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Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

Abstract

Background/Objectives:

To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking.

Subjects/Methods:

A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Subjects were provided (i) control margarine with each meal; (ii) 1.8 g/day plant sterols in margarine with breakfast (single-BF) and control margarine with lunch and supper or (iii) 1.8 g/day plant sterols in margarine divided equally at each of the three daily meals (three times per day).

Results:

Relative to control, end point plasma low-density lipoprotein (LDL) cholesterol concentrations were lower (P<0.05) after consuming plant sterols three times per day but were not different when consumed once per day (3.43±0.62, 3.22±0.58 and 3.30±0.65 mmol/l, control, three times per day and single-BF, respectively). Relative to the control, end point LDL level was 0.21±0.27 mmol/l (6%) lower (P<0.05) at the end of the three times per day phase. Cholesterol fractional synthesis rate was highest (P<0.05) after the three times per day phase (0.0827±0.0278, 0.0834±0.0245 and 0.0913±0.0221 pool/day, control, single-BF and three times per day, respectively). Cholesterol-absorption efficiency decreased (P<0.05) by 36 and 39% after the three times per day and single-BF phase, respectively, relative to control.

Conclusions:

Present data indicate that to obtain optimal cholesterol-lowering impact, plant sterols should be consumed as smaller doses given more often, rather than one large dose.

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References

  • AbuMweis SS, Vanstone CA, Ebine N, Kassis A, Ausman LM, Jones PJH et al. (2006). Intake of a single morning dose of standard and novel plant sterol preparations for 4 weeks does not dramatically affect plasma lipid concentrations in humans. J Nutr 136, 1012–1016.

    Article  CAS  PubMed  Google Scholar 

  • Beaumier-Gallon G, Dubois C, Senft M, Vergnes MF, Pauli AM, Portugal H et al. (2001). Dietary cholesterol is secreted in intestinally derived chylomicrons during several subsequent postprandial phases in healthy humans. Am J Clin Nutr 73, 870–877.

    Article  CAS  PubMed  Google Scholar 

  • Becker M, Staab D, Vonbergmann K (1992). Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate. Pediatrics 89, 138–142.

    CAS  PubMed  Google Scholar 

  • Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB (2000). Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 86, 46–52.

    Article  CAS  PubMed  Google Scholar 

  • Bosner MS, Ostlund RE, Osofisan O, Grosklos J, Fritschle C, Lange LG (1993). Assessment of percent cholesterol absorption in humans with stable isotopes. J Lipid Res 34, 1047–1053.

    CAS  PubMed  Google Scholar 

  • Cleeman JI, Grundy SM, Becker D, Clark LT, Cooper RS, Denke MA et al. (2001). Executive summary of the 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). JAMA 285, 2486–2497.

    Article  Google Scholar 

  • Colgan HA, Floyd S, Noone EJ, Gibney MJ, Roche HM (2004). Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism. J Hum Nutr Diet 17, 561–569.

    Article  CAS  PubMed  Google Scholar 

  • Di Buono M, Jones PJH, Beaumier L, Wykes LJ (2000). Comparison of deuterium incorporation and mass isotopomer distribution analysis for measurement of human cholesterol biosynthesis. J Lipid Res 41, 1516–1523.

    CAS  PubMed  Google Scholar 

  • Doornbos AME, Meynen EM, Duchateau G, van der Knaap HCM, 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  PubMed  Google Scholar 

  • Fletcher B, Berra K, Ades P, Braun LT, Burke LE, Durstine JL et al. (2005). Managing abnormal blood lipids—A collaborative approach. Circulation 112, 3184–3209.

    Article  PubMed  Google Scholar 

  • Folch J, Lees M, Stanley GHS (1957). A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226, 497–509.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Gylling H, Miettinen TA (1994). Serum-cholesterol and cholesterol and cipoprotein metabolism in hypercholesterolemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia 37, 773–780.

    Article  CAS  PubMed  Google Scholar 

  • Gylling H, Radhakrishnan R, Miettinen TA (1997). Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine—women and dietary sitostanol. Circulation 96, 4226–4231.

    Article  CAS  PubMed  Google Scholar 

  • Hallikainen M, Sarkkinen E, Wester I, Uusitupa M (2002). Short-term LDL cholesterol-lowering efficacy of plant stanol esters. BMC Cardiovascular Disordorders 2, 14.

    Article  Google Scholar 

  • Hallikainen MA, Sarkkinen ES, Gylling H, Erkkila AT, Uusitupa MIJ (2000a). 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  PubMed  Google Scholar 

  • Hallikainen MA, Sarkkinen ES, Uusitupa MIJ (2000b). Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutr 130, 767–776.

    Article  CAS  PubMed  Google Scholar 

  • Hendriks HFJ, Brink EJ, Meijer GW, Princen HMG, Ntanios FY (2003). Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr 57, 681–692.

    Article  CAS  PubMed  Google Scholar 

  • Hendriks HFJ, Weststrate JA, van Vliet T, Meijer GW (1999). Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 53, 319–327.

    Article  CAS  PubMed  Google Scholar 

  • Jakulj L, Trip MD, Sudhop T, von Bergmann K, Kastelein JJP, Vissers MN (2005). Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J Lipid Res 46, 2692–2698.

    Article  CAS  PubMed  Google Scholar 

  • Jones PJ, Raeini-Sarjaz M, Ntanios FY, Vanstone CA, Feng JY, Parsons WE (2000). Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J Lipid Res 41, 697–705.

    CAS  PubMed  Google Scholar 

  • Jones PJH, Ausman LM, Croll DH, Feng JY, Schaefer EA, Lichtenstein AH (1998a). Validation of deuterium incorporation against sterol balance for measurement of human cholesterol biosynthesis. J Lipid Res 39, 1111–1117.

    CAS  PubMed  Google Scholar 

  • Jones PJH, Howell T, MacDougall DE, Feng JY, Parsons W (1998b). Short-term administration of tall oil phytosterols improves plasma lipid profiles in subjects with different cholesterol levels. Metab-Clin Exp 47, 751–756.

    Article  CAS  PubMed  Google Scholar 

  • Jones PJH, Leitch CA, Li ZC, Connor WE (1993). Human cholesterol-synthesis measurement using deuterated water—theoretical and procedural considerations. Arterioscler Thromb 13, 247–253.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Kesaniemi YA, Ehnholm C, Miettinen TA (1987). Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J Clin Invest 80, 578–581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kratz M, Kannenberg F, Gramenz E, Berning B, Trautwein E, Assmann G et al. (2007). Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols. Eur J Clin Nutr 61, 896–905.

    Article  CAS  PubMed  Google Scholar 

  • Lichtenstein AH, Matthan NR, Jalbert SM, Resteghini NA, Schaefer EJ, Ausman LM (2006). Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects. Am J Clin Nutr 84, 497–504.

    Article  CAS  PubMed  Google Scholar 

  • Maki KC, Davidson MH, Umporowicz DM, Schaefer EJ, Dicklin MR, Ingram KA et al. (2001). Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am J Clin Nutr 74, 33–43.

    Article  CAS  PubMed  Google Scholar 

  • Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MMA (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  PubMed  Google Scholar 

  • Miettinen TA, Vanhanen H (1994). Dietary sitostanol related to absorption, synthesis and serum Level of cholesterol in different apolipoprotein-E phenotypes. Atherosclerosis 105, 217–226.

    Article  CAS  PubMed  Google Scholar 

  • Miettinen TA, Vuoristo M, Nissinen M, Jarvinen HJ, Gylling H (2000). Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am J Clin Nutr 71, 1095–1102.

    Article  CAS  PubMed  Google Scholar 

  • Muldoon MF, Manuck SB, Matthews KA (1990). Lowering cholesterol concentrations and mortality—a quantitative review of primary prevention trials. BMJ 301, 309–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ntanios F (2001). Plant sterol-ester-enriched spreads as an example of a new functional food. Eur J Lipid Sci Technol 103, 102–106.

    Article  CAS  Google Scholar 

  • Ostlund RE, Racette SB, Okeke A, Stenson WF (2002). Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr 75, 1000–1004.

    Article  CAS  PubMed  Google Scholar 

  • Ostlund RE, Spilburg CA, Stenson WF (1999). Sitostanol administered in lecithin micelles potently reduces cholesterol absorption in humans. Am J Clin Nutr 70, 826–831.

    Article  CAS  PubMed  Google Scholar 

  • Plat J, Bragt MCE, Mensink RP (2005). Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers. J Lipid Res 46, 68–75.

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Plat J, Mensink RP (2002). Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption. Eur J Clin Invest 32, 242–250.

    Article  CAS  PubMed  Google Scholar 

  • Plat J, van Onselen ENM, van Heugten MMA, 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  PubMed  Google Scholar 

  • Shin MJ, Lee JH, Jang Y, Lee-Kim YC, Park E, Kim KM et al. (2005). Micellar phytosterols effectively reduce cholesterol absorption at low doses. Ann Nutr Metab 49, 346–351.

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Spilburg CA, Goldberg AC, McGill JB, Stenson WF, Racette SB, Bateman J et al. (2003). Fat-free foods supplemented with soy stanol-lecithin powder reduce cholesterol absorption and LDL cholesterol. J Am Diet Assoc 103, 577–581.

    Article  PubMed  Google Scholar 

  • Vanhanen HT, Blomqvist S, Ehnholm C, Hyvonen M, Jauhiainen M, Torstila I et al. (1993). Serum-cholesterol, cholesterol precursors, and plant sterols in hypercholesterolemic subjects with different apoe phenotypes during dietary Sitostanol ester treatment. J Lipid Res 34, 1535–1544.

    CAS  PubMed  Google Scholar 

  • Vanstone CA, Raeini-Sarjaz M, Parsons WE, Jones PJ (2002). Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am J Clin Nutr 76, 1272–1278.

    Article  CAS  PubMed  Google Scholar 

  • Varady KA, Jones PJH (2006). Decrease in intestinal cholesterol absorption by plant sterols and exercise improves lipid profiles in hypercholesterolemic adults. FASEB J 20, A1025.

    Google Scholar 

  • Vorlat A, Conraads VM, Vrints CJ (2003). Regular use of margarine-containing stanol/sterol esters reduces total and low-density lipoprotein (LDL) cholesterol and allows reduction of statin therapy after cardiac transplantation: preliminary observations. J Heart Lung Transplant 22, 1059–1062.

    Article  PubMed  Google Scholar 

  • Wang YW, Vanstone CA, Parsons WD, Jones PJH (2004). Validation of a single-isotope-labeled cholesterol tracer approach for measuring human cholesterol absorption. Lipids 39, 87–91.

    Article  CAS  PubMed  Google Scholar 

  • Weststrate JA, Meijer GW (1998). Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 52, 334–343.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We wish to thank Unilever Research for providing the sterol-enriched and control margarines in-kind. We also thank the study subjects for their enthusiastic participation.

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Correspondence to P J H Jones.

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AbuMweis, S., Vanstone, C., Lichtenstein, A. et al. Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans. Eur J Clin Nutr 63, 747–755 (2009). https://doi.org/10.1038/ejcn.2008.36

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