Therapeutic potential of milk fat globule membrane for stress, anxiety, and depression: a meta-analysis

Mental health conditions such as stress and anxiety are increasingly targeted by nutritional strategies that modulate neurobiological and inflammatory pathways (1,2) . Milk fat globule membrane (MFGM) is a complex structure of polar lipids, gangliosides, and glycoproteins that has demonstrated anti-inflammatory, neuroprotective, and gut-modulatory effects in preclinical and human studies (3) . However, its effects on adult psychological outcomes have not been systematically synthesised. We conducted a systematic literature search through to September 2025 across multiple databases, including PubMed, Scopus, Web of Science, the Cochrane Library, Google Scholar, ACS Publications, Academic Search Index, BMJ Journals, and BNP Media. The search strategy combined relevant keywords and MeSH terms, with manual reference checks to ensure comprehensiveness. Of the 35 articles initially identified, 12 underwent full-text review after screening for duplicates and relevance. Three3 randomised controlled trials (RCTs, n = 438) met the inclusion criteria: adult participants (≥20 years), bovine MFGM supplementation, a placebo or control group, and outcomes measuring stress, anxiety, or depression. Exclusion criteria included non-RCT designs, special populations, mixed or acute interventions, and studies lacking appropriate controls. The review was conducted and reported according to PRISMA guidelines. A random-effects meta-analysis was performed, calculating standardised mean differences (Hedge’s g) for stress, anxiety, and depression outcomes. Heterogeneity was evaluated with I2 and publication bias was explored with funnel plots and Egger’s test. Two trials contributed two dose arms each, yielding five comparisons for synthesis. MFGM supplementation produced small but statistically significant reductions in stress (SMD = −0.20; 95% CI −0.41 to −0.00; p = 0.0495; I2 = 0%) and anxiety (SMD = −0.22; 95% CI −0.44 to −0.01; p = 0.044; I2 = 0%). Effects on depression were non-significant though directionally favourable (SMD = −0.15; 95% CI −0.37 to 0.07; p = 0.18; I2 = 0%). Risk-of-bias assessments were conducted using Cochrane criteria and indicated low concerns across trials. Funnel plots and Egger’s tests did not indicate clear publication bias, but interpretation is limited by the small number of studies. These findings suggest that bovine MFGM supplementation may confer modest benefits for stress and anxiety in adults, while evidence for depression is inconclusive. Taken together, the results indicate that MFGM could be part of a nutritional strategy to support overall mental well-being.