SUPLEMENTAÇÃO DE FITOESTERÓIS NO TRATAMENTO DA DISLIPIDEMIA EM CRIANÇAS E ADOLESCENTES: UMA REVISÃO SISTEMÁTICA

Luisa Montone Mantovani Camila Pugliese Sobre os autores

ABSTRACT

Objective:

To carry out a systematic review on the effects of phytosterol supplementation on the treatment of dyslipidemia in children and adolescents.

Data sources:

Review in the SciELO, Lilacs, Bireme, PubMed and Web of Science databases, with no time limit. Descriptors: phytosterols or plant sterols and dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, in English and Portuguese. The articles included were published in Portuguese, English or Spanish and evaluated the effect of phytosterol supplementation in pediatric patients with dyslipidemia. Documents that involved adults or animals, review papers, case studies and abstracts were excluded. Two authors performed independent extraction of articles. Of 113 abstracts, 19 were read in full and 12 were used in this manuscript.

Data synthesis:

Phytosterol supplementation to reduce cholesterol levels has been shown to be effective in reducing LDL-cholesterol levels by approximately 10%, with reductions above 10% in LDL-cholesterol levels observed after 8 to 12 weeks of intervention. Studies have not shown significant changes in HDL-cholesterol and triglyceride levels. Based on the absence of adverse effects, its use seems to be safe and of good tolerance in children and adolescents.

Conclusions:

Phytosterol supplementation seems to be of great therapeutic aid for the treatment of hypercholesterolemia in children and adolescents. Further studies assessing the long-term effect of phytosterol supplementation are necessary.

Keywords:
Phytosterols; Dietary supplements; Dyslipidemias; Hypercholesterolemia; Child

RESUMO

Objetivo:

Realizar uma revisão sistemática sobre os efeitos da suplementação de fitoesteróis no tratamento da dislipidemia em crianças e adolescentes.

Fontes de dados:

Revisão nos bancos SciELO, Lilacs, Bireme, Pubmed e Web of Science, sem limite de tempo. Descritores: phytosterols or plant sterols, dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, nas línguas inglesa e portuguesa. Os artigos incluídos foram publicados nos idiomas português, inglês ou espanhol e avaliaram o efeito da suplementação de fitoesteróis em pacientes pediátricos com dislipidemia. Estudos que envolviam adultos ou animais, trabalhos de revisão, estudos de caso e resumos foram excluídos. A extração independente de artigos foi realizada por dois autores. Do total de 113 resumos, 19 foram lidos na íntegra, e 12 utilizados neste manuscrito.

Síntese de dados:

A suplementação de fitoesteróis para a redução dos níveis de colesterol mostrou-se eficiente, de forma a promover a redução de aproximadamente 10% dos níveis de LDL-colesterol, sendo observadas reduções acima de 10% em 8 a 12 semanas de intervenção. Os estudos não mostraram alterações significantes nos níveis de HDL-colesterol e triglicérides. Com base na ausência de efeitos adversos, seu uso parece ser seguro e de boa tolerância em crianças e adolescentes. Conclusões: A suplementação com fitoesteróis parece ser de grande auxílio terapêutico para o tratamento da hipercolesterolemia em crianças e adolescentes. São necessários mais estudos que avaliem o efeito em longo prazo da suplementação de fitoesteróis.

Palavras-chave:
Fitoesteróis; Suplementos nutricionais; Dislipidemia; Hipercolesterolemia; Criança

INTRODUÇÃO

A dislipidemia em crianças e adolescentes representa um fator de risco determinante de aterosclerose e pode contribuir para a doença coronariana na vida adulta.11. Lozano P, Henrikson NB, Morrison CC, Dunn J, Nguyen M, Blasi PR, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia: evidence report and systematic review for the US preventive services task force. JAMA. 2016;316:634-44. https://doi.org/10.1001/jama.2016.6423
https://doi.org/https://doi.org/10.1001/...
Já está estabelecido que células gordurosas estão presentes na aorta de indivíduos aos 10 anos e nas artérias coronárias aos 20 anos, e que a progressão das estrias gordurosas ocorre a partir dos 15 anos de idade.22. Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
https://doi.org/https://doi.org/10.22565...

A dislipidemia trata-se de um distúrbio metabólico caracterizado por concentrações anormais de lipídeos e/ou lipoproteínas no sangue.22. Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
https://doi.org/https://doi.org/10.22565...
É definida pela elevação dos níveis de colesterol total (CT) ou lipoproteína de baixa densidade (LDL) e/ou triglicérides (TG) e/ou pela diminuição da lipoproteína de alta densidade (HDL).33. Sociedade Brasileira de Cardiologia. I Diretriz brasileira de hipercolesterolemia familiar (HF). Arq Bras Cardiol. 2012;99:1-28. https://doi.org/10.5935/abc.20120202
https://doi.org/https://doi.org/10.5935/...
Além disso, sabe-se que a elevação dos níveis de LDL-colesterol é um fator de risco estabelecido para doença cardiovascular.11. Lozano P, Henrikson NB, Morrison CC, Dunn J, Nguyen M, Blasi PR, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia: evidence report and systematic review for the US preventive services task force. JAMA. 2016;316:634-44. https://doi.org/10.1001/jama.2016.6423
https://doi.org/https://doi.org/10.1001/...

Os distúrbios lipídicos podem ter causas primárias (de origem genética) ou secundárias (decorrentes de estilo de vida inadequado, de certas condições mórbidas ou de medicamentos).44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
Assim, a dislipidemia infantil é multifatorial, podendo estar associada a fatores ambientais e comportamentais e a obesidade, salvo os de etiologia genética, como a hipercolesterolemia familiar (HF).11. Lozano P, Henrikson NB, Morrison CC, Dunn J, Nguyen M, Blasi PR, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia: evidence report and systematic review for the US preventive services task force. JAMA. 2016;316:634-44. https://doi.org/10.1001/jama.2016.6423
https://doi.org/https://doi.org/10.1001/...

A prevalência das dislipidemias na faixa etária infanto-juvenil no Brasil varia entre 24 e 40%.22. Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
https://doi.org/https://doi.org/10.22565...
Estima-se que no mundo existam mais de 10 milhões de indivíduos portadores de HF; no entanto, menos de 10% têm diagnóstico conhecido de HF, e menos de 25% recebem tratamento hipolipemiante.55. World Health Organization. Familial hypercholesterolemia (FH). Report of a WHO consultation. Geneva: WHO; 1997.

A I Diretriz de Prevenção da Aterosclerose na Infância e na Adolescência recomenda o tratamento farmacológico hipolipemiante para crianças a partir dos dez anos de idade, sendo propostas modificações no padrão alimentar e no estilo de vida para crianças maiores de dois anos, as quais incluem dieta reduzida em gorduras saturadas e colesterol e prática de atividade física.66. Sociedade Brasileira de Cardiologia. I Diretriz de prevenção da aterosclerose na infância e na adolescência. Arq Bras Cardiol. 2005;85 (Suppl 6):3-36. https://doi.org/10.1590/S0066-782X2005002500001
https://doi.org/https://doi.org/10.1590/...
Mudanças dietéticas adequadas e estilo de vida ativo auxiliam em reduzir os fatores de risco cardiovasculares e devem ser incentivados, mas na incapacidade de resposta a tais intervenções e na impossibilidade de recomendação de tratamento farmacológico, o uso de fitoesteróis pode ser considerado.33. Sociedade Brasileira de Cardiologia. I Diretriz brasileira de hipercolesterolemia familiar (HF). Arq Bras Cardiol. 2012;99:1-28. https://doi.org/10.5935/abc.20120202
https://doi.org/https://doi.org/10.5935/...

Esteróis e estanóis vegetais são também conhecidos como fitoesteróis, que são compostos bioativos estruturalmente semelhantes ao colesterol, sendo os esteróis as formas insaturadas (sitosterol e campesterol) e os estanóis seus derivados saturados (sitostanol e campestanol).44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
Sua ação principal é a de reduzir o LDL-colesterol por inibição na absorção intestinal de colesterol.77. Malinowski JM, Gehret MM. Phytosterols for dyslipidemia. Am J Health Syst Pharm. 2010;67:1165-73. https://doi.org/10.2146/ajhp090427
https://doi.org/https://doi.org/10.2146/...
São naturalmente encontrados em frutas, vegetais, óleos vegetais, castanhas e sementes.88. Vuorio A, Kovanen PT. Decreasing the cholesterol burden in heterozygous familial hypercholesterolemia children by dietary plant stanol esters. Nutrients. 2018;10:pii:E1842. https://doi.org/10.3390/nu10121842
https://doi.org/https://doi.org/10.3390/...
A ingestão de fitoesteróis por meio de fontes naturais varia de 200 a 400 mg ao dia em dietas habituais.99. Ras RT, van der Schouw YT, Trautwein EA, Sioen I, Dalmeijer GW, Zock PL, et al. Intake of phytosterols from natural sources and risk of cardiovascular disease in the European prospective investigation into cancer and nutrition-the Netherlands (EPIC-NL) population. Eur J Prev Cardiol. 2015;22:1067-75. https://doi.org/10.1177/2047487314554864
https://doi.org/https://doi.org/10.1177/...
Estes podem também ser adicionados a alimentos como margarinas, sucos, iogurtes e cereais. Além do uso em alimentos enriquecidos, também é possível sua suplementação.22. Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
https://doi.org/https://doi.org/10.22565...

Já é comprovada a relação inversa entre o consumo habitual de fitoesteróis na dieta e os níveis séricos de colesterol ou de LDL-colesterol,44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
sendo sua suplementação recomendada por diversas diretrizes.33. Sociedade Brasileira de Cardiologia. I Diretriz brasileira de hipercolesterolemia familiar (HF). Arq Bras Cardiol. 2012;99:1-28. https://doi.org/10.5935/abc.20120202
https://doi.org/https://doi.org/10.5935/...
,44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
,1010. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. https://doi.org/10.1093/eurheartj/ehw272
https://doi.org/https://doi.org/10.1093/...
,1111. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 (Suppl 5):S213-56. https://doi.org/10.1542/peds.2009-2107C
https://doi.org/https://doi.org/10.1542/...
Contudo, seu uso é geralmente reservado para crianças com dislipidemias primárias, não havendo concordância a respeito da dose e segurança dessa prática a todos os pacientes dislipidêmicos. Portanto, esta revisão propõe uma investigação dos efeitos da suplementação de fitoesteróis no tratamento da dislipidemia em crianças e adolescentes.

MÉTODO

Esta revisão foi conduzida com base nas recomendações da Preferred Reporting Items for Systematic Reviews and Meta-Analyses1212. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Loannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100. https://doi.org/10.1371/journal.pmed.1000100
https://doi.org/https://doi.org/10.1371/...
nas seguintes bases de dados: SciELO, Lilacs, Bireme, Pubmed e Web of Science. Os descritores utilizados foram phytosterols or plant sterols, dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, nas línguas inglesa e portuguesa. A pesquisa bibliográfica foi realizada com base no questionamento “Quais os efeitos da suplementação de fitoesteróis no tratamento da dislipidemia em pacientes pediátricos?”, o qual baseou-se no modelo Population, Intervention, Comparison, Outcome.1313. Santos CM, Pimenta CA, Nobre MR. The PICO strategy for the research question construction and evidence search. Rev Latino-Am. Enfermagem. 2007;15:508-11. https://doi.org/10.1590/S0104-11692007000300023
https://doi.org/https://doi.org/10.1590/...

Foram adotados como critérios de inclusão ensaios clínicos nos idiomas inglês, espanhol e português que avaliaram o efeito da suplementação de fitoesteróis em pacientes pediátricos com dislipidemia. Também foram considerados os estudos referenciados pelos artigos selecionados e que preenchiam os critérios de seleção. Documentos que não diziam respeito ao propósito deste estudo, que envolviam adultos ou animais, trabalhos de revisão, estudos de casos, resumos e trabalhos que não incluíam amostra com dislipidemia foram excluídos. Não houve delimitação quanto ao ano de publicação dos artigos.

A identificação dos artigos foi realizada inicialmente por meio de análise por título para exclusão de artigos repetidos ou que não contemplassem os critérios predefinidos. Posteriormente, os resumos restantes foram avaliados em relação à adequação quanto aos critérios de inclusão e exclusão. Os estudos que apresentaram os critérios predeterminados tiveram o texto completo adquirido para análise detalhada e extração de dados. Os artigos selecionados foram lidos por dois avaliadores que decidiram, de modo independente, sobre a inclusão com base nos critérios de elegibilidade. Qualquer problema de divergência sobre a seleção dos artigos foi decidido consensualmente.

Os estudos selecionados tiveram as seguintes características registradas:

  • Características dos participantes do estudo (incluindo idade, tipo de dislipidemia e método de diagnóstico) e critérios de inclusão e exclusão do estudo.

  • Tipo de intervenção (incluindo tipo de fitoesterol, dose, duração, administração e veículo alimentar).

  • Principais resultados (incluindo nível de redução sérica de colesterol e frações lipídicas, tempo de segmento e efeitos não desejados do tratamento).

Posteriormente, foram realizadas síntese e análise crítica dos estudos.

Para verificar a validade dos ensaios clínicos, determinaram-se tamanho da amostra, extensão da perda no acompanhamento dos participantes dos estudos e cegamento de pacientes, profissionais de saúde, coletores de dados e avaliadores de resultados.

RESULTADOS

Foram identificados inicialmente 311 trabalhos nas bases de dados eletrônicas. Após refinamento por título, foram selecionados 113 resumos para serem analisados. Os estudos potencialmente relevantes ao tema tiveram o texto completo adquirido para análise detalhada quanto aos critérios de elegibilidade. Adicionalmente, sete estudos identificados em outras listas de referências dos artigos selecionados e relacionados ao tema foram incluídos. Por fim, a síntese descritiva foi composta de 12 referências, cujos períodos de publicação estiveram entre 1993 e 2017. 1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
A Figura 1 apresenta o diagrama de fluxo das etapas de busca e seleção dos estudos.

Figura 1
Diagrama de fluxo acerca das etapas de identificação, seleção, elegibilidade e inclusão das referências.

Todos os estudos selecionados são ensaios clínicos randomizados1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
e não randomizados1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
publicados em inglês. Dez deles foram realizados na Europa, 1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
um no Japão2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8. e um no Brasil.2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
Todos os estudos randomizados passaram por um período inicial duplo-cego. A perda de acompanhamento dos participantes foi descrita por: não aderência à dieta,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
motivos pessoais não relacionados à pesquisa,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
mudança de estágio puberal,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
palatabilidade do produto ou náusea,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
dificuldade de ingestão do produto.2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
A Tabela 1 expõe uma breve descrição de todas as referências mediante os seguintes itens: autor(es), ano de publicação, delineamento, métodos e conclusão.

Tabela 1
Artigos selecionados, segundo seu(s) autor(es), ano, delineamento, métodos e sua conclusão.

No total foram incluídos 370 crianças e adolescentes entre 2 e 19 anos de idade, sendo a variação do tamanho amostral dos estudos de 9 a 59 participantes. Quanto ao tipo de dislipidemia, nove estudos incluíram crianças/adolescentes com HF,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
e seis com dislipidemia sem causa genética ou sem etiologia determinada.1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
Nenhum estudo incluiu ou relatou a inclusão de crianças/adolescentes em uso de medicamentos hipolipemiantes. Três estudos incluíram pacientes em uso de medicação para asma ou alergia1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
e um em uso de medicação para transtorno do deficit de atenção com hiperatividade.2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
Um ensaio clínico excluiu crianças/adolescentes com diagnóstico de fitosterolemia,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
e cinco excluíram pacientes com doenças crônicas.1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
Dois estudos solicitaram aos participantes a exclusão da ingestão de produtos contendo estanóis ou esteróis vegetais antes do início do estudo a fim de evitar viés em pesquisa.1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...

Em dois ensaios clínicos, 1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
parte dos participantes fez uso de óleo de peixe (fígado de bacalhau ou ácido graxo poli-insaturado ômega-3) e de suplemento vitamínico contendo retinol, tocoferol e vitamina D (nenhum contendo carotenoides). Apesar de serem instruídos a consumir a mesma dose de medicação/suplemento durante todo o estudo, pode haver viés no desfecho da análise dos níveis séricos de vitaminas e antioxidantes lipossolúveis desses estudos.

As crianças e os adolescentes receberam durante o período do estudo uma dieta com baixo teor de gordura saturada e colesterol, preconizada pelos respectivos autores.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
Apenas no estudo de Matsuyama et al.2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8. os participantes não passaram por restrições dietéticas, entretanto, foram orientados a manter os hábitos alimentares durante todo o estudo.

A intervenção realizada nos respectivos estudos quanto a tipo de fitoesterol, dose, duração e veículos alimentares utilizados está representada na Tabela 2. Em todos os ensaios clínicos selecionados o desfecho primário avaliado foi a redução da concentração sérica de LDL-colesterol.

Tabela 2
Ensaios clínicos randomizados avaliando os efeitos da suplementação de fitoesteróis sobre a colesterolemia.

Os estudos não mostraram alterações significantes nos níveis de HDL-colesterol e TG, com exceção dos resultados encontrados em somente um ensaio clínico,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
em que foram observados redução em 12% (p<0,05) nos níveis de HDL-colesterol e aumento significativo (p<0,05) dos TG após três e sete meses de suplementação, mas permaneceu em faixa de normalidade.

Somente dois estudos incluíram a análise do efeito da suplementação de fitoesteróis após o período de ingestão. O estudo de Matsuyama et al.2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8. verificou elevação significativa de CT e LDL-colesterol após quatro meses (p<0,05). Já Amundsen et al.1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
observaram que a eficácia na redução do colesterol foi sustentada durante seis meses posteriores.

Após intervenção, alguns dos ensaios clínicos observaram redução na concentração plasmática de carotenoides hidrocarbonados (β-caroteno,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
α-caroteno1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
e licopeno1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
), α-tocoferol1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
e retinol.2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
Outros estudos identificaram aumento de α-tocoferol1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
e retinol.1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
Os demais estudos não verificaram alteração nos níveis de β-caroteno,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
y-tocoferol2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
e retinol.1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...

Apenas dois estudos2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
identificaram efeito colateral da suplementação de fitoesteróis, sendo a queixa recorrente, em ambos estudos, o desconforto abdominal em seis crianças, comparado a oito do grupo placebo e uma criança no grupo intervenção, respectivamente. Os demais estudos não relataram a ocorrência de efeitos colaterais.

DISCUSSÃO

A suplementação de fitoesteróis para a redução dos níveis de colesterol, de acordo com os ensaios clínicos mencionados neste trabalho, mostrou-se eficiente, de forma a promover a redução de aproximadamente 10% dos níveis de LDL-colesterol. A maioria dos ensaios clínicos considerados apresentou amostra de pacientes com HF.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
Entretanto, aqueles que incluíram crianças e adolescentes com hipercolesterolemia de etiologia não determinada ou sem causa genética também obtiveram resultados benéficos sobre a colesterolemia.1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...

O mecanismo subjacente a esse efeito hipocolesterolêmico é a redução da absorção de colesterol do lúmen intestinal na circulação por uma competição entre estanóis/esteróis vegetais e colesterol intestinal pela incorporação em micelas mistas. Os fitoesteróis são mais hidrofóbicos que o colesterol, dessa forma, agrupam-se melhor no interior da micela.2626. Plat J, Nichols JA, Mensink RP. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J Lipid Res. 2005;46:2468-76. https://doi.org/10.1194/jlr.M500272-JLR200
https://doi.org/https://doi.org/10.1194/...
Assim, impedem a incorporação do colesterol nas micelas, diminuindo sua biodisponibilidade e o fluxo de colesterol do lúmen intestinal para a circulação e aumentando a síntese hepática de colesterol.2727. De Smet E, Mensink RP, Plat J. Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present. Mol Nutr Food Res. 2012;56:1058-72. https://doi.org/10.1002/mnfr.201100722
https://doi.org/https://doi.org/10.1002/...
O colesterol livre que não é então incorporado no interior das micelas é eliminado por meio das fezes, resultando na diminuição da absorção de colesterol nos enterócitos. O efeito da absorção reduzida e da síntese aumentada de colesterol é uma redução nas concentrações séricas de LDL.2828. Gylling H, Plat J, Turley S, Ginsberg HN, Ellegard L, Jessup W, et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis. 2014;232:346-60. https://doi.org/10.1016/j.atherosclerosis.2013.11.043
https://doi.org/https://doi.org/10.1016/...
Embora haja muita pesquisa a respeito dos fitoesteróis, sua ação hipocolesterolêmica não foi completamente elucidada.2929. Obara CE, Nascimento BL, Danziger C, Mattos FR, Ferreira NA. Propriedades químicas dos estanóis e esteróis vegetais. Revista Terra & Cultura. 2018;29:55-60.

A dose média de fitoesteróis administrada foi de cerca de 2,1 g/dia (variação de 0,4 a 6 g/dia) em crianças entre 2 e 19 anos de idade. No entanto, a Sociedade Brasileira de Cardiologia sugere que o uso de fitoesteróis deve ser parte das mudanças de estilo de vida e está indicado para crianças acima de cinco anos com HF, como aprovado para uso no Brasil.44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
Assim, a I Diretriz Brasileira de Hipercolesterolemia Familiar recomenda a ingestão de 1,2 a 1,5 g por dia em crianças portadoras de HF heterozigótica.33. Sociedade Brasileira de Cardiologia. I Diretriz brasileira de hipercolesterolemia familiar (HF). Arq Bras Cardiol. 2012;99:1-28. https://doi.org/10.5935/abc.20120202
https://doi.org/https://doi.org/10.5935/...
A European Society of Cardiology e a European Atherosclerosis Society,1010. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. https://doi.org/10.1093/eurheartj/ehw272
https://doi.org/https://doi.org/10.1093/...
assim como o Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents,1111. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 (Suppl 5):S213-56. https://doi.org/10.1542/peds.2009-2107C
https://doi.org/https://doi.org/10.1542/...
orientam, como medida de suporte, o consumo de 2 g de esteróis/estanóis por dia em crianças com HF. Já o Consenso da Associação Brasileira de Nutrologia propõe que crianças e adolescentes obesos com dislipidemia recebam 1,6 g de fitoesterol diariamente.22. Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
https://doi.org/https://doi.org/10.22565...
Ademais, presume-se que todas as crianças e todos os adolescentes dislipidêmicos sem indicação para tratamento farmacológico se beneficiariam do uso da suplementação de fitoesteróis para a redução dos níveis de CT e LDL, como observado no presente estudo.

Os ensaios clínicos selecionados utilizaram a administração de esteróis ou estanóis vegetais ou ambos para a intervenção. Os principais fitoesteróis utilizados foram o sitosterol e o sitostanol. A respeito das diferentes subclasses de fitoesteróis, os estudos que compararam a eficácia dos estanóis vegetais e dos esteróis vegetais verificaram que, embora ambos tenham produzido reduções no LDL-colesterol, o estanol vegetal ainda em menor dose parece ser capaz de reduzir mais efetivamente o LDL.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
No entanto, uma metanálise realizada por Talati et al.3030. Talati R, Sobieraj DM, Makanji SS, Phung OJ, Coleman CI. The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis. J Am Diet Assoc. 2010;110:719-26. https://doi.org/10.1016/j.jada.2010.02.011
https://doi.org/https://doi.org/10.1016/...
não observou diferenças significativas entre os efeitos dos esteróis e estanóis vegetais sobre o LDL-colesterol, sugerindo que seus efeitos são similares.

A administração dos esteróis/estanóis vegetais ocorreu durante as refeições, principalmente no café da manhã, no almoço e no jantar. Os estudos que utilizaram como matriz alimentar ou veículo de suplementação margarina e spread orientaram seu consumo pela adição em pão,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
sanduíche,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
mingau1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
ou pela mistura a uma refeição quente.1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
É importante que os fitoesteróis sejam consumidos com as refeições, pois os fitoesteróis esterificados são hidrolisados pela enzima colesterol redutase no intestino delgado no período pós-prandial. Assim, quando livres, estão disponíveis para impedir a incorporação de colesterol nas micelas.77. Malinowski JM, Gehret MM. Phytosterols for dyslipidemia. Am J Health Syst Pharm. 2010;67:1165-73. https://doi.org/10.2146/ajhp090427
https://doi.org/https://doi.org/10.2146/...

Os veículos utilizados para a suplementação foram: pastilhas, margarinas, iogurte, leite, pão, spread, emulsões. Apesar de todos reduzirem de forma significativa o LDL-colesterol, a maior redução parece ter ocorrido com o uso de pastilhas, enquanto o uso de pão e emulsão resultou numa redução inferior. De acordo com estudo de Clifton et al.,3131. Clifton PM, Noakes M, Sullivan D, Erichsen N, Ross D, Annison G, et al. Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur J Clin Nutr. 2004;58:503-9. https://doi.org/10.1038/sj.ejcn.1601837
https://doi.org/https://doi.org/10.1038/...
o qual comparou a eficácia individual de alimentos enriquecidos com plantas esteróis, verificou maior redução de LDL-colesterol com o uso de leite desnatado, seguido de iogurte desnatado, e uma redução menor foi observada com o uso de pão e cereal, valendo-se da hipótese de que os fitoesteróis podem ficar presos no centro das gotículas lipídicas e não estão disponíveis até que a gordura seja digerida. Todavia, a queda do LDL-colesterol também é vista com o uso de margarina enriquecida com ésteres de estanóis,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
talvez mais do que o observado nos estudos que utilizaram leite2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
e iogurte desnatado.2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
Assim, pode ser que alimentos enriquecidos com fitoesteróis com baixo teor de gordura sejam igualmente eficazes àqueles com alto teor de gordura. Além dessa comparação, existe também a de alimentos sólidos versus líquidos.3232. Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, et al. Continuous dose‐response relationship of the LDL‐cholesterol‐lowering effect of phytosterol intake. J Nutr. 2009;139:271-84. https://doi.org/10.3945/jn.108.095125
https://doi.org/https://doi.org/10.3945/...
Os resultados obtidos de uma metanálise sugerem que altas doses de fitoesteróis em alimentos sólidos podem ter um efeito redutor de LDL-colesterol mais pronunciado do que em alimentos líquidos. Porém a discussão sobre se o tipo de alimento (matriz alimentar) influencia sua eficácia ainda está em andamento.3232. Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, et al. Continuous dose‐response relationship of the LDL‐cholesterol‐lowering effect of phytosterol intake. J Nutr. 2009;139:271-84. https://doi.org/10.3945/jn.108.095125
https://doi.org/https://doi.org/10.3945/...

É possível também que a eficácia dos fitoesteróis diminua com o maior tempo de suplementação, como observado nos ensaios clínicos selecionados cuja suplementação foi superior a 12 semanas.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
Os estudos que variaram de 8 a 12 semanas apresentaram resultados semelhantes na redução de LDL-colesterol, sendo essa redução superior a 10%, dependendo também da dose de suplementação.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
O único estudo cujo período de intervenção durou quatro semanas apresentou uma redução de LDL-colesterol, apesar de significativa, inferior a 10%.2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...

A despeito do efeito benéfico da suplementação de fitoesteróis sobre a colesterolemia, um potencial efeito deletério é a fitosterolemia, também denominada sitosterolemia, uma desordem autossômica recessiva e hereditária rara que está relacionada a mutações nos genes dos cotransportadores de fitoesteróis/colesterol ABCG5 e ABCG8. Essas mutações promovem aumento de 50 vezes na concentração circulante de esteróis vegetais e estão associadas com aterosclerose precoce.3333. Renner C, Connor WE, Steiner RD. Sitosterolemia presenting as pseudohomozygous familial hypercholesterolemia. Clin Med Res. 2016;14:103-8. https://doi.org/10.3121/cmr.2016.1294
https://doi.org/https://doi.org/10.3121/...
,3434. Buonuomo PS, Iughetti L, Pisciotta L, Rabacchi C, Papadia F, Bruzzi P, et al. Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia. Atherosclerosis. 2017;262:71-7. https://doi.org/10.1016/j.atherosclerosis.2017.05.002
https://doi.org/https://doi.org/10.1016/...
É importante ressaltar que a suplementação de fitoesteróis é contraindicada para os raros pacientes que apresentam fitosterolemia,44. Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune A Neto, et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose - 2017. Arq Bras Cardiol. 2017;109 (2 Suppl 1):1-76. https://doi.org/10.5935/abc.20170121
https://doi.org/https://doi.org/10.5935/...
apesar de o consumo de alimentos enriquecidos com fitoesteróis estar associado, nesses casos, com aumento menor, cerca de 2 vezes, nos esteróis vegetais circulantes.3535. Cabral CE, Klein MR. Fitoesteróis no tratamento da hipercolesterolemia e prevenção de doenças cardiovasculares. Arq Bras Cardiol. 2017;109:475-82. https://doi.org/10.5935/abc.20170158
https://doi.org/https://doi.org/10.5935/...

Outro potencial efeito colateral está relacionado à absorção de vitaminas e antioxidantes lipossolúveis. Os fitoesteróis podem interferir na absorção de vitaminas lipossolúveis88. Vuorio A, Kovanen PT. Decreasing the cholesterol burden in heterozygous familial hypercholesterolemia children by dietary plant stanol esters. Nutrients. 2018;10:pii:E1842. https://doi.org/10.3390/nu10121842
https://doi.org/https://doi.org/10.3390/...
por reduzirem os níveis de LDL-colesterol, já que este é também transportador dessas vitaminas. Portanto, se os níveis forem reduzidos, haverá menor transporte.77. Malinowski JM, Gehret MM. Phytosterols for dyslipidemia. Am J Health Syst Pharm. 2010;67:1165-73. https://doi.org/10.2146/ajhp090427
https://doi.org/https://doi.org/10.2146/...
Os níveis séricos das vitaminas A, D e K1 em geral não são afetados pelo consumo de fitoesteróis.3535. Cabral CE, Klein MR. Fitoesteróis no tratamento da hipercolesterolemia e prevenção de doenças cardiovasculares. Arq Bras Cardiol. 2017;109:475-82. https://doi.org/10.5935/abc.20170158
https://doi.org/https://doi.org/10.5935/...
Entretanto, alguns dos ensaios clínicos selecionados sugerem que os fitoesteróis possam promover redução na concentração plasmática de carotenoides hidrocarbonados (β-caroteno,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
α-caroteno1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
e licopeno1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
), α-tocoferol1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
e retinol.2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
Outros estudos não observaram tais reduções.1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
Apesar da preocupação de que as vitaminas lipossolúveis sejam reduzidas pelos fitoesteróis, as reduções parecem permanecer dentro da faixa de normalidade, não havendo implicações negativas sobre a saúde.3636. Baumgartner S, Ras RT, Trautwein EA, Mensink RP, Plat J. Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant sterol consumption: a meta-analysis of randomized controlled trials. Eur J Nutr. 2017;56:909-23. https://doi.org/10.1007/s00394-016-1289-7
https://doi.org/https://doi.org/10.1007/...
Assim, de forma a evitar reduções nos níveis séricos de carotenoides durante o consumo de fitoesteróis, o aumento no consumo diário de frutas e hortaliças ricas em carotenoides deve ser considerado.77. Malinowski JM, Gehret MM. Phytosterols for dyslipidemia. Am J Health Syst Pharm. 2010;67:1165-73. https://doi.org/10.2146/ajhp090427
https://doi.org/https://doi.org/10.2146/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,3737. Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, McInerney J. An increase in dietary carotenoids when consuming plant sterols or sterols is effective in maintaining plasma carotenoid concentrations. Am J Clin Nutr. 2002;75:79-86. https://doi.org/10.1093/ajcn/75.1.79
https://doi.org/https://doi.org/10.1093/...

Na faixa etária pediátrica poucos estudos avaliaram o efeito da suplementação de fitoesteróis em relação ao perfil lipídico. Entretanto, os estudos publicados até o presente momento recomendam o uso de fitoesteróis como forma de tratamento somente para crianças com hipercolesterolemia que não conseguiram alcançar níveis desejados de LDL-colesterol após mudanças no estilo de vida.1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1515. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.,1616. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-6. https://doi.org/10.1161/01.atv.20.2.500
https://doi.org/https://doi.org/10.1161/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,1919. Amundsen AL, Ntanios F, Put NV, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004;58:1612-20. https://doi.org/10.1038/sj.ejcn.1602015
https://doi.org/https://doi.org/10.1038/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8.,2222. Guardamagna O, Abello F, Baracco V, Federici G, Bertucci P, Mozzi A, et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 2011;48:127-33. https://doi.org/10.1007/s00592-010-0233-1
https://doi.org/https://doi.org/10.1007/...
,2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
,2525. Ribas SA, Sichieri R, Moreira AS, Souza DO, Cabral CT, Gianinni DT, et al. Phytosterol-enriched milk lowers LDL-cholesterol levels in Brazilian children and adolescents: double-blind, cross-over trial. Nutr Metab Cardiovas. 2017;27:971-7. https://doi.org/10.1016/j.numecd.2017.09.010
https://doi.org/https://doi.org/10.1016/...
Além disso, a abordagem de suplementação com fitoesteróis pode diminuir os níveis de colesterol o suficiente para evitar a necessidade de tratamento medicamentoso.1212. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Loannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100. https://doi.org/10.1371/journal.pmed.1000100
https://doi.org/https://doi.org/10.1371/...

Os ensaios clínicos incluídos nesta revisão apresentaram algumas limitações, embora tenham respondido ao questionamento inicial. Alguns fatores limitantes discutíveis foram o tamanho amostral, o curto período de segmento e as possíveis variáveis de confusão. Além disso, cinco estudos não relataram fontes de financiamento,1414. Becker M, Staab D, von Bergmann K. Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr. 1993;122:292-6. https://doi.org/10.1016/s0022-3476(06)80136-8
https://doi.org/https://doi.org/10.1016/...
,1717. Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr. 2002;76:338-44. https://doi.org/10.1093/ajcn/76.2.338
https://doi.org/https://doi.org/10.1093/...
,1818. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-31. https://doi.org/10.1067/mpd.2003.193
https://doi.org/https://doi.org/10.1067/...
,2020. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495-500. https://doi.org/10.1016/j.jpeds.2005.11.023
https://doi.org/https://doi.org/10.1016/...
,2121. Matsuyama T, Shoji K, Takase H, Kamimaki I, Tanaka Y, Otsuka A, et al. Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children. Asia Pac J Clin Nutr. 2007;16:40-8. e poucos declararam conflito de interesse.2323. Garaiova I, Muchová J, Nagyová Z, Mišľanová C, Oravec S, Dukát A, et al. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr J. 2013;12:7. https://doi.org/10.1186/1475-2891-12-7
https://doi.org/https://doi.org/10.1186/...
,2424. Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, et al. Plant sterols-enriched diet decreases small, dense LDL-cholesyerol levels in children with hypercholesterolemia: a prospective study. Ital J Pediatr. 2014;40:42. https://doi.org/10.1186/1824-7288-40-42
https://doi.org/https://doi.org/10.1186/...
Já esta revisão apresenta limitação quanto ao número de autores incluídos, visto a seleção criteriosa utilizada na escolha dos trabalhos que respondessem à questão principal.

Apesar de sua capacidade limitada de redução da fração do LDL-colesterol, principalmente quando administrada em alimentos enriquecidos, a suplementação de fitoesteróis parece ser de grande auxílio terapêutico para a redução do colesterol em crianças e adolescentes com hipercolesterolemia familiar, de etiologia não determinada ou sem causa genética, a partir de 5 anos de idade, conforme preconizado pela Sociedade Brasileira de Cardiologia.

Vale ressaltar que os fitoesteróis devem ser utilizados como forma de tratamento, e não de prevenção, em crianças/adolescentes com hipercolesterolemia que não conseguiram alcançar níveis desejados de LDL-colesterol após mudanças no estilo de vida. A administração nas refeições (almoço e jantar), por um período de 8 a 12 semanas, parece atingir redução significativa de LDL-colesterol superior a 10%, em conjunto a uma dieta adequada.

Além disso, baseado na ausência de efeitos adversos em ensaios experimentais, seu uso parece ser seguro e de boa tolerância. Ainda são necessários mais estudos que analisem o efeito da suplementação de fitoesteróis em longo prazo para verificar se seu efeito hipocolesterolêmico é mantido após o período de ingestão.

Referências bibliográficas

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    Nogueira-de-Almeida CA, Mello ED, Mello PP, Mello PD, Zorzo RA, Ribas-Filho D. Consenso da Associação Brasileira de Nutrologia sobre manejo da dislipidemia secundária à obesidade infanto-juvenil. Int J Nutrol. 2017;10:161-78. https://doi.org/10.22565/ijn.v10i4.328
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    Sociedade Brasileira de Cardiologia. I Diretriz brasileira de hipercolesterolemia familiar (HF). Arq Bras Cardiol. 2012;99:1-28. https://doi.org/10.5935/abc.20120202
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Financiamento

  • O estudo não recebeu financiamento.

Datas de Publicação

  • Publicação nesta coleção
    11 Nov 2020
  • Data do Fascículo
    2021

Histórico

  • Recebido
    02 Dez 2019
  • Aceito
    16 Fev 2020
  • Publicado
    09 Nov 2020
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