Meta-Analysis of Bioaccessibility of Hydrophobic Compounds in Buttermilk Matrices: A Systematic Review and Quantitative Synthesis.

Hydrophobic bioactive compounds, such as curcuminoids, β-carotene and long-chain lipids, as well as amphiphilic structural lipids (milk fat globule membrane (MFGM)-associated phospholipids), often exhibit low bioaccessibility due to poor aqueous solubility and/or susceptibility to degradation, which limits their effective use in functional foods. Buttermilk, a dairy byproduct enriched with proteins, lipids and MFGM components, provides a structurally complex, amphiphilic matrix that can enhance micellar solubilization, protect hydrophobic and amphiphilic compounds during digestion and thereby modulate their potential bioavailability. This systematic review and meta-analysis, conducted and reported in accordance with the PRISMA 2020 guidelines, synthesizes quantitative data from in vitro gastrointestinal digestion studies to evaluate the impact of buttermilk and related matrices (e.g., buttermilk yogurt, ultrafiltered buttermilk, and composite nanosystems) on the bioaccessibility of hydrophobic compounds and MFGM phospholipids compared with aqueous or non-buttermilk controls. We identified a limited but growing body of in vitro evidence indicating that buttermilk-based matrices generally increase the intestinal bioaccessibility of curcuminoids, β-carotene, omega-3 fatty acids, vitamin and MFGM phospholipids relative to non-buttermilk systems, with particularly pronounced effects in structured emulsions, yogurts, ultrafiltered buttermilk and MFGM-enriched nanosystems. Rather than a single effect size, the data point to a compound- and matrix-dependent spectrum of improvements, influenced by both the chemical nature of the bioactive and the supramolecular organization of the dairy matrix. Mechanistically, the available findings support a plausible hypothesis that buttermilk enhances bioaccessibility via MFGM-mediated micellar solubilization, interfacial protection against pH- and enzyme-driven degradation and favorable lipid partitioning, although these pathways remain to be confirmed in dedicated mechanistic and in vivo studies. Methodological heterogeneity and the exclusive reliance on in vitro models are important limitations, but overall, the synthesis supports buttermilk and MFGM-rich ingredients as sustainable, food-grade carriers for lipophilic nutraceuticals and highlights the importance of dairy matrix structure in the design of functional delivery systems.