Research & Education

Huperzine A: Clinical Tool for Alzheimer’s Disease?

Estimates indicate that 6.2 million Americans who are 65 years of age and older live with Alzheimer’s disease, and that number has the potential to grow to 13.8 million by 2060. In 2019, Alzheimer’s disease was the sixth leading cause of death and the fifth leading cause of death among those who were 65 years of age and older. Due to its significant impact, researchers are searching for different, potential ways to prevent, mitigate, and treat this condition. One promising naturally occurring compound is huperzine A.

Derived from the club moss Huperzia serrata, this alkaloid compound may act as an acetylcholinesterase inhibitor. Studies have found that a deficiency of cholinergic neurotransmission may play a role in Alzheimer’s disease and its associated symptoms. Cholinergic neurons use the neurotransmitter acetylcholine. Cholinergic neurotransmitters are widely distributed throughout the central nervous system, with almost all regions of the brain innervated by cholinergic neurons. Cholinergic neurotransmission is involved in attention, learning, memory, stress response, wakefulness, sleep, and sensory information.  

As an acetylcholinesterase inhibitor, huperzine A may inhibit the enzyme acetylcholinesterase, which in turn may increase the available acetylcholine to act on the receptors involved in cognition, learning, and memory. Studies have found that improved cholinergic neurotransmission is associated with stabilization or less than an expected decline in cognition function, behavior, and memory function. 

Studies have also determined that in addition to its effect on acetylcholine, huperzine A may modify the process of beta-amyloid peptides, which also plays a role in the development of Alzheimer’s disease. Additionally, huperzine A may support a normal redox balance. Excessive oxidative stress and neuroinflammation have also been shown to potentially play a role in Alzheimer’s disease. Further beneficial effects of huperzine A on cognition may be a result of the support of a healthy apoptosis cycle and the normal regulation of the expression, secretion, and signaling of the nerve growth factor. One animal study also found that huperzine A reduced inflammation in the hippocampus and increased brain-derived neurotrophic factors and hippocampal nerve growth. 

These potential benefits for Alzheimer’s disease have been supported in clinical studies. In a systematic review and meta-analysis, researchers evaluated the studies using huperzine A in patients with Alzheimer’s disease. They determined that huperzine A provided beneficial effects on improving cognitive function and global clinical assessment in these patients. The studies also found that patients had improvements in their activities of daily living. Another clinical trial found that treatment with huperzine A improved task switching abilities in patients with Alzheimer’s disease, another potential area of cognitive improvement.

Cognitive dysfunction and memory impairment are major symptoms of Alzheimer’s disease, and as such, these are key areas that researchers target when searching for potential beneficial elements for patients with this disorder. A healthy diet and lifestyle and supportive naturally occurring compounds, such as huperzine A, may play a role in supporting normal cognitive function and memory.*

By Kendra Whitmire