# A1 protein free milk benefits mood and subjective cognition in free-living Australian adults: a pragmatic, exploratory, open label randomised controlled trial

**Authors:** Carlene Starck, Michelle Blumfield, Peter Petocz, Emily Duve, Lucy Downey, Kylie Abbott, Flavia Fayet-Moore

PMC · DOI: 10.3389/fnut.2025.1579986 · 2025-06-03

## TL;DR

Switching to A1 β-casein free milk may improve mood and cognition in healthy adults, especially women, without needing to eliminate all A1 milk.

## Contribution

First study to examine the health effects of A1 β-casein free milk in healthy individuals without milk intolerance symptoms.

## Key findings

- Switching to A1PF milk reduced anxiety, depression, stress, and fatigue, particularly in females.
- Females reported improved subjective cognition and fewer gastrointestinal symptoms after switching milk types.
- No significant changes in gut microbiome or immune response markers were observed.

## Abstract

Adverse effects of milk containing A1-type β-casein on digestion, immune response, and cognition have been identified in milk-intolerant individuals, but health effects in healthy individuals without symptoms of milk intolerance are yet to be examined.

The objective was to explore the impact of reducing A1 type β-casein intake via switching milk type from conventional A1/A2-type β-casein milk (A1/A2 milk) to A1-type β-casein protein free milk (A1PF) on brain, immune response, gastrointestinal, and skin (BIGS) outcomes in a real-world setting.

An open-label, pragmatic, exploratory randomised controlled trial was conducted in 997 healthy, free-living Australian older adolescents and adults (16–65 years) who regularly consume A1/A2 protein-containing milk and milk products. Participants were randomised into two groups, to consume ≥250 mL/day of A1/A2 milk (control) or to switch to ≥250 mL/day of A1PF milk (intervention) for 28 days, while continuing to follow their usual diet (including up to 1 serve a day of A1/A2 dairy products). A sub-group of 265 participants conducted stool, saliva and cognitive testing on days 0 and 28. All participants completed subjective questionnaires on days 0, 14, and 28.

No differences in gut microbiome composition, alpha-diversity, or function were found by switching milk type. After switching to A1PF milk, a small increase in stool consistency was reported (−0.16, p = 0.007), and females experienced a marginal reduction in gastrointestinal symptoms (p = 0.015) and improved subjective cognition (p = 0.03). Switching to A1PF milk reduced anxiety (−0.61; p = 0.002), depression (−0.56; p = 0.023), stress (−0.70, p = 0.012) and fatigue (p = 0.001; females only), compared to drinking A1/A2 milk, with stronger effects in females. No consistent effects on markers of immune response or skin health were identified.

Switching from conventional A1/A2 milk to A1PF milk may benefit mood and subjective cognition, particularly in females, without the need for complete elimination of A1 β-casein from the diet. Further investigations are warranted.

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385966, identifier ACTRN12623000628640.

## Full-text entities

- **Genes:** CSN2 (casein beta) [NCBI Gene 1447] {aka CASB, PDC213}
- **Diseases:** gastrointestinal symptoms (MESH:D012817), fatigue (MESH:D005221), anxiety (MESH:D001007), depression (MESH:D003866)
- **Species:** Homo sapiens (human, species) [taxon 9606], gut metagenome (species) [taxon 749906]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12170308/full.md

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Source: https://tomesphere.com/paper/PMC12170308