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Randomized Controlled Trial
. 2025 Jul;29(7):100579.
doi: 10.1016/j.jnha.2025.100579. Epub 2025 May 14.

Milk free of A1 β-casein supports superior gains in cognition and quality of life, relative to conventional milk, in older adults with mild cognitive impairment

Keming Zhang  1 , Jianqin Sun  2 , Mingming Han  1 , Yingfei Diao  1 , Yan Xia  1 , Congqing Yang  1 , Stephen R Robinson  3
Affiliations
Randomized Controlled Trial

Milk free of A1 β-casein supports superior gains in cognition and quality of life, relative to conventional milk, in older adults with mild cognitive impairment

Keming Zhang et al. J Nutr Health Aging. 2025 Jul.

Abstract

Objectives: To determine whether the regular consumption of milk free from A1 β-casein (A1PF milk) improves cognitive performance to a greater extent than conventional milk, and if so, whether such improvements are associated with an increase in the serum titres of reduced glutathione (GSH).

Design: A multi-centre, double-blind, randomised controlled trial with two parallel arms, conducted from 7 March 2023 to 13 October 2023.

Setting: Two hospitals in Tianjin, China.

Participants: Volunteers (N = 96) diagnosed with mild cognitive impairment (MCI) and aged between 65 and 75 years.

Intervention: A1PF skim milk powder or conventional skim milk powder, diluted into liquid form (200 mL) and consumed twice daily for 90 days.

Measurements: The primary outcomes were cognitive performance (assessed with the Subtle Cognitive Impairment Test [SCIT]) and serum titres of GSH. Secondary outcomes included performance on two other cognitive tests, serum levels of 25-hydroxyvitamin D3, subjective quality of life (QoL), muscle strength (hand grip scale), faecal and blood inflammatory markers.

Results: Data from 91 participants were analysed (A1PF milk group: n = 45; conventional milk group: n = 46). A1PF milk improved performance on all three cognitive tests to a greater extent than conventional milk; however, this improvement was not associated with an increase in serum GSH. When compared with conventional milk, A1PF milk resulted in higher increases in serum levels of 25-hydroxyvitamin D3, greater subjective improvements in QoL and improved left hand grip strength. There were no between-group differences in inflammatory markers, calcium absorption or bone density markers.

Conclusion: Daily intake of A1PF milk for 90 days significantly improved cognition, QoL and muscle strength in a sample of older people with MCI. While these outcomes appear to be linked to increased serum titres of 25-hydroxyvitamin D3, further investigations are needed to confirm this association.

Clinical trial registration: NCT05741047 (clinicaltrials.gov).

Keywords: A1 protein-free milk; A2 milk; Beta casein; Handgrip strength.

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Conflict of interest statement

Declaration of competing interest Stephen R. Robinson is a director of Neurotest Pty Ltd. This company markets the SCIT and also provides consultancy services for The a2 Milk Company. The other authors have no conflicts of interest to declare in relation to this study.

Figures

Fig. 1
Fig. 1
1a. Study design and 1b. Participant disposition. Participant withdrawals (n = 3 in the A1PF milk group and n = 2 in the conventional milk group) were because of participants not consuming the study powdered milk.
Fig. 2
Fig. 2
Change from baseline in cognitive function assessments with the 2a. MoCa and 2b. AVLT. 2c. Change from baseline in 25-hydroxyvitamin D3. ​Change from baseline in hand grip strength in the 2d. left hand and 2e. right hand​. Data are shown as least squares mean of change from baseline (baseline values deducted), and error bars show standard error. AVLT, Auditory Verbal Learning Test; MoCA, Montreal Cognitive Assessment.
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