Huperzine A (HUP-er-zeen) is a potent chemical derived from a particular type of club moss ( Huperzia serrata [Thumb] Trev.). Like caffeine and cocaine, huperzine A is a medicinally active, plant-derived chemical that belongs to the class known as alkaloids. It was first isolated in 1948 by Chinese scientists.1 This substance is really more a drug than an herb, but it is sold over the counter as a dietary supplement for memory loss and mental impairment.
Studies in animals suggested that it could improve memory skills.2-17 These finding led to human trials (described below) and the subsequent marketing of the huperzine A as a treatment for Alzheimer’s disease and related conditions. It is also sold as a “brain booster” for enhancing memory and mental function in people without Alzheimer’s disease.
Huperzine A inhibits the enzyme acetylcholinesterase (uh-SEE-tul-co-lin-ES-ter-ase). This enzyme breaks down acetylcholine, a substance that plays an important role in mental function. When the enzyme that breaks it down is inhibited, acetylcholine levels in the brain tend to rise. Drugs that inhibit acetylcholinesterase (such as tacrine and donepezil) improve memory and mental functioning in people with Alzheimer's and other severe conditions. The research on huperzine A indicates that it works in much the same way. The chemical action of huperzine A is very precise and specific. It "fits" into a niche on the enzyme where acetylcholine is supposed to attach.22,23 Because huperzine A is in the way, the enzyme cannot grab and destroy acetylcholine. This mechanism has been demonstrated by considerable scientific work, including sophisticated computer modeling of the shape of the molecule.24 Huperzine may also help protect nerve cells from damage.25-28
Note that, while huperzine A is sold as a dietary supplement, in all essential ways it is simply a typical drug. Huperzine A is highly purified in a laboratory and is just a single chemical. It is simply not much like an herb. Herbs contain hundreds or thousands of chemicals. Huperzine A resembles drugs such as digoxin, codeine, Sudafed, and vincristine (a chemotherapy drug), which are also highly purified chemicals taken from plants. If we wish to call huperzine A a natural treatment, we need to call these (and dozens of other standard drugs) natural as well.
All clinical trials of huperzine to date were performed in China and reported in Chinese.
A double-blind, placebo-controlled study evaluated 103 people with Alzheimer's Disease who received either huperzine A or placebo twice daily for 8 weeks.18 About 60% of the treated participants showed improvements in memory, thinking, and behavioral functions compared to 36% of the placebo-treated group, and the difference was significant. Benefits were also seen in an earlier double-blind trial using injected huperzine in 160 individuals with dementia or other memory disorders.19
However, not all studies have been positive. Another double-blind trial of 60 individuals with Alzheimer's disease found no significant difference in symptoms between the treated and the placebo groups.20 Such contradictory results are common when a treatment is only modestly effective, as may be the case here. In a 2008 detailed review of six randomized controlled trials, researchers concluded that, on balance, huperzine A appears to have some beneficial effects. However, the variable quality of these studies suggests that the evidence to date is not strong.29
Huperzine A is a highly potent compound with a recommended dose of only 100 to 200 micrograms twice a day for age-related memory loss. We recommend using it only under a doctor's supervision.
Perhaps because it works so specifically, huperzine A appears to have few side effects. However, children, pregnant or nursing women, or those with high blood pressure or severe liver or kidney disease should not take huperzine A except on a doctor's recommendation. We also do not know for sure whether huperzine A interacts adversely with any drugs; however, it seems likely that huperzine might interact with drugs that function in a similar fashion (such as standard drugs for Alzheimer's Disease).
1. Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders [in Chinese; English abstract]. Zhongguo Yao Li Xue Bao. 1991;12:250–252.
2. Cheng DH, Tang XC. Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav. 1998;60:377–386.
3. Cheng DH, Ren H, Tang XC. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport. 1996;8:97–101.
4. Xiong ZQ, Tang XC. Effect of huperzine A, a novel acetylcholinesterase inhibitor, on radial maze performance in rats. Pharmacol Biochem Behav. 1995;51:415–419.
5. Zhi QX, Yi FH, XI CT. Huperzine A ameliorates the spatial working memory impairments induced by AF64A. Neuroreport. 1995;6:2221–2224.
6. Zhu XD, Giacobini E. Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines. J Neurosci Res. 1995;41:828–835.
7. Zhang GB, Wang MY, Zheng JQ, et al. Facilitation of cholinergic transmission by huperzine A in toad paravertebral ganglia in vitro [in Chinese; English abstract]. Zhongguo Yao Li Xue Bao. 1994;15:158–161.
8. Laganiere S, Corey J, Tang XC, et al. Acute and chronic studies with the anticholinesterase Huperzine A: effect on central nervous system cholinergic parameters. Neuropharmacology. 1991;30:763–768.
9. Tang XC, De Sarno P, Sugaya K, et al. Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat. J Neurosci Res. 1989;24:276–285.
10. Tang XC, Han YF, Chen XP, et al. Effects of huperzine A on learning and the retrieval process of discrimination performance in rats [in Chinese]. Zhongguo Yao Li Xue Bao. 1986;7:507–511.
11. Guan LC, Chen SS, Lu WH, et al. Effects of huperzine A on electroencephalography power spectrum in rabbits [in Chinese; English abstract]. Zhongguo Yao Li Xue Bao. 1989;10:496–500.
12. Lu WH, Shou J, Tang XC. Improving effect of huperzine A on discrimination performance in aged rats and adult rats with experimental cognitive impairment [in Chinese]. Zhongguo Yao Li Xue Bao. 1988;9:11–15.
13. Wang YE, Feng J, Lu WH. Pharmacokinetics of huperzine A in rats and mice [in Chinese]. Zhongguo Yao Li Xue Bao. 1988;9:193–196.
14. Wang YE, Yue DX, Tang XC. Anti-cholinesterase activity of huperzine A [in Chinese]. Zhongguo Yao Li Xue Bao. 1986;7:110–113.
15. Zhu XD, Tang XC. Improvement of impaired memory in mice by huperzine A and huperzine B [in Chinese]. Zhongguo Yao Li Xue Bao. 1988;9:492–497.
16. Zhu XD, Tang XC. Facilitatory effects of huperzine A and B on learning and memory of spatial discrimination in mice [in Chinese]. Yao Xue Xue Bao. 1987;22:812–817.
17. Yan XF, Lu WH, Lou WJ, et al. Effects of huperzine A and B on skeletal muscle and the electroencephalogram [in Chinese]. Zhongguo Yao Li Xue Bao. 1987;8:117–123.
18. Xu SS, Goa ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao. 1995;16:391–395.
19. Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders [in Chinese; English abstract]. Zhongguo Yao Li Xue Bao. 1991;12:250–252.
20. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease [abstract]. Zhongguo Yao Li Xue Bao. 1999;20:486–490.
21. Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students [abstract]. Zhongguo Yao Li Xue Bao. 1999;20:601–603.
22. Raves ML, Harel M, Pang YP, et al. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol. 1997;4:57–63.
23. Ashani Y, Peggins JO III, Doctor BP. Mechanism of inhibition of cholinesterases by huperzine A. Biochem Biophys Res Commun. 1992;184:719–726.
24. Pang YP, Kozikowski AP. Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies. J Comput Aided Mol Des. 1994;8:669–681.
25. Ved HS, Koenig ML, Dave JR, et al. Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport. 1997;8:963–968.
26. Zhou J, Zhang HY, Tang XC. Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci Lett. 2001;313:137-140.
27. Zhou J, Fu Y, Tang XC. Huperzine A protects rat pheochromocytoma cells against oxygen-glucose deprivation. Neuroreport. 2001;12:2073-2077.
28. Wang LM, Han YF, Tang XC. Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats. Eur J Pharmacol. 2000;398:65-72.
29. Li J, Wu HM, Zhou RL, Liu GJ, Dong BR. Huperzine A for Alzheimer's disease. Cochrane Database of Systematic Reviews. 2008;(2):CD005592
Last reviewed September 2014 by EBSCO CAM Review Board
Last Updated: 9/18/2014
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