Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials

PLoS One. 2013 Sep 23;8(9):e74916. doi: 10.1371/journal.pone.0074916. eCollection 2013.


Background: Huperzine A is a Chinese herb extract used for Alzheimer's disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer's disease.

Methods: We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer's disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249).

Results: 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer's disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A.

Conclusions: Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer's disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alkaloids / therapeutic use*
  • Alzheimer Disease / drug therapy*
  • Humans
  • Placebos
  • Publication Bias
  • Randomized Controlled Trials as Topic*
  • Risk Factors
  • Sesquiterpenes / therapeutic use*


  • Alkaloids
  • Placebos
  • Sesquiterpenes
  • huperzine A

Grants and funding

This review was funded by the Program for Innovative Research Teams of Beijing University of Chinese Medicine (2011-CXTD-09 and -21). Prof Jinzhou Tian and Jian-Ping Liu were supported by the grant the 111 Project (No.B08006), and the Technological Platform of Clinical Evaluation and Research for New Herbal Medicinal Products (2011ZX09302-006-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.