Supplementary information files for "Impact of milk fat globule membrane and its associated polar lipids on markers of cardiometabolic disease and cognitive function: a systematic review and meta-analysis of randomized controlled trials in adults"

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Supplementary files for article "Impact of milk fat globule membrane and its associated polar lipids on markers of cardiometabolic disease and cognitive function: a systematic review and meta-analysis of randomized controlled trials in adults" Milk fat globule membrane (MFGM) and its associated milk polar lipids (MPLs) are bioactive components of dairy fat with emerging relevance for cardiometabolic and cognitive health. This systematic review and meta-analysis evaluated the effects of bovine-derived MFGM/MPL on fasting and postprandial cardiometabolic disease risk markers and cognitive function in disease-free adults, compared with isoenergetic dairy products or supplements low in these components. Searches of PubMed (MEDLINE), Embase, and Cochrane Central identified randomized controlled trials (RCTs) comparing MFGM/MPL-containing foods or supplements with isoenergetic dairy comparators low in these components. Risk of bias (RoB) was assessed using Cochrane RoB 2.0 tool. Random-effects meta-analyses were performed for outcomes reported in ≥ 3 studies, and certainty of evidence for critical outcomes was evaluated using the GRADE approach. Of 730 records screened, 13 studies (14 articles) met inclusion criteria (RoB: low to some concerns). Pooled analyses demonstrated that 2-16 wk intake of MFGM/MPL (19.8 to 5000 mg/d) reduced fasting total cholesterol (weighted mean difference [WMD]: -0.18 mmol/L; 95% CI: -0.30, -0.07), LDL cholesterol (WMD: -0.12 mmol/L; 95% CI: -0.22, -0.03), apolipoprotein B concentrations (WMD: -0.05 g/L; 95% CI: -0.09, -0.01), and the total cholesterol:HDL cholesterol ratio (WMD: -0.17; 95% CI: -0.33, -0.01), with low heterogeneity (I2 = 0-9%) and moderate certainty of evidence. No clear effects were observed for fasting circulating HDL cholesterol, triacylglycerol, glucose, insulin, or blood pressure (low certainty). Evidence for emerging fasting cardiometabolic biomarkers, postprandial responses, and cognitive outcomes was limited and synthesized narratively. This review offers the strongest and most methodologically robust evidence to date that bovine-derived MFGM/MPL modestly improves atherogenic markers in adults, with implications for dietary guidance and future research. Limited data for novel biomarkers and cognitive outcomes highlight priorities for longer-term, adequately powered RCTs to clarify their broader health relevance.This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ asCRD42025636269. © The Author(s), CC BY 4.0

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