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Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects

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Abstract

Background

The number of hypercholesterolemic individuals who do not meet their cholesterol recommended targets is inappropriately high. The use of plant sterol-enriched foods could help in this clinical setting.

Aim of the study

To evaluate the efficacy and side effects of plant sterol-enriched fermented milk in reducing LDL-cholesterol and increasing the number of patients who attain their therapeutic targets.

Methods

This was a multicentre, randomised, double-blind, placebo-controlled, parallel clinical trial. Eighty-three hypercholesterolemic patients that were not at therapeutic goals were studied. The patients received one 100 ml serving of either plain (control) low-fat or phytosterol enriched (1.6 g of free sterol equivalents) drinkable yogurt per day along with the main meal for 42 days. The principal variables were variation on LDL cholesterol (LDL-C) concentration and the number of patients achieving therapeutic goals after intervention.

Results

Patients on phytosterols attained an average LDL-C reduction of more than 10% (12.2% after 3 weeks; 10.6% after 6 weeks) (P = 0.001; 95% CI: 4.03–19.00) regardless of statin therapy compared to the control group. About 50% of the subjects on phytosterols, as compared to 20% of controls, attained their LDL-C target values (<3.3 or <2.6 mmol/l for primary and secondary prevention, respectively) at the end of the study (P < 0.001). HDL-cholesterol (HDL-C) did not change and triglycerides (TG) were decreased by 14% (P < 0.018). The plasma sterols/total cholesterol ratio increased.

Conclusions

Plant sterol-enriched fermented milk significantly reduced LDL-C and increased the number of moderately hypercholesterolemic patients achieving therapeutic targets.

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References

  1. (2003) (Characteristics of the patients with heart disease in a health area of A Coruna province. Barbanza 2000 study). Rev Clin Esp 203:570–576

  2. (1994) Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389

  3. (2000) (Secondary prevention of ischemic heart disease in the Cuidad Real Province, Spain. Effectiveness of lipid-lowering therapy in primary health care). Med Clin (Barc) 115:321–325

  4. (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421

  5. Algorta Pineda J, Chinchetru Ranedo MJ, Aguirre Anda J, Francisco Terreros S (2005) Hypocholesteremic effectiveness of a yogurt containing plant stanol esters. Rev Clin Esp 205:63–66

    Article  CAS  Google Scholar 

  6. Alvarez-Sala LA, Suarez C, Mantilla T, Franch J, Ruilope LM, Banegas JR, Barrios V (2005) [PREVENCAT study: control of cardiovascular risk in primary care]. Med Clin (Barc) 124:406–410

    Article  Google Scholar 

  7. Assmann G, Cullen P, Erbey J, Ramey DR, Kannenberg F, Schulte H (2006) Plasma sitosterol 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  CAS  Google Scholar 

  8. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278

    Article  CAS  Google Scholar 

  9. Bertran N, Camps J, Fernandez-Ballart J, Murphy MM, Arija V, Ferre N, Tous M, Joven J (2005) Evaluation of a high-sensitivity turbidimetric immunoassay for serum C-reactive protein: application to the study of longitudinal changes throughout normal pregnancy. Clin Chem Lab Med 43:308–313

    Article  CAS  Google Scholar 

  10. Clifton PM, Noakes M, Sullivan D, Erichsen N, Ross D, Annison G, Fassoulakis A, Cehun M, Nestel P (2004) Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur J Clin Nutr 58:503–509

    Article  CAS  Google Scholar 

  11. Davidson MH, Maki KC, Umporowicz DM, Ingram KA, Dicklin MR, Schaefer E, Lane RW, McNamara JR, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC (2001) Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J Am Coll Nutr 20:307–319

    CAS  Google Scholar 

  12. Doornbos AM, Meynen EM, Duchateau GS, van der Knaap HC, Trautwein EA (2006) Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects. Eur J Clin Nutr 60:325–333

    Article  CAS  Google Scholar 

  13. Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, Fiol M, Gomez-Gracia E, Lopez-Sabater MC, Vinyoles E, Aros F, Conde M, Lahoz C, Lapetra J, Saez G, Ros E (2006) Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145:1–11

    Google Scholar 

  14. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  Google Scholar 

  15. Garcia Ruiz FJ, Marin Ibanez A, Perez-Jimenez F, Pinto X, Nocea G, Ahumada C, Alemao E, Yin D (2004) Current lipid management and low cholesterol goal attainment in common daily practice in Spain. The reality study. Pharmacoeconomics 22(Suppl3):1–12

    Google Scholar 

  16. Goldberg AC, Ostlund RE, Jr, Bateman JH, Schimmoeller L, McPherson TB, Spilburg CA (2006) Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol 97:376–379

    Article  CAS  Google Scholar 

  17. Hallikainen MA, Sarkkinen ES, Gylling H, Erkkila AT, Uusitupa MI (2000) Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet. Eur J Clin Nutr 54:715–725

    Article  CAS  Google Scholar 

  18. Hallikainen MA, Sarkkinen ES, Uusitupa MI (1999) Effects of low-fat stanol ester enriched margarines on concentrations of serum carotenoids in subjects with elevated serum cholesterol concentrations. Eur J Clin Nutr 53:966–969

    Article  CAS  Google Scholar 

  19. Hansel B, Nicolle C, Lalanne F, Tondu F, Lassel T, Donazzolo Y, Ferrieres J, Krempf M, Schlienger JL, Verges B, Chapman MJ, Bruckert E (2007) Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia. Am J Clin Nutr 86:790–796

    CAS  Google Scholar 

  20. Jauhiainen T, Salo P, Niittynen L, Poussa T, Korpela R (2006) Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects. Eur J Clin Nutr

  21. Jones PJ, Ntanios FY, Raeini-Sarjaz M, Vanstone CA (1999) Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr 69:1144–1150

    CAS  Google Scholar 

  22. Judd JT, Baer DJ, Chen SC, Clevidence BA, Muesing RA, Kramer M, Meijer GW (2002) Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults. Lipids 37:33–42

    Article  CAS  Google Scholar 

  23. Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R (2003) Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78:965–978

    CAS  Google Scholar 

  24. Korpela R, Tuomilehto J, Hogstrom P, Seppo L, Piironen V, Salo-Vaananen P, Toivo J, Lamberg-Allardt C, Karkkainen M, Outila T, Sundvall J, Vilkkila S, Tikkanen MJ (2006) Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur J Clin Nutr 60:633–642

    Article  CAS  Google Scholar 

  25. Lau VW, Journoud M, Jones PJ (2005) Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Am J Clin Nutr 81:1351–1358

    CAS  Google Scholar 

  26. Law M (2000) Plant sterol and stanol margarines and health. BMJ 320:861–864

    Article  CAS  Google Scholar 

  27. Lichtenstein AH (2002) Plant sterols and blood lipid levels. Curr Opin Clin Nutr Metab Care 5:147–152

    Article  CAS  Google Scholar 

  28. Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MM (2002) Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations. Atherosclerosis 160:205–213

    Article  CAS  Google Scholar 

  29. Moruisi KG, Oosthuizen W, Opperman AM (2006) Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: a systematic review with meta-analysis. J Am Coll Nutr 25:41–48

    CAS  Google Scholar 

  30. Nguyen TT (1999) The cholesterol-lowering action of plant stanol esters. J Nutr 129:2109–2112

    CAS  Google Scholar 

  31. Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, McInerney J (2002) An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am J Clin Nutr 75:79–86

    CAS  Google Scholar 

  32. Noakes M, Clifton PM, Doornbos AM, Trautwein EA (2005) Plant sterol ester-enriched milk and yoghurt effectively reduce serum cholesterol in modestly hypercholesterolemic subjects. Eur J Nutr 44:214–222

    Article  CAS  Google Scholar 

  33. O’Neill FH, Brynes A, Mandeno R, Rendell N, Taylor G, Seed M, Thompson GR (2004) Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism. Nutr Metab Cardiovasc Dis 14:133–142

    Article  CAS  Google Scholar 

  34. Pinedo S, Vissers MN, von Bergmann K, Elharchaoui K, Lutjohann D, Luben R, Wareham NJ, Kastelein JJ, Khaw KT, Boekholdt SM (2007) Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study. J Lipid Res 48:139–144

    Article  CAS  Google Scholar 

  35. Plat J, Mensink RP (2000) Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis 148:101–112

    Article  CAS  Google Scholar 

  36. Plat J, van Onselen EN, van Heugten MM, Mensink RP (2000) Effects on serum lipids, lipoproteins and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters. Eur J Clin Nutr 54:671–677

    Article  CAS  Google Scholar 

  37. Richelle M, Enslen M, Hager C, Groux M, Tavazzi I, Godin JP, Berger A, Metairon S, Quaile S, Piguet-Welsch C, Sagalowicz L, Green H, Fay LB (2004) Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am J Clin Nutr 80:171–177

    CAS  Google Scholar 

  38. Robinson JG, Smith B, Maheshwari N, Schrott H (2005) Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 46:1855–1862

    Article  CAS  Google Scholar 

  39. Seppo L, Jauhiainen T, Nevala R, Poussa T, Korpela R (2007) Plant stanol esters in low-fat milk products lower serum total and LDL cholesterol. Eur J Nutr 46:111–117

    Article  CAS  Google Scholar 

  40. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333:1301–1307

    Article  CAS  Google Scholar 

  41. Sierksma A, Weststrate JA, Meijer GW (1999) Spreads enriched with plant sterols, either esterified 4,4-dimethylsterols or free 4-desmethylsterols, and plasma total- and LDL-cholesterol concentrations. Br J Nutr 82:273–282

    CAS  Google Scholar 

  42. Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, Lipka L, Suresh R, Maccubbin D, Veltri E (2004) Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J 148:447–455

    Article  CAS  Google Scholar 

  43. Thomsen AB, Hansen HB, Christiansen C, Green H, Berger A (2004) Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects. Eur J Clin Nutr 58:860–870

    Article  CAS  Google Scholar 

  44. Van Ganse E, Laforest L, Alemao E, Davies G, Gutkin S, Yin D (2005) Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (Reality) study. Curr Med Res Opin 21:1389–1399

    Article  CAS  Google Scholar 

  45. Vanuzzo D, Pilotto L, Ambrosio GB, Pyorala K, Lehto S, De Bacquer D, De Backer G, Wood D (2000) Potential for cholesterol lowering in secondary prevention of coronary heart disease in europe: findings from EUROASPIRE study. European Action on Secondary Prevention through Intervention to Reduce Events. Atherosclerosis 153:505–517

    Article  CAS  Google Scholar 

  46. Volpe R, Niittynen L, Korpela R, Sirtori C, Bucci A, Fraone N, Pazzucconi F (2001) Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia. Br J Nutr 86:233–239

    Article  CAS  Google Scholar 

  47. Wilson PW, Castelli WP, Kannel WB (1987) Coronary risk prediction in adults (the Framingham Heart Study). Am J Cardiol 59:91G–94G

    Article  CAS  Google Scholar 

  48. 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 24:2326–2332

    Article  CAS  Google Scholar 

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Acknowledgments

This study has been performed as part of the ISCIII (Ministry of Health) research network on Diabetes and Metabolism (REDIMET-RD06). Funding was provided by Danone Research. We thank Pascale Rondeau (Danone Research) for her help on the statistical analysis and to Pr Philippe Gambert and his team (CHU Le Bocage—Dijon, France) for his collaboration and the determination of phytosterol plasma levels. We are very grateful to the volunteers involved in this study. We kindly thanks Danone Spain, Jose Antonio Mateos Guardia and Jose Maria Cobo Sanz, for their support.

*The Danacol group: All these contributed to patient recruitment and clinical and dietary control: Hospital Sant Joan: Lluis Masana, Nuria Plana, Raimón Ferré, Rosa Cos, Nuria Guillen, Isabel Mejias, Gemma Godas, Lluís Colomés. CAP Cambrils: Elisabet Téllez, Yolanda Quilez, Mireia Barberá, Montserrat López, Josep Solé, Pilar Gil, Dolors Simón. CAP Hospitalet de l’Infant: Margarita Esquius, Teresa Espejo, Jaime Magre, Cora Jiménez, Montserrat Llort. CAP Reus V: Josepa Mendoza, Esperanza Vallejo, Elisabet Chacón, Angel Lluís Carrillo.CAP La Selva: Julia Valero, Mª Mercé Cots, Mª José Rabadà, Teresa Roca, Mª Carmen Zafra, Francisca Celma, Emilio Abalat. CAP Riudoms: Angel Aguiló, Rafael Carrascosa, Adela Nolla, Yolanda Herranz, Josep Mª Masdeu, Montserrat Salvadó, Mercé Colomer, Dolores Arellano, Marta Ruiz de Velasco. CAP Alcover: Xavier Luque, Ángels Vazquez.

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Authors and Affiliations

  1. Unitat Recerca Lipids and Arteriosclerosi, Hospital Universitari Sant Joan, Universitat Rovira and Virgili, Sant Llorenç, 43201, Reus (Tarragona), Spain

    Nuria Plana, Raimon Ferre, Rosa Cos &  Luis Masana

  2. Danone Research Center, Palaiseau, Paris, France

    Catherine Nicolle

  3. Centre de Recerca Biomèdica, Hospital Universitari Sant Joan, Universitat Rovira and Virgili, Reus, Spain

    Jordi Camps

  4. Medicest, Madrid, Spain

    Jesus Villoria

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  1. Nuria Plana
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  2. Catherine Nicolle
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  3. Raimon Ferre
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  7. Luis Masana
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on behalf of the DANACOL group*

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Correspondence to Luis Masana.

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Plana, N., Nicolle, C., Ferre, R. et al. Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects. Eur J Nutr 47, 32–39 (2008). https://doi.org/10.1007/s00394-007-0693-4

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  • DOI: https://doi.org/10.1007/s00394-007-0693-4

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