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Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Observational studies have frequently reported that low blood folate concentrations are associated with poor cognitive performance. Our previous studies have shown the potential beneficial effect on the metabolite levels of methionine cycle and peripheral blood inflammatory cytokines from 6- and 12-month folic acid supplementation on cognitive function in mild cognitive impairment (MCI). This study aims to continue exploring the effect of 24-month folic acid supplementation on cognitive function and pathological mechanism in MCI.

Methods

180 individuals with MCI were identified and randomly divided into intervention (folic acid 400 µg/day, n = 90) and convention (n = 90) groups. Cognitive function (WAIS-RC) and blood Aβ-related biomarkers were measured at baseline and at 6, 12, 18, and 24 months. Data were analyzed using generalized estimating equation. This trial has been registered with Trial Number: ChiCTR-TRC-13003227.

Results

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 those in the convention group (P < 0.05). In the intervention group, blood homocysteine, S-adenosylhomocysteine (SAH), Aβ-42, and the expression of APP-mRNA were decreased (P < 0.05), while S-adenosylmethionine (SAM), SAM/SAH ratio, and the expression of DNA methyltransferase mRNA were increased (P < 0.05).

Conclusion

Folic acid supplementation appears to improve cognitive function and reduce blood levels of Aβ-related biomarkers in MCI. Larger-scale double-blind placebo-controlled randomized trials of longer duration are needed.

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Abbreviations

Aβ:

β-Amyloid

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

CNS:

Central nervous system

CI:

Confidence intervals

GEE:

Generalized estimating equation

Hcy:

Homocysteine

ITT:

Intention-to-treat

MCI:

Mild cognitive impairment

PIQ:

Performance IQ

PS1:

Presenilin-1

SAH:

S-Adenosylhomocysteine

SAM:

S-Adenosylmethionine

VIQ:

Verbal IQ

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Acknowledgements

The authors thank all of the subjects for their participation. This study was also supported by grants from Tianjin Science and Technology Support Program (Grant Number 15ZCZDSY01040), the National Natural Science Foundation of China (Grant Number 81130053), and Tianjin 13th five plan and TMU talent project (No. 2016KJ0304).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China

    Fei Ma & Weili Xu

  2. Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China

    Qing Li, Xuan Zhou, Wen Li, Huan Liu & Guowei Huang

  3. Community Health Service Center, Sanhuailu Street, Binhai New District, Tianjin, 300456, China

    Jiangang Zhao & Aili Song

  4. Aging Research Center, Department Neurobiology, Care Sciences and Society, Karolinska Institutet, 113 30, Stockholm, Sweden

    Weili Xu

Authors
  1. Fei Ma
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  9. Guowei Huang
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Contributions

The authors’ responsibilities were as follows: G. Huang and F. Ma—study design; Q. Li, J. Zhao, and A. Song—field survey; X. Zhou, W. Li, and H. Liu—data analysis; F. Ma and W. Xu: writing the paper.

Corresponding author

Correspondence to Guowei Huang.

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Ma, F., Li, Q., Zhou, X. et al. Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial. Eur J Nutr 58, 345–356 (2019). https://doi.org/10.1007/s00394-017-1598-5

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  • DOI: https://doi.org/10.1007/s00394-017-1598-5

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