Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects

R T Ras, D Fuchs, W P Koppenol, C G Schalkwijk, A Otten-Hofman, U Garczarek, A Greyling, F Wagner, E A Trautwein, R T Ras, D Fuchs, W P Koppenol, C G Schalkwijk, A Otten-Hofman, U Garczarek, A Greyling, F Wagner, E A Trautwein

Abstract

Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the effect of regular intake of PS on biomarkers of endothelial dysfunction and low-grade inflammation. In a double-blind, randomised, placebo-controlled, parallel-group study, which was primarily designed to investigate the effect of PS intake on vascular function (clinicaltrials.gov: NCT01803178), 240 hypercholesterolaemic but otherwise healthy men and women consumed a low-fat spread with added PS (3 g/d) or a placebo spread for 12 weeks. Endothelial dysfunction biomarkers (both vascular and intracellular adhesion molecules 1 and soluble endothelial-selectin) and low-grade inflammation biomarkers (C-reactive protein, serum amyloid A, IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1) were measured using a multi-array detection system based on electrochemiluminescence technology. Biomarkers were combined using z-scores. Differences in changes from baseline between the PS and the placebo groups were assessed. The intake of PS did not significantly change the individual biomarkers of endothelial dysfunction and low-grade inflammation. The z-scores for endothelial dysfunction (-0·02; 95 % CI -0·15, 0·11) and low-grade inflammation (-0·04; 95 % CI -0·16, 0·07) were also not significantly changed after PS intake compared with placebo. In conclusion, biomarkers of endothelial dysfunction and low-grade inflammation were not affected by regular intake of 3 g/d PS for 12 weeks in hypercholesterolaemic men and women.

Keywords: CRP, C-reactive protein; Dietary interventions; Endothelial dysfunction; FMD, flow-mediated dilation; Low-grade inflammation; PS, plant sterols; Plant sterols; sE-selectin, soluble endothelial-selectin; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular cell adhesion molecule-1.

References

    1. Katan MB, Grundy SM, Jones P, et al. (2003) Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clinic Proc 78, 965–978.
    1. Ras RT, Geleijnse JM & Trautwein EA (2014) LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr 112, 214–219.
    1. Baigent C, Keech A, Kearney PM, et al. (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.
    1. Gylling H, Plat J, Turley S, et al. (2014) Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis 232, 346–360.
    1. Widlansky ME, Gokce N, Keaney JF, et al. (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42, 1149–1160.
    1. Daiber A, Steven S, Weber A, et al. (2016) Targeting vascular (endothelial) dysfunction. Br J Pharmacol (epublication ahead of print version 17 May 2016).
    1. Vogel RA (1999) Cholesterol lowering and endothelial function. Am J Med 107, 479–487.
    1. Bonetti PO, Lerman LO & Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23, 168–175.
    1. Ras RT, Streppel MT, Draijer R, et al. (2013) Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol 168, 344–351.
    1. Ras RT, Fuchs D, Koppenol WP, et al. (2015) The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study. Am J Clin Nutr 101, 733–741.
    1. de Jongh S, Vissers MN, Rol P, et al. (2003) Plant sterols lower LDL cholesterol without improving endothelial function in prepubertal children with familial hypercholesterolaemia. J Inherited Metab Dis 26, 343–352.
    1. Hallikainen M, Lyyra-Laitinen T, Laitinen T, et al. (2006) Endothelial function in hypercholesterolemic subjects: effects of plant stanol and sterol esters. Atherosclerosis 188, 425–432.
    1. Gylling H, Hallikainen M, Raitakari OT, et al. (2009) Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation. Br J Nutr 101, 1688–1695.
    1. Plat J, Mackay D, Baumgartner S, et al. (2012) Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting. Atherosclerosis 225, 521–533.
    1. Becker A, van Hinsbergh VW, Jager A, et al. (2002) Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality? Eur J Clin Invest 32, 1–8.
    1. de Jong A, Plat J, Bast A, et al. (2008) Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment. Eur J Clin Nutr 62, 263–273.
    1. Plat J, Brufau G, Dallinga-Thie GM, et al. (2009) A plant stanol yogurt drink alone or combined with a low-dose statin lowers serum triacylglycerol and non-HDL cholesterol in metabolic syndrome patients. J Nutr 139, 1143–1149.
    1. Gagliardi A, Maranhao R, de Sousa H, et al. (2010) Effects of margarines and butter consumption on lipid profiles, inflammation markers and lipid transfer to HDL particles in free-living subjects with the metabolic syndrome. Eur J Clin Nutr 64, 1141–1149.
    1. Steven S, Munzel T & Daiber A (2015) Exploiting the pleiotropic antioxidant effects of established drugs in cardiovascular disease. Int J Mol Sci 16, 18185–18223.
    1. Karbach S, Wenzel P, Waisman A, et al. (2014) eNOS uncoupling in cardiovascular diseases – the role of oxidative stress and inflammation. Curr Pharm Des 20, 3579–3594.
    1. Hansson GK, Libby P & Tabas I (2015) Inflammation and plaque vulnerability. J Intern Med 278, 483–493.
    1. Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340, 115–126.
    1. Devaraj S, Jialal I, Rockwood J, et al. (2011) Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity. Clin Nutr 30, 668–671.
    1. Rocha VZ, Ras RT, Gagliardi AC, et al. (2016) Effects of phytosterols on markers of inflammation: a systematic review and meta-analysis. Atherosclerosis 248, 76–83.
    1. Ras RT, Koppenol WP, Garczarek U, et al. (2016) Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism. Nutr Metab Cardiovasc Dis 26, 302–309.
    1. van Bussel BC, Schouten F, Henry RM, et al. (2011) Endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness over a 6-year period. Hypertension 58, 588–595.
    1. van Bussel BC, Ferreira I, van de Waarenburg MP, et al. (2013) Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform. PLOS ONE 8, e58576.
    1. Landmesser U, Hornig B & Drexler H (2000) Endothelial dysfunction in hypercholesterolemia: mechanisms, pathophysiological importance, and therapeutic interventions. Semin Thromb Hemost 26, 529–537.
    1. Heggen E, Kirkhus B, Pedersen JI, et al. (2015) Effects of margarine enriched with plant sterol esters from rapeseed and tall oils on markers of endothelial function, inflammation and hemostasis. Scand J Clin Lab Invest 75, 189–192.
    1. Devaraj S, Autret BC & Jialal I (2006) Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am J Clin Nutr 84, 756–761.
    1. Athyros VG, Kakafika AI, Papageorgiou AA, et al. (2011) Effect of a plant stanol ester-containing spread, placebo spread, or Mediterranean diet on estimated cardiovascular risk and lipid, inflammatory and haemostatic factors. Nutr Metab Cardiovasc Dis 21, 213–221.
    1. Cater NB, Garcia-Garcia AB, Vega GL, et al. (2005) Responsiveness of plasma lipids and lipoproteins to plant stanol esters. Am J Cardiol 96, 23D–28D.
    1. Houweling AH, Vanstone CA, Trautwein EA, et al. (2009) Baseline plasma plant sterol concentrations do not predict changes in serum lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a plant sterol-enriched food. Eur J Clin Nutr 63, 543–551.
    1. Liao JK & Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45, 89–118.
    1. Weingartner O, Lutjohann D, Ji S, et al. (2008) Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 51, 1553–1561.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere