Abstract
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).
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding authors, RL and NR on reasonable request.
References
World Health Organization. Global prevalence of vitamin A deficiency in populations at risk 1995-2005: WHO global database on vitamin A deficiency. Geneva: World Health Organization; 2009.
World Health Organization. Micronutrient deficiencies: vitamin A deficiency. 2013. https://apps.who.int/nutrition/topics/vad/en/index.html.
Ngah NF, Moktar N, Isa NH, Selvaraj S, Yusof MS, Sani HA, et al. Ocular manifestation of vitamin A deficiency among Orang Asli (Aborigine) children in Malaysia. Asia Pac J Clin Nutr. 2002;11:88–91. https://doi.org/10.1046/j.1440-6047.2002.00268.x.
Poh BK, Ng BK, Siti Haslinda MD, Nik Shanita S, Wong JE, Budin SB, et al. Nutritional status and dietary intakes of children aged 6 months to 12 years: findings of the Nutrition Survey of Malaysian Children (SEANUTS Malaysia). Br J Nutr. 2013;110:S21–35. https://doi.org/10.1017/S0007114513002092.
Tan PY, Mohd Johari SN, Teng KT, Loganathan R, Lee SC, Ngui R, et al. High prevalence of malnutrition and vitamin A deficiency among schoolchildren of rural areas in Malaysia using a multi-school assessment approach. Br J Nutr. 2022:1–14. https://doi.org/10.1017/s0007114522001398.
Loganathan R, Subramaniam KM, Radhakrishnan AK, Choo YM, Teng KT. Health-promoting effects of red palm oil: evidence from animal and human studies. Nutr Rev. 2017;75:98–113. https://doi.org/10.1093/nutrit/nuw054.
National Coordinating Committee on Food and Nutrition. Recommended nutrient intakes of malaysia. A report of the technical working group on nutritional guidelines. Putrajaya: Ministry of Health Malaysia; 2017.
Aykroyd W, Wright R. Redpalm oil in the treatment of human keratomalacia. Indian J Med Res. 1937;25:7–10.
Mahapatra S, Manorama R. The protective effect of red palm oil in comparison with massive vitamin A dose in combating vitamin A deficiency in Orissa, India. Asia Pac J Clin Nutr. 1997;6:246–50.
Sivan Y, Jayakumar YA, Arumughan C, Sundaresan A, Balachandran C, Job J, et al. Impact of β-carotene supplementation through red palm oil. J Trop Pediatr. 2001;47:67–72. https://doi.org/10.1093/tropej/47.2.67.
Sivan Y, Jayakumar YA, Arumughan C, Sundaresan A, Jayalekshmy A, Suja K, et al. Impact of vitamin A supplementation through different dosages of red palm oil and retinol palmitate on preschool children. J Trop Pediatr. 2002;48:24–8. https://doi.org/10.1093/tropej/48.1.24.
Tan PY, Loganathan R, Teng KT, Lee SC, Mohd Johari SN, Selvaduray KR, et al. Red palm olein-enriched biscuit supplementation lowers Ascaris lumbricoides reinfection at 6-month after anthelmintic treatment among schoolchildren with vitamin A deficiency (VAD). Acta Trop. 2023;240:106860. https://doi.org/10.1016/j.actatropica.2023.106860.
Tan PY, Loganathan R, Teng KT, Mohd Johari SN, Lee SC, Selvaduray KR, et al. Supplementation of red palm olein-enriched biscuits improves levels of provitamin A carotenes, iron, and erythropoiesis in vitamin A-deficient primary schoolchildren: a double-blinded randomised controlled trial. Eur J Nutr. 2024;63:905–18. https://doi.org/10.1007/s00394-023-03314-6.
Seng KBH, Tan PY, Lim CC, Loganathan R, Lim YAL, Teng KT, et al. High prevalence of xerophthalmia linked to socio-demographic and nutritional factors among vitamin A-deficient rural primary schoolchildren in Malaysia. Nutr Res. 2024. https://doi.org/10.1016/j.nutres.2024.07.003.
Mohd Johari SN, Tan PY, Loganathan R, Lim YA, Teng KT, Lee SC, et al. Unveiling soil-transmitted helminth infections and associated risk factors in rural primary schoolchildren in Malaysia. Trop Biomed. 2024;41:345–55. https://doi.org/10.47665/tb.41.3.015.
Zeba AN, Martin Prevel Y, Some IT, Delisle HF. The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso. Nutr J. 2006;5:17. https://doi.org/10.1186/1475-2891-5-17.
Parker K, Nunns M, Xiao Z, Ford T, Ukoumunne OC. Intracluster correlation coefficients from school-based cluster randomized trials of interventions for improving health outcomes in pupils. J Clin Epidemiol. 2023;158:18–26. https://doi.org/10.1016/j.jclinepi.2023.03.020.
Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M. How to design efficient cluster randomised trials. BMJ. 2017;358:j3064. https://doi.org/10.1136/bmj.j3064.
World Health Organization. Report: priorities in the assessment of vitamin A and iron status and in populations. Panama City, Panama: World Health Organization; 2012.
Institute of Medicine (US) Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academies Press; 2001.
World Health Organization. Blindness and vision impairment. 2022. https://www.who.int/news-room/fact-sheets/detail/blindness-and-visual-impairment#:~:text=Mild%20%E2%80%93%20visual%20acuity%20worse%20than,acuity%20worse%20than%203%2F60.
Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67. https://doi.org/10.18637/jss.v067.i01.
Pinheiro J, Bates D. Mixed-effects models in S and S-PLUS. New York: Springer; 2006.
Lenth R. emmeans: estimated marginal means, aka least-squares means. R package version 1.10.5. 2024. https://rvlenth.github.io/emmeans/.
Sommer A. Effects of vitamin A deficiency on the ocular surface. Ophthalmology. 1983;90:592–600. https://doi.org/10.1016/s0161-6420(83)34512-7.
Kam KW, Li AL, Mak CY, Ma B, Young AL. Dry eyes—vitamin A deficiency is a differential diagnosis not to be missed: a case report. Hong Kong J Ophthalmol. 2021;25:17–19.
Amemiya T. The eye and nutrition. Jpn J Ophthalmol. 2000;44:320. https://doi.org/10.1016/s0021-5155(00)00161-1.
Sherwin JC, Samarawickrama C. Conjunctival xerosis caused by vitamin A deficiency. Arch Dis Child. 2017;103. https://doi.org/10.1136/archdischild-2017-313618.
Toshida H, Tabuchi N, Koike D, Koide M, Sugiyama K, Nakayasu K, et al. The effects of vitamin A compounds on hyaluronic acid released from cultured rabbit corneal epithelial cells and keratocytes. J Nutr Sci Vitaminol. 2012;58:223–9. https://doi.org/10.3177/jnsv.58.223.
Kubo Y, Arimura A, Nakayasu K, Kanai A. Effect of vitamin A palmitate on the synthesis of mucins in cultured conjunctiva. Jpn J Ophthalmol. 2000;44:98.
Diao Y, Deng A, Wang J, Hong J. Vitamin A palmitate eye gel improves the density of conjunctival goblet cells and the production of mucin-5 subtype AC in rabbits with dry eye syndrome. Int J Clin Exp Med. 2017;10:16181–8.
Hori Y, Spurr-Michaud SJ, Russo CL, Argüeso P, Gipson IK. Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005;46:4050–61. https://doi.org/10.1167/iovs.05-0627.
Bhatti RA, Yu S, Boulanger A, Fariss RN, Guo Y, Bernstein SL, et al. Expression of β-carotene 15, 15’ monooxygenase in retina and RPE-choroid. Invest Ophthalmol Vis Sci. 2003;44:44–9. https://doi.org/10.1167/iovs.02-0167.
Chichili GR, Nohr D, Frank J, Flaccus A, Fraser PD, Enfissi EM, et al. Protective effects of tomato extract with elevated β-carotene levels on oxidative stress in ARPE-19 cells. Br J Nutr. 2006;96:643–9.
Christian P, West KP Jr, Khatry SK, Katz J, LeClerq S, Pradhan EK, et al. Vitamin A or β-carotene supplementation reduces but does not eliminate maternal night blindness in Nepal. J Nutr. 1998;128:1458–63. https://doi.org/10.1093/jn/128.9.1458.
Mariath JGR, Lima MC, Santos LMP. Vitamin A activity of buriti (Mauritia vinifera Mart) and its effectiveness in the treatment and prevention of xerophthalmia. Am J Clin Nutr. 1989;49:849–53. https://doi.org/10.1093/ajcn/49.5.849.
Maria Pacheco Santos L. Nutritional and ecological aspects of buriti or aguaje (Mauritia flexuosa Linnaeus filius): a carotene-rich palm fruit from Latin America. Ecol Food Nutr. 2005;44:345–58. https://doi.org/10.1080/03670240500253369.
Patel S, Mittal R, Kumar N, Galor A. The environment and dry eye-manifestations, mechanisms, and more. Front Toxicol. 2023;5:1173683. https://doi.org/10.3389/ftox.2023.1173683.
Labrique AB, Palmer AC, Healy K, Mehra S, Sauer TC, West KP, et al. A novel device for assessing dark adaptation in field settings. BMC Ophthalmol. 2015;15:1–9. https://doi.org/10.1186/s12886-015-0062-7.
Namaste SM, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:333S–47S. https://doi.org/10.3945/ajcn.116.142273.
Thurnham DI, Northrop-Clewes CA, Knowles J. The use of adjustment factors to address the impact of inflammation on vitamin A and iron status in humans. J Nutr. 2015;145:1137S–43S. https://doi.org/10.3945/jn.114.194712.
Acknowledgements
We acknowledge with gratitude the MOE Malaysia, MOH Malaysia, and JAKOA, the head of Orang Asli villages (Tok Batin), school principals, and teachers for the permissions to perform sample and data collections from the schoolchildren. Our deepest appreciation extends to Carotino Sdn. Bhd., Noraini’s Cookies Worldwide Sdn. Bhd., Pott Glasses Sdn. Bhd., Focus Point Sdn. Bhd., doctors, medical assistants, nurses, MPOB research assistants, and internship students for their valuable support and assistance throughout the study. Of utmost importance, we thank all the schoolchildren and their parents for their voluntary participation in this study.
Funding
This work was supported by a public funding, RMK-11 (Eleventh Malaysia Plan) Grant [PD219/16], managed by the Malaysian Palm Oil Board.
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Authors and Affiliations
Contributions
RL, YALL, KTT, KRS and NR were involved in the conceptualization and design of the study. PYT, CCL, KBHS and SNMJ performed the project administration including sample, data collection, handling of resources and analysis of the samples. PYT and CCL performed the data analysis and interpretation of results. PYT conducted the manuscript writing and editing. RL, YALL, KTT, KRS and NR reviewed and edited the manuscript. All authors read and approved the final version of the manuscript.
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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.
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Tan, P.Y., Lim, C.C., Seng, K.B.H. et al. Red palm olein supplementation as a potential preventive solution for xerophthalmia among vitamin A-deficient primary schoolchildren: a cluster randomized controlled trial. Eur J Clin Nutr 79, 928–936 (2025). https://doi.org/10.1038/s41430-025-01620-2
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DOI: https://doi.org/10.1038/s41430-025-01620-2


