Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review

Mantovani, Luisa Montone; Pugliese, Camila

doi:10.1590/1984-0462/2021/39/2019389

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Brasil

Revista Paulista de Pediatria

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Brasil

Español English

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REVIEW ARTICLE • Rev. paul. pediatr. 39 • 2021 • https://doi.org/10.1590/1984-0462/2021/39/2019389 copy

Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

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

Author(s), year	Design	Methods		Conclusion
Author(s), year	Design	Type of dyslipidemia	Patients	Conclusion
Becker et al., 1993¹⁴14. 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/...	Clinical trial	FH	n=9 (9-14 years old)	Sitostanol supplementation, even in doses inferior to sitosterol, was significantly more effective in the reduction of LDL-c, and its use can be indicated for the treatment of FH in children.
Gylling et al., 1995¹⁵15. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.	Double-blind randomized clinical trial	FH	n=15 (2-15 years old)	In a balanced diet, the use of sitostanol-ester margarine seems to be effective and safe for the treatment of hypercholesterolemia in children with FH.
Vuorio et al., 2000¹⁶16. 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/...	Clinical trial	FH	n=24 (3-13 years old)	The use of stanol-ester margarine has proven to be effective and safe for lipid lowering treatment in children.
Amundsen et al., 2002¹⁷17. 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/...	Double-blind randomized crossover clinical trial	FH	n=38 (7-12 years old)	In a balanced diet, sterol supplementation induces the reduction of LDL-c, without adverse effects, in children with FH.
Ketomãki et al., 2003¹⁸18. 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/...	Double-blind randomized crossover clinical trial	FH (n=17) Hypercholesterolemia** (n=6)	n=23 (2-9 years old)	Stanol and sterol esters reduce the concentrations of cholesterol in the plasma.
Amundsen et al., 2004¹⁹19. 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/...	Double-blind randomized controlled crossover clinical trial	FH	n=37 (7-13 years old)	Sterol supplementation such as spread is efficient to reduce cholesterol in children with FH in a controlled diet, and such a reduction is maintained for six posterior months.
Jakulj et al., 2006²⁰20. 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/...	Double-blind randomized placebo-controlled clinical trial	FH	n=41 (7-12 years old)	The intake of stanols can be a beneficial and safe strategy, well accepted for the reduction of LDL-c levels in children with FH.
Matsuyama et al., 2007²¹21. 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.	Clinical trial	Hyperlipidemia Type IIa (n=7) Hyperlipidemia* (n=8) FH (n=7)	n=22 (6-17 years old)	Phytosterols are able to reduce cholesterol in children with hyperlipidemia.
Guardamagna et al., 2011²²22. 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/...	Clinical trial	Heterozigous FH (n=29) Combined FH (n=11) Hypercholesterolemia* (n=12)	n=52 (8-16 years old)	The daily consumption of sterol produces favorable changes in lipid profile, reducing LDL-c.
Garaiova et al., 2013²³23. 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/...	Clinical trial	Hyperlipidemia*	n=25 (11-17 years old)	The combined emulsion of sterol plants, fish oil and vitamin B can modulate the lipid profile in children and adolescents with hypercholesterolemia.
Garoufi et al., 2014²⁴24. 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/...	Clinical trial	Hypercholesterolemia*	n=59 (4.5-15.9 years old)	Sterol supplementation can be beneficial for the treatment of hypercholesterolemia in children; not only regarding LDL-c levels, but also more atherogenic particles.
Ribas et al., 2017²⁵25. 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/...	Double-blind randomized clinical trial	Hypercholesterolemia **	n=25 (6-19 years old)	Plant sterol supplementation is effective and safe for the treatment of dyslipidemia in children.

Author(s), year	Type of phytosterol	Dose (g/day)	Duration (in weeks)	Vehicle	↓LDL-c (%)	*p-value (versus* control group)**	↓TC (%)	*p-value (versus* control group)**
Becker et al., 1993¹⁴14. 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/...	Sterols Stanols	6 1.5	12 12 and 28	Tablets	19.5 33.2 and 29.2	<0.01	17.1 25.7 and 23.5	<0.01
Gylling et al., 1995¹⁵15. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-12.	Stanols	3	6	Margarine	15	<0,.01	10.6	<0.01
Vuorio et al., 2000¹⁶16. 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/...	Stanols	2.24	12	Margarine	17.9	<0.001	13.6	<0.001
Amundsen et al., 2002¹⁷17. 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/...	Sterols	1.6	8	Spread*	10.2	<0.01	7.4	<0.01
Ketomãki et al., 2003¹⁸18. 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/...	Sterols Stanols	2	5	Spread*	9 12	<0.001	6 9	<0.01
Amundsen et al., 2004¹⁹19. 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/...	Sterols	1.2	8	Spread*	11.4	<0.001	9.1	<0.001
Jakulj et al., 2006²⁰20. 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/...	Stanols	2	4	Skimmed yogurt	9.2	<0.001	7.5	<0.001
Matsuyama et al., 2007²¹21. 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.	Sterols	0.4	16	Bread	All: 6.3 FH: 11.2	<0.05	All: 2.2 FH: 6	All: NS FH: <0.05
Guardamagna et al., 2011²²22. 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/...	Sterols	1.6 to 2	12	Skimed yogurt	FH: 12.4 UDH: 16	<0.05	FH: 10.2 UDH: 13	<0.05
Garaiova et al., 2013²³23. 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/...	Sterols	1.3	16	Emulsion	8.4	<0.05	7.7	<0.05
Garoufi et al., 2014²⁴24. 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/...	Sterols	2	48	Skimmed yogurt	13	<0.001	9.4	<0.001
Ribas et al., 2017²⁵25. 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/...	Sterols	1.2	8	Skimmed milk	10.2	<0.01	5.9	NS

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[1] *Corresponding author. E-mail: luisa.mmantovani@gmail.com (L.M. Mantovani).