Functional dairy-derived ingredients, including whey protein (WP) and milk fat globule membrane (MFGM), have the potential to improve markers of cardiovascular disease (CVD) and broader cardiometabolic disease risk (1,2) . WP supplementation has been shown to regulate fasting lipid profiles (2) . Similarly, growing evidence suggests that MFGM, or its bioactive milk polar lipids (MPLs), may contribute to lipid regulation (1) . However, the potential synergistic effects of WP and MFGM on fasting blood lipid profiles remain unclear, particularly in ‘at risk’ populations. Hence, we assessed the impact of short-term WP-enriched MFGM supplementation on fasting circulating low-density lipoprotein cholesterol (LDL-C) (primary outcome) and several secondary outcomes serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triacylglycerol (TAG), glucose, and BMI in middle-to-older aged adults living with overweight and at moderate risk for CVD. In a double-blind, randomised, placebo-controlled crossover trial (ClinicalTrials.gov: NCT05939544), 17 participants (9 males; mean ± SD: age: 60 ± 7 y; BMI: 29.9 ± 4.6 kg/m 2 ; TC: 6.06 ± 0.95 mmol/L) received 4-week daily WP-(49.6 g total protein) enriched MFGM (4.7 g MPL) supplement or an isocaloric, WP-based, protein-matched placebo, separated by a 4-week washout. Supplements were coded as A or B to maintain blinding. Fasting serum lipids and glucose were assessed pre- and post-intervention using spectrophotometric assays, with LDL-C estimated using the Friedewald equation. Treatment effects were analysed using linear mixed models, adjusted for baseline, period, sequence, sex, age, and BMI, with data presented as estimated marginal means with 95% CIs for change-from-baseline. There was no differential effect of treatment on the primary or secondary outcomes. However, relative to baseline, both treatments significantly reduced serum LDL-C (Treatment A: -0.28 mmol/L; 95% CI: -0.42, -0.14; Treatment B: -0.32 mmol/L; 95% CI: - 0.46, -0.18; P-treatment = 0.9604). According to epidemiological data (3) , these reductions correspond to an estimated 10.3% decrease in CVD risk for Treatment A, and 11.9% for Treatment B. Similarly, both treatments significantly reduced TC (Treatment A: -0.34 mmol/L; 95% CI: -0.49, -0.19; Treatment B: -0.36 mmol/L; 95% CI: -0.51, -0.21; P-treatment = 0.9966) as well as the LDL-C:HDL-C ratio from baseline (Treatment A: -0.15; 95% CI: - 0.27, -0.02; Treatment B: -0.19 mmol/L; 95% CI: -0.31, -0.06; P-treatment = 0.9408). The TC:HDL-C ratio decreased significantly after Treatment B (-0.23; 95% CI: -0.40, -0.07) but not after Treatment A (-0.15; 95% CI: -0.31, 0.02; P-treatment = 0.6963). Preliminary data suggest that WP supplementation with and without MFGM content benefits the fasting cholesterol profile in middle-to-older aged adults at moderate CVD risk, primarily driven by reductions in circulating LDL-C. However, since small dense LDL particles may be more predictive of coronary heart disease risk than LDL-C (4) , further analysis will determine whether these reductions are accompanied by favourable shifts in LDL particle size and subclass phenotype.
Borkar et al. (Fri,) studied this question.
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