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Lipids and cardiovascular/metabolic health

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

European Journal of Clinical Nutrition volume 74, pages 285–296 (2020)Cite this article

Subjects

Abstract

Background

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

Objective

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.

Results

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.

Conclusions

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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References

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

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Acknowledgements

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

Funding

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

Author information

Authors and Affiliations

  1. Institut de Cancérologie de l’Ouest, Biopathologie, Centre de Recherche en Nutrition Humaine Ouest, EA 2160 - IUML FR3473 CNRS, Université de Nantes, Nantes, France

    Jean-Marie Bard & Christine Bobin-Dubigeon

  2. LTA-IVS INSERM U689, Hôpital Lariboisière, Paris, France

    Ludovic Drouet & Claire Bal dit Sollier

  3. UMR 1062-INSERM/1260-INRA, Faculté de Médecine, Université Aix-Marseille, Marseille, France

    Denis Lairon & Jean-Charles Martin

  4. Biofortis, Saint-Herblain, France

    Murielle Cazaubiel

  5. CNIEL, Paris, France

    Corinne Marmonier & Constance Boyer

  6. Genomics and Pathophysiology of Cardiovascular Diseases, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière, INSERM UMR_S 1166-ICAN, Sorbonne Université, Paris, France

    Ewa Ninio

  7. Lactalis, Laval, France

    Pascale Leruyet

  8. Entremont Alliance, Annecy, France

    Daniel Moreau

  9. Fromagerie Bel, Vendôme, France Jean Noblet, UMR INRA-SENAH, Saint-Gilles, France

    Benoit Goldschmidt

  10. INRA UR910 Cr2i, Jouy en Josas, France

    Michel Bonneau

  11. BBA, Rennes, France

    Philippe Marchal

  12. INSERM UMR_S 1166-ICAN, Sorbonne Université, Paris, France

    Hervé Durand

Authors
  1. Jean-Marie Bard
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Consortia

for the INNOVALAIT Study group

  • Pascale Leruyet
  • , Daniel Moreau
  • , Benoit Goldschmidt
  • , Michel Bonneau
  • , Philippe Marchal
  •  & Hervé Durand

Contributions

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.

Corresponding author

Correspondence to Jean-Marie Bard.

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Members of the INNOVALAIT Study group are listed below acknowledgements

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Bard, JM., 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). https://doi.org/10.1038/s41430-019-0528-4

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