Deficiency of vitamins C and E in women of childbearing age in Brazil

a systematic review and meta-analysis

Authors

Keywords:

Alpha-tocopherol, Ascorbic acid deficiency, Women’s health, Cross-sectional studies, Deficiency diseases, Nutrition surveys, Vitamin E deficiency

Abstract

BACKGROUND: Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. OBJECTIVES: To estimate the prevalence of deficiency or insufficiency of vitamins C and and associated factors among women of childbearing age, in Brazil. DESIGN AND SETTING: Systematic review and meta-analysis conducted at a Brazilian public university. METHODS: A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey double arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. RESULTS: Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding women. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. convenience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of < 1.6-12.0 mmol/l and < 16.2 mmol/l, respectively. The cumulative meta-analysis suggested that a trend to lower prevalence of vitamin E deficiency occurred in recent studies. CONCLUSIONS: Although the studies identified in this systematic review had poor methodological and reporting quality, mild-moderate vitamin C and E deficiencies were identified, especially in breastfeeding women. Thus, designing and implementing policies does not seem to be a priority, because the need has not been properly dimensioned among women of childbearing age in Brazil. REGISTRATION NUMBER IN PROSPERO: CRD42020221605.

Downloads

Download data is not yet available.

Author Biographies

Rosa Camila Lucchetta, School of Pharmaceutical Sciences, Universidade Estadual Paulista

PhD. Pharmacist and Postdoctoral Researcher, Department of Drugs and Medicines, School of Pharmaceutical Sciences, Universidade Estadual Paulista (UNESP), São Paulo (SP), Brazil.

Sophia de Andrade Cavicchioli, School of Pharmaceutical Sciences, Universidade Estadual Paulista

Undergraduate Student, Universidade de Araraquara (UNIARA), Araraquara (SP), Brazil.

Ana Luísa Rodriguez Gini, School of Pharmaceutical Sciences, Universidade Estadual Paulista

Undergraduate Student, Department of Drugs and Medicines, School of Pharmaceutical Sciences, Universidade Estadual Paulista (UNESP), São Paulo (SP), Brazil.

Marcela Forgerini, School of Pharmaceutical Sciences, Universidade Estadual Paulista

Pharmacist and Doctoral Student, Department of Drugs and Medicines, School of Pharmaceutical Sciences, Universidade Estadual Paulista (UNESP), São Paulo (SP), Brazil.

Fabiana Rossi Varallo, School of Pharmaceutical Sciences, Universidade Estadual Paulista

PhD. Pharmacist and Professor, Department of Pharmaceutical Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (FCFRP-USP), Ribeirão Preto (SP), Brazil.

Mariane Nunes de Nadai, School of Pharmaceutical Sciences, Universidade Estadual Paulista

MD, PhD. Professor, Faculdade de Odontologia de Bauru, Universidade de São Paulo (FOB-USP), Bauru (SP), Brazil.

Fernando Fernandez-Llimos, School of Pharmaceutical Sciences, Universidade Estadual Paulista

PhD. Pharmacist and Professor, CINTESIS – Center for Health Technology and Services Research, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, Universidade do Porto, Porto, Portugal.

Patricia de Carvalho Mastroianni, School of Pharmaceutical Sciences, Universidade Estadual Paulista

PhD. Pharmacist and Professor, Department of Drugs and Medicines, School of Pharmaceutical Sciences, Universidade Estadual Paulista (UNESP), São Paulo (SP), Brazil.

References

Pekmezci D. Vitamin E and immunity. Vitam Horm. 2011;86:179-215. PMID: 21419272; https://doi.org/10.1016/B978-0-12-386960-9.00008-3.

Dror DK, Allen LH. Vitamin E deficiency in developing countries. Food Nutr Bull. 2011;32(2):124-43. PMID: 22164974; https://doi.org/10.1177/156482651103200206.

Ferraz L, Albiero C, Boechat SG, et al. Micronutrientes e sua importância no período gestacional. Revista Saber Científico. 2018;7(1):68-82. Available from: Available from: http://revista.saolucas.edu.br/index.php/resc/article/view/787 Accessed in 2021 (Apr 23).

Wang X, Falcone T, Attaran M, et al. Vitamin C and vitamin E supplementation reduce oxidative stress-induced embryo toxicity and improve the blastocyst development rate. Fertil Steril. 2002;78(6):1272-7. PMID: 12477524; https://doi.org/10.1016/s0015-0282(02)04236-x.

Adlard BP, De Souza SW, Moon S. Ascorbic acid in fetal human brain. Arch Dis Child. 1974;49(4):278-82. PMID: 4830116; https://doi.org/10.1136/adc.49.4.278.

Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004069. PMID: 26343254; https://doi.org/10.1002/14651858.CD004069.pub3.

Carr AC, Rosengrave PC, Bayer S, et al. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017;21(1):300. PMID: 29228951; https://doi.org/10.1186/s13054-017-1891-y.

Sarni RO, Souza FI, Cocco RR, Mallozi MC, Solé D. Micronutrientes e sistema imunológico [Micronutrients, immunologic system and allergic diseases]. Rev Bras Alerg Imunopatol. 2010;33(1):8-13. Available from: Available from: http://www.sbai.org.br/revistas/Vol331/ART%201-10%20-%20Micronutrientes%20e%20sistema%20imunol%C3%B3gico.pdf Accessed in 2021 (Apr 23).

Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J Biol Chem. 1994;269(18):13685-8. PMID: 8175804.

Rowe S, Carr AC. Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern? Nutrients. 2020;12(7):2008. PMID: 32640674; https://doi.org/10.3390/nu12072008.

Madruga de Oliveira A, Rondó PH, Mastroeni SS, Oliveira JM. Plasma concentrations of ascorbic acid in parturients from a hospital in Southeast Brazil. Clin Nutr. 2008;27(2):228-32. PMID: 18234398; https://doi.org/10.1016/j.clnu.2007.11.006.

Machado RHV, Bonafe S, Castelo A, Patin RV. Vitamin profile of pregnant women living with HIV/AIDS. e-ESPEN Journal. 2013;8(3):e108-e112. https://doi.org/10.1016/j.clnme.2013.03.002.

Paes-Silva RP, Tomiya MTO, Maio R, et al. Prevalence and factors associated with fat-soluble vitamin deficiency in adolescents. Nutr Hosp. 2018;35(5):1153-62. PMID: 30307300; https://doi.org/10.20960/nh.1785.

de Azeredo VB, Trugo NM. Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations. Nutrition. 2008;24(2):133-9. PMID: 18053685; https://doi.org/10.1016/j.nut.2007.10.011.

Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13(3):147-53. PMID: 26317388; https://doi.org/10.1097/XEB.0000000000000054.

Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Chichester (UK): John Wiley & Sons, 2019.

Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12. PMID: 10789670; https://doi.org/10.1001/jama.283.15.2008.

Lizarondo L, Stern C, Carrier J, et al. Chapter 8: Mixed methods systematic reviews. In: Aromataris E, Munn Z (Editors). JBI Manual for Evidence Synthesis. JBI; 2020. https://doi.org/10.46658/JBIMES-20-09.

Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Chapter 5: Systematic reviews of prevalence and incidence. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. JBI; 2020. https://doi.org/10.46658/JBIMES-20-06.

Lucchetta R. Protocol: Prevalence of micronutrient deficiencies in women of childbearing age in Brazil: systematic review and meta-analysis. OSF. 2020. https://doi.org/10.17605/OSF.IO/J9QMH.

Hane PJ. Newsbreaks: Elsevier announces Scopus service. [Internet]. Inf Today 2004. 2017 [cited 2017 Sep 13]. Available from: Available from: http://www.infotoday.com/newsbreaks/nb040315-1.shtml Accessed in 2021 (Apr 23).

Munn Z, Stern C, Aromataris E, Lockwood C, Jordan Z. What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences. BMC Med Res Methodol. 2018;18(1):5. PMID: 29316881; https://doi.org/10.1186/s12874-017-0468-4.

Team RC. R: A language and environment for statistical computing. [Internet]. Vienna, Austria: R Foundation for Statistical Computing. Available from: Available from: https://www.r-project.org/ Accessed in 2021 (Apr 23).

Wickham H, Hester J, François R. Readr: Read rectangular text data. R package version 1.1.1 [Internet]. 2017. Available from: Available from: https://cran.r-project.org/package=readr Accessed in 2021 (Apr 23).

Schwarzer G. Meta: An R package for meta-analysis. R News. 2007;7(3):40-5. Available from: Available from: https://www.researchgate.net/publication/285729385_meta_An_R_Package_for_Meta-Analysis Accessed in 2021 (Apr 23).

Mahadev S, Laszkowska M, Sundström J, et al. Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis. Gastroenterology. 2018;155(2):374-382.e1. PMID: 29689265; https://doi.org/10.1053/j.gastro.2018.04.016.

Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13(3):147-53. PMID: 26317388; https://doi.org/10.1097/XEB.0000000000000054.

Migliavaca CB, Stein C, Colpani V, et al. Quality assessment of prevalence studies: a systematic review. J Clin Epidemiol. 2020;127:59-68. PMID: 32679313; https://doi.org/10.1016/j.jclinepi.2020.06.039.

Gurgel CSS, Lira LQ de, Azevedo GM, et al. Comparação entre a concentração sérica de alfa-tocoferol de puérperas assistidas em maternidades públicas e privadas no Nordeste do Brasil. Rev Bras Ginecol e Obstet. 2014;36(8):372-6. http://dx.doi.org/10.1590/SO100-720320140005006.

Monteiro JP, Cruz ML, Mussi-Pinhata MM, et al. Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants. Rev Soc Bras Med Trop. 2014;47(6):692-700. PMID: 25626647; https://doi.org/10.1590/0037-8682-0226-2014.

Clemente HA, Ramalho HM, Lima MS, Grilo EC, Dimenstein R. Maternal supplementation with natural or synthetic vitamin E and its levels in human colostrum. J Pediatr Gastroenterol Nutr. 2015;60(4):533-7. PMID: 25419678; https://doi.org/10.1097/MPG.0000000000000635.

Madruga de Oliveira A, Rondó PH, Barros SB. Concentrations of ascorbic acid in the plasma of pregnant smokers and nonsmokers and their newborns. Int J Vitam Nutr Res. 2004;74(3):193-8. PMID: 15296078; https://doi.org/10.1024/0300-9831.74.3.193.

da Silva Ribeiro KD, Lima MS, Medeiros JF, et al. Association between maternal vitamin E status and alpha-tocopherol levels in the newborn and colostrum. Matern Child Nutr. 2016;12(4):801-7. PMID: 26924492; https://doi.org/10.1111/mcn.12232.

Ribeiro KDS, Weigert L, Andrade T, Lima A, Medeiros J, Lima M, et al. The socioeconomic variables influence in the alpha-tocopherol concentration of the maternal serum. Rev Bras Saude Mater Infant. 2017;17(1):179-84. http://dx.doi.org/10.15901806-930420170001000010.

da Silva AGCL, de Sousa Rebouças A, Mendonça BMA, et al. Relationship between the dietary intake, serum, and breast milk concentrations of vitamin A and vitamin E in a cohort of women over the course of lactation. Matern Child Nutr. 2019;15(3):e12772. PMID: 30578660; https://doi.org/10.1111/mcn.12772.

Rodrigues KDDSR. Estado nutricional em vitamina e de mães e crianças pré-termo e termo do nascimento aos 3 meses pós-parto [thesis]. Natal (RN): Universidade Federal do Rio Grade do Norte; 2016.

de Lira LQ, Ribeiro PPC, Grilo EC, Lima MSR, Dimenstein R. Níveis de alfa-tocoferol no soro e colostro de lactantes e associação com variáveis maternas. Rev Bras Ginecol Obstet. 2012;34(8):362-8. https://doi.org/10.1590/S0100-72032012000800004.

Garcia L, Ribeiro K, Araújo K, et al. Alpha-tocopherol concentration in the colostrum of nursing women supplemented with retinyl palmitate and alpha-tocopherol. J Hum Nutr Diet. 2010;23(5):529-34. PMID: 20831709; https://doi.org/10.1111/j.1365-277X.2010.01063.x.

» https://doi.org/https://doi.org/10.1111/j.1365-277X.2010.01063.x

de Lira LQ, Lima MS, de Medeiros JM, da Silva IF, Dimenstein R. Correlation of vitamin A nutritional status on alpha-tocopherol in the colostrum of lactating women. Matern Child Nutr. 2013;9(1):31-40. PMID: 22099335; https://doi.org/10.1111/j.1740-8709.2011.00376.x.

Carr AC, Rowe S. Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective. Nutrients. 2020;12(7):1963. PMID: 32630245; https://doi.org/10.3390/nu12071963.

Hoppu U, Rinne M, Salo-Väänänen P, et al. Vitamin C in breast milk may reduce the risk of atopy in the infant. Eur J Clin Nutr. 2005;59(1):123-8. PMID: 15340369; https://doi.org/10.1038/sj.ejcn.1602048.

Lima MS, Dimenstein R, Ribeiro KD. Vitamin E concentration in human milk and associated factors: a literature review. J Pediatr (Rio J). 2014 Sep-Oct;90(5):440-8. PMID: 24953721; https://doi.org/10.1016/j.jped.2014.04.006.

do Nascimento MB, Issler H. Breastfeeding: making the difference in the development, health and nutrition of term and preterm newborns. Rev Hosp Clin Fac Med Sao Paulo. 2003;58(1):49-60. PMID: 12754591; https://doi.org/10.1590/s0041-87812003000100010.

Guyatt GH, Oxman AD, Kunz R, et al. What is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336(7651):995-8. PMID: 18456631; https://doi.org/10.1136/bmj.39490.551019.BE.

Glasziou P, Chalmers I, Rawlins M, McCulloch P. When are randomised trials unnecessary? Picking signal from noise. BMJ. 2007;334(7589):349-51. PMID: 17303884; https://doi.org/10.1136/bmj.39070.527986.68.

Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Departamento de Assistência Farmacêutica e Insumos Estratégicos. Relação Nacional de Medicamentos Essenciais: Rename 2020 [recurso eletrônico]/Ministério da Saúde, Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde, Departamento de Assistência Farmacêutica e Insumos Estratégicos. Brasília: Ministério da Saúde; 2020. Available from: Available from: http://bvsms.saude.gov.br/bvs/publicacoes/relacao_medicamentos_rename_2020.pdf Accessed in 2021 (Apr 23).

Brasil. Ministério da Saúde. NutriSUS - Estratégia de fortificação da alimentação infantil com micronutrientes (vitaminas e minerais) em pó: manual operacional/Ministério da Saúde, Ministério da Educação. Brasília: Ministério da Saúde ; 2015. Available from: Available from: http://bvsms.saude.gov.br/bvs/publicacoes/nutrisus_estrategia_fortificacao_alimentacao_infantil.pdf Accessed in 2021 (Apr 23).

Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Programa Nacional de Suplementação de Ferro: manual de condutas gerais/Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Brasília: Ministério da Saúde ; 2013. Available from: Available from: http://bvsms.saude.gov.br/bvs/publicacoes/manual_suplementacao_ferro_condutas_gerais.pdf Accessed in 2021 (Apr 23).

Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Manual de condutas gerais do Programa Nacional de Suplementação de Vitamina A/Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Atenção Básica. Brasília: Ministério da Saúde ; 2013. https://bvsms.saude.gov.br/bvs/publicacoes/manual_condutas_suplementacao_vitamina_a.pdf Accessed in 2021 (Apr 23).

Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PMID: 26415762; https://doi.org/10.1002/14651858.CD004072.

Le NK, Kesayan T, Chang JY, Rose DZ. Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels. J Stroke Cerebrovasc Dis. 2020;29(5):104747. PMID: 32151478; https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104747.

Tsai HH, Lin HW, Simon Pickard A, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012;66(11):1056-78. PMID: 23067030; https://doi.org/10.1111/j.1742-1241.2012.03008.x.

Moura MRL, Reyes FGR. Interação fármaco-nutriente: uma revisão. Rev Nutr. 2002;15(2):223-38. http://dx.doi.org/10.1590/S1415-52732002000200011.

Downloads

Published

2021-11-04

How to Cite

1.
Lucchetta RC, Cavicchioli S de A, Gini ALR, Forgerini M, Varallo FR, Nadai MN de, Fernandez-Llimos F, Mastroianni P de C. Deficiency of vitamins C and E in women of childbearing age in Brazil: a systematic review and meta-analysis. Sao Paulo Med J [Internet]. 2021 Nov. 4 [cited 2025 Mar. 9];139(6):545-5. Available from: https://periodicosapm.emnuvens.com.br/spmj/article/view/533

Issue

Section

Original Article