Huperzine-A Additional Information
Huperzine-A is a compound extracted from the club moss, Huperzia serrata that is native to southeast Asia. It has been used in the traditional Chinese medicine, Qiang Ceng Ta. (1,2,3,4) In this setting, huperzine-A was used to aid with inflammation, fever, or contusions. (3,4)
There are two forms of huperzine-A, either (+) or (-). (+)-Huperzine-A is a synthetic form while (-)-huperzine-A is naturally found in Huperzia moss and has shown to have twice the potency of (+). (3,6) In the nootropics community, Huperzine-A has become popular for its acetylcholinesterase (AChE) inhibitory properties. (1,2,3,5) AChE is the enzyme primarily responsible for the breakdown of the neurotransmitter, acetylcholine (ACh), which is the main neurotransmitter for learning, memory, and retention.
In humans, huperzine-A has shown to be absorbed quickly and easily cross the blood-brain barrier allowing a wide distribution. (10)
Huperzine-A vs. Huperzine-B vs. Huperzia Serrata
Like huperzine-A, huperzine-B is extracted from the Huperzia serrata club moss. Although huperzine-B has shown to have AChE inhibitory properties, it is less researched than huperzine-A. (6) Additionally, the studies that have been conducted have shown huperzine-A to be 18% more effective than huperzine-B (6).
Even though huperzine-A is extracted from Huperzia serrata, it is not the same supplement. Huperzia serrata is the raw, powdered, moss. Huperzia serrata contains only .02% of huperzine-A by weight. (14) Studies that have been conducted have been conducted on huperzine-A and not Huperzia serrata. Due to the small amount of huperzine-A in Huperzia serrata, and the slow growth rate of these plants, some manufacturers utilize Huperzia serrate in place of huperzine-A. (2,14) Ensure you’re aware of the ingredients in your supplements by reviewing the nutritional label prior to purchase.
Huperzine A Benefits
Huperzine-A’s primary benefit is to act as an AChE inhibitor, meaning it stops AChE from breaking down ACh, resulting in an increase in ACh. (1,2,3,15) Although there are similar AChE inhibitors, huperzine-A has been found to be the most effective as it can bind and fill the active-site gorge in AChE. (9) As ACh is the primary neurotransmitter related to memory and learning, huperzine-A gives a cognitive boost by preventing its decline.
Huperzine-A also has a neuroprotective role in blocking NMDA ion channels. (1,2,7) Too much glutamate can result in glutamate toxicity. By blocking the NMDA ion channels, huperzine-A prevents excess glutamate from entering cells. (7)
- Enhance memory and learning (17,22)
- Anti-oxidative properties (16,18)
- Protective against Soman (nerve agent, toxic chemical substance) (20,21)
All of these benefits will be discussed further under “Huperzine-A Research”.
How to Use Huperzine-A
Huperzine-A is most commonly found as a tablet but can be found as a powdered capsule. Due to the smaller dosages (dosages are reported in micrograms vs. milligrams), tablets are more common. Individuals purchasing capsules should make sure to read the nutritional label of the product to see what fillers have been used.
When supplementing with huperzine-A, it is recommended to cycle the product due to its long half-life. Some recommendations include cycling for two to four weeks at a time and then taking a week off. Others recommend only taking huperzine-A every third day or no more than twice per week.
Huperzine-A is commonly included in pre-made stacks and therefore you should check the nutritional label prior to additional supplementation of huperzine-A. As huperzine-A is water soluble, it can be taken without food.
Huperzine A Dosage Guidelines
The typical dosage of huperzine-A is between 50 – 200mcg daily. As huperzine-A is commonly found as a tablet, it is easy to split dosages as needed by breaking the tablet. Individuals beginning supplementation with huperzine-A should start with 50mcg and work your way up to 200mcg. The 200mcg dosage can be taken at multiple dosages over the course of a day.
Half-life and Duration of Effects
Huperzine-A has an extremely long half-life. The average half-life of huperzine-A is between 10 to 14 hours but can be as long as 24 hours. (1,2) The extended half-life of huperzine-A is the main reasons cycling of the supplement is recommended.
Huperzine A Safety and Side Effects
Huperzine-A has been shown to be very safe and non-toxic. The LD50 (dosage required to kill half the population who took that dose) was found to be 3mg/kg in female rats, and 4mg/kg in male rats while supplementing over 180 days. (1) The NOAEL (no observable adverse effects limit) is in the range of 1mg/kg to 2mg/kg for rats. (1)
Huperzine-A has been reported to have very few side effects but may result in; nausea, dizziness, vomiting, diarrhea, headache, or thirst. As huperzine-A works to inhibit AChE and increase ACh, it is possible to experience side effects that are associated with too high of levels of ACh. These may include headaches, muscle weakness, or blurry vision.
If you’re suffering from a heart condition, or are using any medications that increase Ach levels Huperzine-A is not recommended.
How Huperzine-A Works
Huperzine-A’s mechanism of action is as an AChE inhibitor. Huperzine-A inhibits the G4 isoform of AChE in the mammalian brain. (1,8) The G4 isoform is the major AChE form in the central nervous system and hippocampus of the brain. G4 consists of four identical catalytic subunits attached to a cellular membrane. In striatum, a nucleus responsible for cognitive function, planning, and decision-making, huperzine-A showed to be the most potent inhibitor of G4 AChE. (8)
A team of scientists at the Weismann Institute in Israel showed additional mechanisms for huperzine-A’s inhibitory properties. (2,9) By rendering a 3-D image of the AChE molecule they were able to find an active-site gorge. AChE blocks acetylcholine (ACh) by funneling it into the interior of the enzyme, this gorge, which is where ACh is cut apart. (2,9)
Huperzine-A, more so than any other AChE inhibitor, has the ability to fit into, and bind tightly, to the active-site gorge. By taking the space in the gorge, it blocks ACh from entering the gorge and allowing it to become available to the brain. (2,9)
Preservation of physiological NMDA receptor activity is paramount to block excessive excitotoxic activity. Huperzine-A acts as a NMDA receptor antagonist which keeps calcium and glutamate at appropriate levels in brain cells preventing any damage. (1,2,7)
In addition to a neuroprotective ability, huperzine-A has shown neurogenesis promise. (11,12) A study aimed at the effects of huperzine-A on neuritogenic activity saw that administration of huperzine-A increased nerve growth factor (NGF). (12) NGF is involved in the regulation of growth, maintenance, and proliferation of neurons while increasing hippocampal cholinergic activity and enhancing survival of new neurons. (13) This suggests that the increase in hippocampal cholinergic activity and survival of new neurons promotes neurogenesis in the adult hippocampus. (13)
Huperzine-A Research
Huperzine as an Acetylcholinesterase Inhibitor (15)
The first study on huperzine-A as an AChE inhibitor was conducted on rats and wanted to investigate the increase of ACh as a result of this mechanism.
An I.V. injection of 183 mcg/kg was administered to the rats. The most pronounced effects occurred in the frontal and parietal cortexes where ACh levels increased by 125% and 105%. For the rest of the brain, the increase in ACh ranged from 22% - 65% with an overall average increase of 40% after 60 minutes. The AChE inhibition at this dosage lasted for 360 minutes.
Enhance Memory and Learning (17,22)
Since ACh is the primary neurotransmitter responsible for memory and learning, several studies have been conducted to determine the effectiveness of inhibiting AChE would be to improve these cognitive areas.
One double-blind and paired study of 34 junior middle school students was conducted as they had complained about memory inadequacy. In this study the students were divided into two groups by similar memory quotient (MQ), same sex, and class. One group was administered 50 mcg of huperzine-A, and the other, a placebo.
The group that was administered huperzine-A saw an increased MQ (115 > 104) and received higher marks in Chinese language lessons.
A separate study conducted was on mice where they were administered huperzine-A for seven days. The cognitive function of the mice was measured utilizing a Y-maze and passive avoidance tests. The mice who were administered huperzine-A saw that AChE was inhibited and they formed better on the tests.
Anti-Oxidative Properties (16,18)
Oxidative damage can occur when blood flow had been constricted from an area only to return to normal flow later. One study conducted on rats determined the role huperzine-A might play in this type of situation. The hepatic artery of the rats was clamped for 30 minutes followed by reperfusion for six hours. Prior to the artery being clamped, huperzine-A was administered in dosages of 167mcg/kg or 500 mcg/kg.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and their ratio, and biomarkers for liver health and were utilized to determine the effectiveness of huperzine-A. Both ALT and AST saw significant reductions following administration of huperzine-A. Other oxidative indicators saw improvement with huperzine-A while liver enzymes were not impacted.
Labil iron pool (LIP) is one of the main determinants of cellular response to oxidative stress. When rat cortical neurons were treated with ferric ammonium citrate (FAC), it was to determine the protective efforts of huperzine-A against iron overload-induced injury in neurons. The administration of huperzine-A blocked the upregulation of LIP level and other iron metabolism changes that would occur as a result of iron overload. Additionally, there was an increase in ATP; the source of energy for cells.
Neuroprotection from Glutamate Toxicity (19)
N-methyl-D-aspartate (NMDA) receptors allow glutamate to pass between cells. And although glutamate is generally good, too much can cause glutamate toxicity. One study showed that huperzine-A acts a non-competitive NMDA antagonist which aids in regulating glutamate levels and helps to prevent glutamate toxicity.
Protective Against Soman (20,21)
Soman is an extremely toxic chemical substance that can be used in biological warfare as a nerve agent. It works by interfering with the functioning of the central nervous system.
A study conducted on guinea pigs aimed to compare the efficacy of huperzine-A to that of pyridostigmine against Soman related health issues. The animals were either given .5mg/kg of huperzine-A or pyridostigmine (a medication that is used as an AChE inhibitor) prior to intoxication. Pretreatment of huperzine-A led to a decrease in central AChE activity. The huperzine-A guinea pigs worked to entirely prevent seizures as a result of Soman intoxication. Additionally, neuropathological chances that commonly occur with this intoxication were reported at a significantly lower rate for huperzine-A than pyridostigmine.
Huperzine A FAQ
Does huperzine-A raise blood pressure?
Although there is not enough testing that has been conducted, huperzine-A may raise your heart rate which in turn can increase blood pressure. As with most dietary supplements, it is recommended to speak with a physician before beginning the supplement.
Is huperzine-A popular for bodybuilders?
Huperzine-A has attracted interest from the body building community for its ability to add a boost to your focus and muscle contraction during workouts.
Is Huperzia serrata the same as huperzine-A?
Huperzine-A is extracted from Huperzia serrata but as a supplement is not the same. Powdered Huperzia serrata contains only .02% of huperzine-A by weight. Before taking a supplement that claims to be huperzine-A, it is best to check the nutrition label to ensure it’s not actually Huperzia serrata.
What is μg?
μg is the international symbol for micrograms (mcg). Huperzine-A is measured in micrograms due to small dosages and may be seen as μg.
Do I need to take huperzine-A with a meal?
Huperzine-A is water soluble and therefore does not need to be taken with food.
Is huperzine-A safe if I’m pregnant?
Huperzine-A should not be taken if pregnant. Not enough human studies have been conducted to determine its effect on pregnancy.
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