Effects of milk fat globule membrane and its associated polar lipids on fasting blood lipids and blood pressure: Preliminary insights from a systematic review and meta-analysis of randomised controlled trials

The milk fat globule membrane (MFGM), an integral part of the dairy matrix, is rich in bioactive milk polar lipids (MPLs) (primarily phospholipids and sphingolipids) and proteins (1,2) . MFGM is well-preserved in dairy fractions that retain native milk fat globules (2) . It can also be recovered from dairy side-streams such as MFGM-enriched whey protein concentrates (3) . Growing evidence suggests that MFGM, or membrane-associated MPLs, may beneficially modulate cardiometabolic disease (CMD) risk, particularly through effects on blood lipid regulation (2) . This systematic review and meta-analysis synthesises current evidence on MFGM/MPL consumption and its effects on CMD risk markers, including lipid profiles and blood pressure (BP) in disease-free adults. This review followed PRISMA guidelines (PROSPERO: CRD42025636269). PubMed (Medline), Cochrane Central and Embase databases were searched, with supplementary searches continued until 23 September 2025. Eligible studies were randomised controlled trials (RCTs) in weight-stable adults (≥18 y), either healthy or at CMD risk, comparing food- or supplement-based MFGM/MPL interventions with isoenergetic, low-MFGM/MPL comparators. Outcomes assessed included fasting plasma/serum lipids and BP. Data were pooled using inverse-variance random-effects meta-analysis with Hartung-Knapp adjustment and expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Heterogeneity was assessed using I 2 . Risk of bias (RoB) was evaluated using the Cochrane RoB 2 tool. Subgroup analyses were conducted by baseline health status: healthy vs at-risk [defined as overweight/obesity and/or with elevated circulating LDL-cholesterol (LDL-C)]. Of the 728 citations identified, 13 studies (reported across 14 articles) were included, of which 12 were supplement-based. RoB assessment rated ten trials with some concerns and four as low risk. Pooled analysis of 10 RCTs indicated that MFGM/MPL consumption significantly reduced total cholesterol (TC) (WMD: -0.18 mmol/L; 95% CI: -0.30, -0.06; I 2 = 0%); LDL-C (WMD: -0.12 mmol/L; 95% CI -0.22, -0.03; I 2 = 0%) and TC:HDL ratio (WMD: -0.17; CI: -0.33, -0.01; I 2 = 9%; n = 6). No significant effects were observed for HDL-cholesterol, triacylglycerol (TAG) concentrations (n = 10), or systolic/diastolic BP (n = 5). Subgroup analyses by health status revealed no differences in cholesterol profile or BP. However, TAG lowering was evident in the ‘at-risk’ subgroup (WMD: -0.20 mmol/L; 95% CI: -0.34, -0.06; I 2 = 0%), but not in healthy individuals (WMD: -0.01 mmol/L; 95% CI: -0.17, 0.14; I 2 = 41%), indicating a possible differential response by health status. Overall, these findings support a modest cholesterol-lowering effect of MFGM/MPL consumption, with low heterogeneity across trials, consistent with its proposed role in cardiovascular risk reduction. Although no significant effects were observed for TAG concentrations overall, subgroup analyses suggest a potential TAG-lowering effect in individuals at CMD risk. Further large, high-quality RCTs are warranted to confirm effects on other CMD risk markers and explore potential benefits in specific subgroups.