Skip to main content

Advertisement

Log in

Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Plant sterols lower serum cholesterol concentration. Available data have confirmed the lipid-lowering efficacy in adults, while there is a relative dearth of data in children and almost exclusively restricted to subjects with familial hypercholesterolemia (FH). Aim of the present study was to evaluate the efficacy, tolerability and safety of plant sterol supplementation in children with different forms of primary hyperlipidemias. The effect of plant sterol consumption on plasma lipids was evaluated in 32 children with heterozygous FH, 13 children with Familial Combined Hyperlipidemia (FCH) and 13 children with Undefined Hypercholesterolemia (UH) in a 12-week open-label intervention study using plant sterol–enriched yoghurt. Plasma lipids and apolipoproteins were measured by routine methods. Markers of cholesterol synthesis (lathosterol) and absorption (campesterol and sitosterol) were measured by GC–MS. Tolerability and adherence to recommended regimen was very high. A significant reduction was observed in LDL-cholesterol in the three groups (10.7, 14.2 and 16.0% in FH, FCH and UH, respectively). Lathosterol concentrations were unchanged, reflecting a lack of increased synthesis of cholesterol. Of the two absorption markers, only sitosterol showed a slight but significant increase. Daily consumption of plant sterol dairy products favorably changes lipid profile by reducing LDL-cholesterol. To our knowledge, this is the first report of the use of plant sterols–enriched foods in treating children with primary hyperlipidemia such as FCH and UH, likely to be the most frequent form also in the young age in the western populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pontiroli AE (2004) Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. Acta Diabetol 41:85–90

    Article  PubMed  CAS  Google Scholar 

  2. Berenson GS, Srinivasan SR, Bao W, Newman WP III, Tracy RE, Wattigney WA, For the Bogalusa heart study (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med 338:1650–1656

    Article  PubMed  CAS  Google Scholar 

  3. Third report of the national cholesterol education program (NCEP) (2002) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) Final report. Circulation 106:3143–3421

    Google Scholar 

  4. American academy of pediatrics (1998) Committee on nutrition. Cholesterol in childhood. Pediatrics 101:141–147

    Google Scholar 

  5. Taskinen MR (2002) Controlling lipid levels in diabetes. Acta Diabetol 39(2):S29–S34

    Article  PubMed  Google Scholar 

  6. Daniels SR, Greer FR, The Committee on Nutrition (2008) Lipid screening and cardiovascular health in childhood. Pediatrics 122:198–208

    Article  PubMed  Google Scholar 

  7. Grundy SM, Ahrens EH Jr, Davignon J (1969) The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res 10:304–315

    PubMed  CAS  Google Scholar 

  8. Heinemann T, Kullak-Ublick GA, Pietruck B, von Bergmann K (1991) Mechanisms of action of plant sterols on inhibition of cholesterol absorption: comparison of sitosterol and sitostanol. Eur J Clin Pharmacol 40(1):S59–S63

    Article  PubMed  CAS  Google Scholar 

  9. Nissinen M, Gylling H, Vuoristo M, Miettinen TA (2002) Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol 282:G1009–G1015

    PubMed  CAS  Google Scholar 

  10. Tammi A, Rönnemaa T, Gylling H, Rask-Nissilä L, Viikari J, Tuominen J et al (2000) Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. J Pediatr 136:503–510

    Article  PubMed  CAS  Google Scholar 

  11. Berge KE, von Bergmann K, Lutjohann D, Guerra R, Grundy SM, Hobbs HH et al (2002) Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res 43:486–494

    PubMed  CAS  Google Scholar 

  12. Gylling H, Miettinen TA (2002) Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption. J Lipid Res 43:1472–1476

    Article  PubMed  CAS  Google Scholar 

  13. Stone NJ, Van Horn L (2002) Therapeutic lifestyle change and Adult Treatment Panel III: evidence then and now. Curr Atheroscler Rep 4:433–443

    Article  PubMed  Google Scholar 

  14. Ketomäki AM, Gylling H, Antikainen M, Siimes MA, Miettinen TA (2003) Red cell and plasma plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr 142:524–531

    Article  PubMed  Google Scholar 

  15. Nicholls DP, Cather M, Byrne C, Graham CA, Young IS (2008) Diagnosis of heterozygous familial hypercholesterolemia in children. Int J Clin Pract 62:990–994

    Article  PubMed  CAS  Google Scholar 

  16. Veerkamp MJ, de Graaf J, Bredie SJH, Hendriks JCM, Demacker PNM, Stalenhoef AFH (2002) Diagnosis of combined familial hyperlipidemia based on lipid phenotype expression in 32 families. Results of a 5-year follow-up study. Arterioscler Thromb Vasc Biol 22:274–282

    Article  PubMed  CAS  Google Scholar 

  17. Ahmida HSM, Bertucci P, Franzò L, Massoud R, Cortese C, Lala A et al (2006) Simultaneous determination of plasmatic phytosterols and cholesterol precursors using gas cromatography-mass spectrometry (GS-MS) with selective ion monitoring (SIM). J Chromatogr B Analyt Technol Biomed Life Sci 842:43–47

    Article  PubMed  CAS  Google Scholar 

  18. Peterson DW (1951) Effect of soybean sterols in the diet on plasma and liver cholesterol in chicks. Proc Soc Exp Biol Med 78:143–147

    PubMed  CAS  Google Scholar 

  19. Thompson G, Grundy MS (2005) History and development of plant sterols and stanol esters for cholesterol lowering purposes. Am J Cardiol 96(1):3D–9D

    Article  PubMed  CAS  Google Scholar 

  20. Brynes AE, Thomson GR (2003) Functional foods in lipid-lowering and coronary prevention. In: Gaw A, Shepherd J (eds) Lipids and Atherosclerosis Annual. Martin Dunitz, London, pp 119–138

    Google Scholar 

  21. Hedman M, Miettinen TA, Gylling H, Ketomaki A, Antikainen M (2006) Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy. J Pediatr 148:241–246

    Article  PubMed  CAS  Google Scholar 

  22. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJP (2006) Plant stanols do not restore endothelial function in prepubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr 148:495–500

    Article  PubMed  CAS  Google Scholar 

  23. Ketomaki A, Gylling H, Siimes NA, Vuorio A, Miettinen TA (2003) Squalene and non cholesterol sterols in serum and lipoproteins of children with and without familial hypercholesterolemia. Pediatr Res 53:648–653

    Article  PubMed  Google Scholar 

  24. García-Otín AL, Cofán M, Junyent M, Recalde D, Cenarro A, Pocoví M, Ros E, Civeira F (2007) Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes. J Clin Endocrinol Metab 92(9):3667–3673

    Article  PubMed  Google Scholar 

  25. Inazu A, Koizumi J, Mabuchi H, Kajinami K, Takeda R (1992) Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia. Horm Metab Res 24:284–288

    Article  PubMed  CAS  Google Scholar 

  26. Weingartner O, Bohm M, Laufs U (2009) Controversial role of plant sterol ester in the management of hypercholesterolemia. Eur Heart J 30:404–409

    Article  PubMed  Google Scholar 

  27. Mannucci L, Guardamagna O, Bertucci P, Pisciotta L, Liberatoscioli L, Bertolini S, Irace C, Gnasso A, Federici G, Cortese C (2007) Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene. Eur J Clin Invest 37(12):997–1000

    Article  PubMed  CAS  Google Scholar 

  28. Glueck CJ, Speirs J, Tracy T, Streicher P, Illig E, Vandegrift J (1991) Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 40:842–848

    Article  PubMed  CAS  Google Scholar 

  29. Assmann G, Cullen P, Erbey J, Ramey DR, Kannenberg F, Schulte H (2006) Plasma sistosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the prospective cardiovascular munster (PROCAM) study. Nutr Metab Cardiovasc Dis 16:13–21

    Article  PubMed  CAS  Google Scholar 

  30. Thiery J, Ceglarek U, Fiedler GM, Leichtle A, Baumann S, Teupser D, Lang O, Baumert J, Meisinger M, Loewell H, Doering A (2006) Elevated campesterol serum levels—a significant predictor of incident myocardial infarction: results of the population-based MONICA/KORA follow-up study 1994–2005. Circulation 114:II_884

    Google Scholar 

  31. Wilund KR, Yu L, Xu F, Vega GL, Grundy SM, Cohen JC, Hobbs HH (2004) No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 24(12):2326–2332

    Article  PubMed  CAS  Google Scholar 

  32. Fassbender K, Lütjohann D, Dik MG, Bremmer M, König J, Walter S, Liu Y, Letièmbre M, von Bergmann K, Jonker C (2008) Moderately elevated plant sterol levels are associated with reduced cardiovascular risk–the LASA study. Atherosclerosis 196(1):283–288

    Article  PubMed  CAS  Google Scholar 

  33. Saleheen D, Soranzo N, Rasheed A et al (2010) Genetic determinants of major blood lipids in Pakistanis compared with Europeans. Circ Cardiovasc Genet 3:348–357

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This investigation was partly supported by COFIN_MIUR 2008 and by Turin University funds.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Gnasso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guardamagna, O., Abello, F., Baracco, V. et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol 48, 127–133 (2011). https://doi.org/10.1007/s00592-010-0233-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-010-0233-1

Keywords

Navigation