Natural Club Moss Extract Shows Promise for Treating Alzheimer’s, Enhancing Memory and Alertness

By Jim English

Alzheimer’s Disease (AD) is a progressive degenerative disease that most commonly appears after the age of 50. Currently, Alzheimer’s afflicts approximately 40 percent of all individuals over the age of 85, for a total of 4 million people in the U.S. alone. When symptoms occur before the age of 65 the disease is designated Presenile Dementia of the Alzheimer’s Type (PDAT). When symptoms occur after age 65 the syndrome is referred to as Senile Dementia of the Alzheimer’s Type (SDAT). Symptoms include a gradual yet inexorable loss of memory, mental performance, communication skills, abstract thinking and personality. Ultimately, Alzheimer’s ends in the death of the patient, with a mean life expectancy of 8 years.

As well as being a profound personal tragedy for afflicted individuals and their loved ones, the financial costs of caring for victims of the disease exceed $80 billion per year. The current trend towards longer life expectancy, combined with the increased incidence of senile dementia with age, means that cases of Alzheimer’s increase alarmingly as the median age of the population grows, underscoring the urgency for finding an effective treatment for this disorder.

Huperzine-A is a new supplement derived from an ancient traditional Chinese herbal medicine that offers hope to those suffering from Alzheimer’s disease and other age-related mental conditions. In addition to benefiting patients suffering from Alzheimer’s, Huperzine’s memory-enhancing properties suggest that it may be an effective agent for improving memory and learning in healthy humans as well.

Cholinergic Dysfunction in Alzheimer’s 

Alzheimer’s is characterized by the destruction of nerve cells in several key areas of the brain devoted to mental functions. This results in tangles of nerve fibers and plaque formation of an abnormal, insoluble protein called amyloid. While there is a general reduction in the concentration of all neurotransmitting substances, a marked clinical feature of the disease is a dramatic decrease in the neurotransmitter acetylcholine.

Acetylcholine is a vital neurotransmitter with a fundamental role in memory. It is also necessary for proper intracellular communication between nerve cells. Research has shown that levels of acetylcholine are deficient in the brains of patients with Alzheimer’s disease.

Biopsy and postmortem studies have shown that there is a substantial loss of presynaptic cholinergic neurons in brains of patients with Alzheimer’s.1 What little acetylcholine that is still produced in the patient’s brain is quickly broken down by the brain enzyme, acetylcholinesterase (AchE), leading to a shortage of the neurotransmitter and contributing to the patient’s loss of memory and other cognitive functions.

Prescription Alzheimer’s Drugs 

Two drugs are currently approved for use in the U.S. to treat Alzheimer’s – Tacrine™ and Donepezil hydrochloride (Aricept™). Both drugs are moderately effective cholinesterase inhibitors, that work by interfering with the actions of AChE. Since acetylcholine is normally degraded and recycled by acetylcholinesterase, this approach counteracts any further reduction of already low levels of acetylcholine.

By inhibiting the actions of AChE it is hoped that the small amounts of acetylcholine still being produced will persist longer within the synaptic cleft and lead to improvements in memory and cognitive abilities. While both drugs are effective cholinesterase inhibitors, they suffer from a number of drawbacks. First, they are available only by prescription; second, they are expensive, costing between $100 – $240 per month; and third, both drugs can cause debilitating side effects including liver toxicity (Tacrine), and nausea and diarrhea (Donepezil). (1)

Huperzine A: A Safe Alternative 

Huperzine A is a natural compound derived from an ancient Chinese remedy, Qian Ceng Ta. This traditional herbal medicine was prepared from Huperzia serrata, a clubmoss that grows on the ground in damp forests and rock crevices. Brewed as an herbal tea, Qian Ceng Ta has been used in China to treat fever, inflammation, and irregular menstruation, and has been used as a diuretic.

In the late 1980’s, researchers in China discovered that a purified alkaloid extracted from Huperzia, Huperzine A, was a potent, reversible inhibitor of acetylcholinesterase (AChE). Huperzine A readily crosses the blood-brain barrier to prevent acetylcholinesterase (AchE) from destroying acetylcholine.

Molecular Monkey Wrench 

A study at the Weizmann Institute in Israel uncovered how Huperzine A (Hup-A) works to block acetylcholinesterase. (2) Scientists had previously learned that AchE inhibitors such as tacrine and donepezil worked by sliding into the AChE molecule to “jam up” its molecular machinery and impair its ability to degrade acetylcholine.

By imaging a 3-dimensional structure of the AChE molecule, the researchers were able to peer into the complex folded protein structure to discover a deep chasm, called the active-site gorge. The scientists determined that the active-site gorge acts as a guide to funnel acetylcholine into the interior of the enzyme where it is cut apart prior to recycling.

This study revealed that Huperzine A has a strong specificity for AChE, and is exceptionally well suited to its new role, fitting into the active sites of acetylcholinesterase much like a key slipping into a lock. “Hup-A appears to bind more tightly and specifically to acetylcholinesterase than the other AChE inhibitors,” crystallographer Prof. Joel Sussman, one of the authors of the study said. “It is as if this natural substance were ingeniously designed to fit into the exact spot in AChE where it will do the most good.”

Clinical Studies 

Hup-A has undergone double blind, placebo-controlled clinical trials in China in patients suffering from various memory disorders, including AD. In fact, it is estimated that in the past few years 100,000 people have been treated in China with Hup-A. Researchers in China claim that it helps normal elderly with memory problems as well as people with AD.

Double-blind, placebo-controlled clinical trials in China have demonstrated that patients suffering from Alzheimer’s and various other memory disorders gain significant benefit, both in terms of memory and life quality. Xu et al. conducted a placebo-controlled, double-blind study in which subjects with AD were given 200 mcg/day Hup-A or placebo for 8 weeks. Statistically significant improvement was achieved in 58 percent of the treated group with respect to cognitive function and their ability to retrieve past memories. (3)

In one study, Chinese researchers of the Department of Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou, China, examined the effects of Hup-A on six volunteers. They concluded that Hup-A had a high rate of absorption and distribution in the body, and was without adverse side effects. (4)

A second study conducted by researchers at Zhejiang Medical University, focused on the efficacy of Hup-A on memory, cognition, and behavior in Alzheimer’s disease. This multicenter, double-blind, placebo controlled study found that about 58 percent (29/50) of patients treated with Hup A showed improvements in their memory, cognition, and behavioral functions. No severe side effects were found. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. Their conclusion was that “Hup-A is a promising drug for symptomatic treatment of Alzheimer’s disease.” (4)

In the U.S., a recent paper by noted neurologist, Alan A. Mazurek, M.D., reported on the results of an office-based trial studying the safety and efficacy of Hup-A as a treatment for Alzheimer’s disease. Mazurek evaluated the safety and efficacy of Hup-A in an open-label trial involving 29 patients with mild to moderate AD. (5)

Twenty-two patients (75.9 percent) completed the three month study. Only two patients reported adverse effects, one being an apparently unrelated hemorrhagic infarct that resolved without treatment. No gastrointestinal side effects, nausea, diarrhea, cardiac effects or headache were reported. Status Examinations’ (SMMSE) improvement of one point or greater was seen at one, two and three months. Mazurek reported that improvements appeared to be dose related, with those on the higher dosages exhibiting the greatest improvement. Wrote Mazurek, “Huperzine A appears to be safe, well tolerated, and effective in the symptomatic treatment of AD.”

Other Benefits 

In addition to its activity as an AChE inhibitor, ongoing research suggests that Hup-A has a wider role to play in supporting neuroprotective functions. Researchers recently discovered that Hup-A inhibits glutamate-induced cytotoxicity, protecting neonatal hippocampal and cerebellar neuronal cells in culture from death caused by the amino acid glutamate. In addition to protecting from glutamate-induced cytotoxicity, researchers were also surprised to learn that Huperzine A promotes new dendrite outgrowth of neuronal cultures.

Potential Protection for Chemical Warfare 

Researchers at the Walter Reed Army Institute of Research in Washington D.C. are conducting studies into Huperzine’s potential role as a pretreatment drug to protect against chemical warfare nerve agent poisoning. In one study, Huperzine A was found to be twice as effective in protecting mice against the lethal effects of the nerve agent soman when compared to physostigmine. (6) Huperzine A’s effects lasted for six hours compared to only 90 minutes for physostigmine, providing further evidence for the slow clearance of Huperzine from the body.


Huperzine A has a wide margin of safety. Toxicology studies show Huperzine A to be non-toxic even when administered at 50-100 times the human therapeutic dose! The extract is active for 6 hours at a dose of 2 µg/kg with no remarkable side effects.


Huperzine A appears to be a safe memory supplement. Clinical research has shown that Huperzine A is superior to other cholinesterase inhibitors such as tacrine and donepezil. Huperzine A is rapidly absorbed when taken orally, and possesses a very slow rate of dissociation from the enzyme and a longer duration of action. Studies in rodents show that AChE remains inhibited by 33 percent after 6 hours.

Huperzine A has been shown to be effective in inhibiting the actions of AChE to increase acetylcholine concentrations and alleviate some of the symptoms associated with acetylcholine deficiencies. Significant effects have been noted in patients both in terms of their life quality and their ability to retrieve past memories. In view of the fact that Huperzia serrata was used for many years in Chinese folklore medicine, and in accord with the Dietary Supplement Health & Education Act of 1994 (DSHEA) in this country, it has been possible to introduce Hup-A into the US market as a dietary supplement.

These findings suggest that Hup-A not only protect from the actions of Alzheimer’s and senile memory deficits, but also provides a unique and exciting supplement for supporting memory in the healthy aging human as well. Accordingly, Huperzine A is currently available as an over the counter “nutriceutical” for those individuals looking for support for memory.


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3. Xu SS; Gao ZX; Weng Z; Du ZM; Xu WA; Yang JS; Zhang ML; Tong ZH; Fang YS;Chai XS; et al, Efficacy of tablet huperzine-A on memory’ cognition’ and behavior in Alzheimer`s disease. Chung Kuo Yao Li, Hsueh Pao16:391-5, 1995.
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5. Mazurek, A. An open label trial of Huperzine A in the treatment of Alzheimer’s disease. Alternative Therapies, March 1999. Vol. 5, No. 2:97.
6. Saxena A, Qian N, Kovach IM, Kozikowski AP, Pang YP, Vellom DC, Radic Z, Quinn D, Taylor P, Doctor BP. Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases. Protein Sci 1994 Oct;3(10):1770-8.


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