(3), Begum K(2), Hussain A(2), Iqbal J(2), Aufreiter S(3), Beggs MR(3), Duan L(4), Greco A(3), Huang C(4), Soofi S(2), Bandsma RH(5), Bhutta ZA(6), O'Connor DL(7). Author information: (1)Department of Nutritional Sciences, University of Toronto, Ontario, Canada; Centre for Global Child Health, Hospital for Sick Children, Ontario, Canada. Electronic address: joanna.baxter@mail.utoronto.ca. (2)Centre of Excellence in Women and Child Health, Aga Khan University, Sindh, Pakistan. (3)Department of Nutritional Sciences, University of Toronto, Ontario, Canada; Translational Medicine Program, Hospital for Sick Children, Ontario, Canada. (4)Department of Nutritional Sciences, University of Toronto, Ontario, Canada. (5)Department of Nutritional Sciences, University of Toronto, Ontario, Canada; Centre for Global Child Health, Hospital for Sick Children, Ontario, Canada; Translational Medicine Program, Hospital for Sick Children, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Ontario, Canada. (6)Department of Nutritional Sciences, University of Toronto, Ontario, Canada; Centre for Global Child Health, Hospital for Sick Children, Ontario, Canada; Centre of Excellence in Women and Child Health, Aga Khan University, Sindh, Pakistan; Institute for Global Health and Development, Aga Khan University, Sindh, Pakistan. (7)Department of Nutritional Sciences, University of Toronto, Ontario, Canada; Translational Medicine Program, Hospital for Sick Children, Ontario, Canada; Department of Paediatrics, Mount Sinai Hospital, Ontario, Canada. 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. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ClinlicalTrials.gov: NCT04451395 (https://clinicaltrials.gov/study/NCT04451395) and NCT03287882 (https://clinicaltrials.gov/study/NCT03287882). Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.ajcnut.2025.05.019 PMCID: PMC12308085 PMID: 40409469 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest The authors have no conflicts of interest to declare.

The effect of crocetin (a saffron carotenoid) supplementation on antioxidant and inflammatory indexes and serum leptin concentration in patients with coronary artery disease.

12. Food Funct. 2025 Jun 3;16(11):4604-4614. doi: 10.1039/d4fo03396e. The effect of crocetin (a saffron carotenoid) supplementation on antioxidant and inflammatory indexes and serum leptin concentration in patients with coronary artery disease. Moeini Badi F(1), Bathaie SZ(2)(3), Borazjani F(4)(5), Hosseini SA(5)(6), Sheikhi MA(7), Shariful Islam SM(8), Ahmadi Angali K(9)(10), Taban Sadeghi M(11), Rahimi P(12). Author information: (1)Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. moeinibadifaezeh@gmail.com. (2)Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. bathai_z@modares.ac.ir. (3)Institute for Natural Products & Medicinal Plants (INPMP), Tarbiat Modares University, Tehran, Iran. (4)Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. fa.borazjani@gmail.com. (5)Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (6)Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. seyedahmadhosseini@yahoo.com. (7)Department of Cardiac Surgery, Atherosclerosis Research Center, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. mohammadalisheikhi2016@gmail.com. (8)Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Victoria, Australia. shariful.islam@deakin.edu.au. (9)Department of Biostatistics, School of Health Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Iran.kzfir4@gmail.com. (10)Social Determinant of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (11)Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. m_r_taban@yahoo.com. (12)Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. prs.rahimi@gmail.com. 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 studies are needed to confirm these results in a larger population, crocetin administration may be recommended to prevent CAD. DOI: 10.1039/d4fo03396e PMID: 40400479 [Indexed for MEDLINE]

Randomized Controlled Clinical Trial of Pediatric Pneumococcus and Hepatitis A Vaccinations With or Without a High-Dose Oral Vitamin A Supplement.

13. Biomolecules. 2025 Apr 7;15(4):540. doi: 10.3390/biom15040540. Randomized Controlled Clinical Trial of Pediatric Pneumococcus and Hepatitis A Vaccinations With or Without a High-Dose Oral Vitamin A Supplement. Patel N(1), Surman SL(1), Jones BG(1), Penkert RR(2), Ringwald-Smith K(3), DeLuca K(1), Richardson J(4), Zheng Y(5), Tang L(5), Hurwitz JL(1). Author information: (1)Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. (2)Department of Chemistry and Biochemistry, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA. (3)Department of Clinical Nutrition, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. (4)Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. (5)Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. 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. DOI: 10.3390/biom15040540 PMCID: PMC12024622 PMID: 40305237 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript or in the decision to publish the results.

Red palm olein supplementation as a potential preventive solution for xerophthalmia among vitamin A-deficient primary schoolchildren: a cluster randomized controlled trial.

14. Eur J Clin Nutr. 2025 Sep;79(9):928-936. doi: 10.1038/s41430-025-01620-2. Epub 2025 Apr 17. Red palm olein supplementation as a potential preventive solution for xerophthalmia among vitamin A-deficient primary schoolchildren: a cluster randomized controlled trial. Tan PY(1)(2), Lim CC(3), Seng KBH(3), Loganathan R(4), Lim YA(2), Teng KT(1), Mohd Johari SN(2), Selvaduray KR(1), Ramli N(5). Author information: (1)Product Development and Advisory Services Division, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia. (2)Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. (3)Universiti Malaya Eye Research Centre, Department of Ophthalmology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. (4)Product Development and Advisory Services Division, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia. radhika@mpob.gov.my. (5)Universiti Malaya Eye Research Centre, Department of Ophthalmology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. norlina@ummc.edu.my. 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. DOI: 10.1038/s41430-025-01620-2 PMID: 40247111 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: PYT, RL and KRS are employees of the Malaysian Palm Oil Board, who received and managed funding from the RMK-11 (Eleventh Malaysia Plan) Grant-PD219/16 (public funding), and conducted the study. KTT was formerly employed by the Malaysian Palm Oil Board when the study was conducted. The funder was not involved in the study design, collection, analysis and interpretation of data, the writing of the article, or the decision to submit it for publication. Other authors declare no conflicts of interest. Ethical approval: The study adhered to the principles outlined in the Declaration of Helsinki and was registered at ClinicalTrials.gov under the identifier NCT03256123. Ethical approval was received from the Medical Research Ethics Committee, Ministry of Health (MOH) Malaysia (NMRR No: NMRR-16-1905-32547). The study was also approved with the participation of the respective health and education authorities. Before the study began, all literate parents provided written informed consents, while illiterate parents gave verbal consents and marked their thumbprints on the consent form, which were witnessed and formally documented. The parents were fully informed about the voluntary nature of their child’s participation, and their right to withdraw at any time. No child was withheld from receiving necessary medical care as part of the study protocol. Furthermore, the participants themselves signed an assent form.

The effects of nutritional supplementation for children and adolescents with sickle cell disease: A systematic review and meta-analyses.

15. Clin Nutr. 2025 Apr;47:157-168. doi: 10.1016/j.clnu.2025.02.016. Epub 2025 Feb 17. The effects of nutritional supplementation for children and adolescents with sickle cell disease: A systematic review and meta-analyses. Orsi BC(1), Gorski D(2), Krul NE(3), Wiens A(4), Brito M(5), Tonin FS(6), Pontarolo R(7). Author information: (1)Pharmaceutical Care Postgraduate Program, Federal University of Paraná, Curitiba, Brazil. Electronic address: bruna.orsi@ufpr.br. (2)Pharmaceutical Sciences Postgraduate Program, Federal University of Paraná, Curitiba, Brazil. Electronic address: danielagorski@ufpr.br. (3)Pharmaceutical Sciences Postgraduate Program, Federal University of Paraná, Curitiba, Brazil. Electronic address: nailakrul@ufpr.br. (4)Department of Pharmacy, Federal University of Paraná, Curitiba, Brazil. (5)H&TRC - Health and Technology Research Center, ESTeSL - Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisbon, Portugal. Electronic address: miguel.brito@estesl.ipl.pt. (6)H&TRC - Health and Technology Research Center, ESTeSL - Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisbon, Portugal; Pharmacy and Pharmaceutical Technology Department, Social and Legal Pharmacy Section, University of Granada, Spain. Electronic address: ffstonin@gmail.com. (7)Department of Pharmacy, Federal University of Paraná, Curitiba, Brazil. Electronic address: pontarolo@ufpr.br. 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. Copyright © 2025 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. DOI: 10.1016/j.clnu.2025.02.016 PMID: 40022955 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest The authors declare to have no competing interests regarding this study.