Huperzine A is an alkaloid compound extracted from a club moss called Huperzia serrata . It has been touted to have a number of neuroprotective and “ nootropic ” (cognitive-enhancing) properties, and has even suggested as a possible treatment for Alzheimer’s disease. But what does the science actually say about this plant-based supplement? Read on to learn more about Huperzine A, its potential effects, and how it might work!
Huperzine A (HupA) is an alkaloid compound extracted from club moss ( Huperzia serrata ).
Club moss (“ Qian Ceng Ta ”) has traditionally been used in Chinese medicine for fever, inflammation, and even schizophrenia [ 1 , 2 ].
Because of its long history of use in traditional medicine, huperzine A has been studied as a compound of interest for its potential effects on a number of important systems in the body and brain. While not all of its touted effects have been validated by science, there are a number of promising early findings that may suggest some potential applications of this supplement, which we’ll review in this post.
There are two forms of huperzine A: ‘(+)’ and ‘(-)’. The ‘(-)’ form is found naturally in the huperzia moss, and is believed to be more potent than the ‘(+)’ form.
Although the effects of huperzine A are still being actively studied by scientists, there are a few mechanisms that have been identified so far which may be responsible for some of its reported effects. Increases Acetylcholine
Huperzine A has been reported to be a potent, reversible, and specific inhibitor of the enzyme acetylcholine esterase (ACHE). This enzyme breaks down the major neurotransmitter acetylcholine , suggesting that some of huperzine A’s effects may come from generally increased levels of acetylcholine throughout the brain [ 3 ].
For example, according to one animal study, huperzine A was reported to increase acetylcholine levels in rat brains for up to 6 hours after administration [ 4 ].
Several animal studies have reported that huperzine A may result in a more prolonged increase in acetylcholine in the whole brain when compared to other compounds that raise acetylcholine levels, such as tacrine , physostigmine , and metrifonate [ 5 , 6 , 7 ].
According to one study, Huperzine A may work in similar ways to some Alzheimer’s disease medications which are also believed to affect the acetylcholine system of the brain, such as donepezil , rivastigmine , tacrine , and galantamine – although with fewer side effects and somewhat more favorable pharmacokinetics [ 8 ].
This potential increase in acetylcholine levels seems to differ between different parts of the rat brain. According to a few animal studies, following administration, maximum acetylcholine levels were observed in the hippocampus after 30 min, and in the frontal and prefrontal cortex after 60 min. These observations suggest that huperzine A may influence the function of different parts of the brain at different times [ 6 , 7 ].
However, some researchers have also stressed that huperzine A likely also has effects on other brain mechanisms that do not involve ACHE – so this effect alone is probably not the whole story [ 3 ]. Increases Norepinephrine and Dopamine – but not Serotonin
According to one animal study, huperzine A was reported to increase the levels of norepinephrine and dopamine in the brains of rats, while not affecting the levels of serotonin [ 9 ].
However, a lot more studies will be needed to know if these effects apply to the human brain as well. Neuroprotective Mechanisms
Early evidence from a few studies suggests that huperzine A may have a few mechanisms that could help protect the brain from stress and harm. Some of these suggestive findings include: Muscarinic and GABA receptors may play a role in some of the reports that huperzine A protects against seizures (mouse study) [ 10 ].
One literature review on huperzine A hypothesizes that it may help promote neuronal growth by stimulating the production and secretion of nerve growth factor (NGF) [ 3 ].
One in vitro cell study proposed that huperzine A may help prevent or reduce cell damage from lack of oxygen ( hypoxia ). This protective effect may be partly mediated by the “cholinergic anti-inflammatory pathway” through alpha7 nicotinic acetylcholine receptors [ 11 ].
However, all of these findings come primarily from animal and cell studies, which means that they are still quite far from having been proven. A lot more research will be needed to see what role, if any, huperzine A may have in protecting brain health in normal human users. Other Mechanisms
One animal study has reported that Huperzine A may help with inflammation in rats – in particular by reducing activities of NF-kB signaling, which may happen both through inhibition of acetylcholine esterase or in other ways [ 12 ].
Once again, though, a lot more follow-up studies will be needed to find out for sure how strong the effect is, as well as if it would apply to human users in any significant way.
In a systematic review of different interventions for Alzheimer’s, combined data from multiple studies was used to suggest that huperzine A may have a statistically significant effect in reducing cognitive decline during Alzheimer‘s disease [ 13 ].
However, while the early results are promising, there are some important limitations to note. For example, the quality of these studies is somewhat lower than the quality of studies of other medical interventions in Alzheimer’s disease and other dementia-related conditions. Many such studies are poorly-controlled or were not designed to rule out biases from the authors. In addition, most of the studies and clinical trials were from China, which raises some questions about their overall validity.
Nonetheless, according to some other researchers, huperzine A has been reported to prevent neuron loss during Alzheimer’s – specifically, by inhibiting the inflammatory responses caused by the build-up of amyloid beta , the main factor believed to be responsible for Alzheimer’s disease) [ 14 ].
In a related study, huperzine A was reported to inhibit the NF-kB pathway in immune cells in the brain. […]