Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Abstract

ObjectiveTo investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.DesignA 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.ResultsOver 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.ConclusionThe 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 numberNCT02099032 and NCT02146339; Results.

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

“…While the pre-clinical findings reporting modulation of the gut microbiome by milk polar lipids are promising, only one human clinical trial has been conducted investigating this area. In a recent study by Vors et al [110], post-menopausal women who supplemented their diets for four weeks with either 3 g or 5 g of milk polar lipids daily through butter serum showed no significant changes in major phylogenetic groups or bacterial species of gut microbiota when compared with the control group fed only butter oil. This may be attributed to the much lower dosage used in this study when compared to animal studies.…”

“…Additionally, (2) how are lipoprotein particle characteristics that are known predictors of CVD risk (e.g., LDL size and HDL particle number) affected by milk polar lipids? While Vors et al [110] did not observe changes in major bacterial phyla composition after four weeks (i.e., who is there), the increased coprostanol conversion in feces with milk polar lipid consumption suggests significant changes in gut microbiome metabolic capacity; thus, (3) are there effects of milk polar lipids on the metagenome of gut bacteria (i.e., what they are doing)? Finally, while the study by Vors et al [110] was conducted in moderately hyperlipidemic, overweight post-menopausal women, (4) do milk polar lipid health effects differ between men and women?…”

“…This would equate to a dose of 7-14 g of milk PLs in a 70 kg human. However, Vors et al [110] reported there was a significantly greater amount of fecal coprostanol, as well as a higher coprostanol/cholesterol ratio in those supplemented with milk polar lipids compared to control. While not examined further, these effects suggest there were changes in gut microbiome metabolism specific to increased coprostanol conversion in the gut with milk polar lipid supplementation.…”

“…The lower plasma LDL-C concentrations observed with buttermilk were associated with changes in plasma β-sitosterol, a marker of cholesterol absorption. In a clinical trial in postmenopausal women by Vors et al [110], a dose of 5 g/day of milk PLs (1.3 g/day milk SM) via a butter serum concentrate lowered total and LDL-C, as well as decreased total/HDL-cholesterol and decreased apoB:apoA-I ratio, compared to a control cream cheese devoid of milk PL. Overall, it appears that the hypolipidemic effects of milk PLs observed in animal studies were also observed in several human studies, even when using lower dosages than in animal studies.…”

“…However, very little research has been conducted to investigate how milk polar lipids affect lipoprotein profiles, inflammation, and gut health in men and women at risk for CVD. Vors et al [110] recently reported that postmenopausal women who consumed 5 g/day of milk polar lipids had beneficial effects on plasma lipids and increased the coprostanol/cholesterol ratio in feces. While crucial data were revealed with this important study, there are many questions that remain.…”