Huperzine A continues to show its clinical efficacy for treatment for adults suffering of ongoing Alzheimer’s disease despite being virtually ignored by conventional medicine in the United States.
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| Huperzine or Club Moss |
What is Huperzine?
Huperzine A is extracted from the club moss plant (Huperzia serrata and other Huperzia species). These are collectively referred to as fir mosses or firmosses. There are numerous varieties of firmosses that grow on different continents.
Huperzine A, and its more newly found molecular relatives Huperzine B and Huperzine U, is a sesquiterpene that has a mechanism of blocking the enzyme acetylcholinesterase. Acetylcholinesterase will break down acetylcholine, an important neurotransmitter that allows information to be carried from one nerve to another.
Excess acetylcholinesterase has been observed among a number of cognitive disorders, including Alzheimer’s, Parkinson’s and other dementia forms.
As I first reported two years ago, the effectiveness of huperzine A on current Alzheimer’s and other dementia has been confirmed by a significant amount of clinical research. More recently, we have more evidence to add to this.
Combination therapy shows superiority of Huperzine A
Huperzine A is a acetylcholinesterase inhibitor. Four acetylcholinesterase inhibitors have been approved by the FDA – these are donepezil, rivastigmine, tacrine, rivastigmine and galantamine. Don’t see a mention of Huperzine in this list? So is Huperzine A less effective? Nope.
Researchers from the Department of Neurology at the China-Jan Friendship Hospital in Beijing recently conducted a study of 110 patients with Alzheimer’s disease. They were split into four groups and treated for six months with one of four possible treatments.
These included three of the FDA-approved acetylcholinesterase inhibitors just mentioned, along with huperzime A.
One group was treated with treatment was given the drug memantine with donepezil. Another was given memantine and rivastigmine, and another group was given memantine and galantamine. And another group of 22 patients was given the memantine along with huperzine A.
The last group was given the memantine together with a placebo.
The reason each group was given memantine is because other research has found that while memantine doesn’t world so well for Alzheimer’s disease by itself, for some reason it works great in combination with what are called acetylcholinesterase inhibitors because they block acetylcholinesterase.
Anyway, the patients were tested at the beginning, after three months and after six months of their treatment protocols.
The testing used the highly standardized Mini-mental state examination (MMSE), along with Activities of Daily Living (ADCS-ADL) scoring. This tests the ability of a person to do daily tasks without assistance – a test developed by the Alzheimer Disease Cooperative Study.
The researchers found that the group given the memantine with the huperzine A improved the most compared with the other groups.
Cholinesterase blocking activity confirmed
One of the mechanisms of this plant extract is that it naturally inhibits the enzyme acetylcholinesterase. This enzyme breaks down acetylcholine – which is necessary for the brain’s ability to transmit electrical activity through the nervous system.
A study published in 2015 by researchers from the Walter Reed Army Institute of Research studied 84 healthy young adults to test the extent of blocking acetylcholinesterase and affecting neurological behavior.
The researchers tested the drugs galantamine (doses at 4 or 8 milligrams), donepezil (doses at 2.5 or 5 milligrams) along with huperzine A (at either 100 or 200 μg). They gave the last group a placebo.
The researchers found that the huperzine A blocked acetylcholinesterase as well as increased recall and memory tasks – illustrating its ability to treat dementia.
Clinical research from the U.S. proves Huperzine A
The fact that Huperzine A is not used in the U.S. is puzzling, given that even U.S. researchers have proven its efficacy in clinical studies. A study from the School of Medicine at the University of California, San Diego (UCSD) tested 177 Alzheimer’s disease patients for up to four months.
They treated half the patients with either 200 milligrams or 400 milligrams of huperzine A. The researchers gave 70 patients a placebo for the period.
The research found that while the 200-milligram dose of huperzine A had little effect, the 400-milligram dosage of huperzine resulted in a significant improvement in the huperzine patients.
Their scores in the Alzheimer’s Disease Assessment Scale-cognitive test increased by 2.27 points at 11 weeks and 1.92 points at 16 weeks. This compares with little or no improvement among the placebo group.
42 studies confirm cognitive improvement for Alzheimer’s disease and other dementias
We can add to these studies the reality that international research – most of it from China – has proven Huperzine A’s efficacy over two decades of research.
A meta-study was conducted by researchers from the School of Public Health at China Medical University has confirmed that the plant constituent called Huperzine A can significantly improve cognitive function among Alzheimer’s disease patients.
The researchers found and analyzed 42 clinical studies that have investigated Huperzine A. They eliminated all studies that did not fit inclusion criteria for quality research. The researchers were left with eight high-quality placebo-controlled and randomized studies – five being double-blind and three being single-blind – involving more than 10 human subjects each.
In all, the eight studies followed 733 patients with Alzheimer’s disease. The fewest number of patients in a study was 28 and the most was 197. The studies ranged from 8 weeks to 24 weeks long.
All of the studies used the mini-mental state examination (MMSE) and the activities of daily living scale (ADL) to measure the results of the plant extract. These two tests are standardized tests that gauge the cognitive, consciousness and lifestyles of dementia patients.
They are often used to diagnose Alzheimer’s disease and other types of dementia. The MMSE test gauges orientation, repetition, attention, recall, language and complex commands.
The meta-analysis calculations of these studies found that Huperzine A significantly increased cognition among those patients compared to those taking the placebo.
The average drop in MMSE scores among the Huperzine A groups compared with the placebo groups – indicating improved condition – was 4.84 points.
Among those subjects with vascular dementia, the rate of improvement in MMSE scores was similar – dropping 4.92 in comparison with the placebo group.
The point system on the MMSE goes up to 30, with the higher scores being indicative of cognitive decline. An improvement of nearly 5 out of 30 points is a significant change – though its percentage change does not necessarily indicate a straight-line relationship.
Activities of daily living scale (ADL) scores also were significantly better among the Huperizine A groups. The difference between the Huperzine A and placebo groups among the vascular dementia cases was a significant 10.24 points lower.
The researchers added:
“The results from our meta-analysis of eight randomized controlled trials showed that Huperzine A could significantly improve the MMSE and ADL score of AD patients.”
Huperzine A more intelligent
The first study I discussed above illustrates that Huperzine A is a more effective acetylcholinesterase inhibitor compared with pharmaceutical acetylcholinesterase inhibitors. It is also smarter.
A recent study from India’s Integral University found that the acetylcholinesterase-inhibiting properties of Huperzine B provides a more intelligent “docking” potential with acetylcholinesterase compared with pharmaceutical acetylcholinesterase-inhibitors, which can come with significant side effects including dizziness.
Studies on Huperzine A have indicated a history of safety, with the few side effects noted as minor stomach upsets.
Other medicinal plants contain natural acetylcholinesterase-inhibitors. These include alkaloids such as quinolizidine, isoquinoline and indoles. Salix alba L. – Willow – for example, was found to have a 50% inhibition for acetylcholinesterase.
Researchers from Turkey’s Gazi University found that Heptaptera triquetra – also named Colladonia triquetra, a Mediterranean flowering plant in the parsley family – inhibited acetylcholinesterase over 80% in their laboratory studies.
Scientific References
Shao ZQ. Comparison of the efficacy of four cholinesterase inhibitors in combination with memantine for the treatment of Alzheimer’s disease. Int J Clin Exp Med. 2015 Feb 15;8(2):2944-8.
Morasch KC, Aaron CL, Moon JE, Gordon RK. Physiological and neurobehavioral effects of cholinesterase inhibition in healthy adults. Physiol Behav. 2015 Jan;138:165-72. doi: 10.1016/j.physbeh.2014.09.010.
Rafii MS, Walsh S, Little JT, Behan K, Reynolds B, Ward C, Jin S, Thomas R, Aisen PS; Alzheimer’s Disease Cooperative Study. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology. 2011 Apr 19;76(16):1389-94. doi: 10.1212/WNL.0b013e318216eb7b.
Shu-huai Xing, Chun-xiao Zhu, Rui Zhang, and Li An, “Huperzine A in the Treatment of Alzheimer’s Disease and Vascular Dementia: A Meta-Analysis,” Evidence-Based Complementary and Alternative Medicine, vol. 2014, Article ID 363985, 10 pages, 2014. doi:10.1155/2014/363985
Alam A, Shaikh S, Ahmad SS, Shakil S, Rizvi Smd, Shakil S, Imran M, Tabrez S, Kamal MA. Molecular Interaction of Human Brain Acetylcholinesterase with a Natural Inhibitor Huperzine-B: An Enzoinformatics Approach. CNS Neurol Disord Drug Targets. 2013 Sep 19.
Konrath EL, Passos Cdos S, Klein LC Jr, Henriques AT. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer’s disease. J Pharm Pharmacol. 2013 Dec;65(12):1701-25. doi: 10.1111/jphp.12090.
Jukic M, Burcul F, Carev I, Politeo O, Milos M. Screening for acetylcholinesterase inhibition and antioxidant activity of selected plants from Croatia. Nat Prod Res. 2012;26(18):1703-7. doi: 10.1080/14786419.2011.602639.
Şenol FS, Yilmaz G, Şener B, Koyuncu M, Orhan I. Preliminary screening of acetylcholinesterase inhibitory and antioxidant activities of Anatolian Heptaptera species. Pharm Biol. 2010 Mar;48(3):337-41. doi: 10.3109/13880200903133837.
Konrath EL, Passos Cdos S, Klein LC Jr, Henriques AT. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer’s disease. J Pharm Pharmacol. 2013 Dec;65(12):1701-25. doi: 10.1111/jphp.12090