Knoitol makes prescription drugs for Alzheimer’s look like snake oil.
Huperzine-A (HupA), a substance found in the club moss Huperzia serrata, has been used in China for centuries.
The Chinese Academy of Sciences took a renewed interest in HupA in the 1980s and developed it as a treatment for dementia,
particularly the dementia of Alzheimer’s Disease.
Medical research has so far provided support for the following applications of HupA:
- reduction of brain inflammation
- cognitive improvement and memory enhancement in Alzheimer’s patients
- cognitive improvement and memory enhancement in healthy people
- amelioration of dementia, including Alzheimer’s dementia
- repair of stroke damage in the brain.
In most respects HupA appears to be superior to all
anti-Alzheimer’s drugs currently approved by the U.S. Food and Drug
— drugs such as tacrine, donepezil, and rivastigmine. Unlike
these expensive prescription drugs, huperzine-A
- protects nerve cells from free radicals generated in the ‘beta-amyloid’ protein plaques found in Alzheimer’s brain tissue;
- interferes with the formation of these destructive beta-amyloid plaques;
- interferes with the ‘suicide’ programming that causes nerve cells to die when they receive spurious ‘time-to-die’ signals,
as they do under Alzheimer’s conditions;
- increases the brain’s production of nerve growth factor (NGF) — a substance involved in replacing lost cells;
- increases the brain’s production of NGF receptors — cell-surface proteins that are required for NGF activity.
Most recent clinical studies of huperzine-A use 400–800 mcg/day.
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Huperzine-A (HupA), a substance found in the club moss Huperzia serrata, has been used in China for centuries to treat swelling, fever, and blood disorders.
The Chinese Academy of Sciences took an interest in HupA in the 1980s
and developed it as a treatment for dementia, particularly the dementia
of Alzheimer’s Disease.
What we can’t tell you
the U.S. and some other industrialized countries, government agencies
like the U.S. Food and Drug Administration have adopted censorship as a
method for intensifying their control over the supplement industry and
its customers. Thus, FDA regulations prohibit us from telling you that
any of our products are effective as medical treatments, even if they are, in fact, effective.
Accordingly, we will limit our discussion of huperzine-A to a brief summary of recent research, and let you draw your own
conclusions about what medical conditions it may be effective in treating.
most respects HupA appears to be superior to all anti-Alzheimer’s drugs
currently approved by the U.S. Food and Drug Administration — drugs
such as tacrine, donepezil, and rivastigmine. HupA has better
penetration through the blood-brain barrier, higher oral
bioavailability, fewer side effects, and a longer duration of action
than these expensive prescription drugs.
The medical studies
all medical research on huperzine is the work of researchers in China
who conducted animal studies and human clinical trials. During the
1980s, 1990s, and early 2000s, they reported that HupA enhances memory
and protects nerve cells from the kinds of damage typically seen in
Alzheimer’s Disease. Double-blind, placebo-controlled clinical trials
in patients with and without Alzheimer’s resulted in significant
improvements in cognitive function and in the quality of life.
But these results had little impact in the medical world outside China.
Finally, in 2004 the U.S. National Institutes of Health (in
collaboration with a company that hopes to turn HupA into a
prescription drug) organized a clinical trial to study HupA in
Alzheimer’s patients. The trial was completed in 2006, but the results
have not yet been published.
Animal studies have shown that HupA protects the nervous system from organophosphate nerve-gas agents.
This fact has no relevance to supplement buyers except insofar as it
provides further evidence of huperzine’s powerful neuroprotective
How does huperzine work?
HupA appears to affect multiple biochemical pathways in the brain, several of which are involved in Alzheimer’s Disease. The
best understood of these pathways is the one in which the neurotransmitter acetylcholine
carries signals from one nerve cell to another in certain parts of the
brain. In Alzheimer’s Disease, there is a shortage of acetylcholine,
and consequently an impaired signalling ability. HupA is an inhibitor
of the enzyme that breaks down acetylcholine. Thus, HupA causes this
neurotransmitter to accumulate in the space between the cells,
permitting higher levels of signalling to take place.
If this were huperzine’s only effect on
Alzheimer’s, it would have no advantage (other than price) over the
prescription drugs currently available — i.e., it would merely
compensate temporarily for the impairment caused by damaged and dead
nerve cells, but it would not slow the destruction of nerve cells or
bring about the repair of damaged tissue. But as luck would have it,
HupA has additional modes of action:
- It protects nerve cells from free radicals generated by the ‘beta-amyloid’ protein plaques found in Alzheimer’s brain tissue.
- It interferes with the formation of these destructive beta-amyloid plaques.
- It interferes with the ‘suicide’ programming that causes nerve cells to die when they receive spurious ‘time-to-die’ signals,
as they do under Alzheimer’s conditions.
- It increases the brain’s production of nerve growth factor (NGF) — a substance involved in generating replacements for lost
- It increases the brain’s production of NGF receptors — cell-surface proteins that are required for NGF activity.
Dosage used in Alzheimer’s studies
recently, supplement companies sold huperzine as a cognitive enhancer
for people whose cognitive abilities fell into the normal range, and
the dosages were small — 50 mcg/day, for example. But now that the
Chinese studies on Alzheimer’s patients have become known outside of
China, it is realized that larger doses are needed. The latest clinical
studies use 400–800 mcg/day.LifeLink has therefore increased the dosage in its hupA product Knoitol to 200 mcg.
Does huperzine repair stroke damage?
the final word has not been heard on this subject, preliminary
experiments with gerbils and other animals indicate that HupA limits
memory deficits and neuronal damage after stroke-like brain injuries.
Gerbils were given HupA orally at 0.1 mg/kg twice per day for 14 days.
(This is a much larger dose than is used in human Alzheimer’s studies.)
Are huperzine supplements useful for the conditions and purposes mentioned above? We aren’t allowed to tell you, so you should
take a look at some of the references cited here, and then decide for yourself.
 The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in
the treatment of Alzheimer's disease. Pharmacol Biochem Behav. 2003 Jun; 75(3):675-86 Zangara A
 Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006 Jan; 27(1):1-26 Wang R, Yan H, Tang XC
 Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese
medicine origin for the treatment of Alzheimer's disease. Curr Med Chem. 2003 Nov; 10(21):2231-52 Jiang H, Luo X, Bai D
 [Drug evaluation of huperzine A in the treatment of senile memory disorders] Zhongguo Yao Li Xue Bao. 1991 May; 12(3):250-2 Zhang RW, Tang XC, Han YY, Sang GW, Zhang YD, Ma YX, Zhang CL, Yang RM
 Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo Yao Li Xue Bao. 1999 Jul; 20(7):601-3 Sun QQ, Xu SS, Pan JL, Guo HM, Cao WQ
 Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao. 1999 Jun; 20(6):486-90 Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B
 [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; 82 :941-4 Zhang Z, Wang X, Chen Q, Shu L, Wang J, Shan G
 Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao. 1995 Sep; 16 :391-5 Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS
 Huperzine A in Alzheimer's Disease ClinicalTrials.gov website
 Review of the value of huperzine as pretreatment of organophosphate poisoning. Neurotoxicology. 2002 May; 23(1):1-5 Lallement G, Baille V, Baubichon D, Carpentier P, Collombet JM, Filliat P, Foquin A, Four E, Masqueliez C, Testylier G, Tonduli
L, Dorandeu F
 Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci. 2006 Dec; 27(12):619-25 Zhang HY, Tang XC
 Stereoselectivities of enantiomers of huperzine A in protection against beta-amyloid(25-35)-induced injury in PC12 and NG108-15
cells and cholinesterase inhibition in mice. Neurosci Lett. 2002 Jan 14; 317(3):143-6 Zhang HY, Liang YQ, Tang XC, He XC, Bai DL
 Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive
oxygen species formation and caspase-3 activation. J Neurosci Res. 2002 Jan 1; 67(1):30-6 Xiao XQ, Zhang HY, Tang XC
 Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neurosci Lett. 2000 Sep 29; 292(1):41-4 Zhang HY, Tang XC
 Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. J Neurosci. 2003 Jun 1; 23(11):4590-600 Angelastro JM, Ignatova TN, Kukekov VG, Steindler DA, Stengren GB, Mendelsohn C, Greene LA
 Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci Lett. 2001 Nov 9; 313(3):137-40 Zhou J, Zhang HY, Tang XC
 [Huperzine A attenuates cognitive deficits and brain injury after hypoxia-ischemic brain damage in neonatal rats] Zhonghua Er Ke Za Zhi. 2003 Jan; 41(1):42-5 Wang LS, Zhou J, Shao XM, Tang XC