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Supplements

huperzine A

What Is It?
Health Benefits
Forms

Dosage Information

Guidelines for Use

General Interaction

Possible Side Effects

Cautions

References
Evidence Based Rating Scale

 

What Is It?

For centuries in the Far East, traditional healers have used a rare moss (Huperzia serrata) found in the colder regions of China to remedy fever and Inflammation. Only recently did scientists uncover a remarkable quality in a substance they isolated in the moss. Called huperzine A, the compound appears to sharpen the mind and potentially ward off the devastating effects of the memory-robbing disease known as Alzheimer's, particularly in its earliest stages. Huperzine A has also been proposed for countering normal bouts of forgetfulness in the general population.

Huperzine A has been used as a prescription drug in China since the early 1990s, with no reports of serious adverse effects from the hundreds of thousands of consumers who used it. (1) However, in the U.S.A, it continues to be marketed as a dietary supplement as the FDA has not given it drug status.

Health Benefits

Huperzine A has been used in China for centuries to treat swelling, fever and blood disorders, and it has also been used to increase alertness and energy, and to improve muscle fatigue in the neuromuscular disease Myasthenia gravis. But huperzine A has gained the most popularity in the United States for its potential to improve brain function and to treat Alzheimer's Disease.

Specifically, huperzine A may help to:

Improve memory loss/impairment. Mental improvements associated with huperzine A appear to stem from the compound's ability to inhibit the breakdown of and maintain healthy levels of acetylcholine, a brain chemical essential to memory function. While mild memory lapses are usually not a cause for concern, forgetfulness is often preventable or reversible when it is not associated with Alzheimer's disease or other forms of irreversible dementia. Taking huperzine A seems to improve memory function. In a preliminary small-scale, placebo-controlled trial, 34 Chinese middle school students complaining of poor memory showed significant improvement in memory quotient scores compared to a placebo group after taking 50 mcg of huperzine A twice daily for four weeks. (2) Several studies in animals have since shown huperzine A improves memory and is actually more effective than conventional medications, such as tacrine (Cognex). (3-7) In one study, huperzine A was shown to be 64 times more potent than tacrine, due to its increased bioavailability and penetration of the blood-brain barrier. (3)

Treat Alzheimer's Disease. The only Alzheimer's drugs currently approved by the U.S. Food and Drug Administration work in much the same way as does huperzine A to inhibit acetylcholinesterase, making it potentially important in the treatment of this degenerative disease. In fact, some laboratory findings indicate that huperzine A may be more precise than conventional medications in the manner in which it protects acetylcholine, raising hopes that it could counter memory loss with relatively few side effects. Several Chinese studies have shown huperzine A seems to improve memory, cognitive function, and behavioral function in patients with Alzheimer's Disease (AD) and other forms of dementia. (8-11) In one of the studies, more than 100 patients with AD received 200 mcg of huperzine A or placebo four times daily for eight weeks. Patients in the treatment group showed significant improvement in memory, cognitive, and behavioral functions compared to placebo at the end of the study, and no severe side effects were reported. (10) In a 2002 study, 202 patients diagnosed with possible or probable AD were treated with either 400 mcg of huperzine A daily or placebo for 12 weeks. The treatment group showed significant improvement in all assessment areas (cognition, behavior, activity of daily life, and mood) compared to placebo. (12)

In 2008, the National Institute on Aging conducted the first controlled trial outside of China evaluating the efficacy and toxicity of huperzine A to improve cognitive function in patients with AD. In this multi-center, double-blind, placebo-controlled Phase II trial, 210 participants with mild to moderate AD received either 200 mcg of huperzine A, 400 mcg of huperzine A, or placebo twice daily for 16 weeks. While no statistical difference in cognitive scores was noted in patients in the lower dose huperzine A group compared to placebo, the higher dose (400 mcg) of huperzine A led to improved cognition and activities of daily living. However, no significant changes were noted in any of the three groups in overall change in disease or in psychiatric ratings according to the AD Assessment Scale-Cognitive (ADAS-Cog) scale. Huperzine A was safe and well tolerated in the study. (13) The same year, a Cochrane Database review examined studies evaluating the efficacy and safety of huperzine A in the treatment of AD. The review included six randomized, controlled trials involving 454 patients. Huperzine A seemed to have beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and function performance with no serious side effects for patients with AD. However, researchers found only one study that was of adequate quality and size to rate the use of huperzine A to treat AD. (14) More large, high quality randomized studies are needed.

Prevent seizures in epilepsy. In this chronic neurological disorder, bursts of abnormal electrical activity in the brain produce recurrent seizures – sudden changes in consciousness, sensation, and muscle control. By protecting against neuronal damage through the maintenance of healthy levels of acetylcholine, huperzine A may protect against seizures. (15-17) A 1997 study in guinea pigs evaluated the use of huperzine A as a pre-treatment to prevent seizures from occurring when induced with soman, a toxic nerve agent that typically produces seizures. The study showed huperzine A completely prevented soman-induced seizures and ensured the survival of all animals for 24 hours after treatment. (18) Another study found similar results in mice, with 93 percent of mice treated with huperzine A surviving without any seizures. (19) And a small study in primates showed similar results, with huperzine A leading to a higher tolerance against soman than the conventional drug pyridostigmine. (20) Human studies are needed to confirm efficacy of huperzine A in preventing seizures related to epilepsy.  

Forms

  • Capsule
  • Intramuscular 

Dosage Information

For Alzheimer's disease:  Studies have shown 400 mcg twice daily to be most effective.

For epilepsy: Doses have not been established for humans.

For memory loss/impairment: 50 to 100 mcg twice daily has been used.

Guidelines for Use

Although apparently safe over the short term, there is no information on whether huperzine A will lead to long-term complications, especially when used in conjunction with other medications. Consult a doctor for guidance. 

Use only 99% purified compounds of huperzine A; crude extracts of the moss are potentially toxic and could have sedative effects. 

General Interaction

Huperzine A is believed to have a synergistic effect when combined with acetylcholinesterase inhibitors, drugs that act in a similar fashion to combat Alzheimer's-related memory loss. So while the combination of these two agents could potentially boost the benefits of both, it may also lead to as yet unidentified negative reactions. Consult a physician for guidance.

Possible Side Effects

No severe side effects have been reported. 

Cholinergic side effects of huperzine A may include nausea, vomiting, diarrhea, headache, and muscle cramps. 

Consult a physician if taking huperzine A seems to cause unusual confusion or memory loss; it's important to have such symptoms professionally examined and treated if necessary. 

Cautions

  • Given its mode of action, huperzine A may affect heart rate. For this reason, don't take huperzine A if you have Hypertension (high blood pressure) or are pregnant. People with asthma or other respiratory diseases should also use huperzine A with care.

  • Patients with gastrointestinal conditions, such as a gastrointestinal tract obstruction or peptic ulcers, should avoid taking huperzine A, as it may exacerbate the conditions. 

  • Avoid confusing the huperzine A brand name Cerebra with the prescription drugs Celebrex, Celexa, and Cerebyx.

  • Huperzine A is also called selagine. Avoid confusing it with the prescription drug selegiline (Eldepryl).

References 

1. Skolnick A. Old Chinese herbal medicine used for fever yields possible new Alzheimer disease therapy. JAMA. 1997;277:776.
2. Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Chung Kuo Yao Li Hseuh Pao. 1999;20:601-3.
3. Pepping J. Huperzine A. Am J Health Syst Pharm. 2000;57:530-4.
4. Ou LY, Tang XC, Cai JX. Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys. Eur J Pharmacol. 2001 Dec 21;433(2-3):151-6.
5. Filliat P, Foquin A, Lallement G. Effects of chronic administration of huperzine A on memory in guinea pigs. Drug Chem Toxicol. 2002 Feb;25(1):9-24.
6. Zhang C, Wang SZ, Zuo PP, Cui X, Cai J. Effect of tetramethylpyrazine on learning, memory and cholinergic system in D-galactose-lesioned mice. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Oct;25(5):553-6.
7. Xu Z, Zheng H, Law SL, et al. Effects of a memory enhancing peptide on cognitive abilities of brain-lesioned mice: additivity with huperzine A and relative potency to tacrine. J Pept Sci. 2006 Jan;12(1):72-8.
8. Zhang SL. Therapeutic effects of huperzine A on the aged with memory impairment. [Article in Chinese]. New Drugs and Clinical Remedies 1986;5:260-2.
9. Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. [Article in Chinese]. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2.
10. Xu SS, Gao 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;16:391-5.
11. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486-90.
12. Zhang Z, Wang X, Chen Q, et al. Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. Zhonghua Yi Xue Za Zhi. 2002 Jul 25;82(14):941-4.
13. National Institute on Aging; Georgetown University Medical Center. A multi-center, double-blind, placebo-controlled, therapeutic trial to determine whether natural Huperzine A improves cognitive function. ClinicalTrials.gov. Washington (D.C.): 2008 Feb [cited 2010 Jan 4]. Available from http://clinicaltrials.gov/show/ NCT00083590. NLM Identifier: NCT00083590.
14. Li J, Wu HM, Zhou RL, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005592.
15. Grunwald J, Raveh L, Doctor BP, Ashani Y. Huperzine A as a pretreatment candidate drug against nerve agent toxicity. Life Sci 1994;54:991-7.
16. Skolnick AA. Old Chinese herbal medicine used for fever yields possible new Alzheimer Disease therapy. JAMA 1997;277:776.
17. Lallement G, Veyret J, Masqueliez C, et al. Efficacy of huperzine in preventing soman-induced seizures, neuropathological changes and lethality. Fundam Clin Pharmacol 1997;11:387-94.
18. Lallement G, Veyret J, Masqueliez C, et al. Efficacy of huperzine in preventing soman-induced seizures, neuropathological changes and lethality. Fundam Clin Pharmacol. 1997;11(5):387-94.
19. Tonduli LS, Testylier G, Masqueliez C, et al. Effects of Huperzine used as pre-treatment against soman-induced seizures. Neurotoxicology. 2001 Feb;22(1):29-37.
20. Lallement G, Demoncheaux JP, Foquin A, et al. Subchronic administration of pyridostigmine or huperzine to primates: compared efficacy against soman toxicity. Drug Chem Toxicol. 2002 Aug;25(3):309-20.

Evidence Based Rating Scale

The Evidence Based Rating Scale is a tool that helps consumers translate the findings of medical research studies and what our clinical advisors have found to be efficacious in their personal practice into a visual and easy to interpret format. This tool is meant to simplify the information on supplements and therapies that demonstrate promise in the treatment of certain conditions.

 

Condition

Rating

Explanation

 

Alzheimer's disease

   

Several studies, traditional use with favorable patient results in China, and Cochrane Database Review indicate efficacy in improving memory, cognitive function, and behavioral function in patients with AD. (8-14)

Epilepsy  
Several studies in animals indicate efficacy in preventing seizures. No human studies have been reported. (15-20)

Memory loss/ impairment

 
Several animal studies and a preliminary study in adolescents indicate efficacy in improving memory greater than conventional medication. Larger studies in humans are needed to confirm or refute efficacy. (2-7)

 


Date Published: 04/18/2005
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