Lipids and cardiovascular/metabolic health

Effect of milk fat on LDL cholesterol and other cardiovascular risk markers in healthy humans: the INNOVALAIT project



Milk has a specific saturated fatty acid profile and its calcium content may change the kinetics of fat absorption.


The goal of this study was to compare the effect on LDL Cholesterol and other risk markers of four isolipidic diets differing by their fat food source, vegetable fat, spring milk fat, winter milk fat or winter milk fat supplemented with calcium, in healthy moderately hypercholesterolemic humans.

Individuals and methods

This double-blind, randomized trial with four parallel arms included 172 healthy adults with plasma LDL cholesterol (LDL-C) from 130 to 220 mg/dL and triglycerides below 300 mg/dL. Individual meal plans ensured a stable energy intake. In the three diets containing milk fat, milk fat provided 38% of energy. Vegetable fat and spring milk fat diets provided the same amount of saturated fatty acids while the winter milk fat diets were slightly richer in saturated fatty acids. Vegetable fat diet and winter milk fat diets provided the same amount of palmitic acid (7.0% EI), while the spring milk fat diet was slightly poorer in this fatty acid (5.1% EI). Cardiovascular risk markers were analyzed after 8 weeks of dietary intervention.


There was no significant difference in LDL-C and other markers, except total cholesterol (TC), apo C3 and CRP. TC was significantly higher with spring milk fat than with vegetable fat.


In this trial, the chosen vegetable fat did not have a significant beneficial effect on LDL-C compared to dairy fat. However, sub-group analysis showed differences in TC, apo C3 and CRP. These results need confirmation and long-term studies aiming at cardiovascular endpoints are warranted.

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Fig. 1


  1. 1.

    Kris-Etherton PM, Yu S. Individual fatty acid effects on plasma lipids and lipoproteins: human studies. Am J Clin Nutr. 1997;65 5 Suppl:1628S–44S.

    CAS  PubMed  Google Scholar 

  2. 2.

    Yu S, Derr J, Etherton TD, Kris-Etherton PM. Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Am J Clin Nutr. 1995;61:1129–39.

    CAS  PubMed  Google Scholar 

  3. 3.

    Ginsberg HN, Barr SL, Gilbert A, Karmally W, Deckelbaum R, Kaplan K, et al. Reduction of plasma cholesterol levels in normal men on an American Heart Association Step 1 diet or a Step 1 diet with added monounsaturated fat. New Engl J Med. 1990;322:574–9.

    CAS  PubMed  Google Scholar 

  4. 4.

    Kelly FD, Sinclair AJ, Mann NJ, Turner AH, Raffin FL, Blandford MV, et al. Short-term diets enriched in stearic or palmitic acids do not alter plasma lipids, platelet aggregation or platelet activation status. Eur J Clin Nutr. 2002;56:490–9.

    CAS  PubMed  Google Scholar 

  5. 5.

    Mensink RP. Effects of stearic acid on plasma lipid and lipoproteins in humans. Lipids 2005;40:1201–5.

    CAS  PubMed  Google Scholar 

  6. 6.

    de Gomez Dumm IN, Brenner RR. Oxidative desaturation of alpha-linoleic, linoleic, and stearic acids by human liver microsomes. Lipids 1975;10:315–7.

    PubMed  Google Scholar 

  7. 7.

    Hegsted DM, McGandy RB, Myers ML, Stare FJ. Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr. 1965;17:281–95.

    CAS  PubMed  Google Scholar 

  8. 8.

    Keys A, Anderson JT, Grande F. Prediction of serum-cholesterol responses of man to changes in fats in the diet. Lancet 1957;273:959–66.

    CAS  PubMed  Google Scholar 

  9. 9.

    Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet. Metab: Clin Exp. 1965;14:776–87.

    CAS  Google Scholar 

  10. 10.

    Xue C, Liu Y, Wang J, Zheng Z, Zhang Y, Zhang Y, et al. Chinese hypertriglycerideamic subjects of different ages responded differently to consuming oil with medium- and long-chain fatty acids. Biosci Biotechnol Biochem. 2009;73:1711–7.

    CAS  PubMed  Google Scholar 

  11. 11.

    Zhang YH, Liu YH, Zheng ZX, Wang J, Zhang Y, Zhang RX, et al. Medium- and long-chain fatty acid triacylglycerol reduce body fat and serum triglyceride in overweight and hypertriglyceridemic subjects. Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43:765–71.

    CAS  PubMed  Google Scholar 

  12. 12.

    Cater NB, Heller HJ, Denke MA. Comparison of the effects of medium-chain triacylglycerols, palm oil, and high oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and lipoprotein concentrations in humans. Am J Clin Nutr. 1997;65:41–5.

    CAS  PubMed  Google Scholar 

  13. 13.

    Tholstrup T, Ehnholm C, Jauhiainen M, Petersen M, Hoy CE, Lund P, et al. Effects of medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities. Am J Clin Nutr. 2004;79:564–9.

    CAS  PubMed  Google Scholar 

  14. 14.

    Gardner CD, Kraemer HC. Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis. Arteriosclerosis Thromb Vasc Biol. 1995;15:1917–27.

    CAS  Google Scholar 

  15. 15.

    Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014;160:398–406.

    PubMed  Google Scholar 

  16. 16.

    Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr. 2010;91:535–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Harcombe Z, Baker JS, Cooper SM, Davies B, Sculthorpe N, DiNicolantonio JJ, et al. Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2015;2:e000196.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ (Clin Res ed). 2015;351:h3978.

    Google Scholar 

  19. 19.

    Praagman J, Beulens JW, Alssema M, Zock PL, Wanders AJ, Sluijs I, et al. The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr. 2016;103:356–65.

    PubMed  Google Scholar 

  20. 20.

    de Oliveira Otto MC, Nettleton JA, Lemaitre RN, Steffen LM, Kromhout D, Rich SS, et al. Biomarkers of dairy fatty acids and risk of cardiovascular disease in the Multi-ethnic Study of Atherosclerosis. J Am Heart Assoc 2013;2:e000092.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    de Oliveira Otto MC, Mozaffarian D, Kromhout D, Bertoni AG, Sibley CT, Jacobs DR Jr., et al. Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr. 2012;96:397–404.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    de Oliveira Otto MC, Lemaitre RN, Song X, King IB, Siscovick DS, Mozaffarian D. Serial measures of circulating biomarkers of dairy fat and total and cause-specific mortality in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2018;108:476–84.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    O’Sullivan TA, Hafekost K, Mitrou F, Lawrence D. Food sources of saturated fat and the association with mortality: a meta-analysis. Am J Public Health. 2013;103:e31–42.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Strauss EW, Jacob JS. Some factors affecting the lipid secretory phase of fat absorption by intestine in vitro from golden hamster. J Lipid Res. 1981;22:147–56.

    CAS  PubMed  Google Scholar 

  25. 25.

    Vinarova L, Vinarov Z, Tcholakova S, Denkov ND, Stoyanov S, Lips A. The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model. Food Funct. 2015;7:151–63.

    CAS  Google Scholar 

  26. 26.

    Lorenzen JK, Nielsen S, Holst JJ, Tetens I, Rehfeld JF, Astrup A. Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake. Am J Clin Nutr. 2007;85:678–87.

    CAS  PubMed  Google Scholar 

  27. 27.

    Bachorik PS, Ross JW. National Cholesterol Education Program recommendations for measurement of low-density lipoprotein cholesterol: executive summary. The National Cholesterol Education Program Working Group on Lipoprotein Measurement. Clin Chem. 1995;41:1414–20.

    CAS  PubMed  Google Scholar 

  28. 28.

    Bobin-Dubigeon C, Jaffre I, Joalland MP, Classe JM, Campone M, Herve M, et al. Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence. Clin Biochem. 2012;45:1503–5.

    CAS  PubMed  Google Scholar 

  29. 29.

    Tselepis AD, Dentan C, Karabina SA, Chapman MJ, Ninio E. PAF-degrading acetylhydrolase is preferentially associated with dense LDL and VHDL-1 in human plasma. Catalytic characteristics and relation to the monocyte-derived enzyme. Arteriosclerosis, thrombosis, Vasc Biol. 1995;15:1764–73.

    CAS  Google Scholar 

  30. 30.

    Martin JC, Berton A, Ginies C, Bott R, Scheercousse P, Saddi A, et al. Multilevel systems biology modeling characterized the atheroprotective efficiencies of modified dairy fats in a hamster model. Am J Physiol Heart Circ Physiol. 2015;309:H935–45.

    CAS  PubMed  Google Scholar 

  31. 31.

    Gordon DJ, Hyde J, Trost DC, Whaley FS, Hannan PJ, Jacobs DR, et al. Cyclic seasonal variation in plasma lipid and lipoprotein levels: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. J Clin Epidemiol. 1988;41:679–89.

    CAS  PubMed  Google Scholar 

  32. 32.

    Rodriguez M, Funke S, Fink M, Demmelmair H, Turini M, Crozier G, et al. Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium-chain triglycerides. J Lipid Res. 2003;44:41–8.

    CAS  PubMed  Google Scholar 

  33. 33.

    Du Q, Martin JC, Agnani G, Pages N, Leruyet P, Carayon P, et al. Dairy fat blends high in alpha-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats. J Nutr Biochem. 2012;23:1573–82.

    CAS  PubMed  Google Scholar 

  34. 34.

    Blankenhorn DH, Alaupovic P, Wickham E, Chin HP, Azen SP. Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors. Circulation. 1990;81:470–6.

    CAS  PubMed  Google Scholar 

  35. 35.

    Chivot L, Mainard F, Bigot E, Bard JM, Auget JL, Madec Y, et al. Logistic discriminant analysis of lipids and apolipoproteins in a population of coronary bypass patients and the significance of apolipoproteins C-III and E. Atherosclerosis 1990;82:205–11.

    CAS  PubMed  Google Scholar 

  36. 36.

    Genest JJ Jr., Bard JM, Fruchart JC, Ordovas JM, Wilson PF, Schaefer EJ. Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease. Atherosclerosis 1991;90:149–57.

    PubMed  Google Scholar 

  37. 37.

    Hodis HN, Mack WJ, Azen SP, Alaupovic P, Pogoda JM, LaBree L, et al. Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin. Circulation 1994;90:42–9.

    CAS  PubMed  Google Scholar 

  38. 38.

    Koren E, Corder C, Mueller G, Centurion H, Hallum G, Fesmire J, et al. Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease. Atherosclerosis 1996;122:105–15.

    CAS  PubMed  Google Scholar 

  39. 39.

    Luc G, Fievet C, Arveiler D, Evans AE, Bard JM, Cambien F, et al. Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. Etude Cas Temoins sur ‘Infarctus du Myocarde. J Lipid Res. 1996;37:508–17.

    CAS  PubMed  Google Scholar 

  40. 40.

    Gervaise N, Garrigue MA, Lasfargues G, Lecomte P. Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes. Diabetologia 2000;43:703–8.

    CAS  PubMed  Google Scholar 

  41. 41.

    Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation 2000;102:1886–92.

    CAS  PubMed  Google Scholar 

  42. 42.

    Onat A, Hergenc G, Sansoy V, Fobker M, Ceyhan K, Toprak S, et al. Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis 2003;168:81–9.

    CAS  PubMed  Google Scholar 

  43. 43.

    Chardigny JM, Destaillats F, Malpuech-Brugere C, Moulin J, Bauman DE, Lock AL, et al. Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study. Am J Clin Nutr. 2008;87:558–66.

    CAS  Google Scholar 

  44. 44.

    Mensink RP, Stolwijk AM, Katan MB. Effect of a monounsaturated diet vs. a polyunsaturated fatty acid-enriched diet on blood pressure in normotensive women and men. Eur J Clin Investig 1990;20:463–9.

    CAS  Google Scholar 

  45. 45.

    Ascherio A, Willett WC. Metabolic and atherogenic effects of trans fatty acids. J Intern Med. 1995;238:93–6.

    CAS  PubMed  Google Scholar 

  46. 46.

    Dallongeville J, Tiret L, Visvikis S, O’Reilly DS, Saava M, Tsitouris G, et al. Effect of apo E phenotype on plasma postprandial triglyceride levels in young male adults with and without a familial history of myocardial infarction: the EARS II study. European Atherosclerosis Research Study. Atherosclerosis 1999;145:381–8.

    CAS  PubMed  Google Scholar 

  47. 47.

    Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, Pennells L, Wood AM, White IR, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367:1310–20.

    Google Scholar 

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The authors acknowledge the contribution of the members of the INNOVALAIT Study group in the set up and follow up of the study.

Members of the INNOVALAIT Study group

Pascale Leruyet7, Daniel Moreau8, Benoit Goldschmidt9, Michel Bonneau10, Philippe Marchal11, Hervé Durand12


This study was supported by grants from French government, CNIEL, BBA and local funding (Pays de la Loire and Britany).

Author information





All authors contributed to the study and paper preparation. In addition, JMB, LD, DL, MC, CM were involved in the study protocol writing and result review. MC was involved in study organization and monitoring. JMB, MC, CBdS, EN and JCM were involved in biological analyses. CBD was involved in diet inquiry analysis.

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Correspondence to Jean-Marie Bard.

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Members of the INNOVALAIT Study group are listed below acknowledgements

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Bard, J., Drouet, L., Lairon, D. et al. Effect of milk fat on LDL cholesterol and other cardiovascular risk markers in healthy humans: the INNOVALAIT project. Eur J Clin Nutr 74, 285–296 (2020).

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