Skip to main content

Advertisement

SpringerLink
Log in

Milk phospholipid and plant sterol-dependent modulation of plasma lipids in healthy volunteers

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Hypolipidemic and/or hypocholesterolemic effects are presumed for dietary milk phospholipid (PL) as well as plant sterol (PSt) supplementation. The aim was to induce changes in plasma lipid profile by giving different doses of milk PL and a combination of milk PL with PSt to healthy volunteers.

Methods

In an open-label intervention study, 14 women received dairy products enriched with moderate (3 g PL/day) or high (6 g PL/day) dose of milk PL or a high dose of milk PL combined with PSt (6 g PL/day + 2 g PSt/day) during 3 periods each lasting 10 days.

Results

Total cholesterol concentration and HDL cholesterol concentration were reduced following supplementation with 3 g PL/day. No significant change in LDL cholesterol concentration was found compared with baseline. High PL dose resulted in an increase of LDL cholesterol and unchanged HDL cholesterol compared with moderate PL dose. The LDL/HDL ratio and triglyceride concentration remained constant within the study. Except for increased phosphatidyl ethanolamine concentrations, plasma PL concentrations were not altered during exclusive PL supplementations. A combined high-dose PL and PSt supplementation led to decreased plasma LDL cholesterol concentration, decreased PL excretion, increased plasma sphingomyelin/phosphatidyl choline ratio, and significant changes in plasma fatty acid distribution compared with exclusive high-dose PL supplementation.

Conclusion

Milk PL supplementations influence plasma cholesterol concentrations, but without changes of LDL/HDL ratio. A combined high-dose milk PL and PSt supplementation decreases plasma LDL cholesterol concentration, but it probably enforces absorption of fatty acids or fatty acid-containing hydrolysis products that originated during lipid digestion.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CD36:

Cluster of differentiation 36

DM:

Dry matter

FA:

Fatty acid

FABP:

Fatty acid binding protein

FAME:

Fatty acid methyl ester

MUFA:

Mono-unsaturated fatty acid

PC:

Phosphatidyl choline

PE:

Phosphatidyl ethanolamine

PI:

Phosphatidyl inositol

PL:

Phospholipid

PSt:

Plant sterol

PUFA:

Poly-unsaturated fatty acid

SFA:

Saturated fatty acid

SM:

Sphingomyelin

SMFA:

Milk sphingomyelin-related fatty acid

SR-BI:

Scavenger receptor class B type I

TG:

Triglyceride

References

  1. Bitman J, Wood DL (1990) Changes in milk fat phospholipids during lactation. J Dairy Sci 73:1208–1216

    Article  CAS  Google Scholar 

  2. Nyberg L, Duan RD, Nilsson A (1998) Sphingomyelin: a dietary component with structural and biological function. Prog Colloid Polym Sci 108:119–128

    Article  CAS  Google Scholar 

  3. Cohn JS, Kamili A, Wat E, Chung RWS, Tandy S (2010) Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications. Atheroscler Suppl 11:45–48

    Article  CAS  Google Scholar 

  4. Tso P, Fujimoto K (1991) The absorption and transport of lipids by the small intestine. Brain Res Bull 27:477–482

    Article  CAS  Google Scholar 

  5. Ikeda I, Imaizumi K, Sugano M (1987) Absorption and transport of base moieties of phosphatidylcholine and phosphatidylethanolamine in rats. Biochim Biophys Acta 921:245–253

    Article  CAS  Google Scholar 

  6. Richmond BL, Boileau AC, Zheng S, Huggins KW, Granholm NA, Tso P, Hui DY (2001) Compensatory phospholipids digestion is required for cholesterol absorption in pancreatic phospholipase A2-deficient mice. Gastroenterology 120:1193–1202

    Article  CAS  Google Scholar 

  7. Nilsson A (1968) Metabolism of sphingomyelin in the intestinal tract of the rat. Biochim Biophys Acta 164:575–584

    Article  CAS  Google Scholar 

  8. Schmelz EM, Crall KJ, Larocque R, Dillehay DL, Merrill AH Jr (1994) Uptake and metabolism of sphingolipids in isolated intestinal loops of mice. J Nutr 124:702–712

    CAS  Google Scholar 

  9. Iqbal J, Hussain MM (2009) Intestinal lipid absorption. Am J Physiol Endocrinol Metab 296:E1183–E1194

    Article  CAS  Google Scholar 

  10. Kamili A, Wat E, Chung RWS, Tandy S, Weir JM, Meikle PJ, Cohn JS (2010) Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids. Nutr Metab 7:90

    Article  CAS  Google Scholar 

  11. Wat E, Tandy S, Kapera E, Kamili A, Chung RWS, Brown A, Rowney M, Cohn JS (2009) Dietary phospholipids-rich dairy milk extract reduces hepatomegaly, hepatic steatosis and hyperlipidemia in mice fed a high-fat diet. Atherosclerosis 205:144–150

    Article  CAS  Google Scholar 

  12. Müller H, Hellgren LI, Olsen E, Skrede A (2004) Lipids rich in phosphatidylethanolamine from natural gas-utilizing bacteria reduce plasma cholesterol and classes of phospholipids: a comparison with soybean oil. Lipids 39:833–841

    Article  Google Scholar 

  13. Jiang Y, Noh SK, Koo SI (2001) Egg phosphatidylcholine decreases the lymphatic absorption of cholesterol in rats. J Nutr 131:2358–2363

    CAS  Google Scholar 

  14. Nieuwenhuizen WF, Duivenvoorden I, Voshol PJ, Rensen PCN, van Duyvenvoorde W, Romijn JA, Emeis JJ, Havekes LM (2007) Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis. Eur J Lipid Sci Technol 109:994–997

    Article  CAS  Google Scholar 

  15. Nyberg L, Duan RD, Nilsson A (2000) A mutual inhibitory effect on absorption of sphingomyelin and cholesterol. J Nutr Biochem 11:244–249

    Article  CAS  Google Scholar 

  16. Micallef MA, Garg ML (2009) Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia. J Nutr Biochem 20:927–939

    Article  CAS  Google Scholar 

  17. Rideout TC, Harding SV, Mackay D, Abumweis SS, Jones PJH (2010) High basal fractional cholesterol synthesis is associated with nonresponse of plasma LDL cholesterol to plant sterol therapy. Am J Clin Nutr 92:41–46

    Article  CAS  Google Scholar 

  18. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  CAS  Google Scholar 

  19. Xu G, Waki H, Kon K, Ando S (1996) Thin-layer chromatography of phospholipids and their lyso forms: application to determination of extracts from rat hippocampal CA1 region. Microchem J 53:29–33

    Article  CAS  Google Scholar 

  20. Colarow L (1990) Quantitative transmittance densitometry of phospholipids after their specific detection with a molybdate reagent on silica gel plates. J Planar Chromatogr Mod TLC 3:228–231

    CAS  Google Scholar 

  21. Lendrath G, Bonekamp-Nasner A, Kraus LJ (1991) Analytical possibilities of qualitative and quantitative determination of phospholipids of different sources. Eur J Lipid Sci Tech 93:53–61

    CAS  Google Scholar 

  22. Rouser G, Fleischer S, Yamamoto A (1970) Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5:494–496

    Article  CAS  Google Scholar 

  23. Goodman DS, Shiratori T (1964) Fatty acid composition of human plasma lipoprotein fractions. J Lipid Res 5:307–313

    CAS  Google Scholar 

  24. McDowell AKR (1958) Phospholipids in New Zealand dairy products: II. Seasonal variations in the phospholipid content of butter and of milk and cream. J Dairy Res 25:202–214

    Article  CAS  Google Scholar 

  25. Singleton JA, Pattee HE (1981) Computation of conversion factors to determine the phospholipid content in peanut oils. J Am Oil Chem Soc 58:873–875

    Article  CAS  Google Scholar 

  26. Valeur A, Olsson NU, Kaufmann P, Wada S, Kroon CG, Westerdahl G, Odham G (1994) Quantification and comparison of some natural sphingomyelins by on-line high-performance liquid chromatography/discharge-assisted thermospray mass spectrometry. Biol Mass Spectrom 23:313–319

    Article  CAS  Google Scholar 

  27. Keller S, Jahreis G (2004) Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces. J Chromatogr B Biomed Sci Appl 813:199–207

    Article  CAS  Google Scholar 

  28. D-A-CH (2008) The reference values for nutrient intake. Umschau/Braus, Frankfurt/Main

    Google Scholar 

  29. Ohlsson L, Burling H, Nilsson A (2009) Long term effect on human plasma lipoproteins of a formulation enriched in butter milk polar lipid. Lipids Health Dis. doi:10.1186/1476-511X-8-44

    Google Scholar 

  30. Ohlsson L (2010) Dairy products and plasma cholesterol levels. Food Nutr Res. doi:10.3402/fnr.v54i0.5124

    Google Scholar 

  31. Tholstrup T, Hoy CE, Andersen LN, Christensen RDK, Sandström B (2004) Does fat in milk, butter and cheese affect blood lipids and cholesterol differently? J Am Coll Nutr 23:169–176

    Google Scholar 

  32. Andrade S, Borges N (2009) Effect of fermented milk containing Lactobacillus acidophilus and Bifidobacterium longum on plasma lipids of women with normal or moderately elevated cholesterol. J Dairy Res 76:469–474

    Article  CAS  Google Scholar 

  33. Ridgway ND (2000) Interactions between metabolism and intracellular distribution of cholesterol and sphingomyelin. Biochim Biophys Acta 1484:129–141

    Article  CAS  Google Scholar 

  34. Imaizumi K, Tominaga A, Sato M, Sugano M (1992) Effects of dietary sphingolipids on levels of serum and liver lipids in rats. Nutr Res 12:543–548

    Article  CAS  Google Scholar 

  35. Merrill AH, Jones DD (1990) An update of the enzymology and regulation of sphingomyelin metabolism. Biochim Biophys Acta 1044:1–12

    Article  CAS  Google Scholar 

  36. Tijburg LBM, Geelen MJH, van Golde LMG (1989) Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. Biochim Biophys Acta 1004:1–19

    Article  CAS  Google Scholar 

  37. Sundler R, Akesson B (1975) Regulation of phospholipids biosynthesis in isolated rat hepatocytes. Effect of different substrates. J Biol Chem 250:3359–3367

    CAS  Google Scholar 

  38. Levy E, Spahis S, Sinnett D, Peretti N, Maupas-Schwalm F, Delvin E, Lambert M, Lavoie MA (2007) Intestinal cholesterol transport proteins: an update and beyond. Curr Opin Lipidol 18:310–318

    Article  CAS  Google Scholar 

  39. Gupta AK, Savopoulos CG, Ahuja J, Hatzitolios AI (2011) Role of phytosterols in lipid-lowering: current perspectives. Q J Med 104:301–308

    Article  CAS  Google Scholar 

  40. Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V (1992) Sitosterolemia. J Lipid Res 33:945–955

    CAS  Google Scholar 

  41. Vergès B, Athias A, Petit JM, Brindisi MC (2009) Extravascular lipid deposit (xanthelasma) induced by a plant sterol-enriched margarine. BMJ Case Rep. doi:10.1136/bcr.10.2008.1108

    Google Scholar 

  42. Kelly ER, Plat J, Mensink RP, Berendschot TT (2011) Effects of long term plant sterol and stanol consumption on the retinal vasculature: a randomized controlled trial in statin users. Atherosclerosis 214:225–230

    Article  CAS  Google Scholar 

  43. Teupser D, Baber R, Ceglarek U et al (2010) Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Gene 3:331–339

    Article  CAS  Google Scholar 

  44. 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-control analysis of the prospective cardiovascular münster (PROCAM) study. Nutr Metab Cardiovas 16:13–21

    Article  CAS  Google Scholar 

  45. Vanmierlo T, Weingärtner O, van der Pol S, Husche C, Kerksiek A, Friedrichs S, Sijbrands E, Steinbusch H, Grimm M, Hartmann T, Laufs U, Böhm M, de Vries HE, Mulder M, Lütjohann D (2012) Dietary intake of plant sterols stably increases plant sterol levels in the murine brain. J Lipid Res 53:726–735

    Article  CAS  Google Scholar 

  46. Weingärtner O, Lütjohann D, Ji S, Weisshoff N, List F, Sudhop T, von Bergmann K, Gertz K, König J, Schäfers HJ, Endres M, Böhm M, Laufs U (2008) Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 51:1553–1561

    Article  Google Scholar 

  47. Kreuzer J (2011) Phytosterols and phytostanols: is it time to rethink that supplemented margarine? Cardiovasc Res 90:397–398

    Article  CAS  Google Scholar 

  48. Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR (2000) Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 20:2614–2618

    Article  CAS  Google Scholar 

  49. Nilsson A, Duan RD (2006) Absorption and lipoprotein transport of sphingomyelin. J Lipid Res 47:154–171

    Article  CAS  Google Scholar 

  50. Schlitt A, Hojjati MR, von Gizycki H, Lackner KJ, Blankenberg S, Schwaab B, Meyer J, Rupprecht HJ, Jiang XC (2005) Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles. J Lipid Res 46:196–200

    Article  CAS  Google Scholar 

  51. King IB, Lemaitre RN, Kestin M (2006) Effect of a low-fat diet on fatty acid composition in red cells, plasma phospholipids, and cholesterol esters: investigation of a biomarker of total fat intake. Am J Clin Nutr 83:227–236

    CAS  Google Scholar 

  52. Hodson L, Skeaff CM, Fielding BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47:348–380

    Article  CAS  Google Scholar 

  53. Brufau G, Canela MA, Rafecas M (2006) A high-saturated fat diet enriched with phytosterol and pectin affects the fatty acid profile in guinea pigs. Lipids 41:159–168

    Article  CAS  Google Scholar 

  54. Brufau G, Canela MA, Rafecas M (2007) Phytosterols, but not pectin, added to a high-saturated-fat diet modify saturated fatty acid excretion in relation to chain length. J Nutr Biochem 18:580–586

    Article  CAS  Google Scholar 

  55. Wang DQH, Carey MC (1996) Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems. J Lipid Res 37:606–630

    CAS  Google Scholar 

  56. Bietrix F, Yan D, Nauze M, Rolland C, Bertrand-Michel J, Comera C, Schaak S, Barbaras R, Groen AK, Perret B, Terce F, Collet X (2006) Accelerated lipid absorption in mice overexpressing intestinal SR-BI. J Biol Chem 281:7214–7219

    Article  CAS  Google Scholar 

  57. Engelmann B, Wiedmann MK (2010) Cellular phospholipid uptake: flexible paths to coregulate the functions of intracellular lipids. Biochim Biophys Acta 1801:609–616

    Article  CAS  Google Scholar 

  58. Poirier H, Degrace P, Niot I, Bernard A, Besnard P (1996) Localization and regulation of the putative membrane fatty-acid transporter (FAT) in the small intestine. Comparison with fatty acid-binding proteins (FABP). Eur J Biochem 238:368–373

    Article  CAS  Google Scholar 

  59. Nauli AM, Nassir F, Zheng S, Yang Q, Lo CM, Vonlehmden SB, Lee D, Jandacek RJ, Abumrad NA, Tso P (2006) CD36 is important for chylomicron formation and secretion and may mediate cholesterol uptake in the proximal intestine. Gastroenterology 131:1197–1207

    Article  CAS  Google Scholar 

  60. Stremmel W (1988) Uptake of fatty acids by jejunal mucosal cells is mediated by a fatty acid binding membrane protein. J Clin Invest 82:2001–2010

    Article  CAS  Google Scholar 

  61. Méndez-González J, Süren-Castillo S, Calpe-Berdiel L, Rotllan N, Vázquez-Carrera M, Escolà-Gil JC, Blanco-Vaca F (2010) Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice. Br J Nutr 103:153–160

    Article  Google Scholar 

  62. Ruiu G, Pinach S, Veglia F, Gambino R, Marena S, Uberti B, Alemanno N, Burt D, Pagano G, Cassader M (2009) Phytosterol-enriched yogurt increases LDL affinity and reduces CD36 expression in polygenic hypercholesterolemia. Lipids 44:153–160

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank our volunteers for their engaged participation in the study. Nasim Kroegel is acknowledged for language editing. This research project was supported by the German Ministry of Economics and Technology (via AiF) and the FEI (Forschungskreis der Ernährungsindustrie e.V., Bonn). Project AiF 316ZBG.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743, Jena, Germany

    Sylvia Keller, Angelika Malarski, Carolin Reuther, Romy Kertscher & Gerhard Jahreis

  2. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital, Friedrich Schiller University Jena, Erlanger Allee 101, 07747, Jena, Germany

    Michael Kiehntopf

Authors
  1. Sylvia Keller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angelika Malarski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carolin Reuther
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Romy Kertscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Kiehntopf
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerhard Jahreis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sylvia Keller.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 25 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keller, S., Malarski, A., Reuther, C. et al. Milk phospholipid and plant sterol-dependent modulation of plasma lipids in healthy volunteers. Eur J Nutr 52, 1169–1179 (2013). https://doi.org/10.1007/s00394-012-0427-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-012-0427-0

Keywords

Search

Navigation