Milk Polar Lipid Supplementation Improves Cholesterol Metabolism in Postmenopausal Women: Gut-Related Mechanisms

Cécile Vors, Laurie Joumard-Cubizolles, Manon Lecomte, Mélanie Le Barz, David Cheillan, Florent Joffre, Lemlih Ouchchane, Stéphanie Lambert-Porcheron, Hubert Vidal, Corinne Malpuech-Brugère

Univ Lyon, Université Claude Bernard Lyon 1, CarMeN laboratory, France; Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine; Univ Lyon, Université Claude Bernard Lyon 1, CarMeN laboratory; Univ Lyon, Université Claude Bernard Lyon 1, CarMeN laboratory; Unité Maladies Héréditaires du Métabolisme, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon; ITERG; Université Clermont Auvergne, CNRS, SIGMA Clermont, Institut Pascal; CRNH Rhône-Alpes; INSERM, CarMeN laboratory; Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine

Objective/Hypothesis: Nutritional strategies are relevant to manage CVD risk in postmenopausal women. Preclinical studies reported benefits on cholesterolemia of milk polar lipids (MPL), but effects in humans remained to be clarified. We hypothesized that MPL could improve cholesterol metabolism by modifying cholesterol absorption and fate in the gut.

Methods Used: In a double-blind randomized controlled trial, 58 postmenopausal women with fasting HDL-cholesterol<1.6 mM were subjected to a 4-week dietary intervention with daily consumption of a cream-cheese containing 12g of milkfat including either 0g (control, n=19), 3g (n=19) or 5g (n=20) of MPL (among which 0.8 or 1.2g of sphingomyelin). Before/after intervention, blood lipids were measured; fecal lipids were analyzed in a subgroup. A proof-of-concept mechanistic crossover study was performed in 4 ileostomized subjects (8h-postprandial tests after consuming the experimental cheeses labelled with 2H-cholesterol).

Results: Milkfat enriched with MPL induced dose-response reductions in serum total cholesterol (-6.8% in 5g 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. MPL supplementations increased fecal coprostanol excretion (p<0.05). The fecal coprostanol/cholesterol ratio was inversely correlated with LDL-cholesterol after intervention (r=-0.5, p<0.05). 2H-cholesterol content in postprandial plasma and chylomicrons of ileostomized subjects was reduced after MPL-cheeses (p<0.05 vs control). Cholesterol and milk sphingomyelin increased in ileal efflux after MPL-cheeses (p<0.05).

Conclusions: A dietary strategy based on lipid quality, including MPL, can contribute to improve the cardiometabolic health of postmenopausal women. This can be via cholesterol fate in the gut, through interactions with sphingomyelin and conversion to coprostanol.