Firmoss plant

Huperzine A

  • Vitamins & Supplements
  • Updated August 30, 2016

Huperzine A is a dietary supplement derived from several species of firmoss plants. It may increase the levels of acetylcholine and other neurotransmitters in the brain and has been studied as a possible treatment for the symptoms of Alzheimer's disease. Huperzine A might slightly improve memory and cognition for patients with vascular dementia and Alzheimer's disease; however, the small size of the studies prevents firm conclusions. It appears safe for short-term use, but evidence for long-term safety is lacking.

Evidence

Though several clinical trials have examined the effect of huperzine A on Alzheimer’s patients, it is difficult to conclude whether it is effective. Our search identified:

• 5 meta-analyses or systematic reviews of small clinical trials for the treatment of Alzheimer's disease or vascular dementia
• 2 clinical trials in healthy individuals
• 0 observational studies or clinical trials on the prevention of dementia or cognitive decline
• Multiple preclinical studies

Potential Benefit

Preclinical trials suggest that huperzine A may benefit and protect the brain through multiple pathways [1-3], but it is not yet clear whether these benefits translate to humans. No studies have tested whether huperzine A can prevent dementia or cognitive decline. Huperzine A supplements are often promoted as nootropic (i.e., promoting cognitive function) but a quasi-randomized double-blind study of 84 healthy individuals in the military reported that huperzine A did not improve cognitive function [4]. Another randomized double-blind clinical trial in China reported that 50 ug of huperzine A twice per day for four weeks improved memory in junior high students with subjective memory problems. However, the trial was small, and it is not clear whether the effect was large enough to be noticed in daily life [5].

For Dementia Patients

Many small clinical trials have tested huperzine A as a treatment for Alzheimer's disease. These were reviewed in four meta-analyses [6-9]. Another two trials tested the drug for vascular dementia [10][11]. While most trials saw clinically meaningful improvements, the trials were small, short, and at a high risk of bias that casts some doubt on the conclusions [9]. Because huperzine A is thought to work in a similar manner to most Alzheimer's drugs, including Aricept, it is unclear whether it would have added benefit on patients who already take these drugs. Indeed, the addition of huperzine A may raise the risk of side effects [12].

Safety

Serious side effects have not been reported in the small clinical trials completed for huperzine A. However, there have been occasional reports of headaches, dizziness, and blurred vision as well as gastrointestinal side effects. Since all trials lasted 36 weeks or less, long-term safety is unknown. One study did find that huperzine A might lower heart rate and worsen some epilepsy symptoms [13].

Although the Drugs.com Interactions Checker lists no harmful interactions between huperzine A and prescription medications, not every medication has been evaluated. Since huperzine A and common Alzheimer's disease drugs such as Aricept behave similarly, it may exacerbate the side effects of these drugs. It may also reduce the effectiveness of other drugs with anti-cholinergic effects such as some anti-histamines and anti-depressants [14].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Huperzine A is available as a dietary supplement and is often marketed as a nootropic, a substance that may enhance memory. A variety of manufacturers offer huperzine A oral supplements in doses of 0.05 to 0.2 mg. Clinical trials in dementia patients have used doses between 0.2 to 0.4 mg/day [6]. A Phase 2 clinical trial reported that 0.4 mg twice per day, but not 0.2 mg twice per day, showed some benefit in patients with Alzheimer's disease [15][16]. Huperzine A is also found in several multi-supplement formulations.

Learn More

Huperzine A on Drugs.com

Huperzine A on alzforum.org

References

  1. Zhang HY, Yan H, Tang XC (2008) Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cell Mol Neurobiol 28, 173-183.
  2. Ma T, Gong K, Yan Y et al. (2013) Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res 1506, 35-43.
  3. Ratia M, Gimenez-Llort L, Camps P et al. (2013) Huprine X and huperzine A improve cognition and regulate some neurochemical processes related with Alzheimer's disease in triple transgenic mice (3xTg-AD). Neuro-degenerative diseases 11, 129-140.
  4. Morasch KC, Aaron CL, Moon JE et al. (2015) Physiological and neurobehavioral effects of cholinesterase inhibition in healthy adults. Physiol Behav 138, 165-172.
  5. Sun QQ, Xu SS, Pan JL et al. (1999) Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo Yao Li Xue Bao 20, 601-603.
  6. Li J, Wu HM, Zhou RL et al. (2008) Huperzine A for Alzheimer's disease. The Cochrane database of systematic reviews, CD005592.
  7. Wang BS, Wang H, Wei ZH et al. (2009) Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. Journal of neural transmission 116, 457-465.
  8. Xing SH, Zhu CX, Zhang R et al. (2014) Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evidence-based complementary and alternative medicine : eCAM 2014, 363985.
  9. Yang G, Wang Y, Tian J et al. (2013) Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PloS one 8, e74916.
  10. Hao Z, Liu M, Liu Z et al. (2009) Huperzine A for vascular dementia. The Cochrane database of systematic reviews, CD007365.
  11. Xu ZQ, Liang XM, Juan W et al. (2012) Treatment with Huperzine A improves cognition in vascular dementia patients. Cell biochemistry and biophysics 62, 55-58.
  12. Drugs.com Huperzine A Safety (accessed 09/19 2016).
  13. Bialer M, Johannessen SI, Levy RH et al. (2015) Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII). Epilepsy research 111, 85-141
  14. WebMD Huperzine A Drug Interactions (accessed 9/8 2016).
  15. Aisen PS, Cummings J, Schneider LS (2012) Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer disease. Cold Spring Harb Perspect Med 2, a006395.
  16. Rafii MS, Walsh S, Little JT et al. (2011) A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology 76, 1389-1394.