Abstract
Purpose
Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren.
Methods
We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8–12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration.
Results
Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and β-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (− 21.8%) and high inflammation (− 8.1%) was only observed in the experimental group.
Conclusion
The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions.
Clinical trial registration
ClinicalTrials.gov (NCT03256123).
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Data availability
The data that support the findings of this study are available on request from the corresponding authors, RL and YALL. The data are not publicly available due to their containing information that could compromise the privacy of research participants.
References
World Health Organization (2009) Global prevalence of vitamin A deficiency in populations at risk 1995–2005: WHO global database on vitamin a deficiency. World Health Organization, Geneva
Cañete A, Cano E, Muñoz-Chápuli R, Carmona R (2017) Role of vitamin A/retinoic acid in regulation of embryonic and adult hematopoiesis. Nutrients 9(2):159. https://doi.org/10.3390/nu9020159
Schweigert FJ, Klingner J, Hurtienne A, Zunft HJ (2003) Vitamin A, carotenoid and vitamin E plasma concentrations in children from Laos in relation to sex and growth failure. Nutr J 2(1):1–6. https://doi.org/10.1186/1475-2891-2-17
Al-Mekhlafi HM, Al-Zabedi EM, Al-Maktari MT, Atroosh WM, Al-Delaimy AK, Moktar N, Sallam AA, Abdullah WA, Jani R, Surin J (2013) Effects of vitamin A supplementation on iron status indices and iron deficiency anaemia: a randomized controlled trial. Nutrients 6(1):190–206. https://doi.org/10.3390/nu6010190
World Health Organization (2019) Micronutrient deficiencies: iron deficiency anaemia. https://apps.who.int/nutrition/topics/ida/en/index.html. Accessed 2 July 2022 2022
Bruins M, Kraemer K (2013) Public health programmes for vitamin A deficiency control. Community Eye Health 26(84):69
Greiner T (2013) Vitamin A: Moving the food-based approach forward. Paper presented at the FAO/WHO Second International Conference on Nutrition (ICN2), Rome, Italy,
Adams AM, Ahmed R, Latif AM, Rasheed S, Das SK, Hasib E, Farzana FD, Ferdous F, Ahmed S, Faruque A (2017) Impact of fortified biscuits on micronutrient deficiencies among primary school children in Bangladesh. PLoS ONE 12(4):e0174673. https://doi.org/10.1371/journal.pone.0174673
van Stuijvenberg ME, Benadé AJS (2000) South African experience with the use of red palm oil to improve the vitamin A status of primary schoolchildren. Food Nutr Bull 21(2):212–214. https://doi.org/10.1177/156482650002100216
Penniston KL, Tanumihardjo SA (2006) The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 83(2):191–201. https://doi.org/10.1093/ajcn/83.2.191
Loganathan R, Subramaniam KM, Radhakrishnan AK, Choo YM, Teng KT (2017) Health-promoting effects of red palm oil: evidence from animal and human studies. Nutr Rev 75(2):98–113. https://doi.org/10.1093/nutrit/nuw054
Ping B, May CY (2000) Valuable minor constituents of commercial red palm olein: carotenoids, vitamin E, ubiquinones and sterols. J Oil Palm Res 12(1):14–24
Rao BN (2000) Potential use of red palm oil in combating vitamin A deficiency in India. Food Nutr Bull 21(2):202–211. https://doi.org/10.1177/156482650002100215
Lietz G, Henry CJK, Mulokozi G, Mugyabuso JK, Ballart A, Ndossi GD, Lorri W, Tomkins A (2001) Comparison of the effects of supplemental red palm oil and sunflower oil on maternal vitamin A status. Am J Clin Nutr 74(4):501–509. https://doi.org/10.1093/ajcn/74.4.501
van Stuijvenberg ME, Dhansay MA, Lombard CJ, Faber M, Benadé AJS (2001) The effect of a biscuit with red palm oil as a source of β-carotene on the vitamin A status of primary school children: a comparison with β-carotene from a synthetic source in a randomised controlled trial. Eur J Clin Nutr 55(8):657–662. https://doi.org/10.1038/sj.ejcn.1601196
Zeba AN, Martin Prevel Y, Some IT, Delisle HF (2006) The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso. Nutr J 5:17. https://doi.org/10.1186/1475-2891-5-17
Manorama R, Brahmam G, Rukmini C (1996) Red palm oil as a source of β-carotene for combating vitamin A deficiency. Plant Foods Hum Nutr 49(1):75–82. https://doi.org/10.1007/BF01092524
Liu T, Yang Y, Zhang Y, Wang Z, Wang N, Wang Y (2018) Effects of vitamin A supplementation on school aged children in the rural areas of Gansu Province. Acta Nutrimenta Sinica 40(1):32–35. https://doi.org/10.13325/j.cnki.acta.nutr.sin.2018.01.010
Guo K, Yang Y, Liu T, Zhang Y, Liu Wei YuW (2018) Improvement study of the vitamin A in school age children from 7–12 Years old in rural areas, Gansu Province. Chin J Dis Control Prevention 22(5):481–484. https://doi.org/10.16462/j.cnki.zhjbkz.2018.05.012
Mahapatra S, Manorama R (1997) 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 6(4):246–250
Aparna K, Manorama K (2009) Effect of supplementation of red palmolein, iron and vitamin C on vitamin A, and iron status of adolescent girls. J Oilseeds Res 26(1):47–49
Tan PY, Mohd Johari SN, Teng KT, Loganathan R, Lee SC, Ngui R, Selvaduray KR, Lim YAL (2022) High prevalence of malnutrition and vitamin A deficiency among schoolchildren of rural areas in Malaysia using a multi-school assessment approach. Br J Nutr:1–14. https://doi.org/10.1017/s0007114522001398
Tolonen M (1990) Vitamins and minerals in health and nutrition. Woodhead Publishing Limited, Cambridge, England
Poh BK, Ng BK, Siti Haslinda MD, Nik Shanita S, Wong JE, Budin SB, Ruzita AT, Ng LO, Khouw I, Norimah AK (2013) 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 110(Suppl 3):S21-35. https://doi.org/10.1017/S0007114513002092
World Health Organization (2012) Report: priorities in the assessment of vitamin A and iron status and in populations, Panama City, Panama, 15–17 September 2010.
Institute of Medicine (US) Panel on Micronutrients (2001) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academies Press, Washington (DC)
Kand’ár R, Novotná P, Drábková P, (2013) Determination of retinol, α-tocopherol, lycopene, and β-carotene in human plasma using HPLC with UV-Vis detection: application to a clinical study. J Chem 2013:1–7. https://doi.org/10.1155/2013/460242
Loganathan R, Vethakkan SR, Radhakrishnan AK, Abd Razak G, Teng KT (2019) Red palm olein supplementation on cytokines, endothelial function and lipid profile in centrally overweight individuals: a randomised controlled trial. Eur J Clin Nutr 73(4):609–616. https://doi.org/10.1038/s41430-018-0236-5
de Pee S, Dary O (2002) Biochemical indicators of vitamin A deficiency: serum retinol and serum retinol binding protein. J Nutr 132(9):2895S-2901S. https://doi.org/10.1093/jn/132.9.2895s
World Health Organization (2011) Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. http://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed 9 Sept 2021
Janus J, Moerschel SK (2010) Evaluation of anemia in children. Am Fam Physician 81(12):1462–1471
World Health Organization (2011) Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. http://www.who.int/vmnis/indicators/serum_ferritin.pdf. Accessed 8 Sept 2021
Ngui R, Lim YAL, Liam CK, Chow SC, Jaffar S (2012) Association between anaemia, iron deficiency anaemia, neglected parasitic infections and socioeconomic factors in rural children of West Malaysia. PLoS Negl Trop Dis 6(3):e1550. https://doi.org/10.1371/journal.pntd.0001550
Kundu S, Rai B, Shukla A (2021) Prevalence and determinants of vitamin A deficiency among children in India: findings from a national cross-sectional survey. Clin Epidemiol Global Health 11. https://doi.org/10.1016/j.cegh.2021.100768
Tan PY, Loganathan R, Teng K-T, Lee SC, Johari SNM, Selvaduray KR, Ngui R, Lim YA-L (2023) 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 240:106860. https://doi.org/10.1016/j.actatropica.2023.106860
Ribaya-Mercado JD, Solon FS, Solon MA, Cabal-Barza MA, Perfecto CS, Tang G, Solon JAA, Fjeld CR, Russell RM (2000) Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status. Am J Clin Nutr 72(2):455–465. https://doi.org/10.1093/ajcn/72.2.455
Jalal F, Nesheim M, Agus Z, Sanjur D, Habicht J (1998) Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment. Am J Clin Nutr 68(3):623–629. https://doi.org/10.1093/ajcn/68.3.623
Yao Y, Tan P, Kim JE (2022) Effects of dietary fats on the bioaccessibility and bioavailability of carotenoids: a systematic review and meta-analysis of in vitro studies and randomized controlled trials. Nutr Rev 80(4):741–761. https://doi.org/10.1093/nutrit/nuab098
Palmer AC, Siamusantu W, Chileshe J, Schulze KJ, Barffour M, Craft NE, Molobeka N, Na K, Arguello MA, Mitra M (2016) Provitamin A–biofortified maize increases serum β-carotene, but not retinol, in marginally nourished children: a cluster-randomized trial in rural Zambia. Am J Clin Nutr 104(1):181–190. https://doi.org/10.3945/ajcn.116.132571
Zagré N, Delpeuch F, Traissac P, Delisle H (2003) Red palm oil as a source of vitamin A for mothers and children: impact of a pilot project in Burkina Faso. Public Health Nutr 6(8):733–742. https://doi.org/10.1079/phn2003502
Sivan Y, Jayakumar YA, Arumughan C, Sundaresan A, Jayalekshmy A, Suja K, Kumar DS, Deepa S, Damodaran M, Soman C (2002) Impact of vitamin A supplementation through different dosages of red palm oil and retinol palmitate on preschool children. J Trop Pediatr 48(1):24–28. https://doi.org/10.1093/tropej/48.1.24
Tanumihardjo SA (2004) Assessing vitamin A status: past, present and future. J Nutr 134(1):290S-293S. https://doi.org/10.1093/jn/134.1.290s
Pereira SM, Begum A (1971) Failure of massive single oral dose of vitamin A to prevent deficiency. Arch Dis Child 46(248):525. https://doi.org/10.1136/adc.46.248.525
Tanumihardjo SA, Permaesih D, Rustan E, Rusmil K, Fatah AC, Wilbur S, Karyadi D, Olson JA (1996) Vitamin a status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin a supplements and albendazole. J Nutr 126(2):451–457. https://doi.org/10.1093/jn/126.2.451
Dougherty KA, Schall JI, Kawchak DA, Green MH, Ohene-Frempong K, Zemel BS, Stallings VA (2012) No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease. Am J Clin Nutr 96(4):932–940. https://doi.org/10.3945/ajcn.112.035725
Vuong LT, Dueker SR, Murphy SP (2002) Plasma beta-carotene and retinol concentrations of children increase after a 30-d supplementation with the fruit Momordica cochinchinensis (gac). Am J Clin Nutr 75(5):872–879. https://doi.org/10.1093/ajcn/75.5.872
Sivan Y, Jayakumar YA, Arumughan C, Sundaresan A, Balachandran C, Job J, Deepa S, Shihina S, Damodaran M, Soman C (2001) Impact of β-carotene supplementation through red palm oil. J Trop Pediatr 47(2):67–72. https://doi.org/10.1093/tropej/47.2.67
Burri BJ, Neidlinger TR, Clifford AJ (2001) Serum carotenoid depletion follows first-order kinetics in healthy adult women fed naturally low carotenoid diets. J Nutr 131(8):2096–2100. https://doi.org/10.1093/jn/131.8.2096
Garcı́a-Casal MaN, Layrisse M, Solano L, Barón MaA, Arguello F, Llovera D, Ramı́rez J, Leets I, Tropper E (1998) Vitamin A and β-carotene can improve nonheme iron absorption from rice, wheat and corn by humans. The Journal of Nutrition 128 (3):646-650. doi:https://doi.org/10.1093/jn/128.3.646
García-Casal MN, Leets I, Layrisse M (2000) β-Carotene and inhibitors of iron absorption modify iron uptake by Caco-2 cells. J Nutr 130(1):5–9. https://doi.org/10.1093/jn/130.1.5
Honarmand Ebrahimi K, Hagedoorn P-L, Hagen WR (2015) Unity in the biochemistry of the iron-storage proteins ferritin and bacterioferritin. Chem Rev 115(1):295–326. https://doi.org/10.1021/cr5004908
Muslimatun S, Schmidt MK, Schultink W, West CE, Hautvast JG, Gross R (2001) Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women. J Nutr 131(1):85–90. https://doi.org/10.1093/jn/131.1.85
Zimmermann MB, Biebinger R, Rohner F, Dib A, Zeder C, Hurrell RF, Chaouki N (2006) Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron. Am J Clin Nutr 84(3):580–586. https://doi.org/10.1093/ajcn/84.3.580
Maramag C, Ribaya-Mercado J, Rayco-Solon P, Solon J, Tengco L, Blumberg J, Solon F (2010) Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren. Eur J Clin Nutr 64(5):468–474. https://doi.org/10.1038/ejcn.2010.23
Ncube TN, Greiner T, Malaba LC, Gebre-Medhin M (2001) Supplementing lactating women with puréed papaya and grated carrots improved vitamin A status in a placebo-controlled trial. J Nutr 131(5):1497–1502. https://doi.org/10.1093/jn/131.5.1497
Tanumihardjo SA (2015) Vitamin A fortification efforts require accurate monitoring of population vitamin A status to prevent excessive intakes. Procedia Chemistry 14:398–407. https://doi.org/10.1016/j.proche.2015.03.054
Tanumihardjo SA (2011) Vitamin A: biomarkers of nutrition for development. Am J Clin Nutr 94(2):658S-665S. https://doi.org/10.3945/ajcn.110.005777
Law LS, Norhasmah S, Gan WY, Mohd Nasir MT (2018) Qualitative study on identification of common coping strategies practised by Indigenous Peoples (Orang Asli) in Peninsular Malaysia during periods of food insecurity. Public Health Nutr 21(15):2819–2830. https://doi.org/10.1017/s136898001800160x
Acknowledgements
We gratefully acknowledge the Ministry of Education (MOE), Ministry of Health (MOH), and Department of Orang Asli Development (JAKOA), the head of Orang Asli villages (Tok Batin), school principals, and teachers for permitting to conduct sample and data collections from the schoolchildren. Special acknowledgement to Assoc. Prof. Dr. Khang Tsung Fei and Ms. Lim Kah Xuan from Universiti Malaya for the consultation in statistical analysis. We would also like to express our deepest appreciation to Carotino Sdn Bhd., Noraini’s Cookies Worldwide Sdn. Bhd., doctors, medical assistants, nurses, MPOB research assistants, and internship students for their assistance and support throughout the study. Most importantly, we thank all the schoolchildren and their parents for their voluntary participation in this study.
Funding
The study was supported by the RMK-11 (Eleventh Malaysia Plan) Grant (PD219/16), which managed by Malaysian Palm Oil Board. This research was supported (in part) by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (NIAID).
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RL, KTT, YALL and SCL contributed to the design of this study. RL, KTT and KRS were involved in the funding acquisition. PYT and SNMJ were involved in the data collection. PYT performed the data analyses and wrote the manuscript. PYT, RL, KTT, YALL, SCL, RN and KRS reviewed and edited the manuscript. All the authors read, revised critically and approved the final manuscript.
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P.Y.T, K.T.T., R.L. and K.R.S are employees of the Malaysian Palm Oil Board, which received and managed grant RMK-11 (Eleventh Malaysia Plan) Grant-PD219/16 (public funding) and conducted the study. The other authors declare no conflict of interest.
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Tan, P.Y., Loganathan, R., Teng, KT. 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 63, 905–918 (2024). https://doi.org/10.1007/s00394-023-03314-6
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DOI: https://doi.org/10.1007/s00394-023-03314-6