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Research Article | Open Access

Docosahexaenoic acid, folic acid, and phosphatidylserine co-intervention alleviate cognitive impairment in D-galactose-induced aged mice

Yingying Lina,bYi Cuib,cYi XuebXiaoya LinbYuning Zhanga,bYiran WangbLining ChenbZenghui XiabHuiyuan Guoa,b,c ( )
Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100191, China
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
National Center of Technology Innovation for Dairy, Hohhot 010110, China

Peer review under responsibility of Beijing Academy of Food Sciences.

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• The DFP treatment restored cognitive performance by regulating antioxidant levels, inhibiting microglia activation, and reducing inflammation.

• The DFP treatment could improve neurotrophic factor expression and decrease neuroinflammation in the brain of mice, thus reducing neuron damage and enhancing synaptic plasticity.

• The combined supplementation of DFP may improve cognition, and may be more effective than supplement with DHA alone.

Abstract

Following the aging of the population, cognitive impairment is becoming a major public health issue. Research in recent years has highlighted the potential of docosahexaenoic acid (DHA), folic acid (FA), and phosphatidylserine (PS) to improve synaptic plasticity and reduce inflammatory response. However, whether a combined intervention is more effective than using these supplements alone remains unclear. To investigate this, we conducted an experiment on D-galactose-induced aging mice and found that the combining DHA, FA, and PS (DFP) improved spatial learning memory. Moreover, the DFP treatment restored cognitive performance by regulating antioxidant levels, inhibiting microglia activation, and reducing inflammation. The treatment also increased the expression of neurotrophic factors and synaptic-related proteins in the hippocampal region of the brain. Our findings suggest that the supplementation of DPF could be more beneficial than using DHA alone. This combined intervention could improve neurotrophic factor expression and decrease neuroinflammation in the brain of mice, thus reducing neuron damage and enhancing synaptic plasticity. In summary, our results indicate that the combined supplementation of DFP may improve cognition, and may be more effective than supplement with DHA alone.

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Food Science and Human Wellness
Article number: 9250436

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Cite this article:
Lin Y, Cui Y, Xue Y, et al. Docosahexaenoic acid, folic acid, and phosphatidylserine co-intervention alleviate cognitive impairment in D-galactose-induced aged mice. Food Science and Human Wellness, 2026, 15(4): 9250436. https://doi.org/10.26599/FSHW.2024.9250436

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Received: 30 April 2024
Revised: 07 August 2024
Accepted: 10 October 2024
Published: 01 June 2026
© 2026 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).