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Evidence Based

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Huperzine A Benefits: Just Another Brain Health Trend?

Written by Dr. Michael Ruscio, DC on June 16, 2022

Written by Dr. Michael Ruscio, DC on June 16, 2022 — Reviewed by Dr. Hannah Hamlin

Where Huperzine A Holds Up and Falls Short, According to the Research

• Huperzine A Benefits|
• Is Huperzine A Safe?|
• Research-Backed Supplements for Brain Health|
• Back to the Basics|
• The Verdict Is Still Out|

Supplements that promise to boost your brainpower, often referred to as nootropics, have recently flooded the market, with huperzine A at the top of the list. With its protective effect on the brain and promises to increase cognition, it’s become a popular supplement for warding off cognitive decline. 

That being said, nearly all of the research supporting the use of this supplement has been done on those already experiencing cognitive impairment or dementia. There’s little evidence to back up whether huperzine A benefits extend to healthy populations. 

While it appears to stand up to traditional prescriptions for reducing the symptoms of dementia, the lack of research surrounding its safety for short- and long-term use and its relatively high side-effect profile make it a less-viable option at this time for increasing cognition. Even more, it’s hard to trust brain health supplements containing huperzine A when many have unidentified compounds, are missing ingredients listed on the label, and have no research to back up their medical claims.

When opting for ways to boost your brainpower, it’s probably best to stick to supplements that are more heavily supported by research, and the tried-and-true methods of diet, sleep, and exercise. However, huperzine A does show some promising health benefits, so read on for a closer look at what it can and can’t do for you. 

Huperzine A Benefits

Huperzine A (known as Qian ceng ta in China) is an alkaloid isolated from Huperzia serrata, or Chinese club moss, that mainly acts upon the nervous system [1]. Its neuroprotective and neurotrophic (cognition-enhancing) benefits have shown to be effective in treating cognitive decline and certain forms of dementia, like Alzheimer’s disease [1].

Huperzine A is a reversible acetylcholinesterase inhibitor, meaning it increases the levels of acetylcholine in the body by blocking the enzyme that’s responsible for breaking it down [1]. Acetylcholine is an important neurotransmitter that acts upon the nervous system to help with learning, memory, sleep, mood, and many other bodily functions [2]. By preventing the degradation of acetylcholine, huperzine A is thought to boost cognitive function [3].

Huperzine A benefits also include an increase in brain-derived neurotrophic factor (BDNF) [4]. BDNF is an important molecule that resides in the central nervous system (CNS), and increases the processing of information and creates lasting changes in memory and learning [5].

It may also reduce the harmful effects of excess glutamate, an excitatory neurotransmitter, by modulating NMDA receptors in the brain. It has an overall neuroprotective effect in the CNS, as it can reduce oxidative stress and promote the survival of neurons [4].

Huperzine A benefits may be considered to be closely related to that of nicotine, as they both increase acetylcholine levels and are shown to increase cognition [6]. However, these two alkaloids have vastly different effects on the body, and, unlike huperzine A, nicotine is a highly addictive CNS stimulant [7].

What Conditions Is Huperzine A Used For? 

Research on huperzine A benefits is mostly concerning the treatment of Alzheimer’s, where it shows significant enhancement in cognition. A 2018 systematic review/meta-analysis found that while prescription medications were most effective in treating vascular dementia, huperzine A was better than other treatments [8].

Huperzine A is fairly well-tolerated and effective for improving cognition in those with Alzheimer’s disease and vascular dementia, but it should be used cautiously (more on this later) [9].

Overall, acetylcholinesterase inhibitors, including huperzine A, are considered the best treatments for alleviating cognitive deficits and improving performance of daily living activities in those with Alzheimer’s disease [10, 11]. Another study found it to be the third most useful drug for improving cognition in those experiencing mild to moderate cognitive decline (with traditional pharmaceuticals being the most helpful in severe cognitive decline) [12].

The effects of huperzine A on improving and protecting cognition may extend to select health conditions, including: 

• Schizophrenia [13]
• Major depressive disorder (MDD) [14]
• Multiple sclerosis [15]
• Myasthenia gravis (an autoimmune condition that causes weakness) [16]

Can Huperzine A Help Boost My Memory or Cognition?

Research on the use of huperzine A in healthy populations is significantly lacking, and only one, small trial found it to be beneficial in improving memory and learning in healthy teenagers [17]. However, just because the research behind huperzine A is sparse doesn’t mean that it can’t improve cognitive function in healthy individuals, and many have anecdotally found it to be helpful.

While huperzine A may be a promising supplement for boosting cognition, it may not be the best place to start, as we don’t have enough information on its safety or long-term effects. Fortunately, there are plenty of supplements (a few of which we’ll discuss later) that do have research-backed benefits for brain health.

Is Huperzine A Safe?

In short — we don’t know. While, anecdotally, huperzine A is considered safe when taken in small doses for a short period of time, there’s really not enough research on its safety for short-term or long-term use at this time. 

The pharmacokinetics of huperzine A show that it has a half-life of about 12 hours (meaning it’s out of your system in about two days) and its levels can build up in your body when taken daily over a long period of time. This is why many who use huperzine A recommend “cycling” its use (e.g. four weeks on, one week off). Dosing is very small and is typically between 30 mcg (micrograms) and 100 mcg per day. 

This likely reduces the risk of side effects that can occur due to excess acetylcholine levels in the body, which include [18]:

• Nausea and vomiting
• Diarrhea
• Sweating
• Blurred vision
• Muscle twitching
• Dizziness

While several studies have found huperzine A to be fairly well-tolerated [19, 20], there are a few studies that suggest the contrary, where participants experienced more side effects when compared to placebo [21].

I have personally experimented with huperzine A, and while I found that I benefited from a broader vocabulary and sharper memory, I had to discontinue due to an unwanted side effect of insomnia. Overall, there’s too little evidence regarding its safety and toxicity to be able to recommend it for either short-term or long-term use. 

However, the research is pretty clear on who should not be using huperzine A, as it should be avoided in the following conditions [18]:

• Those taking cholinesterase inhibitors (donepezil) or anticholinergic drugs
• Pregnancy
• Epilepsy
• Cardiac arrhythmias
• Asthma
• Irritable bowel syndrome (IBS)
• Inflammatory bowel disease (IBD)
• Malabsorption syndromes

Where Brain Health Supplements Fall Short

A big concern with brain health supplements, including huperzine A, is that many are adulterated and misbranded. A 2020 analysis of commercially available nootropic supplements (most of which contained huperzine A) found that nearly 70% of the tested supplements had an ingredient listed on the bottle that wasn’t found in the supplement itself. Of the 12 supplements analyzed, 10 contained compounds not listed on the Supplement Facts label [22].

Furthermore, the supplement companies made false claims, such as their product being “clinically proven” or containing “the most scientifically researched supplements,” but only one of the tested products offered research to back up their claims, and the results were contradictory [22].

While it’s always best to seek out medical advice from your healthcare provider before starting a new dietary supplement, the following questions can help you avoid unsafe and ineffective nootropic products [22]:

• Are there less than six ingredients listed on the label?
• Does the product have a seal stating that it’s third-party verified?
• Is the amount of caffeine limited to 200 mg or less?
• Is the label free of questionable claims?
• Is the label free of the terms “proprietary,” “blend,” “matrix,” or “complex”? 

If your brain health supplement doesn’t fulfill the above criteria, it may be best to leave it on the shelf. 

Research-Backed Supplements That Boost Cognition

While the verdict may still be out on huperzine A benefits and its overall safety, there are plenty of safe, research-supported supplements that can help give your brain a boost. 

Probiotics

These mighty microbes come with hard-hitting effects of boosting cognition, improving memory, and reducing stress and anxiety in highly stressed adults [23]. Like huperzine A, the benefits of cognitive function appear to be most significant in those already experiencing cognitive impairment [24, 25, 26].

However, unlike huperzine A, they have relatively no side effects, even when used daily and long-term. Even more, they have a wide-array of health benefits and are a safe and easy option for improving overall well-being.

Ashwagandha

Ashwagandha has numerous health benefits, with many of them extending to brain function. Research shows that this botanical can help [27, 28]:

• Increase cognitive performance
• Lengthen attention span
• Heighten reaction time
• Improve memory

A 2020 systematic review shows that ashwagandha can improve cognitive dysfunction, cognitive performance, attention, and reaction time in a variety of populations and is safe for regular use [27].

Phosphatidylserine

Phosphatidylserine levels are thought to naturally decline with age, and research shows that phosphatidylserine supplements can significantly improve memory and attention in those suffering with complaints of low memory [29]. Supplementing with this fatty acid-containing product can likely improve memory, mood, and cognition in those with Alzhiemer’s disease [30].

Choline

Research on choline (a precursor to acetylcholine) shows that this compound may help with cognitive enhancement and improve memory in healthy populations. Furthermore, it can slow the progression and limit the adverse effects of dementia [31].

While the above supplements have more research on their benefits and safety than huperzine A, it doesn’t make any of them a “magic pill.” To get the most out of your brain-boosting supplements, it’s best to make sure that your gut health is in check and your diet and lifestyle are up to par. 

Back to the Basics of Brain Health

Our brain health is highly influenced by diet, exercise, stress, and sleep, and it’s important to get the proper foundations dialed in before adding on supplements. 

Diet and Weight Loss

Maintaining a healthy weight is one of the most important things you can do to protect yourself against cognitive decline [32], and those who are overweight during midlife are more likely to develop dementia [33]. As research shows that a variety of diets are beneficial for boosting cognition in both healthy adults and those with cognitive deficits, it’s probably less important to rely on one specific diet and better to find one that fits your individual needs [34, 35, 36, 37].

Figuring out your food sensitivities, balancing your blood sugar, and eating anti-inflammatory foods can go miles when trying to improve your brain health. For more support on finding the right diet for you, check out one of our many articles on diet and gut health. 

Physical Activity

Exercise can significantly decrease inflammation and improve sleep quality, which are incredibly important for optimizing brain function [38, 39]. Even better, its cognitive benefits are seen in healthy populations, and regular exercise can [40]:

• Increase processing speed and attention
• Improve working memory
• Reduce inhibition related to academic performance
• Enhance language skills

It’s also beneficial for older adults to engage in regular exercise, as it can improve mild cognitive impairment, cognitive function, and executive function [41].

Sleep

Lastly, sleep has an extremely important role in keeping your brain healthy. While we sleep, we solidify in our memory what we learned throughout the day, and the healthy functioning of nerve cells is restored [42]. When we cut our sleep short, we’re likely short-changing our brains as well.

Amyloid plaques (abnormal protein deposits found in the brains of Alzheimer’s patients) are cleared during sleep, and elevated amyloid plaque levels are associated with sleep deprivation [42, 43]. Sleep is vital for warding off dementia, and is clinically proven to help improve memory and emotional well-being [44, 45].

Huperzine A Benefits: The Verdict Is Still Out

Unless you’re suffering from cognitive decline or dementia, the verdict is still out on whether huperzine A can improve your cognition. Even then, it’s probably better to stick with traditional pharmaceuticals and research-backed supplements, as the short- and long-term effects of huperzine A are unclear at this time. 

While supplements can certainly give your brain a boost, remember to focus on your diet and lifestyle first before adding them in, so that you can get the maximum benefit. You can find more information on improving your brain health in my book, Healthy Gut, Healthy You, or by reaching out to the clinic at the Ruscio Institute for Functional Medicine for an appointment. 

The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you.