# Milk polar lipids reduce cholesterolemia by decreasing cholesterol absorption in humans (P06-041-19)

Cécile Vors, Manon Lecomte, Laurie Joumard-Cubizolles, Emilie Blond, Laure Meiller, Florent Joffre, Jocelyne Drai, Emmanuel Combe, Mélanie Le Barz, Ketsia Raynal, et al.

► To cite this version:

Cécile Vors, Manon Lecomte, Laurie Joumard-Cubizolles, Emilie Blond, Laure Meiller, et al. Milk polar lipids reduce cholesterolemia by decreasing cholesterol absorption in humans (P06-041-19). Nutrition 2019, Jun 2019, Baltimore, United States. Current Developments in Nutrition, 2019, 10.1093/cdn/nzz031.P06-041-19. [https://doi.org/10.1093/cdn/nzz031](https://doi.org/10.1093/cdn/nzz031). [hal-02734267](https://hal.inrae.fr/hal-02734267)

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Submitted on 2 Jun 2020

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Distributed under a Creative Commons Attribution 4.0 International License
Milk Polar Lipids Reduce Cholesterolemia by Decreasing Choles-
terol Absorption in Humans (P06-041-19)

Cecile Vors,¹ Manon Lecomte,¹ Laurie Joumard-Cubizolles,²
Emilie Blond,³ Laure Meiller,⁴ Florent Joffre,⁵ Jocelyne Drai,⁴
Emmanuel Combe,¹ Melanie Le Barz,¹ Ketsia Raynal,⁶
Patrice Gaborit,⁷ Genevieve Gesan-Guiziou,⁸ Lemlih
Ouchchane,⁹ Eddy Cotte,³ Martine Laville,¹⁰ Corinne Malpuech-
Brugere,¹¹ Stephanie Lambert-Porcheron,⁴ and Marie-Caroline
MICHALSKI¹²

¹Université Claude Bernard Lyon 1, CarMeN laboratory; ²INRA - Université Clermont Auvergne; ³Hospices Civils de Lyon; ⁴Centre de Recherche en Nutrition Humaine Rhône-Alpes; ⁵ITERG; ⁶ENILIA ENSMIC; ⁷ACTALIA Produits Laitiers; ⁸INRA - Science et Technologie du Lait et de l'Oeuf; ⁹Université Clermont Auvergne - CHU de Clermont Ferrand; ¹⁰Universite de Lyon; ¹¹Centre de Recherche en Nutrition Humaine Auvergne; and ¹²INRA, CarMeN laboratory

**Objectives:** Nutritional strategies can play a major role in the management of cholesterolemia, notably in postmenopausal women at risk of CVD. Interest has recently grown on the potential health benefits of milk polar lipids (MPL). We showed that isolipidic enrichment of the diet with MPL improved several lipid CV risk factors but underlying mechanisms remained unclear. We hypothesized that MPL reduce intestinal cholesterol absorption in humans.

**Methods:** We performed a double-blind randomized controlled trial in 58 postmenopausal women with fasting HDL-cholesterol < 1.6 mM. They were subjected to a 4-week dietary intervention with daily consumption of a cream-cheese containing 12 g of milk fat including

either 0 g (control, n = 19), 3 g (n = 19) or 5 g (n = 20) of MPL. Before and after each intervention, blood lipids were measured in the whole cohort whereas fecal lipids and coprostanol were analyzed in a subgroup (n = 7-9 per group). A proof-of-concept mechanistic crossover study was also carried out in 4 ileostomized subjects who performed 8h-postprandial tests after consuming 0g-, 3g- or 5g-MPL enriched cheese labelled with 2H-cholesterol tracer. Plasma, chylomicrons and ileal efflux were analyzed.

**Results:** Milk fat enriched with 3 to 5 g MPL induced dose-response reductions in serum total cholesterol (up to -6.8% in 5 g group, p < 0.05), LDL-cholesterol (-8.7%, p < 0.05) and HDL/total-cholesterol ratio (p < 0.001), compared to the control that had no effect. Fecal excretion of coprostanol increased after MPL supplementation (p < 0.05, 3g- and 5g-MPL vs control), and the fecal coprostanol/cholesterol ratio was inversely correlated with serum total- and LDL-cholesterol after intervention (r = -0.5, p < 0.05). In ileostomized subjects, postprandial accumulation of 2H-cholesterol in plasma and chylomicrons was reduced after 3 to 5 g MPL consumption (p < 0.05, vs control). Both cholesterol and milk sphingomyelin increased in ileal efflux after MPL enriched cheeses (p < 0.05).

**Conclusions:** Present results suggest that milk polar lipids decrease cholesterol absorption in humans through interactions with sphingomyelin and by increasing conversion of cholesterol to coprostanol.

**Funding Sources:** ANR (French National Research Agency, VALOBAB project, ANR-11-ALID-007-01), PHRC-I (French Clinical Research Program, 14-007), CNIEL (French Dairy Interbranch Organization).