No evidence from randomised controlled trials for or against the use of huperzine A in the treatment of people with mild cognitive impairment

Mild cognitive impairment (MCI) is a condition in which a person has problems with memory, language or another mental function severe enough to be noticeable to other people and to show up on tests, but not serious enough to interfere with daily life. Research has shown that individuals with MCI have an increased risk of developing Alzheimer's disease (AD) over the following few years, especially when their main problem is memory. Currently available drug treatments for AD are thought to work by inhibiting the enzyme acetylcholinesterase and hence increasing acetylcholine levels in the brain. However, these drugs have not been shown to be effective for MCI and have numerous side effects. Huperzine A is a herbal medicine that is an alkaloid isolated from the Chinese herb Huperzia serrata. It has also been found to be an inhibitor of acetylcholinesterase and to possess other properties (such as protecting the brain against glutamate-induced damage, and increasing levels of nerve growth factor), which may have some beneficial effects in MCI. It is used to treat MCI in China, but because no randomised controlled trials of huperzine A versus placebo were found its efficacy and safety could not be analysed in this review. There is a need for randomised placebo-controlled trials of huperzine A for people with MCI.

Authors' conclusions: 

The currently available evidence is insufficient to assess the potential for huperzine A in the treatment of MCI. Randomised double-blind placebo-controlled trials are needed.

Read the full abstract...

Mild cognitive impairment (MCI) has been proposed as a condition of intermediate symptomatology between the cognitive changes of ageing and fully developed symptoms of dementia. Treatment in the stages of MCI may delay the deterioration of cognitive impairment and delay the progression to dementia. Currently, the treatments for Alzheimer's disease have been focused on increasing acetylcholine levels in the brain. However, these drugs have not been proven to be effective for MCI and have numerous side effects. Huperzine A may have some beneficial effects in MCI.


To assess the clinical efficacy and safety of huperzine A for the treatment of patients with MCI.

Search strategy: 

We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 23 May 2011 using the terms: huperzine, ayapin, scoparon. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. Additional searches were also performed separately in MEDLINE, EMBASE, PsycINFO, LILACS,, the ICTRP (WHO portal), CENTRAL (The Cochrane Library) and Web of Science with Conference Proceedings.

The following Chinese databases were searched: The Chinese Biomedical Database, VIP Chinese Science and Technique Journals Database, China National Knowledge Infrastructure and The Chinese Clinical Trials Register. In addition, we handsearched 20 Chinese traditional medicine journals from between 1970 and 1989.

Selection criteria: 

Randomised, parallel-group, placebo-controlled trials comparing huperzine A with placebo in patients with MCI were eligible for inclusion.

Data collection and analysis: 

Two review authors independently assessed studies for their eligibility for inclusion.

Main results: 

No eligible trials were identified. In the absence of any suitable randomised placebo-controlled trials in this area, we were unable to perform a meta-analysis.