TY - JOUR
T1 - The effect of milk fat globule membrane phospholipid supplementation on cognitive function in older adults with subjective memory complaints—a randomized, double-blind, placebo-controlled trial
AU - Zajac, Ian T.
AU - Kakoschke, Naomi
AU - Evas, Stefanie
AU - Kuhn-Sherlock, Barbara
AU - Wood, Katie
AU - King, Rebecca
AU - Arnoldy, Lizanne
AU - Dekker, James
AU - Gunn, Caroline
AU - Fuad, Maher
AU - Scholey, Andrew
AU - MacGibbon, Alastair
AU - White, David J.
PY - 2025/11/1
Y1 - 2025/11/1
N2 - Background: Milk fat globule membrane (MFGM) phospholipids have been linked to improved cognitive function, especially in infants, but evidence in healthy older adults is limited. Objectives: This project investigated MFGM phospholipid supplementation in older adults and focused on clinically meaningful cognitive function and other health-related outcomes. Methods: This study was a multicenter, repeated-measures, parallel groups, randomized, double-blind, placebo-controlled trial. A total of N = 263 participants aged 55-75 y were randomly assigned to receive: 1) powdered milk fortified with low-dose MFGM (1.7-g phospholipid/d); 2) powdered milk fortified with high-dose MFGM (4.0-g phospholipid/d); or 3) rice starch powder (Control). Randomization used minimization to balance groups across study sites, sex, age, and Montreal Cognitive Assessment scores (MoCA). Participants consumed the product daily for 16 wk and attended their local study site at baseline, week 8, and endpoint. At each visit, they completed various cognitive, behavioral, biochemical, and physical measures. Results: For the primary cognitive outcome, Repeatable Battery for Neuropsychological Status (RBANS), there were no significant treatment effects, nor for the secondary cognitive outcome, Computerized Mental Performance Assessment System (COMPASS); however, alertness (Bond-Lader Visual Analogue Scales) was better maintained during cognitive testing at endpoint in the high-dose group. TNF-α was reduced in the high-dose group, whereas γ-aminobutyric acid (GABA) and serotonin increased in both MFGM groups. Cholesterol and low-density lipoprotein (LDL) were also reduced in both MFGM groups. Active B12 increased, and homocysteine tended to decrease in the high-dose group. Conclusions: Although no significant effects were evident for cognitive function, subjective alertness during cognitive testing was improved in the high-dose group. Reduced inflammation, cholesterol, and LDL impacts for long-term cardiovascular health, linked with cognitive decline in aging. MFGM supplementation positively impacted active B12 (high and low dose) and homocysteine (high dose only), which have been associated with brain health. Longer study durations are needed to demonstrate cognitive benefits. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12620000270910; www.anzctr.org.au.
AB - Background: Milk fat globule membrane (MFGM) phospholipids have been linked to improved cognitive function, especially in infants, but evidence in healthy older adults is limited. Objectives: This project investigated MFGM phospholipid supplementation in older adults and focused on clinically meaningful cognitive function and other health-related outcomes. Methods: This study was a multicenter, repeated-measures, parallel groups, randomized, double-blind, placebo-controlled trial. A total of N = 263 participants aged 55-75 y were randomly assigned to receive: 1) powdered milk fortified with low-dose MFGM (1.7-g phospholipid/d); 2) powdered milk fortified with high-dose MFGM (4.0-g phospholipid/d); or 3) rice starch powder (Control). Randomization used minimization to balance groups across study sites, sex, age, and Montreal Cognitive Assessment scores (MoCA). Participants consumed the product daily for 16 wk and attended their local study site at baseline, week 8, and endpoint. At each visit, they completed various cognitive, behavioral, biochemical, and physical measures. Results: For the primary cognitive outcome, Repeatable Battery for Neuropsychological Status (RBANS), there were no significant treatment effects, nor for the secondary cognitive outcome, Computerized Mental Performance Assessment System (COMPASS); however, alertness (Bond-Lader Visual Analogue Scales) was better maintained during cognitive testing at endpoint in the high-dose group. TNF-α was reduced in the high-dose group, whereas γ-aminobutyric acid (GABA) and serotonin increased in both MFGM groups. Cholesterol and low-density lipoprotein (LDL) were also reduced in both MFGM groups. Active B12 increased, and homocysteine tended to decrease in the high-dose group. Conclusions: Although no significant effects were evident for cognitive function, subjective alertness during cognitive testing was improved in the high-dose group. Reduced inflammation, cholesterol, and LDL impacts for long-term cardiovascular health, linked with cognitive decline in aging. MFGM supplementation positively impacted active B12 (high and low dose) and homocysteine (high dose only), which have been associated with brain health. Longer study durations are needed to demonstrate cognitive benefits. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12620000270910; www.anzctr.org.au.
KW - Acute mood
KW - Clinical trial
KW - Cognitive function
KW - Complex milk lipids
KW - Dairy intake
KW - Dietary supplementation
KW - GABA
KW - Milk fat globule membrane
KW - Phospholipids
KW - Serotonin
UR - https://www.scopus.com/pages/publications/105017322540
U2 - 10.1016/j.ajcnut.2025.09.005
DO - 10.1016/j.ajcnut.2025.09.005
M3 - Article
C2 - 40939691
AN - SCOPUS:105017322540
SN - 0002-9165
VL - 112
SP - 1161
EP - 1173
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 5
ER -