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Research paper
DHA supplementation improves cognitive function via enhancing Aβ-mediated autophagy in Chinese elderly with mild cognitive impairment: a randomised placebo-controlled trial
  1. Yan-Ping Zhang1,
  2. Yinyin Lou2,
  3. Jing Hu3,
  4. Rujuan Miao3,
  5. Fei Ma3
  1. 1 Department of Infectious Diseases, Tianjin Medical University General Hospital, Tianjin, China
  2. 2 Library, Tianjin Medical University, Tianjin, China
  3. 3 Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
  1. Correspondence to Dr Fei Ma, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China; mf2002245mf{at}


Background Higher docosahexaenoic acid (DHA) intake is inversely correlated with relative risk of Alzheimer’s disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined.

Objective Our study aimed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (Aβ)-mediated autophagy in elderly subjects with MCI.

Methods This was a randomised, double-blind, placebo-controlled trial in Tianjin, China. A total of 240 individuals with MCI were identified and randomly divided into intervention (DHA 2 g/day, n=120) and control (corn oil as placebo, n=120) groups. Cognitive function and blood Aβ-related biomarkers were measured at baseline, 6, 12, 18 and 24 months. Data were analysed using generalised estimating equation.

Results A total of 217 participants (DHA: 109, placebo: 108) completed the trial. During the follow-up, scores of full-scale IQ, verbal IQ and subdomains of information and digit span were significantly higher in the intervention group than the convention group (p<0.05). In the intervention group, blood Aβ-42 level and expression of Aβ protein precursor mRNA were decreased (p<0.05), while Beclin-1 and LC3-II levels and expression of LC3-II mRNA were increased (p<0.05).

Conclusion Daily oral DHA supplementation (2 g/day) for 24 months may improve cognitive function and change blood biomarker-related Aβ-mediated autophagy in people with MCI. Larger longer-term confirmatory studies are warranted.

Trial registration number ChiCTR-IOR-15006058.

  • alzheimer’s disease
  • cognition
  • epidemiology
  • neurobiology
  • randomised trials

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  • Contributors FM: study concept or design and critical revision of the manuscript; Y-PZ: analysed data or performed statistical analysis and drafting of the manuscript for content; YL and JH: field survey and data collection; RM: hands-on conduct of the experiments and data collection. No potential conflicts of interest relevant to this article were reported.

  • Funding This study was supported by grants from 2012 Chinese Nutrition Society Nutrition Research Foundation—DSM Research Fund (grant number: 2014-003) and the National Natural Science Foundation of China (grant number: 81573148).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study adheres to the principles of the Declaration of Helsinki. The protocol was approved by the Ethics Committee at Tianjin Medical University, China.

  • Provenance and peer review Not commissioned; externally peer reviewed.