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Original article
Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay
  1. Cécile Vors1,2,
  2. Laurie Joumard-Cubizolles3,
  3. Manon Lecomte1,
  4. Emmanuel Combe1,
  5. Lemlih Ouchchane4,5,
  6. Jocelyne Drai1,6,
  7. Ketsia Raynal7,
  8. Florent Joffre8,
  9. Laure Meiller1,2,
  10. Mélanie Le Barz1,
  11. Patrice Gaborit7,
  12. Aurélie Caille9,
  13. Monique Sothier2,
  14. Carla Domingues-Faria3,
  15. Adeline Blot9,
  16. Aurélie Wauquier10,
  17. Emilie Blond1,6,
  18. Valérie Sauvinet1,2,
  19. Geneviève Gésan-Guiziou11,
  20. Jean-Pierre Bodin12,
  21. Philippe Moulin1,13,
  22. David Cheillan1,14,
  23. Hubert Vidal1,
  24. Béatrice Morio1,
  25. Eddy Cotte15,16,
  26. Françoise Morel-Laporte9,
  27. Martine Laville1,2,
  28. Annick Bernalier-Donadille10,
  29. Stéphanie Lambert-Porcheron2,17,
  30. Corinne Malpuech-Brugère3,
  31. Marie-Caroline Michalski1,2
  1. 1Univ Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Charles Mérieux Medical School, 69600, Oullins, France
  2. 2CRNH Rhône-Alpes, Hospices Civils de Lyon, CENS, Centre de Recherche en Nutrition Humaine Rhône-Alpes, 69310, Pierre-Bénite, France
  3. 3Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000, Clermont-Ferrand, France
  4. 4Université Clermont Auvergne, CNRS, SIGMA Clermont, Institut Pascal, 63000, Clermont-Ferrand, France
  5. 5CHU Clermont-Ferrand, Unité de Biostatistique-Informatique Médicale, 63000, Clermont-Ferrand, France
  6. 6Unité de Nutrition Endocrinologie Métabolisme, Service de Biochimie, Centre de Biologie et de Pathologie Sud, Hospices Civils de Lyon, 69310, Pierre-Bénite, France
  7. 7ACTALIA Dairy Products and Technologies, 17700, Surgères, France
  8. 8ITERG, 33610, Canéjan, France
  9. 9CHU Clermont-Ferrand, CRNH Auvergne, 63000, Clermont-Ferrand, France
  10. 10Université Clermont Auvergne, INRA, UMR 454, MEDIS, 63000, Clermont-Ferrand, France
  11. 11STLO, Science et Technologie du Lait et de l’Œuf, INRA, AGROCAMPUS OUEST, 35000, Rennes, France
  12. 12ENILIA-ENSMIC, 17700, Surgères, France
  13. 13Fédération d’Endocrinologie, Maladies Métaboliques, Diabète et Nutrition, Hôpital Louis Pradel, Hospices Civils de Lyon, 69500, Bron, France
  14. 14Unité Maladies Héréditaires du Métabolisme, Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 69500, Bron, France
  15. 15Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud-Charles Mérieux, EMR 3738, 69600, Oullins, France
  16. 16Centre Hospitalier Lyon Sud, Service de Chirurgie Digestive, Hospices Civils de Lyon, 69310, Pierre-Bénite, France
  17. 17Hospices Civils de Lyon, 69000, Lyon, France
  1. Correspondence to Dr Marie-Caroline Michalski, INRA, UMR1397, CarMeN laboratory, INSERM U1060, Univ Lyon, CENS-ELI Building, 165 chemin du Grand Revoyet, 69310 Pierre-Bénite, France; marie-caroline.michalski{at}


Objective To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.

Design A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients.

Results Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut.

Conclusion The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota.

Trial registration number NCT02099032 and NCT02146339; Results.

  • lipid absorption
  • lipoprotein-cholesterol
  • colonic microflora
  • lipid metabolism
  • nutrition

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  • CV and LJC contributed equally to the VALOBAB-C clinical trial.

  • MLe, EmC and LO contributed equally.

  • Twitter @Michalski_MC, @cecile_vors

  • Contributors M-CM, CM-B, CV, MLe, BM, MLa, SL-P: conception of the studies. M-CM, CM-B, LO, CV, LJ-C, SL-P, BM, EmCo, JD, FJ: methodology. CV, LJ-C, MLe, LM, FJ, SL-P, JD, ABD: validation of data. LO, CV, LJ-C, EmCo, MLe, LM, FJ, ABD: formal analysis of data. CV, LJ-C, MLe, JD, EB, LM, FJ, SL-P, ABD, CD-F, MS, AC, AB, AW, VS, FM-L, DC, KR, PG: performed clinical and analytical investigations. EdCo, KR, PG, J-PB, GG-G: provided essential resources. CV, LO, EmCo, LJ-C, MLe: performed data curation. CV, LJ-C, M-CM, EmCo, MLe, LO, MLB, CM-B: wrote original draft. All: reviewed and edited the original draft. CV, LJ-C, EmCo, MLe, MLB, M-CM: performed data visualisation. PM, MLa, HV: contributed to results interpretation and revised manuscript. M-CM: coordinated the project and has primary responsibility for final article content. All authors read, revised and approved the final manuscript.

  • Funding This work was supported by (i) the Agence Nationale de la Recherche under reference ANR-11-ALID-007-01 (VALOBAB project "sustainable VALOrization of Buttermilk: nutritionAl Benefits, functional value in food products and consumer perception", coordinated by MC Michalski; endorsed by competitiveness cluster VALORIAL), (ii) the regional hospital clinical research programme (Programme Hospitalier de Recherche Clinique Interrégional 2014: VALOBAB, n°14-007) and (iii) the French Dairy Interbranch Organization (CNIEL). The Hospices Civils de Lyon was the study sponsor.

  • Competing interests This work was supported in part by a grant from the French Dairy Interbranch Organization (CNIEL). M-CM has received research funding for other research projects from CNIEL, Danone-Nutricia Research, Sodiaal-Candia R&D. M-CM has consultancy activities for food, fats and oils and dairy companies. M-CM is a member of the scientific advisory board of ITERG, the Industrial Technical Centre for the oils and fats business sector. These activities had no link with the present study. BM has received research funding from Sofiprotéol with no link with the present study. PG is an employee of ACTALIA Produits Laitiers, an Agri-Food Technical Institute, with a strong specialisation in dairy research and development, and food safety. KR was an employee of ACTALIA Produits Laitiers and is now employee of Terra Lacta, a dairy cooperative. J-PB: ENILIA had research funding from dairy companies Laiterie des Fayes and Eurial. These activities had no link with the present study. GG-G has received research funding for other research projects from Savencia, Danone, Sodiaal-Candia R&D, Boccard. She has consultancy activities for dairy companies and filtration equipment providers. These activities had no link with the present study. MLa is a member of the Scientific Committee of Roquette and had research collaborations with Mondelez and Bridor. These activities had no link with the present study. The authors have no additional financial interests. Other authors declared no conflict of interest. There are no awarded or filed patents pertaining to the results presented in the paper.

  • Ethics approval Scientific Ethics Committee (CPP) of Lyon Sud-Est-IV and ANSM (French Agency for the Safety of Health Products).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement According to French law on the publication of biomedical research/clinical trials, we are not allowed to make the clinical database publicly available on the web, nor send it to third parties, nor to make visible the location of the study associated with the database.

  • Patient consent for publication Not required.

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