What is Huperzine A?
Huperzine A (HupA) was first isolated from Huperzia serrata (Thunb) Trev., a Chinese club moss, in the early 1980s. This plant has been used as a Traditonal Chinese Medicine compound for treating contusions, strains, swelling, and even schizophrenia. The HupA sold today is a highly extracted and purified version of the active compound found in Chinese club moss (the average yield of HupA is 0.011%).
How does it work?
The mechanism of HupA is its strong inhibition of the enzyme acetylcholinesterase (AChE). This was suspected for many years and confirmed in the 1980s and 1990s. Crystal structure studies demonstrated that HupA tightly binds to the active site of AChE, thereby preventing it from breaking down the neurotransmitter acetylcholine. The end result is a significant increase in acetylcholine levels. HupA also increases norepinephrine and dopamine levels, presumably because acetylcholine pathways activate downstream norepinephrine and dopamine circuits. All of these neurotransmitters bind to receptors on neurons and stimulate brain activity.
Many basic research labs continue to study to novel HupA benefits. It is hypothesized to protect neurons against insults that cause cell death, promote neuronal growth and maintenance, and shows potential to protect against toxic nerve agents used in biological warfare (sarin, organophosphorus esters, etc.).
Huperzine A benefits
Cholinergic circuits in the brain are stimulated by acetylcholine, and some of these pathways are among the first to be affected in Alzheimer’s disease. For this reason, increasing acetylcholine signaling in the brain has long been a target of pharmaceutical companies. There is evidence that this plant-derived compound may do an even better job than synthetic acetylcholinesterase inhibitors because it binds more tightly and specifically to the enzyme. Moreover, the acetylcholinesterase inhibitors sold by pharmaceutical companies can cost hundreds of dollars a month and could cause severe liver damage or other serious side effects.
In addition to possible treating cognitive dysfunction associated with Alzheimer’s or other forms of dementia, healthy people can benefit from taking HupA regularly. It is reported to help improve short-term memory and learning ability. Others have found that it allows them to articulate their thoughts faster and more clearly.
Huperzine A side effects
Because of its effects on acetylcholine levels, HupA can increase intestinal secretions and may upset the gastrointestinal tract. This could result in side effects including nausea, vomiting, and diarrhea. It may also exacerbate pre-existing ulcers in the stomach. Other reported side effects include sweating, restlessness, loss of appetite, muscle twitches, high blood pressure, and bradycardia (slowed heart rate). Many of these are also attributable to HupA’s effect on acetylcholine transmission.
Patients that take other cholinesterase inhibitors, e.g., donepezil (Aricept), rivastigmine (Exelon), or galantamine (Razadyne) should not take HupA, as it could cause nausea, vomiting, diarrhea, dizziness, and muscle cramps due to excessive cholinergic signaling.
Huperzine A dosage
HupA is quickly absorbed through the gastrointestinal tract and readily crosses the blood-brain barrier, so the required doses are much lower than what you normally see on a bottle (micrograms as opposed to milligrams!). It is also very safe. Studies have demonstrated that taking 50-100 times more than the recommended therapeutic dose does not result in toxicity.
Dementia patients are typically prescribed twice-daily doses that range from 50-200 micrograms (mcg). Healthy people often take 50-100 mcg twice a day. Most formulations are 50 mcg/capsule. The effects of HupA last for approximately 6 hours, so it is recommended to take one does in the morning and another in the early afternoon for maximum benefits.
HupA is also sometimes prescribed as a treatment for the neurological disease myasthenia gravis (MG). However, MG patients receive a daily shot of HupA, whereas it is taken orally to help with memory.
Bai, D. L., X. C. Tang, and X. C. He. “Huperzine A, A Potential Therapeutic Agent for Treatment of Alzheimer’s Disease.” Current Medicinal Chemistry 7.3 (2000): 355-74. Print.
“HUPERZINE A.” WebMD. WebMD. Web. 13 Mar. 2012. <http://www.webmd.com/vitamins-supplements/ingredientmono-764-HUPERZINE%20A.aspx?activeIngredientId=764&activeIngredientName=HUPERZINE%20A>.
Raves, Mia L., Michal Harel, Yuan-Ping Pang, Israel Silman, Alan P. Kozikowski, and Joel L. Sussman. “Structure of Acetylcholinesterase Complexed with the Nootropic Alkaloid, (–)-huperzine A.” Nature Structural Biology 4.1 (1997): 57-63. Print.
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